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WILLIAMS, NICOLE C., e STEVEN C. INGHAM. "Thermotolerance of Escherichia coli O157:H7 ATCC 43894, Escherichia coli B, and an rpoS-Deficient Mutant of Escherichia coliO157:H7 ATCC 43895 Following Exposure to 1.5% Acetic Acid". Journal of Food Protection 61, n.º 9 (1 de setembro de 1998): 1184–86. http://dx.doi.org/10.4315/0362-028x-61.9.1184.
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On a beef carcass, Escherichia coli may sequentially encounter acid- and heat-intervention steps. This study tested whether acid stress (1.5% [vol/vol] acetic acid, pH 4.0, 37°C, 15 min) would enhance subsequent heat resistance of E. coli. Initially, cells (E. coli O157:H7 ATCC 43894, nonpathogenic E. coli B [strain FRIK-124], and rpoS-deficient mutant 813-6 [derived from E. coli O157:H7 ATCC 43895]) were acid stressed and transferred to 54°C tiypticase soy broth (TSB), and survivors were immediately enumerated after at least three intervals of 12, 2, and 6 min, respectively, by plating. The ATCC 43894 and 813-6 strains survived the acid stress but strain FRIK-124 did not. Acid-stressed ATCC 43894 had significantly lower D values than the non-acid-stressed controls. Strain 813-6 had significantly lower D values than strain ATCC 43894, with no significant difference between acid-stressed and non-acid-stressed cells. In a second experiment, cooling of cells prior to plating resulted in an increased D value for acid-stressed ATCC 43894 cells, such that it was not significantly different from the D value for non-acid-stressed Controls. Using this protocol, there was no significant difference in D values between acid-stressed and non-acid-stressed ATCC 43894 cells in prewarmed TSB (54, 58, and 62°C), in prewarmed ground beef slurry (GBS; 58°C), or in TSB and GBS inoculated at 5°C and heated to 58°C. The acid stress tested does not enhance subsequent heat resistance of E. coli.
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Zhang, Xiangyan, Wenwen Ran, Jie Wu, Hong Li, Huamin Liu, Lili Wang, Yujing Xiao, Xiaonan Wang, Yujun Li e Xiaoming Xing. "Deficient mismatch repair and RAS mutation in colorectal carcinoma patients: a retrospective study in Eastern China". PeerJ 6 (5 de fevereiro de 2018): e4341. http://dx.doi.org/10.7717/peerj.4341.
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Objectives To investigate the frequency and prognostic role of deficient mismatch repair (dMMR) and RAS mutation in Chinese patients with colorectal carcinoma. Methods Clinical and pathological information from 813 patients were reviewed and recorded. Expression of mismatch repair proteins was tested by immunohistochemistry. Mutation analyses for RAS gene were performed by real-time polymerase chain reaction. Correlations of mismatch repair status and RAS mutation status with clinicopathological characteristics and disease survival were determined. Results The overall percentage of dMMR was 15.18% (121/797). The proportion of dMMR was higher in patients <50 years old (p < 0.001) and in the right side of the colon (p < 0.001). Deficient mismatch repair was also associated with mucinous production (p < 0.001), poor differentiation (p < 0.001), early tumor stage (p < 0.05) and bowel wall invasion (p < 0.05). The overall RAS mutation rate was 45.88%, including 42.56% (346/813) KRAS mutation and 3.69% (30/813) NRAS mutation (including three patients with mutations in both). KRAS mutation was significantly associated with mucinous production (p < 0.05), tumor stage (p < 0.05) and was higher in non-smokers (p < 0.05) and patients with a family history of colorectal carcinoma (p < 0.05). Overall, 44.63% (54/121) dMMR tumors harbored KRAS mutation, however, dMMR tumors were less likely to have NRAS mutation. Moreover, dMMR, KRAS and NRAS mutation were not prognostic factors for stage I–III colorectal carcinoma. Conclusions This study confirms that the status of molecular markers involving mismatch repair status and RAS mutation reflects the specific clinicopathological characteristics of colorectal carcinoma.
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Bhamani, Shireen Shehzad, Omrana Pasha, Rozina Karmaliani, Nargis Asad e Iqbal Azam. "Validation of the Urdu Version of Wagnild and Young’s Long and Short Resilience Scales Among 20- to 40-Year-Old Married Women Living in Urban Squatter Settlements of Karachi, Pakistan". Journal of Nursing Measurement 23, n.º 3 (2015): 425–35. http://dx.doi.org/10.1891/1061-3749.23.3.425.
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Background: There were no instrument exists in South Asia to assess resilience. Thus, this study assessed the validity and reliability of the Urdu version of Wagnild and Young’s long and short Resilience Scales. Methods: Study was carried out in two urban squatter settlements of Karachi, Pakistan. Resilience Scales were validated against the depression, anxiety, and life satisfaction scales among 20- to 40-year-old married women. Sample size for validity and reliability were 636 and 319. Results: Moderate negative correlation with the depression and anxiety and moderate positive significant correlation with life satisfaction were found with both scales. The test–retest correlation were .54 and .49, respectively. Internal consistency were found acceptable. Concurrent validity were .729 and .813. Conclusions: Study found a valid and reliable resilience scale in Urdu language.
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Ruusunen, Anu, Soili M. Lehto, Tommi Tolmunen, Jaakko Mursu, George A. Kaplan e Sari Voutilainen. "Coffee, tea and caffeine intake and the risk of severe depression in middle-aged Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study". Public Health Nutrition 13, n.º 8 (1 de abril de 2010): 1215–20. http://dx.doi.org/10.1017/s1368980010000509.
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AbstractObjectiveOnly a few cross-sectional studies have assessed the association between coffee, tea and caffeine and the risk of depression. Our aim was to determine the association in a population-based cohort study.DesignThe population-based Kuopio Ischaemic Heart Disease Risk Factor Study cohort was recruited between 1984 and 1989 and followed until the end of 2006. We investigated the association between the intake of coffee, tea and caffeine and depression.SettingEastern Finland.SubjectsMiddle-aged men (n 2232).ResultsAltogether, forty-nine men received a discharge diagnosis of depression. We classified subjects into quartiles according to their mean daily coffee intake: non-drinkers (n 82), light drinkers (<375 ml/d, n 517), moderate drinkers (375–813 ml/d, n 1243) and heavy drinkers (>813 ml/d, n 390). Heavy drinkers had a decreased risk (RR = 0·28, 95 % CI 0·08, 0·98) for depression when compared with non-drinkers, after adjustment for age and examination years. Further adjustment for socio-economic status, alcohol consumption, smoking, maximal oxygen uptake, BMI and the energy-adjusted daily intakes of folate and PUFA did not attenuate this association (relative risk (RR) = 0·23, 95 % CI 0·06, 0·83). No associations were observed between depression and intake of tea (drinkers v. non-drinkers; RR = 1·19, 95 % CI 0·54, 2·23) or caffeine (highest quartile v. lowest quartile; RR = 0·99, 95 % CI 0·40, 2·45).ConclusionsCoffee consumption may decrease the risk of depression, whereas no association was found for tea and caffeine intake.
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Trac, Hy, Renyue Cen e Philip Mansfield. "SCORCH. I. THE GALAXY–HALO CONNECTION IN THE FIRST BILLION YEARS". Astrophysical Journal 813, n.º 1 (28 de outubro de 2015): 54. http://dx.doi.org/10.1088/0004-637x/813/1/54.
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Teo, Seng Chong, Kok Jun Liew, Mohd Shahir Shamsir, Chun Shiong Chong, Neil C. Bruce, Kok-Gan Chan e Kian Mau Goh. "Characterizing a Halo-Tolerant GH10 Xylanase from Roseithermus sacchariphilus Strain RA and Its CBM-Truncated Variant". International Journal of Molecular Sciences 20, n.º 9 (9 de maio de 2019): 2284. http://dx.doi.org/10.3390/ijms20092284.
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A halo-thermophilic bacterium, Roseithermus sacchariphilus strain RA (previously known as Rhodothermaceae bacterium RA), was isolated from a hot spring in Langkawi, Malaysia. A complete genome analysis showed that the bacterium harbors 57 glycoside hydrolases (GHs), including a multi-domain xylanase (XynRA2). The full-length XynRA2 of 813 amino acids comprises a family 4_9 carbohydrate-binding module (CBM4_9), a family 10 glycoside hydrolase catalytic domain (GH10), and a C-terminal domain (CTD) for type IX secretion system (T9SS). This study aims to describe the biochemical properties of XynRA2 and the effects of CBM truncation on this xylanase. XynRA2 and its CBM-truncated variant (XynRA2ΔCBM) was expressed, purified, and characterized. The purified XynRA2 and XynRA2ΔCBM had an identical optimum temperature at 70 °C, but different optimum pHs of 8.5 and 6.0 respectively. Furthermore, XynRA2 retained 94% and 71% of activity at 4.0 M and 5.0 M NaCl respectively, whereas XynRA2ΔCBM showed a lower activity (79% and 54%). XynRA2 exhibited a turnover rate (kcat) of 24.8 s−1, but this was reduced by 40% for XynRA2ΔCBM. Both the xylanases hydrolyzed beechwood xylan predominantly into xylobiose, and oat-spelt xylan into a mixture of xylo-oligosaccharides (XOs). Collectively, this work suggested CBM4_9 of XynRA2 has a role in enzyme performance.
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Rubio Rincón, Gina Sorel, e Claudia Xiomara Amaya Perozzo. "Miopía, alteración visual en habitantes de Bogotá y Cundinamarca". Ciencia & Tecnología para la Salud Visual y Ocular, n.º 9 (1 de dezembro de 2007): 43. http://dx.doi.org/10.19052/sv.1514.
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<p>Objetivo: conocer la prevalencia de la miopía en dos instituciones médicas de Bogotá y tres de Cundinamarca durante marzo de 2006 y febrero de 2007, a través de una investigación descriptiva. Materiales y métodos: se examinaron 813 pacientes, de bajos estratos socioeconómicos y principalmente afiliados al régimen subsidiado en salud, que asistieron a la consulta de optometría de los Hospitales Rafael Uribe Uribe, Centro Médico San Camilo de Bogotá, Hospitales El Salvador de Ubaté, San Rafael de Girardot y Mario Gaitán Yanguas de Soacha, de Cundinamarca; mediante valoración optométrica y previa estandarización de la prueba, se recolectó la información en bases de datos SPSS 15.0, determinando aquellas refracciones para ambos ojos, que tuvieran esferas negativas y cilindros menores o iguales a su tercera parte. Resultados: se advirtió que la prevalencia de la miopía fue 17,5% (20/114) en el grupo de 54 - 71 años seguido por el grupo de 18 – 35 años en 16% (24/150). E igualmente la prevalencia por sexo fue en un 10,3% (53/515) en mujeres y en 9,1% (27/298) en hombres. Conclusiones: la miopía se presenta principalmente en personas adultas en edad económicamente productiva, lo que refleja la importancia del diagnóstico y el tratamiento oportuno de la misma por presentar una prevalencia media y significativas alteraciones visuales en la población.</p>
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Moravec, Jaromír, Miloš Mičian, Miloslav Málek e Martin Švec. "Determination of CCT Diagram by Dilatometry Analysis of High-Strength Low-Alloy S960MC Steel". Materials 15, n.º 13 (1 de julho de 2022): 4637. http://dx.doi.org/10.3390/ma15134637.
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High-strength steels are used more than general structural steel due to their combination of properties such as high strength, good toughness and weldability. They are mainly used in the manufacture of heavy vehicles for the mining industry, cranes, transportation, etc. However, welding these grades of steel brings new challenges. Also, a simulation for welding high-strength steel is required more often. To insert a material database into the simulation program, it is necessary to conduct investigations using CCT (Continuous Cooling Transformation) diagrams, welded joints research, and more. To investigate the behavior of S960MC steel during heating and cooling, we used dilatometry analysis supported by EBSD (Electron Backscatter Diffraction) analysis. A CCT diagram was constructed. The transformation temperatures of Ac1 and Ac3 increase with increasing heating rate. The Ac1 temperature increased by 54 °C and the Ac3 temperatures by 24 °C as the heating rate increased from 0.1 °C/s to 250 °C/s. The austenite decomposition temperatures have a decreasing trend in the cooling phase with increasing cooling rate. As the cooling rate changes from 0.03 °C/s to 100 °C/s, the initial transformation temperature drops from 813 °C to 465 °C. An increase in the cooling rate means a higher proportion of bainite and martensite. At the same time, the hardness increases from 119 HV10 to 362 HV10.
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Ivanova, Elena S., Anna P. Geraskina e Sergei E. Spiridonov. "Two new species of Phasmarhabditis Andrássy, 1976 (Nematoda: Rhabditidae) associated with land snails in Northwest Caucasus, Russian Federation: description and molecular affiliation". Nematology 22, n.º 2 (10 de fevereiro de 2020): 179–97. http://dx.doi.org/10.1163/15685411-00003299.
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Summary Two new nematode species of Phasmarhabditis were isolated from land snails in North and West Caucasus, Russian Federation. Phasmarhabditis circassica sp. n. originated from Oxychilus sp. collected by the Nickel settlement in the Adygea Republic while P. clausiliiae sp. n. came from Clausiliidae gen. sp. in the Stavropol district. Phasmarhabditis circassica sp. n. is characterised morphologically by male spicules with a hollow tip, a widely conoid, spicate female tail, ensheathed dauer juveniles 896 (813-982) μm long with a tiny but distinct cuticular apical cap and a long filamentous tail, and exsheathed dauers 773 (670-950) μm long with a tail half as long as in the ensheathed dauers and with a rounded tip. Phasmarhabditis clausiliiae sp. n. is very close to P. circassica sp. n. in having similar morphological traits and is differentiated mainly in having a longer female tail of 94 (79-111) vs 82 (54-125 μm) and the much smaller ratio c of 13.7 (10.3-18.4) vs 22.7 (16.8-27.5) and by its molecular characteristics. The molecular analysis based on partial sequences of LSU rDNA, and ITS rDNA regions has been performed and showed that the closest match for both new species was P. bohemica. Despite the morphological similarity between the species described, significant difference between these two new species was reported both for LSU rDNA and ITS rDNA.
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Yang, Eu, Ye Shim, Heung Kim, Young Lim, Ho Im, Kyung-Nam Koh, Hyery Kim et al. "Genetic Confirmation and Identification of Novel Variants for Glanzmann Thrombasthenia and Other Inherited Platelet Function Disorders: A Study by the Korean Pediatric Hematology Oncology Group (KPHOG)". Genes 12, n.º 5 (6 de maio de 2021): 693. http://dx.doi.org/10.3390/genes12050693.
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The diagnosis of inherited platelet function disorders (IPFDs) is challenging owing to the unavailability of essential testing methods, including light transmission aggregometry and flow cytometry, in several medical centers in Korea. This study, conducted by the Korean Pediatric Hematology Oncology Group from March 2017 to December 2020, aimed to identify the causative genetic variants of IPFDs in Korean patients using next-generation sequencing (NGS). Targeted exome sequencing, followed by whole-genome sequencing, was performed for diagnosing IPFDs. Of the 11 unrelated patients with suspected IPFDs enrolled in this study, 10 patients and 2 of their family members were diagnosed with Glanzmann thrombasthenia (GT). The variant c.1913+5G>T of ITGB3 was the most common, followed by c.2333A>C (p.Gln778Pro) of ITGB2B. Known variants of GT, including c.917A>C (p.His306Pro) of ITGB3 and c.2975del (p.Glu992Glyfs*), c.257T>C (p.Leu86Pro), and c.1750C>T (p.Arg584*) of ITGA2B, were identified. Four novel variants of GT, c.1451G>T (p.Gly484Val) and c.1595G>T (p.Cys532Phe) of ITGB3 and c.1184G>T (p.Gly395Val) and c.2390del (p.Gly797Valfs*29) of ITGA2B, were revealed. The remaining patient was diagnosed with platelet type bleeding disorder 18 and harbored two novel RASGRP2 variants, c.1479dup (p.Arg494Alafs*54) and c.813+1G>A. We demonstrated the successful application of NGS for the accurate and differential diagnosis of heterogeneous IPFDs.
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BENHAMOU, MATHILDE, NATHALIE RINCHEVAL, CARINE ROY, VIOLAINE FOLTZ, SYLVIE ROZENBERG, JEAN SIBILIA, THIERRY SCHAEVERBEKE, PIERRE BOURGEOIS, PHILIPPE RAVAUD e BRUNO FAUTREL. "The Gap Between Practice and Guidelines in the Choice of First-line Disease Modifying Antirheumatic Drug in Early Rheumatoid Arthritis: Results from the ESPOIR Cohort". Journal of Rheumatology 36, n.º 5 (13 de março de 2009): 934–42. http://dx.doi.org/10.3899/jrheum.080762.
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Objective.To compare rheumatologists’ prescription for first disease modifying antirheumatic drug (DMARD) in early rheumatoid arthritis (RA) in real-life settings with 2 clinical practice guidelines (CPG), the French Society of Rheumatology/STPR 2004 and EULAR/ESCISIT 2007, and thus assess the gap between practices and guidelines.Method.ESPOIR was a French multicenter cohort study of 813 patients with early arthritis between 2002 and 2005. “Definite” and “probable” RA were defined according to ACR criteria and the level of diagnostic certainty. The objectives were to assess conformity between the observed first-line DMARD prescribed for those patients and the DMARD recommended in the guidelines; and to conduct a mail survey of patients’ usual rheumatologists to investigate the reasons for their nonconformity with guidelines.Results.In total 627 patients with definite or probable RA were identified. Conformity rates were 58% for STPR guidelines and 54% for EULAR guidelines. At 6 months, 83 (34%) patients with early RA did not receive any DMARD. Main determinants associated with conformity to guidelines were disease activity and presence of severity-predictive factors. The main reason leading to a discrepancy between guidelines and daily practice appeared to be diagnostic uncertainty, i.e., the difficulty to reliably assess RA diagnosis as early as the first visits to the rheumatologist.Conclusion.There is a substantial gap between CPG and rheumatologists’ daily practice concerning the first DMARD to prescribe in early RA. This is explained mainly by diagnostic uncertainty. More attention should be paid in future guidelines to the diagnostic difficulties of early RA.
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Shrestha, Sharmila, Nirmala Pradhan, Shyam Lamsal e Rambha Sigdel. "Prevalence of Substance Use among Youths in Selected Ward of Gadhi Rural Municipality, Sunsari, Nepal: A Descriptive Cross-sectional Study". Journal of BP Koirala Institute of Health Sciences 3, n.º 2 (31 de dezembro de 2020): 28–32. http://dx.doi.org/10.3126/jbpkihs.v3i2.36066.
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Background: Tobacco and alcohol are the most prevalent substances in Nepal and their use is becoming a serious health problem. We aimed to find out the prevalence of substance use among youths and assess the association with selected demographic variables.
Methods: A descriptive cross-sectional study was conducted among 813 youths residing in Gadhi Rural Municipality, ward number 1. The youths were selected through total enumerative sampling and eligible candidates were interviewed using semi-structured questionnaires on substance use. Data were analyzed using descriptive and inferential statistics.
Results: Nearly 54% of the youths belonged to the age group 16-25 years and 51.2% were females. Tarai Janajati ethnic group represented 64.2%, and 99.8% were Hindu by religion. The prevalence of substance use was 26.4%. The majority of the youths (62.2%) had started the consumption of substances between the age of 13-20 years. Many (36.2%) had been using the substances for 6-10 years. Almost two-thirds (62.2%) had a family history of substance use. Curiosity was the main reason (29.7%) for the youths to consume the substance. Nearly 37% of the youths were found to be alcohol dependent. Age, sex, ethnicity, and income were significantly associated with substance use (p < 0.05).
Conclusion: About one in every four youths was involved in substance use. In addition, it was more prevalent in male youths and the majority had started using substances at the age of 13 to 20 years.
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Aranzazu Ceballos, Andrés David, Juan Sebastián Marín Cárdenas, Daniel Gallego González e Jorge Hernando Donado Gómez. "Análisis de la heterogeneidad en revisiones sistemáticas de cardiología publicadas entre 2000-2005 y 2011-2016". Medicina UPB 42, n.º 1 (2023): 37–48. http://dx.doi.org/10.18566/medupb.v42n1.a06.
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Introducción: la cardiología es una de las especialidades médicas que cuenta con más revisiones sistemáticas y metanálisis. Estudiar la metodología de las revisiones y analizar su heterogeneidad estadística es fundamental para garantizar su validez científica. Objetivo: describir la comparación de medidas de asociación, modelos estadísticos y grado de heterogeneidad en metanálisis de revisiones sistemáticas de intervenciones farmacológicas en cardiología, publicadas entre 2000-2005 y 2011-2016. Metodología: estudio analítico basado en la descripción y comparación de métodos estadísticos de revisiones sistemáticas de intervenciones farmacológicas en cardiología, publicadas en la biblioteca Cochrane. Para las variables cualitativas se estimaron frecuencias absolutas y relativas, mientras que para las cuantitativas se determinaron medias y desviaciones estándar, o medianas y rangos intercuartílicos, según su distribución. Para establecer la diferencia de medias se realizó la prueba t de Student y para la diferencia de proporciones el Chi cuadrado. Resultados: se incluyeron 54 revisiones sistemáticas, con un total de 1053 metanálisis, 6 revisiones con 240 metanálisis entre 2000-2005 y 48 revisiones con 813 metanálisis entre 2011-2016. La mayoría de metanálisis utilizaron el tratamiento estándar como grupo de comparación (56.6%), midieron desenlaces cualitativos nominales (86.3%), determinaron riesgos relativos (63.3%) y aplicaron modelos de efectos fijos (57.8%). En 2011-2016 se encontró una media del Índice de Higgins 17.5 menor que en 2000-2005 (p<0.05). Conclusión: se evidenció una disminución de la heterogeneidad estadística y un aumento en la implementación de modelos de efectos aleatorios, lo que da cuenta de una mayor rigurosidad a la hora de demostrar resultados verdaderamente significativos.
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Zekavat, Seyedeh Maryam, Vineet K. Raghu, Mark Trinder, Yixuan Ye, Satoshi Koyama, Michael C. Honigberg, Zhi Yu et al. "Deep Learning of the Retina Enables Phenome- and Genome-Wide Analyses of the Microvasculature". Circulation 145, n.º 2 (11 de janeiro de 2022): 134–50. http://dx.doi.org/10.1161/circulationaha.121.057709.
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Background: The microvasculature, the smallest blood vessels in the body, has key roles in maintenance of organ health and tumorigenesis. The retinal fundus is a window for human in vivo noninvasive assessment of the microvasculature. Large-scale complementary machine learning-based assessment of the retinal vasculature with phenome-wide and genome-wide analyses may yield new insights into human health and disease. Methods: We used 97 895 retinal fundus images from 54 813 UK Biobank participants. Using convolutional neural networks to segment the retinal microvasculature, we calculated vascular density and fractal dimension as a measure of vascular branching complexity. We associated these indices with 1866 incident International Classification of Diseases –based conditions (median 10-year follow-up) and 88 quantitative traits, adjusting for age, sex, smoking status, and ethnicity. Results: Low retinal vascular fractal dimension and density were significantly associated with higher risks for incident mortality, hypertension, congestive heart failure, renal failure, type 2 diabetes, sleep apnea, anemia, and multiple ocular conditions, as well as corresponding quantitative traits. Genome-wide association of vascular fractal dimension and density identified 7 and 13 novel loci, respectively, that were enriched for pathways linked to angiogenesis (eg, vascular endothelial growth factor, platelet-derived growth factor receptor, angiopoietin, and WNT signaling pathways) and inflammation (eg, interleukin, cytokine signaling). Conclusions: Our results indicate that the retinal vasculature may serve as a biomarker for future cardiometabolic and ocular disease and provide insights into genes and biological pathways influencing microvascular indices. Moreover, such a framework highlights how deep learning of images can quantify an interpretable phenotype for integration with electronic health record, biomarker, and genetic data to inform risk prediction and risk modification.
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Panabières, C., J. Vendrell, O. Pellé, X. Rebillard, S. Riethdorf, V. Müller, M. Fabbro e K. Pantel. "Identification of biologically active cancer cells in blood and bone marrow of cancer patients". Journal of Clinical Oncology 25, n.º 18_suppl (20 de junho de 2007): 1001. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.1001.
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1001 Background: Metastasis is the main cause of cancer-related death. Single disseminated tumor cells (DTC) can be detected by sensitive immunocytochemical and molecular technologies, but it is still unclear whether these cells are viable and biologically active. Methods: We applied a novel enzyme-linked immunospot assay (‘EPISPOT‘) that reveals a fingerprint of specific proteins secreted from single viable epithelial tumor cells. The membrane of ELISPOT plates were coated with monoclonal antibodies against the tumor-associated marker proteins mucin-1 (MUC1) for breast cancer and prostate-specific antigen (PSA) for prostate cancer. In addition, dual fluorescent EPISPOT assays were developed to characterize MUC1+ and PSA+ cells (i.e. CK19, FGF2 secretion). Results: Even in the absence of overt metastases (stage M0), the EPISPOT assay revealed viable tumor cells in the peripheral blood of 65% of prostate cancer patients (n=31) and the bone marrow of 54% of breast cancer patients (n=37). Respective samples from non-carcinoma controls were EPISPOT- negative, whereas 80 to 100% of samples from metastatic patients (stage M1, n=40) were positive. The number of EPISPOT-positive cells in M0-patients ranged from 2 to 197 in the blood of prostate cancer patients and 1 to 262 in the bone marrow of breast cancer patients, while M1- patients showed significantly higher counts (prostate cancer, 1–684; breast cancer, 4–813). Interestingly, subsets of MUC1- or PSA-secreting cells expressed a breast stem cell-like phenotype (MUC1-/CK19+) or secreted FGF-2 as factor relevant for the growth of DTC, respectively. Conclusions: A significant fraction of cancer patients harbor viable and biologically active tumor cells in their blood and bone marrow, even in the absence of overt metastases. The multiparameter EPISPOT assay helps to identify these putative metastatic precursor cells. No significant financial relationships to disclose.
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Fizazi, Karim, Neal D. Shore, Matthew Raymond Smith, Rodrigo Ramos, Robert J. Jones, Guenter Niegisch, Egils Vjaters et al. "Efficacy and safety outcomes of darolutamide in patients with nonmetastatic castration-resistant prostate cancer with comorbidities and concomitant medications from ARAMIS." Journal of Clinical Oncology 40, n.º 6_suppl (20 de fevereiro de 2022): 256. http://dx.doi.org/10.1200/jco.2022.40.6_suppl.256.
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256 Background: Patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) are primarily older, have comorbidities, and take concomitant medications. Darolutamide (DARO), a structurally distinct and highly potent androgen receptor inhibitor, significantly reduced the risk of metastasis by ̃2 years and the risk of death by 31% versus placebo (PBO) and demonstrated favorable safety and tolerability in the phase 3 ARAMIS trial. DARO also has low potential for drug−drug interactions. This post hoc analysis of ARAMIS evaluated overall survival (OS) and safety in pts with ongoing comorbidities and concomitant medications. Methods: Pts with nmCRPC were randomized 2:1 to DARO (n=955) or PBO (n=554) while continuing androgen-deprivation therapy. At the final data cutoff (Nov 15, 2019), OS and adverse events (AEs) were evaluated in pts with a median of ≤ and >6 comorbidities or ≤ and >10 concomitant medications in the double-blind period. HRs (95% CIs) were determined from univariate analysis using Cox regression. Results: The majority of pts had ≥6 comorbidities (53%; 795/1509) or received ≥10 concomitant medications (54%; 813/1509). For pts with ≤6 and >6 comorbidities, DARO prolonged OS vs PBO (HR 0.65 and 0.73, respectively). OS benefit of DARO vs PBO was consistent for pts with metabolic, cardiovascular (CV), and other comorbid disorders (HR range: 0.39–0.88). For pts receiving ≤10 and >10 concomitant medications, OS was prolonged with DARO vs PBO (HR 0.76 and 0.66, respectively). Subgroups of pts receiving concomitant medications for gastrointestinal/metabolic disorders, CV disease, urologic disorders, and pain/inflammation achieved similar OS benefit with DARO vs PBO (HR range: 0.45–0.80). Incidence of AEs and AEs leading to treatment discontinuation with DARO was comparable to PBO across subgroups by number of comorbidities and concomitant medications (Table). Conclusions: The OS benefit and safety of DARO remained consistent with that observed in the overall ARAMIS population, even in patients with a high number of comorbidities or concomitant medications. Clinical trial information: NCT02200614. [Table: see text]
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Fernández-García, Silvia, Laura del Campo-Albendea, Dharshini Sambamoorthi, Jameela Sheikh, Karen Lau, Nana Osei-Lah, Anoushka Ramkumar et al. "Effectiveness and safety of COVID-19 vaccines on maternal and perinatal outcomes: a systematic review and meta-analysis". BMJ Global Health 9, n.º 4 (abril de 2024): e014247. http://dx.doi.org/10.1136/bmjgh-2023-014247.
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ObjectiveTo assess the effects of COVID-19 vaccines in women before or during pregnancy on SARS-CoV-2 infection-related, pregnancy, offspring and reactogenicity outcomes.DesignSystematic review and meta-analysis.Data sourcesMajor databases between December 2019 and January 2023.Study selectionNine pairs of reviewers contributed to study selection. We included test-negative designs, comparative cohorts and randomised trials on effects of COVID-19 vaccines on infection-related and pregnancy outcomes. Non-comparative cohort studies reporting reactogenicity outcomes were also included.Quality assessment, data extraction and analysisTwo reviewers independently assessed study quality and extracted data. We undertook random-effects meta-analysis and reported findings as HRs, risk ratios (RRs), ORs or rates with 95% CIs.ResultsSixty-seven studies (1 813 947 women) were included. Overall, in test-negative design studies, pregnant women fully vaccinated with any COVID-19 vaccine had 61% reduced odds of SARS-CoV-2 infection during pregnancy (OR 0.39, 95% CI 0.21 to 0.75; 4 studies, 23 927 women; I2=87.2%) and 94% reduced odds of hospital admission (OR 0.06, 95% CI 0.01 to 0.71; 2 studies, 868 women; I2=92%). In adjusted cohort studies, the risk of hypertensive disorders in pregnancy was reduced by 12% (RR 0.88, 95% CI 0.82 to 0.92; 2 studies; 115 085 women), while caesarean section was reduced by 9% (OR 0.91, 95% CI 0.85 to 0.98; 6 studies; 30 192 women). We observed an 8% reduction in the risk of neonatal intensive care unit admission (RR 0.92, 95% CI 0.87 to 0.97; 2 studies; 54 569 women) in babies born to vaccinated versus not vaccinated women. In general, vaccination during pregnancy was not associated with increased risk of adverse pregnancy or perinatal outcomes. Pain at the injection site was the most common side effect reported (77%, 95% CI 52% to 94%; 11 studies; 27 195 women).ConclusionCOVID-19 vaccines are effective in preventing SARS-CoV-2 infection and related complications in pregnant women.PROSPERO registration numberCRD42020178076.
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Amein, T., C. H. B. Olsson, M. Wikström, R. Findus, D. AB e S. A. I. Wright. "First Report in Sweden of Downy Mildew on Parsley Caused by Plasmopara petroselini". Plant Disease 90, n.º 1 (janeiro de 2006): 111. http://dx.doi.org/10.1094/pd-90-0111a.
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During September 2004, downy mildew of parsley caused by a species of Plasmopara was observed in an experimental field of parsley (Petroselinum crispum subsp. crispum L. cv. Gigante d'Italia/Hilmar) in Borgeby in southern Sweden. The summer of 2004 was exceptionally wet and humid. Disease became widespread throughout the field in just a few days. Local growers reported that symptoms consistent with downy mildew had appeared in their parsley fields every year since 2001. Plasmopara, under P. nivea, has been reported on parsley in Europe since the middle of the 19th century (4). In recent years, this disease has caused severe damage to parsley grown in several European countries, e.g., France, Germany, Switzerland, and Belgium (1,3). The first symptoms appeared as faint chlorotic spots on the upper surfaces of the leaves. On the corresponding lower surfaces, mycelium and sporangiophores grew profusely and developed a white mat that in part turned dark gray. Eventually, the leaves and stalks became necrotic and died. The sporangiophores were monopodially branched, 248.4 ± 13.36 μm long (n = 17), each branch ending in 2 to 5 ultimate branchlets tapered toward the tip. The trunk diameter measured 7.0 ± 0.77 μm (n = 9) above the basal part and 6.1 ± 0.81 μm just below the first branch. The sporangia were broadly ellipsoidal to ellipsoidal, hyaline, 22.5 ± 0.73 μm long and 16.6 ± 0.48 μm wide (n μ 40). They were mostly nonpapillate when young, although exit pores 4.8 ± 0.32 μm (n = 10) were visible. Mature sporangia exhibited a dehiscence apparatus and a plug in the exit pore. On the basis of the characteristics above, the pathogen was identified as P. petroselini (= P. nivea pro parte [2]). Independent verification of the identity was done by O. Constantinescu at the Botanical Museum, Uppsala, Sweden. A voucher specimen was deposited at the Herbarium UPS, in Uppsala under the number UPS F-118873. To our knowledge, this is the first report of P. petroselini on parsley in Sweden. References: (1) E. Bèliard and J. Thibault. Phytoma 554:2, 2002. (2) O. Constantinescu. Taxon 54:813, 2005. (3) C. Crepel and S. Inghelbrecht. Plant Dis. 87:1266, 2003. (4) A. de Bary, Ann. Sci. Nat. Bot., Sér. 4, 20:5, 1863.
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Raisingani, Manish Gope. "Risk of Complications in Children With Type 1 Diabetes and Covid-19". Journal of the Endocrine Society 5, Supplement_1 (1 de maio de 2021): A62. http://dx.doi.org/10.1210/jendso/bvab048.126.
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Abstract Background: There is some data available in adults which suggests that Type 1 diabetes may be associated with higher risk with Covid-19 (1). Limited data has been available in pediatric Type 1 diabetes with Covid-19. Methods: We used TriNetX, with a large COVID-19 database, collecting real-time electronic medical records data. We compared children (0–18 years) who were diagnosed with Covid-19 with and without Type 1 diabetes. This database collected information from 54 health care organizations. Results: Mortality rate in children with Covid-19 and Type 1 diabetes was 0.618% (10/1618). Mortality rate in children with Covid-19 without Type 1 diabetes was 0.102% (257/251517). Relative risk of mortality for children with Covid-19 and Type 1 diabetes was 6.05 with a p value of < 0.0001. Endotracheal intubation rate in children with Covid-19 and Type 1 diabetes was 0.618% (10/1618). Endotracheal intubation rate in children with Covid-19 without Type 1 diabetes was 0.071% (178/251517). Relative risk of endotracheal intubation for children with Covid-19 and Type 1 diabetes was 8.73 with a p value of < 0.0001. Pneumonia rate in children with Covid-19 and Type 1 diabetes was 0.804% (13/1618). Pneumonia rate in children with Covid-19 without Type 1 diabetes was 0.562% (1414/251517). Relative risk of pneumonia for children with Covid-19 and Type 1 diabetes was 1.43 with a p value of < 0.1959. Septic shock rate in children with Covid-19 and Type 1 diabetes was 1.05% (17/1618). Septic shock rate in children with Covid-19 without Type 1 diabetes was 0.293% (737/251517). Relative risk of septic shock for children with Covid-19 and Type 1 diabetes was 3.59 with a p value of < 0.00001. Conclusion: Mortality rate, endotracheal and septic shock were increased in children with Type 1 diabetes and Covid-19 versus children with Covid-19 and no Type 1 diabetes. Further studies with larger sample size are needed to study complication rate of Covid-19 and Type 1 diabetes. References 1) Associations of type 1 and type 2 diabetes with COVID-19-related mortality in England: a whole-population study. Lancet Diabetes Endocrinol 2020 Oct;8(10):813–822. doi: 10.1016/S2213-8587(20)30272-2. Epub 2020 Aug 13.
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AlKindi, Fatima, Nihal AlBashir, Ahmad Chaaban, Abraham George, Mohamed Saad, Mohammad Al Hakim, Mohammed Budruddin, Imran Khan e Yousef Boobes. "Abstract 25 — Remitting Seronegative Symmetric Synovitis with Pitting Edema (RS3PE) in Dialysis Patient". Journal of Clinical Rheumatology and Immunology 23, Supp01 (novembro de 2023): 53. http://dx.doi.org/10.1142/s2661341723740413.
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Background Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is characterized by acute symmetrical synovitis, and pitting edema involving, the dorsal part of hands and feet. It affects more men aged more than 50 years. The inflammatory markers are usually elevated, with negative rheumatoid factor. The underlying etiology is not clear but has been associated with drugs exposure, infections, malignancy in 30% of cases, and coexist with other autoimmune diseases. The clinical course is benign with significant improvement to low-dose prednisolone therapy for 2 to 3 months. It has been rarely reported in dialysis patients. Methods and case description A 54 years old male, known to have long standing uncontrolled diabetes mellitus, hypertension, chronic kidney disease and diabetic retinopathy. Recently, he was treated for left foot cellulitis and advanced renal failure (813 micromol/L) initiated on hemodialysis. He presented one week later with progressive painful bilateral upper limb and lower limb pitting edema, with limited range of movement in hands and reduce urine output. He was resumed on hemodialysis for management of volume overload. Despite removal of almost 12 liters of fluids during consecutive dialysis sessions and improvement of lower limb edema, his bilateral hand edema was persistence with pain and limited movement. Further investigations were done to evaluate for rheumatological condition. Results Hand X ray was normal and ultrasound of the hand revealed features of synovitis, diffuse subcutaneous oedema and possible cellulitis. He was started on IV antibiotics without major improvement and blood culture was negative. CT chest showed left pleural effusion. The ESR was elevated 120, while serology for HBV. HCV, HIV, and parvovirus were negative. In addition, the autoimmune workup were negative (CCP, RF, ANA, ANCA, C3, C4, ACEI). He was diagnosed with remitting seronegative symmetric synovitis with pitting edema (RS3PE). He was treated with IV hydrocortisone once 100 mg, followed by oral prednisolone 10 mg for 5 days with dramatic improvement in bilateral hand edema and movement. He had hyperglycemia steroid related managed with adjustment of insulin therapy. At follow up in 1 week, patient regain full function of both hands, and he was on regular hemodialysis trice per week. Conclusion RS3PE is rare in hemodialysis patients, with favorable response to steroid therapy. We used shorter duration of 5 days steroid therapy with complete recovery and no recurrence at 1 year follow up. Screening for underlying autoimmune, infection or malignancy in RS3PE is essential.
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Penz, Daniela, Elisabeth Waldmann, Monika Hackl, Lena Jiricka, Lisa-Maria Rockenbauer, Irina Gessl, Jasmin Zessner-Spitzenberg, Arnulf Ferlitsch, Michael Trauner e Monika Ferlitsch. "Colorectal Cancer and Precursor Lesion Prevalence in Adults Younger Than 50 Years Without Symptoms". JAMA Network Open 6, n.º 12 (6 de dezembro de 2023): e2334757. http://dx.doi.org/10.1001/jamanetworkopen.2023.34757.
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ImportanceIncidence of colorectal cancer (CRC) is increasing among younger adults. However, data on precursor lesions in patients who are asymptomatic, especially those aged younger than 50 years, are lacking.ObjectiveTo analyze the prevalence and number needed to screen (NNS) for adenomas, advanced adenomas, and serrated lesions, as well as the incidence of CRC in patients older than age 20 years.Design, Setting, and ParticipantsThis cohort study was conducted among 296 170 patients who received a screening colonoscopy within a national screening colonoscopy registry from 2012 to 2018 in Austria, including 11 103 patients aged younger than 50 years. CRC incidence was analyzed using data from Statistic Austria from 1988 to 2018. Data were analyzed in September 2021.Main Outcome and MeasuresThe prevalence of adenomas and other lesions and the incidence of CRC in individuals aged 20 years or older were assessed.ResultsAmong 296 170 patients included in the study (median [IQR] age, 60 [54-68] years; 150 813 females [50.9%]), 11 103 patients (3.7%) were aged younger than 50 years and 285 067 patients (96.3%) were aged 50 years or older. Among patients younger than age 50 years, 1166 individuals (10.5%; NNS = 9) had adenomas and 389 individuals (3.9%; NNS = 26) had at least 1 advanced adenoma, while among those aged 50 years or older, 62 384 individuals (21.9%; NNS = 5) had adenomas and 19 680 individuals (6.9%; NNS = 15) had at least 1 advanced adenoma. Among 1128 males aged 40 to 44 years, 160 individuals (14.2%; NNS = 7) had at least 1 adenoma, and among 1398 females aged 40 to 44 years, 114 individuals (8.1%; NNS = 12) had at least 1 adenoma. The prevalence of adenomas for individuals aged 45 to 49 years vs 50 to 54 years was 490 of 2879 males (17.1%; NNS = 6) vs 8269 of 40 935 males (20.2%; NNS = 5) and 284 of 2792 females (10.2%; NNS = 10) vs 4997 of 40 303 females (12.4%; NNS = 8), respectively. Prevalence of adenomas changed from 61 of 498 individuals (12.4%) in 2008 to 150 of 1064 individuals (14.1%) in 2018 among those younger than 50 years and from 2646 of 12 166 individuals (21.8%) to 10 673 of 37 922 individuals (28.2%) among those aged 50 years and older. The prevalence of advanced adenomas changed from 20 individuals (4.0%) in 2008 to 55 individuals (5.2%) in 2018 in individuals younger than 50 years and from 888 individuals (7.3%) in 2008 to 2578 individuals (6.8%) in 2018 among those aged 50 years and older. Among individuals younger than age 50 years, CRC incidence per 100 000 individuals changed from 9.1 incidents in 1988 to 10.2 incidents in 2018 among males (average annual percentage change [AAPC], 0.5%; 95% CI, 0.1% to 1.0%) and from 9.7 incidents in 1988 to 7.7 incidents in 2018 among females, with a nonsignificant AAPC (−0.2%; 95% CI, −0.7% to 0.3%). Among individuals aged 50 years or older, CRC incidence per 100 000 individuals changed from 168 incidents in 1988 to 97 incidents in 2018 among females (AAPC, −1.8%; 95% CI, −1.9% to −1.6%), and 217 incidents in 1988 to 143 incidents in 2018 among males (AAPC, −1.2%; 95% CI, −1.3% to −1.1%).ConclusionIn this study, CRC incidence decreased after 1988 in Austria among individuals older than 50 years, while among patients younger than 50 years, incidence increased among males but decreased among females. Prevalence of adenomas increased in all age groups, while advanced adenoma prevalence increased among patients younger than 50 years but decreased in patients aged 50 years and older.
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Ertenli, A. İ., U. Kalyoncu, O. Karadag, L. Kiliç, A. Akdoğan, I. Dogan, Ş. A. Bilgen et al. "AB0200 TRENDS IN THE CHOICE OF FIRST BIOLOGIC AND TARGETED SYNTHETIC DMARD IN RHEUMATOID ARTHRITIS PATIENTS: 20-YEARS JOURNEY OF HUR-BIO REAL-LIFE REGISTRY". Annals of the Rheumatic Diseases 80, Suppl 1 (19 de maio de 2021): 1124.2–1124. http://dx.doi.org/10.1136/annrheumdis-2021-eular.693.
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Background:In the last 20 years, there have been extraordinary improvements and practice-changing developments in the management of rheumatoid arthritis (RA). Exploring the pathogenetic mechanisms first enabled clinicians to use anti-tumor necrosis factor (TNF) alpha agents, then drugs targeting different molecules. Parallel to these developments, treatment guidelines have been changed accordingly. Meanwhile, how these developments have been reflected into the real-word practice is a question of interest.Objectives:In this study, we aimed to explore the first biologic agent trends of our 20-years of single-center experience.Methods:HUR-BIO (Hacettepe University Rheumatology Biologic Registry) is a single center biological disease modifying anti-rheumatic drug (DMARD) registry since 2005. Patients who were started biologics before 2005 were registered retrospectively. In brief; demographic data, treatment-related data (including adverse events) and disease-related data of RA patients have been recorded in HUR-BIO. Until the end of the 2020, 21 different rheumatologists contributed to the development of HUR-BIO. In this study, distribution of the first-line biologic agents was calculated according to 5-year periods starting from the 2001. Also, demographic and serologic data of RA patients were reported.Results:A total of 2080 RA patients was registered in HUR-BIO by the end of 2020. Of these patients, 79.5% was female. Mean age at the starting of bDMARD was 53.3 ± 17.8 years. Rate of rheumatoid factor and anti-cyclic citrullinated peptide positivity was 67.6% and 61.0%, respectively. 65 (3.2%), 335 (16.1%), 858 (41.2%) and 822 (39.5%) patients were prescribed with their first bDMARD in 2001-2005, 2006-2010, 2011-2015 and 2016-2020, respectively. There was a trend towards the increasing prescription of non-Anti-TNF bDMARDs over time.Table 1.Distribution of first biologic DMARDs in RA patients according to 5-years periods2001-20052006-20102011-20152016-2020TotalAdalimumab15 (23.1)111 (33.0)187 (21.8)153 (18.6)466 (22.4)Etanercept30 (46.2)154 (45.8)229 (26.7)54 (6.6)467 (22.4)İnfliximab20 (30.8)58 (17.3)64 (7.5)7 (0.9)149 (7.1)Golimumab0037 (4.3)43 (5.2)80 (3.8)Certolizumab0037 (4.3)68 (8.3)105 (5.0)Anti-TNF65 (100)323 (96.4)554 (64.5)325 (39.5)1267 (60.9)Tofacitinib006 (0.7)212 (25.8)218 (10.5)Tocilizumab009 (1.0)102 (12.4)111 (5.3)Rituximab012 (3.6)136 (15.8)84 (10.2)232 (11.1)Abatacept00153 (17.8)99 (12.0)252 (12.1)Non-Anti-TNF012 (3.6)304 (35.5)497 (60.5)813 (39.1)Total65 (100)335 (100)858 (100)822 (100)2080 (100)Approval years of drugs in Turkey; Infliximab: 2003, etanercept:2004, adalimumab: 2005, golimumab: 2013, certolizumab: 2014, abatacept: 2010, tocilizumab: 2013, rituximab:2009, tofacitinib: 2015,Conclusion:Real-life practice in RA seems consistent with treatment guidelines. Use of non-Anti-TNF bDMARDs becoming more frequent year-by-year. Jak kinase inhibitor has rised through the last 5 years. Next decade may be the years of Jak kinases inhibitors.Disclosure of Interests:None declared
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Baker-Smith, Carissa M., Wei Yang, Mary J. McDuffie, Erin P. Nescott, Bethany J. Wolf, Cathy H. Wu, Zugui Zhang e Robert E. Akins. "Association of Area Deprivation With Primary Hypertension Diagnosis Among Youth Medicaid Recipients in Delaware". JAMA Network Open 6, n.º 3 (15 de março de 2023): e233012. http://dx.doi.org/10.1001/jamanetworkopen.2023.3012.
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ImportanceThe association between degree of neighborhood deprivation and primary hypertension diagnosis in youth remains understudied.ObjectiveTo assess the association between neighborhood measures of deprivation and primary hypertension diagnosis in youth.Design, Setting, and ParticipantsThis cross-sectional study included 65 452 Delaware Medicaid-insured youths aged 8 to 18 years between January 1, 2014, and December 31, 2019. Residence was geocoded by national area deprivation index (ADI).ExposuresHigher area deprivation.Main Outcomes and MeasuresThe main outcome was primary hypertension diagnosis based on International Classification of Diseases, Ninth Revision and Tenth Revision codes. Data were analyzed between September 1, 2021, and December 31, 2022.ResultsA total of 65 452 youths were included in the analysis, including 64 307 (98.3%) without a hypertension diagnosis (30 491 [47%] female and 33 813 [53%] male; mean [SD] age, 12.5 (3.1) years; 12 500 [19%] Hispanic, 25 473 [40%] non-Hispanic Black, 24 565 [38%] non-Hispanic White, and 1769 [3%] other race or ethnicity; 13 029 [20%] with obesity; and 31 548 [49%] with an ADI ≥50) and 1145 (1.7%) with a diagnosis of primary hypertension (mean [SD] age, 13.3 [2.8] years; 464 [41%] female and 681 [59%] male; 271 [24%] Hispanic, 460 [40%] non-Hispanic Black, 396 [35%] non-Hispanic White, and 18 [2%] of other race or ethnicity; 705 [62%] with obesity; and 614 [54%] with an ADI ≥50). The mean (SD) duration of full Medicaid benefit coverage was 61 (16) months for those with a diagnosis of primary hypertension and 46.0 (24.3) months for those without. By multivariable logistic regression, residence within communities with ADI greater than or equal to 50 was associated with 60% greater odds of a hypertension diagnosis (odds ratio [OR], 1.61; 95% CI 1.04-2.51). Older age (OR per year, 1.16; 95%, CI, 1.14-1.18), an obesity diagnosis (OR, 5.16; 95% CI, 4.54-5.85), and longer duration of full Medicaid benefit coverage (OR, 1.03; 95% CI, 1.03-1.04) were associated with greater odds of primary hypertension diagnosis, whereas female sex was associated with lower odds (OR, 0.68; 95%, 0.61-0.77). Model fit including a Medicaid-by-ADI interaction term was significant for the interaction and revealed slightly greater odds of hypertension diagnosis for youths with ADI less than 50 (OR, 1.03; 95% CI, 1.03-1.04) vs ADI ≥50 (OR, 1.02; 95% CI, 1.02-1.03). Race and ethnicity were not associated with primary hypertension diagnosis.Conclusions and RelevanceIn this cross-sectional study, higher childhood neighborhood ADI, obesity, age, sex, and duration of Medicaid benefit coverage were associated with a primary hypertension diagnosis in youth. Screening algorithms and national guidelines may consider the importance of ADI when assessing for the presence and prevalence of primary hypertension in youth.
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Abisror, N., Y. Nguyen, L. Marozio, E. Esteve-Valverde, S. Udry, D. E. Pleguezuelo, P. Billoir et al. "AB0457 OBSTETRICAL OUTCOME AND TREATMENTS DURING PREGNANCY IN SERONEGATIVE PRIMARY APS: DATA FROM EUROPEAN RETROSPECTIVE STUDY". Annals of the Rheumatic Diseases 79, Suppl 1 (junho de 2020): 1527.1–1527. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3537.
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Background:Objectives:To compare clinical characteristics, pregnancies, and treatments during pregnancies of seronegative and seropositive APS, and analyse factors associated with adverse obstetrical outcomes.Methods:Inclusion criteria were: (1) thrombotic arterial and/or venous; and /or obstetrical primary clinical APS (Sydney criteria); (2) absence of conventional antiphospholipid antibodies; (3) presence of at least one non-conventional APL among IgA ACL, IgA antiB2GPI, anti-vimentin G/M, anti-annexin V G/M, anti-PE G/M, anti-PS/PT G/M antibodies. The exclusion criteria were: (1) seropositive APS with conventional APS; (2) associated SLE or SLE like (SLE features and / or positive antinuclear autoantibodies); (3) other systemic connective tissue disease (Sjogren’s syndrome, systemic sclerosis, myositis).Results:187 women (mean 33±5 years) with seronegative APS were included from 12 centers in the world and compared to 285 patients with seropositive APS. Seronegative APS have mostly obstetrical phenotypes rather than venous thrombosis in comparison to seropositive APS. The maternal and fetal outcomes and the rates of live births were not significantly different in seronegative and seropositive APS, except for higher rates of intrauterine deaths (15% vs 5%; p=0.03) and lower live birth term (36±3 vs 38±3 weeks of gestation; p=0.04) in the seropositive APS group. The cumulative incidence of adverse obstetrical events was significantly improved in treated seronegative APS vs untreated ones (log rank<0.05), whereas there was no difference between patients who received aspirin or aspirin-LMWH combinationConclusion:Patients with clinical manifestations of APS without conventional APL should undergo testing for non-criteria APL. The diagnosis of seronegative APS could be important for a better care of these patients.Table 1.Characteristics of seronegative and seropositive APS women.Seronegative APSN=187Seropositive APSN=285APS featuresThrombotic APS Arterial APS (n;%)0105 (37)* Venous APS (n;%)9 (6)154 (54)*Obstetrical APS (n;%)168 (89)89 (31)*Mix APS (n;%)8 (4)16 (6)Non criteria features (n;%)16 (9)141 (49)*Obstetrical history Miscarriages (n;%)66 (35)18 (6)* Intrauterine deaths (n;%)60 (32)46 (16)* Prematurity <34 wg (n;%)43 (23)31 (11)*Table 2.Pregnancy outcome and treatment in seronegative and seropositive APS.Seronegative APS pregnanciesN=108Seropositive APS pregnanciesN=75Thrombotic APS Arterial APS (n;%)020 (27)* Venous APS (n;%)8 (7)42 (56)*Obstetrical APS (n;%)93 (86)36 (48)*Mix APS (n;%)6 (6)18 (24)Aspirin (n;%) / Aspirin alone95 (88) / 32 (30)57 (76)* / 2 (3)*LMWH isocoagulant amounts (n;%)63 (58)39 (52)Aspirin-LMWH (n;%)65 (60)55 (73)Preeclampsia/HELLP syndrome (n;%)7 (7)12 (16)*IUGR (n;%)5 (5)7 (10)Fetal loss (n;%)33 (31)22 (29)Miscarriage / Intrauterine deaths23 (21) / 5 (5)11 (15) / 11 (15)*Prematurity<34 weeks of gestation (n;%)6 (6)9 (12)Term of fetal loss (weeks gestation)10±813±7Live births (n;%)75 (69)53 (70)Term of live birth (weeks gestation)38±336±3*Disclosure of Interests: :None declared
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Cho, Seongkoo, Steven F. Buchsbaum, Monika M. Biener, Justin T. Jones e Roger Qiu. "The Importance of Electrochemically Active Surface Area in the Corrosion Behavior of Additively Manufactured 316L Stainless Steel". ECS Meeting Abstracts MA2022-01, n.º 16 (7 de julho de 2022): 1015. http://dx.doi.org/10.1149/ma2022-01161015mtgabs.
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Surfaces of additively manufactured (AM) stainless steel (SS) by fusing metallic powders are known to be much rougher than those produced by conventionally fabrication methods. The measured surface roughness (Sa or Sq) can range from a few to tens of microns depending on the build angle. Recent studies have shown that the large surface roughness associated with printing conditions makes the AM SS surfaces susceptible to localized corrosion and open-circuit corrosion [1, 2]. Sa or Sq have also long been used to characterize the corrosion behavior of traditionally manufactured metals [3]. However, the open-circuit corrosion rate of the traditional metals has been mainly studied in the submicron-scale surface roughness, and some results have showed that changes in the roughness of hundreds of nanometers or more have little effect on the change in the corrosion rate [4]. In addition, when applied to AM materials, no consistent correlation between the pitting breakdown potential (Eb) and surface roughness has been observed. In this study, the dependence of the corrosion behavior on the electrochemically active surface area of AM 316L SS, defined as the total area of the curvilinear surface that is exposed to the electrolyte, has been explored. The localized corrosion susceptibility was evaluated under full immersion in 3.5 wt% NaCl solution through potentiodynamic polarization for testing articles with different surface roughness. While no correlation to Sa or Sq was displayed, the Eb values showed a clear statistical trend with respect to the electrochemically active surface area: the lager the active surface area, the smaller the Eb. The observed correlation fits well with a previously reported stochastic pitting model on metal surfaces [5]. In addition, by normalizing linear polarization resistance and electrochemical impedance spectra with the electrochemically active surface area, it can be confirmed that the as-printed surface roughness of AM 316L SS did not have a significant effect on the change of the open-circuit corrosion phenomenon under static immersion conditions. Our results suggest that electrochemically active surface area is an appropriate parameter to characterize the corrosion behavior of AM metal surfaces. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. References 1. Melia, M.A., et al., How build angle and post-processing impact roughness and corrosion of additively manufactured 316L stainless steel. Npj Materials Degradation, 2020. 4(1). 2. Ni, C., Y. Shi, and J. Liu, Effects of inclination angle on surface roughness and corrosion properties of selective laser melted 316L stainless steel. Materials Research Express, 2019. 6(3). 3. Walter, R. and M.B. Kannan, Influence of surface roughness on the corrosion behaviour of magnesium alloy. Materials & Design, 2011. 32(4): p. 2350-2354. 4. Li, W. and D.Y. Li, Influence of surface morphology on corrosion and electronic behavior. Acta Materialia, 2006. 54(2): p. 445-452. 5. Shibata, T., 1996 W R Whitney Award lecture: Statistical and stochastic approaches to localized corrosion. Corrosion, 1996. 52(11): p. 813-830.
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Roland, Virginie, Michel Attal, Philippe Moreau, Claire Mathiot, Catherine Charbonnel, Denis Caillot, Thierry Facon et al. "Patients Under 50 Years of Age Do Not Present Specific Prognostic Characteristics: An IFM Study in 1897 Patients Under 65 Years of Age." Blood 114, n.º 22 (20 de novembro de 2009): 2837. http://dx.doi.org/10.1182/blood.v114.22.2837.2837.
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Abstract Abstract 2837 Poster Board II-813 Age is a critical prognostic factor in many hematological malignancies. The reasons for this major prognostic impact are not univocal. For a large part, its prognostic value is in fact related to the therapy intensity tolerated by the patients. Because of frequent renal, hepatic, cardiac impairments, intensive therapies are not tolerated after 60 or 65 years, leading physicians to dramatically reduce treatment intensity in elderly patients. The question of a specific prognostic value of age in a more homogeneous population is an unresolved issue. In myeloma, it has been suggested that patients under 50 years of age presented more favorable features, explaining the better outcome observed in these patients (Ludwig et al., Blood 2008). However, the population was highly heterogeneous, treated both with conventional and intensive therapeutic strategies. In order to address this question, we reviewed the files of 1897 patients under 65 years of age, homogeneously treated within the IFM with high-dose melphalan, from 2000 to 2007. The median age was 56 years (range=23-65), the sex-ratio male/female was 54%. We addressed the issues of the prognostic impact of young age (<50), but also of older patients (60 to 65). The following prognostic parameters were tested: b2-microglobuline, high creatinine (>177 μmol/l), hypercalcemia, low hemoglobin (<10 g/dl), thrombocytopenia (<130 G/l), ISS, del(13), t(4;14), and del(17p). In the first comparison (<50 vs others), the only statistically different parameters were b2-microglobuline (p=.009) and ISS distribution (p=.004). All the other parameters were not significantly different. Similar results were observed in the second comparison (<60 vs 60-65). Only b2-microglobuline values (p=.0001) and ISS distribution (p<.0001) were different. These differences in b2-microglobuline levels probably reflect the decrease of glomerular filtration with age. We then looked at the impact of age on outcome. We found that patients under 50 years of age displayed a better overall survival than patients between 50 and 65 (p=.007), with no difference in PFS. We also found that patients between 60 and 65 presented a poorer outcome than younger patients (OS, p=0.002, EFS, p=0.01). However, when patients under 50 were compared with those between 50 and 60, no difference was observed, both for OS and EFS. Thus, in conclusion, young age is not a prognostic factor in multiple myeloma. In contrast, older age (60 to 65) remains an adverse prognostic parameters, even in patients treated with high-dose melphalan. Disclosures: Attal: Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees. Moreau:Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees. Facon:Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees. Harousseau:Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees.
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Sachdev, Devika, Rei Yamada, Rachel Lee, Mark V. Sauer e Cande V. Ananth. "Risk of Stroke Hospitalization After Infertility Treatment". JAMA Network Open 6, n.º 8 (30 de agosto de 2023): e2331470. http://dx.doi.org/10.1001/jamanetworkopen.2023.31470.
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ImportanceStroke accounts for 7% of pregnancy-related deaths in the US. As the use of infertility treatment is increasing, many studies have sought to characterize the association of infertility treatment with the risk of stroke with mixed results.ObjectiveTo evaluate the risk of hospitalization from hemorrhagic and ischemic strokes in patients who underwent infertility treatment.Design, Setting, and ParticipantsThis population-based, retrospective cohort study used data abstracted from the Nationwide Readmissions Database, which stores data from all-payer hospital inpatient stays from 28 states across the US, from 2010 and 2018. Eligible participants included individuals aged 15 to 54 who had a hospital delivery from January to November in a given calendar year, and any subsequent hospitalizations from January to December in the same calendar year of delivery during the study period. Statistical analysis was performed between November 2022 and April 2023.ExposureHospital delivery after infertility treatment (ie, intrauterine insemination, assisted reproductive technology, fertility preservation procedures, or use of a gestational carrier) or after spontaneous conception.Main Outcomes and MeasuresThe primary outcome was hospitalization for nonfatal stroke (either ischemic or hemorrhagic stroke) within the first calendar year after delivery. Secondary outcomes included risk of stroke hospitalization at less than 30 days, less than 60 days, less than 90 days, and less than 180 days post partum. Cox proportional hazards regression models were used to estimate associations, which were expressed as hazard ratios (HRs), adjusted for confounders. Effect size estimates were corrected for biases due to exposure misclassification, selection, and unmeasured confounding through a probabilistic bias analysis.ResultsOf 31 339 991 patients, 287 813 (0.9%; median [IQR] age, 32.1 [28.5-35.8] years) underwent infertility treatment and 31 052 178 (99.1%; median [IQR] age, 27.7 [23.1-32.0] years) delivered after spontaneous conception. The rate of stroke hospitalization within 12 months of delivery was 37 hospitalizations per 100 000 people (105 patients) among those who received infertility treatment and 29 hospitalizations per 100 000 people (9027 patients) among those who delivered after spontaneous conception (rate difference, 8 hospitalizations per 100 000 people; 95% CI, −6 to 21 hospitalizations per 100 000 people; HR, 1.66; 95% CI, 1.17 to 2.35). The risk of hospitalization for hemorrhagic stroke (adjusted HR, 2.02; 95% CI, 1.13 to 3.61) was greater than that for ischemic stroke (adjusted HR, 1.55; 95% CI, 1.01 to 2.39). The risk of stroke hospitalization increased as the time between delivery and hospitalization for stroke increased, particularly for hemorrhagic strokes. In general, these associations became larger for hemorrhagic stroke and smaller for ischemic stroke following correction for biases.Conclusions and RelevanceIn this cohort study, infertility treatment was associated with an increased risk of stroke-related hospitalization within 12 months of delivery; this risk was evident as early as 30 days after delivery. Timely follow-up in the immediate days post partum and continued long-term follow-up should be considered to mitigate stroke risk.
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Blanco Cáceres, B. A., Á. Andreu-Suárez, M. Valero, D. Benavent, M. Sanz, J. Campos Esteban, O. Rusinovich et al. "POS1574 SAPHO SYNDROME, CLINIC CHARACTERISTICS FROM THE SAPHO-SORCOM COHORT". Annals of the Rheumatic Diseases 82, Suppl 1 (30 de maio de 2023): 1163–64. http://dx.doi.org/10.1136/annrheumdis-2023-eular.6386.
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BackgroundThe SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is a rare disease (<1/10,000) with multiple cutaneous and musculoskeletal manifestations [1]. The most common dermatological manifestations are palmoplantar pustulosis (PPP) and severe acne (SA). Musculoskeletal manifestations are diverse, including the thoracic wall, spine, temporomandibular joint, and peripheral joints [2]. It is considered as part of spondyloarthropathies, however, no significant relationship with HLA-B27 has been found [3]. For treatment, non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying drugs (DMARDs) and bisphosphonates have been traditionally used. More recently, new therapies such as apremilast and biological DMARDs (4) are being used more frequently.ObjectivesTo examine the characteristics of individuals diagnosed with SAPHO syndrome during follow-up at multiple Rheumatology Services in Spain.MethodsThis is a descriptive, cross-sectional, multi-center study, carried out in the Rheumatology Services of several hospitals in Spain. A convenience sampling was carried out, including all patients with SAPHO under active follow-up.Results50 patients were included (76% women), with a mean age of 48.56 (±12,28) years. The mean BMI was 24.84 (±4.31). Regarding cardiovascular risk factors, 36.2% and 23.4% were smokers and ex-smokers, respectively. 18% had hypertension, 28% had dyslipidaemia and 8% were diabetic.Regarding of the musculoskeletal involvement, the most affected region was the anterior chest wall (74%), followed by peripheral arthritis (56%) and the spine (34%). 24% presented enthesitis and only 6% dactylitis. The most frecuent skin involvement was palmpplantar pustulosis in 54% (27), the distribution of dermatological manifestations is shown in Figure 1.Figure 1.Skin manifestations in SAPHO syndrome.In laboratory tests at diagnosis, acute phase reactants were slightly elevated, with a mean of CRP of 11.13 (±17.34) and ESR of 21.21 (±24.56). HLA-B27 and CW6 were positive in 12% (6) and 6% (3) of patients, respectively. The most commonly used imaging tests in the diagnosis and follow-up were plain x-rays (90%), MRI (76%), bone scintigraphy (72%), and CT scan (52%). The least used test was ultrasound, used in 17 patients (34%).The treatment was mostly based in NSAIDs, 94% of patients received it at some point. 60% used DMARDsc (mostly methotrexate). 50% of patients received bDMARDs, and 9 patients received more than two bDMARDs throughout the follow-up. The distribution of the first bDMARD used is shown in Table 1.Table 1.First bDMARD used in the treatment of SAPHO syndrome in our cohort.bDMARDN% patients (25/50)% FAMEb/other molec’s (25/25)Adalimumab122448Infliximab4816Etanercept3612Ustekinumab248Secukinumab124Anakinra124Apremilast124Cartolizumab-pegol124Total2550100The course of the disease was mostly recurrent (54%) with asymptomatic periods between flare-ups. About half of the patients (44%) in follow-up currently have active disease.ConclusionOur cohort presented axial involvement like other series and significant peripheral involvement. The most frequent skin condition was PPP. Half of the patients in our cohort required bDMARD, with ADL being the most widely used.References[1]Heldmann F, Kiltz U, Baraliakos X, Braun J. [SAPHO syndrome]. Z Rheumatol. Octubre de 2014;73(8):729-41.[2]Hayem G, Bouchaud-Chabot A, Benali K, Roux S, Palazzo E, Silbermann-Hoffman O, et al. SAPHO syndrome: a long-term follow-up study of 120 cases. Semin Arthritis Rheum. diciembre de 1999;29(3):159-71.[3]Colina M, Govoni M, Orzincolo C, Trotta F. Clinical and radiologic evolution of synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome: A single center study of a cohort of 71 subjects. Arthritis Care Res. 2009;61(6):813-21.[4]Daoussis D, Konstantopoulou G, Kraniotis P, Sakkas L, Liossis S-N. Biologics in SAPHO syndrome: A systematic review. Semin Arthritis Rheum. febrero de 2019;48(4):618-25.AcknowledgementsTo the Sociedad de Reumatología de la Comunidad de Madrid (SORCOM).Disclosure of InterestsBoris Anthony Blanco Cáceres Speakers bureau: MSD, Janssen, Novartis, UCB, Grant/research support from: Gebro, Pfizer, Novartis, Janssen, MSD, África Andreu-Suárez: None declared, Marta Valero: None declared, Diego Benavent: None declared, María Sanz: None declared, José Campos Esteban: None declared, Olga Rusinovich: None declared, Juan Molina Collada: None declared, patricia Castro: None declared, Vega Jovani: None declared, María Jesús Montesa: None declared, Eva Tomero Muriel: None declared, Álvaro García Martos: None declared, RAQUEL ALMODOVAR: None declared, Fernando Lozano Morillo: None declared.
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Cunsolo, Alessandra, David Bourdon, Ernest Lam, Giuseppe Di Caro, Nilesh Dharajiya, Timothy Pluard e Lee Schwartzberg. "Abstract PO4-06-12: Distinction of basal-like and triple-negative basal-like breast cancers utilizing a novel comprehensive single-cell liquid biopsy-based test". Cancer Research 84, n.º 9_Supplement (2 de maio de 2024): PO4–06–12—PO4–06–12. http://dx.doi.org/10.1158/1538-7445.sabcs23-po4-06-12.
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Abstract Introduction: Breast cancer is a highly heterogeneous disease and is a leading cause of death for women worldwide. Triple-negative breast cancer (TNBC), the most aggressive form of the disease, is clinically defined by the lack of expression of estrogen receptor (ER) and progesterone receptor (PR), as well as lack of over-expression of human epidermal growth factor receptor-2 (HER2). Approximately 70% of all TNBC cases exhibit basal-like cells, characterized by high basal expression of keratins as well as extensive genomic instability with copy number gains and losses across most chromosomes. In this study we show that novel single cell genomic evaluation coupled with immunofluorescence (IF) protein analysis of CTCs can detect TNBC with basal-like genomic features as well as basal-like tumors with expression of ER and HER2. Materials and Methods: Epic Sciences’ DefineMBC™ liquid biopsy test characterizes CTC proteomics and genomics as well as ctDNA for the treatment of metastatic breast cancer. Blood samples from 813 metastatic breast cancer patients, with either newly diagnosed or progressing disease, with historical tissue subtype [HR(+)HER2(-), HR(+/-)HER2(+), and TNBC] supplied by the referring physician were collected and tested. Up to 5 CTCs were selected and isolated from each sample based on morphology and IF signal. DNA was extracted from individual cells, and whole genome amplified and sequenced at low coverage. Copy number analysis was performed to determine copy number gains and losses across chromosomes, as well as large scale-state transitions (LSTs) and ERBB2 amplification. CTCs characterized with high chromosomal instability (e.g., exhibiting >30 LSTs; 1Q firestorm and 8Q stair step) and high levels of cytokeratin expression (mean fluorescence intensity signal >10K) were categorized as basal-like. Results: By previous metastatic tissue biopsy, 77% were HR(+), 8% were HER2(+), and 12% were TNBC. CTCs categorized in DefineMBC as basal-like subtype (9.8 % of all samples tested) showed to be highly present in patients called as TNBC (79% basal-like). Additionally, 54% of HR(+) and 23% of HER2(+) had basal-like CTCS. Patients characterized with TNBC by metastatic tissue biopsy and by DefineMBC exhibited basal-like cells in 88% of the cases. Conclusion: The results show a novel clinical assay which utilizes CTC protein detection as well as single-cell genomic analysis to identify tumors driven by basal-like cells. Generally, TNBC is classified with negative biomarker expression. We show that CTCs in TNBC display genomically basal-like cells. CTCs from HR(+) and HER2(+) tumors may express basal-like features with preserved ER and HER2 expression. The comprehensive nature of DefineMBC™ utilizing genomic analysis of detected CTCs has provided a new tool to diagnose both basal-like TNBC and basal-like hormone receptor positive and HER2 over-expressing tumors. Citation Format: Alessandra Cunsolo, David Bourdon, Ernest Lam, Giuseppe Di Caro, Nilesh Dharajiya, Timothy Pluard, Lee Schwartzberg. Distinction of basal-like and triple-negative basal-like breast cancers utilizing a novel comprehensive single-cell liquid biopsy-based test [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-06-12.
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Watts, Michael J., Stuart J. Ings, Carmen Balsa, Caroline Penn, David Leverett e David C. Linch. "Successful Customization of Peripheral Blood Stem Cell Harvest Volume and Cell Concentration during Apheresis." Blood 104, n.º 11 (16 de novembro de 2004): 4992. http://dx.doi.org/10.1182/blood.v104.11.4992.4992.
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Abstract The high white cell counts associated with peripheral blood stem cell (PBSC) harvests make these products particularly prone to cellular damage during storage in the liquid phase. We recently described unexpectedly high thaw clonogenic losses of PBSC stored overnight at 4 deg C prior to cryopreservation. This was associated with high harvest white cell counts and delayed engraftment in a cohort of patients receiving autologous transplantation procedures (Watts et al 2003 Blood 102:113 abstract 127). We showed in this study that pre-diluting the cells in autologous plasma to a WBC of 100x10^9/L preserved clonogenic yields during liquid storage and post freeze-thaw and suggested an upper WBC threshold of 200x10^9/L for liquid storage. In many patients however, to achieve this count or below would require further dilution of the cells. Conversely, where cells are to be frozen immediately, it is advantageous to collect a low PBSC harvest volume to fully utilize cryostorage space and to achieve this without centrifugation. The present study demonstrates that the collection of either a low white count or low volume PBSC harvest can be controlled successfully using the GAMBRO BCT Spectra AutoPBSC apheresis machine (version 6.1) and avoids the need for any further laboratory manipulations. This machine allows the adjustment of the amount of autologous plasma used to rinse each cycle of PBSC cells into the collection bag and is referred to as the “plasma chase volume”. The plasma chase volume was set to maximum (20ml/cycle) for healthy donor harvests for shipping, and to minimum (4ml/cycle) where the cells were for immediate cryopreservation. A total of 114 harvests from 99 mobilised healthy donors were collected using the maximum plasma chase volume whereas 527 autograft harvests from 365 mobilised patients were collected using the lowest plasma chase setting. The median (range) WBC and volume of the 114 healthy donor harvests was 100 (28–174)x10^9/L and 473 (54–871) ml respectively. The median (range) WBC and volume of the 527 “small volume” harvests for cryopreservation was 254 (51–495)x10^9/L and 66 (20–180) ml respectively. To determine whether the maximal plasma chase setting affected the progenitor dose collected, we compared the first day harvest of the 99 mobilised healthy donors obtained with the Spectra autoPBSC with that from 114 healthy donors collected on the standard manual Spectra (n=63) and CS3000 (n=51) apheresis machines. The median (range) CD34+ cell yield was 361 (34–1,380), 291 (21–1,356) and 259 (37–738)x10^6 respectively. The first day median (range) CD34+ cell yield x10^6 of the 365 mobilised patients where small volume autograft harvests were collected on the Spectra AutoPBSC was 202 (0–7,569) compared to 195 (0–5,054) using the manual Spectra (n=142) and 152 (0–4,830) x10^6 using the CS3000 machine (n=813). Our policy is to dilute any harvest for storage/shipping with a nucleated cell count greater than 200x10^9/L with autologous plasma, but none of the donor harvests exceeded this threshold and no laboratory manipulation was required. In the case of the autograft harvests for immediate cryopreservation, 502/527(95%) of the collections were 100ml or less. In conclusion, this study demonstrates for the first time that the cell count and volume of the PBSC harvest required can be customized at apheresis, that this is not detrimental to progenitor yields and results in a product that is optimal for storage/shipping without laboratory intervention.
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Wang, Z., L. Jiaxi e Y. Liu. "POS1384 DIFFERENT CLINICAL CHARACTERISTICS OF IGG4-RRD PATIENTS AND NON-IGG4-RRD PATIENTS: A LARGE CHINESE COHORT STUDY". Annals of the Rheumatic Diseases 80, Suppl 1 (19 de maio de 2021): 975.1–975. http://dx.doi.org/10.1136/annrheumdis-2021-eular.4277.
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Background:IgG4-related disease (IgG4-RD) is an autoimmune disorder and frequently involve multiple organs. The respiratory tract is one of the most frequently involved sites.Objectives:This study aimed to compare the demographic and clinical characteristics of IgG4-related respiratory disease (IgG4-RRD) and non-IgG4-RRD patients in a large cohort.Methods:We carried out a retrospective study of 452 cases of IgG4-RD (104 IgG4-RRD patients and 348 non-IgG4-RRD patients) diagnosed at Peking University People’s Hospital between 2003 and 2020.Results:IgG4-RRD patients had an elder age of disease onset and diagnosis. Multiorgan involvement and hypocomplementemia were more common in IgG4-RRD. Besides, the level of ESR, eosinophilia, IgG and IgG4 were higher in IgG4-RRD patients. In IgG4-RRD group, salivary gland, lacrimal gland, lymph nodes, biliary system and kidney were more commonly involved than those in the non-IgG4-RRD group. Also, more numbers of organ involvement and biliary involvement were independent risk factors for the development of respiratory involvement in IgG4-RD patients.Conclusion:Our study revealed demographic, clinical, laboratory and imaging features of IgG4-RRD patients and the underlying differences in pathogenesis between the two phenotypes, which have important implications for the diagnosis and treatment of the disease.References:[1]Morales AT, Cignarella AG, Jabeen IS, Barkin JS, Mirsaeidi M. An update on IgG4-related lung disease. European journal of internal medicine. 2019;66:18-24.[2]Stone JH, Zen Y, Deshpande V. IgG4-related disease. The New England journal of medicine. 2012;366(6):539-51.[3]Vasaitis L. IgG4-related disease: A relatively new concept for clinicians. European journal of internal medicine. 2016;27:1-9.[4]Matsui S, Yamamoto H, Minamoto S, Waseda Y, Mishima M, Kubo K. Proposed diagnostic criteria for IgG4-related respiratory disease. Respiratory investigation. 2016;54(2):130-2.[5]Cao L, Chen YB, Zhao DH, Shi WF, Meng S, Xie LX. Pulmonary function tests findings and their diagnostic value in patients with IgG4-related disease. Journal of thoracic disease. 2017;9(3):547-54.[6]Wallace ZS, Perugino C, Matza M, Deshpande V, Sharma A, Stone JH. Immunoglobulin G4-related Disease. Clinics in chest medicine. 2019;40(3):583-97.[7]Matsui S. IgG4-related respiratory disease. Modern rheumatology. 2019;29(2):251-6.[8]Johansson SG, Hourihane JO, Bousquet J, Bruijnzeel-Koomen C, Dreborg S, Haahtela T, et al. A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy. 2001;56(9):813-24.[9]Fei Y, Shi J, Lin W, Chen Y, Feng R, Wu Q, et al. Intrathoracic Involvements of Immunoglobulin G4-Related Sclerosing Disease. Medicine. 2015;94(50):e2150.[10]Wallace ZS, Deshpande V, Mattoo H, Mahajan VS, Kulikova M, Pillai S, et al. IgG4-Related Disease: Clinical and Laboratory Features in One Hundred Twenty-Five Patients. Arthritis & rheumatology (Hoboken, NJ). 2015;67(9):2466-75.[11]Yamada K, Yamamoto M, Saeki T, Mizushima I, Matsui S, Fujisawa Y, et al. New clues to the nature of immunoglobulin G4-related disease: a retrospective Japanese multicenter study of baseline clinical features of 334 cases. Arthritis research & therapy. 2017;19(1):262.[12]Borges T, Silva S. IgG4-related disease: How to place it in the spectrum of immune-mediated and rheumatologic disorders? Modern rheumatology. 2020;30(4):609-16.[13]Liu Y, Xue M, Wang Z, Zeng Q, Ren L, Zhang Y, et al. Salivary gland involvement disparities in clinical characteristics of IgG4-related disease: a retrospective study of 428 patients. Rheumatology (Oxford, England). 2020;59(3):634-40.[14]Matsui S, Taki H, Shinoda K, Suzuki K, Hayashi R, Tobe K, et al. Respiratory involvement in IgG4-related Mikulicz’s disease. Modern rheumatology. 2012;22(1):31-9.Disclosure of Interests:None declared
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Aggarwal, A., R. Gupta, R. Chatterjee, V. Negi, B. K. Das, P. Ghosh, D. Danda e V. Shobha. "POS0773 AUTOANTIBODIES IN A MULTI-INSTITUTIONAL INDIAN COHORT (INSPIRE) OF SLE PATIENTS: PREVALENCE, CLUSTER ANALYSIS AND PHENOTYPE ASSOCIATION". Annals of the Rheumatic Diseases 81, Suppl 1 (23 de maio de 2022): 673. http://dx.doi.org/10.1136/annrheumdis-2022-eular.4173.
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BackgroundSystemic Lupus Erythematosus (SLE) is characterized by an array of autoantibodies. Different autoantibodies have been associated with different clinical features like anti-dsDNA antibodies with nephritis and anti-phospholipid antibodies with pregnancy loss. However, the prevalence of autoantibodies has been variable across different ethnic groups. Data on the Indian population is limited.ObjectivesTo assess the prevalence of different autoantibodies in a multi-institutional cohort (INSPIRE) of Indian SLE patients and to test their association with various clinical features using cluster analysisMethodsThe patients (n=1053) enrolled in a multi-institutional cohort of Indian patients (Indian SLE inception cohort for Research [INSPIRE]) were included.1 Antibodies were assayed using Immunoline (Euroimmune, Germany) 17 antigen kit. Anti-phospholipid antibodies (IgG and IgM anti-cardiolipin antibodies (ACLs), IgG anti-Beta 2 GpI antibodies) were measured using ELISA (Euroimmune). Lupus anticoagulant was available in a subset of patients.The prevalence data for autoantibodies were analyzed using an intensity of only ++ and above on Immunoline assay as significant. Univariate analysis by Chi-square test was done to identify associations between individual autoantibodies and their clusters with clinical manifestations.ResultsThe clinical features were fever in 702, alopecia in 813, oral ulcers in 628, acute cutaneous lupus (ACLE) in 520, proteinuria in 400, pleural effusion in 181, thrombocytopenia in 250 and autoimmune hemolytic anemia in 137 patients.The prevalence of various autoantibodies by ELISA was anti-dsDNA antibodies in 70.2% (551/784), IgG Anti- beta-2 GpI in 4.47% (42/938), IgG ACL in 6.14% (61/992) and IgM ACL in 7.1% (54/760). Lupus anticoagulant was present in 13.9% (112/ 805). By Immunoline assay, the prevalence for anti-Ro 52, anti-Ro 60, anti-La and anti-Ribosomal P was 28.49%, 33.14%, 10.07% and 24.03% respectively (Table 1).Table 1.Prevalence of different autoantibodies in the INSPIRE lupus cohortS. No.AutoantibodyPrevalence (%) (n=1053)1.dsDNA28.112.Nucleosomes27.833.Histones24.884.Ro_52_SSA28.495.Ro_60_SSA33.146.SSB-La10.077.Ribosomal P24.038.nRNP36.759.Sm33.1410.Scl-703.2311.PM-Scl0.3812.Jo-10.0913.CENP-B0.3814.PCNA1.3315.AMA-M22.28Cluster analysis (Figure 1) revealed association (Odds ratio with 95% confidence interval) of Cluster 1 (antibodies against dsDNA, histones and nucleosomes) with arthritis (1.51 [1.18-1.94]), proliferative nephritis (3.05[2.08-4.48]) and pleural effusion (1.49[1.08-2.05]), cluster 2 (antibodies against Sm, nRNP, Ro52, Ro60 and Ribosomal P) with ACLE (1.3[1.02-1.65]) and non-proliferative nephritis (1.64[1.09-2.46]) and cluster 3 (antiphospholipid antibodies) with thrombocytopenia (3.34[1.57-7.11]).Figure 1.Cluster analysis of autoantibodies (Cluster 1: dsDNA, histone and nucleosome; cluster 2: Sm, nRNP, Ro52, Ro60 and Ribosomal P; cluster 3: cardiolipin, β2GP1 and La and lupus anticoagulant; cluster 4: Scl-70, Jo-1, PCNA, AMA-M2, PM-SCL and CENP-B)ConclusionThe prevalence of anti-Sm antibody and Anti-Ribosomal P antibody is higher whereas that of anti-La antibody is lesser in the Indian SLE patients as compared to other cohorts of SLE patients with different ethnicities.2 Cluster analysis reveals co-occurrence of different autoantibodies in our patients and their significant association with various clinical manifestations which suggests a possible pathogenic role of autoantibodies or a common genetic basis for it.References[1]Shobha V, Aggarwal A, Rajasekhar L, Jain A, Gupta R, Das B, et al. Indian SLE Inception cohort for Research (INSPIRE): the design of a multi-institutional cohort. Rheumatol Int. 2021 May;41(5):887-894.[2]Yang J, Xu Z, Sui M, Han J, Sun L, Jia X, et al. Co-Positivity for Anti-dsDNA, -Nucleosome and -Histone Antibodies in Lupus Nephritis Is Indicative of High Serum Levels and Severe Nephropathy. PLoS One. 2015 Oct 14;10(10):e0140441.Disclosure of InterestsAmita Aggarwal: None declared, Ranjan Gupta Grant/research support from: Dr. Ranjan Gupta has received 2 grants for educating patients and primary care physicians about rheumatoid arthritis managment., Rudrarpan Chatterjee: None declared, Vir Negi: None declared, Bidyut Kumar Das: None declared, Parasar Ghosh: None declared, Debashish Danda: None declared, Vineeta Shobha: None declared
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Jalagadugula, Gauthami S., Guangfen Mao, Lawrence E. Goldfinger, Jeremy Wurtzel, Michele P. Lambert e Angara Koneti Rao. "RAB31-Mediated Endosomal Trafficking Is Defective in RUNX1 Haplodeficiency". Blood 132, Supplement 1 (29 de novembro de 2018): 519. http://dx.doi.org/10.1182/blood-2018-99-118312.
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Abstract RAB GTPases are key players in vesicle trafficking, granule targeting of proteins, granule biogenesis and secretion. RAB31 (Ras-related protein 31) has been implicated in the regulation of vesicular trafficking between the Golgi/TGN and endosomes, and from early endosome (EE) to late endosome (LE). Studies in neuronal cells have implicated RAB31 in the transport of epidermal growth factor receptor (EGFR) from EE to LE. RUNX1, a major hematopoietic transcription factor, plays a critical role in megakaryocyte (MK) maturation and platelet production. Patients with RUNX1 haplodeficiency have thrombocytopenia, abnormal platelet function, and impaired granule contents and secretion. Our studies in a patient with a heterozygous RUNX1 mutation (c.969-323G>T ) (Sun et al, Blood 103: 948-54, 2004) associated with thrombocytopenia, platelet dysfunction, granule deficiency and impaired platelet responses revealed decreased platelet expression of RAB31. The role of RAB31 in MK and platelets is unknown. We addressed the hypothesis that RAB31 is a transcriptional target of RUNX1. We studied the role of RAB31 on vesicle transport in MK cells in human erythroleukemia (HEL) cells transformed into megakaryocytic cells by PMA (phorbol 12-myristate 13-acetate). RAB31 mRNA was decreased on platelet expression profiling of the patient (fold change: 0.28, p<0.0076, Sun et al J Thromb Haemost 5: 146-154). With real-time PCR platelet platelet RAB31 mRNA was decreased compared to 5 healthy controls by 60-80% in our patient (P1) and in two additional unrelated patients (siblings, P2 and P3) with RUNX1 mutation (c.508+1G>A). Platelet RAB31 protein was decreased compared to that in 5 healthy controls in patients P2 and P3. RAB31 promoter region (-2023/-1bp from the ATG) revealed 4 RUNX1 consensus sites: site I (-813/-808), site II (-972/-967), site III (-1500/-1495) and site IV (-2007/-2002). Chromatin immunoprecipitation (ChIP) revealed RUNX1 binding to RAB31 sites II and IV but not to other sites. Electrophoretic mobility shift assays using HEL cell proteins showed RUNX1 binding to sites II and IV. In luciferase reporter assays, mutation of individual sites II and IV decreased promoter activity indicating that they are functional sites. RAB31 promoter activity and protein expression were inhibited by RUNX1 siRNA and enhanced by RUNX1 overexpression. These indicate that RAB31 is a direct RUNX1 target, providing a mechanism for decreased RAB31 in patient platelets. We investigated putative roles of RUNX1 and its target RAB31 in endosomal dynamics in PMA treated HEL cells. We used immunofluorescent staining for markers of early endosomes (EE, EEA1) and late endosomes/multivesicular bodies (LE/MVB, CD63) in RUNX1- or RAB31-depleted cells by siRNA transfection. Either RUNX1 or RAB31 siRNA yielded a striking enlargement of early endosomes, as indicated by the EE marker EEA1. This finding suggests a role for RUNX1/RAB31 in EE maturation, either by mediating vesicle fission, or maturation to late endosomes by fusion with other endosomal vesicles. This effect of RUNX1 knockdown on EE enlargement was partially reversed by reconstitution of RAB31 by plasmid co-transfection, indicating that RAB31 is a significant but non-exclusive contributor to this RUNX1 function. Conclusions: These studies provide the first evidence that RAB31 is a direct transcriptional target of RUNX1 and a mechanism for RAB31 downregulation in RUNX1 haplodeficient patients. Downregulation of RAB31 or RUNX1 results in impaired endosomal maturation/trafficking, and this may contribute to the defective handling of α-granule proteins recognized in patients with RUNX1 mutations. Disclosures Lambert: Sysmex: Consultancy; Rigel: Consultancy; Bayer: Membership on an entity's Board of Directors or advisory committees; Educational Concepts in Medicine: Consultancy; CSL: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Summus: Consultancy; Amgen: Membership on an entity's Board of Directors or advisory committees; Shionogi: Consultancy.
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Mesa, Ruben, Carole B. Miller, Maureen Thyne, James Mangan, Sara Goldberger, Salman Fazal, Xiaomei Ma et al. "Impact of Myeloproliferative Neoplasms (MPNs) on Patients’ Overall Health and Productivity: Results from the MPN LANDMARK SURVEY in the United States". Blood 124, n.º 21 (6 de dezembro de 2014): 3183. http://dx.doi.org/10.1182/blood.v124.21.3183.3183.
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Abstract Background: Myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET), are chronic MPNs associated with a broad array of symptoms that may negatively impact patients’ quality of life (QoL). To enhance patient care, it is important to have a current and clear understanding of how MPNs affect the overall health and daily lives of patients. The MPN LANDMARK SURVEY was developed to examine patients’ perceptions of these MPNs related to disease burden, QoL, productivity, and activities of daily living (ADLs). Methods: Eligible patients diagnosed with an MPN were recruited to participate in an online survey conducted from May–July 2014in the US. Patients were asked about the overall burden of disease and impact of symptoms on their QoL, productivity, and ADLs. Descriptive analyses were conducted to assess these outcomes and examined by calculated (not reported) prognostic risk score (MF - DIPSS: Passamonti, Blood 2010; PV: Tefferi, Leuk 2013; ET - IPSET: Passamonti, Blood 2012) and symptom severity quartiles, which were determined using the MPN Symptom Assessment Form (MPN-SAF) total symptom scores. Results: 813 patients (MF=207; PV=380; ET=226) responded to the survey. A majority of patients were female (MF, 54%; PV, 62%; ET, 72%), approximately half were aged 60–74 years (MF, 55%; PV, 51%; ET, 46%), and most were covered by health insurance (>98%). Nearly half (48%) were diagnosed within the last 5 years and average time to diagnosis from first symptoms was >2 years. A high proportion of patients had intermediate to high prognostic risk scores (MF, 94%; PV, 87%; ET, 44%). The majority of patients reported feeling anxious or worried about their MPN (MF, 91%; PV, 78%; ET, 74%). Among all groups, fatigue was the most severe symptom reported (mean MPN-SAF score=6.0–6.4 on a scale of 0–10). A subset of patients in each group described their symptoms as very severe (severity score ≥7 on a scale of 0–10; MF: fatigue [59%], problems with sexual desire [49%], inactivity [46%]; PV: inactivity [48%], fatigue [49%], problems with sexual desire [49%]; and ET: problems with sexual desire [49%], fatigue [50%], headaches [40%]). The majority of patients reported that MPN-related symptoms reduced their QoL (MF, 81%; PV, 66%; ET, 57%); this was reported in all risk groups but more frequently by patients with a high risk score vs a low risk score in MF and ET (MF, 89% vs 69%; PV, 63% vs 65%; ET, 71% vs 59%). A more substantial QoL impact was reported by patients in high vs low symptom quartiles (MF, 95% vs 51%; PV, 94% vs 33%; ET, 93% vs 15%). Similarly, MPNs also had a marked negative impact on reduced work hours, sick days, voluntary job termination, receipt of medical disability, early retirement, and ADLs (Table 1). For example, among patients employed, approximately one fourth reported missing ≥1 day of work (MF, 29%; PV, 19%; ET, 23%) in the last 30 days before the survey. Even patients with low prognostic risk scores often reported missing ≥1 day of work (MF, 33%; PV, 23%; ET, 22%) or cancelling ≥1 day of planned activities (MF, 46%; PV, 35%; ET, 34%). Patients in the high vs low symptom quartiles were more likely to call in sick to work (MF, 48% vs 0%; PV, 52% vs 4%; ET, 38% vs 0%) or cancel ≥1 day of planned activities (MF, 77% vs 5%; PV, 56% vs 7%; ET, 67% vs 3%). Conclusion: The findings from this large, first-of-its-kind survey demonstrate a marked burden of disease across all 3 MPNs that is not limited to symptoms but extends to QoL, productivity, and ADLs. Although high prognostic risk scores have long been associated with a significant burden of disease, in this study, patients with a low risk score also reported significant burden. The symptom burden reported is consistent with previous studies, thus validating the present dataset. MPN treatment considerations should include reducing the symptom burden and improving QoL and productivity to enhance the overall health and lives of MPN patients. Disclosures Mesa: Incyte Corporation: Research Funding; CTI: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Eli Lilly: Research Funding; Promedior: Research Funding; NS Pharma: Research Funding; Sanofi: Research Funding; Celgene: Research Funding. Miller:Incyte Corporation: Honoraria, Research Funding. Thyne:Incyte Corporation: Speakers Bureau. Mangan:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Goldberger:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Fazal:Incyte Corporation: Consultancy, Research Funding, Speakers Bureau; Gilead: Research Funding, Speakers Bureau. Ma:Incyte Corporation: Consultancy. Wilson:Incyte Corporation: Honoraria. Dubinski:Incyte Corporation: Employment, Equity Ownership. Boyle:ICF International: Employment, Equity Ownership. Mascarenhas:Incyte Corporation: Consultancy, Research Funding; Novartis Pharmaceuticals Corporation: Research Funding.
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Mesa, Ruben, Carole B. Miller, Maureen Thyne, James Mangan, Sara Goldberger, Salman Fazal, Xiaomei Ma et al. "Gaps in Perception Between Patients and Physicians Regarding Symptomatology and Treatment Attitudes for Myeloproliferative Neoplasms: MPN LANDMARK SURVEY". Blood 124, n.º 21 (6 de dezembro de 2014): 4827. http://dx.doi.org/10.1182/blood.v124.21.4827.4827.
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Abstract Background : Patients diagnosed with myeloproliferative neoplasms (MPNs), including myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET), experience disease burdens that can negatively affect their quality of life. Disconnects between patient and physician perceptions of disease burden or poor patient-physician communication may delay or prevent achievement of treatment goals. The MPN LANDMARK SURVEY is the first large US-based survey designed to evaluate disease burden and patient-physician communication in MPN disease settings. Methods : All eligible patients diagnosed with 1 of the 3 MPNs and physicians treating patients with MPNs that were recruited were surveyed in the US during May-July 2014.The surveys included ≤67 questions (depending on the type of MPN and respondent) and required approximately 20–25 minutes to complete. Descriptive analyses were conducted to identify gaps in perceptions of disease burden and patient-physician communication. Results : The MPN LANDMARK SURVEY was completed by 813 patients (MF=207; PV=380; ET=226) and 457 physicians. Approximately half of the patients were 60–74 years of age (MF, 55%; PV, 51%; ET, 46%), the majority were female (MF, 54%; PV, 62%; ET, 72%) and had a degree from a 4-year college or postgraduate institution (MF, 65%; PV, 65%; ET, 58%), and >98% had health insurance. The majority of physicians graduated from medical school 5–24 years before the survey (67%) and practiced in outpatient settings (single specialty groups, 42%; academic hospitals, 31%). Patient-physician communication gaps were identified in several important areas: (1) Prognostic assessment: most patients did not recall receiving a prognostic risk score, but most physicians reported classifying patients by prognostic risk (Table 1). (2) Symptom assessment: physicians were more likely than patients to report that physicians ask about patients' most important disease-related symptoms or about a full and comprehensive list of symptoms (Table 1). (3) Treatment goals: the most important treatment goals were different in MF (patients: delay disease progression; physicians: improve symptoms) and PV (patients: delay disease progression; physicians: prevent vascular/thrombotic events) settings (Table 2). Patients and physicians in the ET setting both reported that prevention of vascular/thrombotic events was the most important treatment goal. Patients and physicians in the MF and PV settings reported fatigue as the most pressing disease manifestation that patients would like to resolve (MF: patients, 47%; physicians, 65%; PV: patients, 33%; physicians, 31%), whereas patients and physicians differed in the ET setting (patients: fatigue, 33%; physicians: stroke, 29%). Most patients reported a desire to be ≥50% responsible for their treatment decisions (MF, 72%; PV, 71%; ET, 75%). Physicians reported that most patients sometimes or often did not wish to comply with their primary treatment recommendation (MF, 77%; PV, 84%; ET, 79%). (4) Treatment satisfaction: overall, more than one third of patients were somewhat satisfied or dissatisfied with their physician's communication about their condition and treatment (MF, 34%; PV, 43%; ET, 45%) and with their physician's overall management of their disease (MF, 36%; PV, 40%; ET, 42%). Among patients who changed their MPN doctor (MF, 47%; PV, 46%; ET, 56%), dissatisfaction with prior care received was the most frequently reported reason for the change (MF, 40%; PV, 37%; ET, 33%). Approximately one fifth to one fourth of patients included their doctor's office among the most helpful sources of information about their diagnosis (MF, 27%; PV, 22%; ET, 20%), and most patients included the internet among the most helpful sources (MF, 90%; PV, 87%; ET, 89%). Conclusion : Important disconnects exist between patients' and physicians' perceptions in MPN disease settings. In addition, the majority of physicians report classifying patients by prognostic risk, including PV and ET settings, which do not have widely accepted prognostic risk scores. Although physicians generally appreciate the burden that MPNs have on patients, patient management may be enhanced with improved elucidation of patient symptoms and clear communication regarding the goals and potential benefits of interventions. Disclosures Mesa: Incyte Corporation: Research Funding; CTI: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Eli Lilly: Research Funding; Promedior: Research Funding; NS Pharma: Research Funding; Sanofi: Research Funding; Celgene: Research Funding. Miller:Incyte Corporation: Honoraria, Research Funding. Thyne:Incyte Corporation: Speakers Bureau. Mangan:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Goldberger:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Fazal:Incyte Corporation: Consultancy, Research Funding, Speakers Bureau; Gilead: Research Funding, Speakers Bureau. Ma:Incyte Corporation: Consultancy. Wilson:Incyte Corporation: Honoraria. Dubinski:Incyte Corporation: Employment, Equity Ownership. Boyle:ICF International: Employment, Equity Ownership. Mascarenhas:Novartis Pharmaceuticals: Research Funding; Incyte Corporation: Consultancy, Research Funding.
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Magnus, Dan, Santosh Bhatta e Julie Mytton. "432 Establishing injury surveillance in emergency departments in Nepal: epidemiology and burden of paediatric injuries". Emergency Medicine Journal 37, n.º 12 (23 de novembro de 2020): 825.2–827. http://dx.doi.org/10.1136/emj-2020-rcemabstracts.7.
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Aims/Objectives/BackgroundGlobally, injuries cause more than 5 million deaths annually. Children and young people are a particularly vulnerable group and injuries are the leading cause of death in people aged 5–24 years globally and a leading cause of disability.In most low and middle-income countries where the majority of global child injury burden occurs, systems for routinely collecting injury data are limited. There is a continuing need for better data on childhood injuries and for injury surveillance.The aim of our study was to introduce a hospital-based injury surveillance tool – the first of its kind in Nepal and explore its feasibility. We undertook prospective collection of data on all injuries/trauma presenting to 2 hospital emergency departments to describe the epidemiology of paediatric hospital injury presentations and associated risk factors.Methods/DesignA new injury surveillance system for use in emergency departments in Nepal was designed and used to collect data on patients presenting with injuries. Data were collected prospectively in two hospitals 24 h a day over 12 months (April 2019 - March 2020) by trained data collectors using tablet computers.Abstract 432 Table 1Socio-demographic profile and characteristics of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020 (N=2696)CharacteristicsFrequencyGender Male 1778 Female 918 Age groups 0–4 years 653 5–9 years 866 10–14 years 680 15–17 years 497 Median year (IRQ) 8 (5 – 13) Ethnicity/caste Janajati 1384 Brahmin/Chhetri 892 Dalit 148 Madhesi 146 Muslim 74 Others 50 Unknown 2 Place where injury occurred Home/Compound 1576 Highway/road/street 636 School 233 Recreational area 138 Workplace 76 Other 37 Activities at the time injury occurred Leisure/Play 1889 Travelling (other than to/from school/work) 296 Work 202 Travelling (to/from school/work) 184 Education 42 Organised sports 11 Other 52 Unknown 20 Intent of injury Unintentional 2560 Intentional (self-harm) 61 Intentional (assault) 75 Unintentional (n=2560) Fall 912 Animal or insect related 728 Road traffic injury 356 Injured by a blunt force 201 Stabbed, cut or pierced 176 Fire, burn or scald 65 Poisoning 52 Suffocation/choking 36 Electrocution 12 Drowning and submersion 7 Other 13 Unknown 2 Self-harm (n=61) Poisoning 38 Hanging, strangulation, suffocation 12 Stabbed, cut or pierced 6 Injured by blunt object 4 Other 1 Assault (n=75) Bodily force (physical violence) 43 Injured by blunt object 18 Stabbed, cut or pierced 8 Pushing from a high place 2 Poisoning 2 Sexual assault 1 Other 1 Nature of injury (one most severe) Cuts, bites or open wound 1378 Bruise or superficial injury 383 Fracture 299 Sprain, strain or dislocation 243 Internal injury 124 Head Injury/Concussion 83 Burns 67 Other 115 Unknown 2 Not recorded 2 Severity of injury No apparent injury 125 Minor 1645 Moderate 813 Severe 111 Not recorded 2 Disposition Discharged 2317 Admitted to hospital 164 Transferred to another hospital 179 Died 21 Leave Against Medical Advice (LAMA) 11 Unknown 2 Not recorded 2 Note:Not recorded = missing cases95% CI calculated using one proportion test and normal approximation method in Minitab.Abstract 432 Table 2Distribution of injuries by age-group, sex and mechanism of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Age groups & Sex0 - 4 years5 - 9 years10–14 years15–17 yearsMaleFemaleTotalIntent & mechanismsn (%)n (%)n (%)n (%)n (%)n (%)n (%)Unintentional Fall 239 (26.2) 328 (36.0) 249 (27.3) 96 (10.5) 636 (69.7) 276 (30.3) 912 (100) Animal or insect related 175 (24.0) 260 (35.7) 190 (26.1) 103 (14.1) 470 (64.6) 258 (35.4) 728 (100) Road traffic injury 49 (13.8) 108 (30.3) 86 (24.2) 113 (31.7) 223 (62.6) 133 (37.4) 356 (100) Injured by a blunt force 54 (26.9) 74 (36.8) 49 (24.4) 24 (11.9) 150 (74.6) 51 (25.4) 201 (100) Stabbed, cut or pierced 20 (11.4) 56 (31.8) 49 (27.8) 51 (29.0) 127 (72.2) 49 (27.8) 176 (100) Fire, burn or scald 42 (64.6) 10 (15.4) 9 (13.8) 4 (6.2) 27 (41.5) 38 (58.5) 65 (100) Poisoning 33 (63.5) 6 (11.5) 5 (9.6) 8 (15.4) 26 (50.0) 26 (50.0) 52 (100) Suffocation/choking 24 (66.7) 5 (13.9) 2 (5.6) 5 (13.9) 20 (55.6) 16 (44.4) 36 (100) Electrocution 2 (15.7) 0 (0.0) 3 (25.0) 7 (58.3) 10 (83.3) 2 (16.7) 12 (100) Drowning and submersion 1 (14.3) 1 (14.3) 3 (42.9) 2 (28.6) 3 (42.9) 4 (57.1) 7 (100) Other 6 (46.2) 4 (30.8) 3 (23.1) 0 (0.0) 10 (76.9) 3 (23.1) 13 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) 2 (100) Total 647 (25.3) 852 (33.3) 648 (25.3) 413 (16.1) 1702 (66.5) 858 (33.5) 2560 (100) Self-harm Poisoning 0 (0.0) 0 (0.0) 6 (15.8) 32 (84.2) 7 (18.4) 31 (81.6) 38 (100) Hanging 0 (0.0) 0 (0.0) 3 (25.0) 9 (75.0) 4 (33.3) 8 (66.7) 12 (100) Stabbed, cut or pierced 0 (0.0) 0 (0.0) 2 (33.3) 4 (66.7) 1 (16.7) 5 (83.3) 6 (100) Injured by blunt object 0 (0.0) 2 (50.0) 2 (50.0) 0 (0.0) 4 (100) 0 (0.0) 4 (100) Other 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) 1 (100) 0 (0.0) 1 (100) Total 0 (0.0) 2 (3.3) 13 (21.3) 46 (75.4) 17 (27.9) 44 (72.1) 61 (100) Assault Bodily force (physical violence) 3 (7.0) 1 (2.3) 11 (25.6) 28 (65.1) 37 (86.0) 6 (14.0) 43 (100) Injured by blunt object 2 (11.1) 8 (44.4) 4 (22.2) 4 (22.2) 13 (72.2) 5 (27.8) 18 (100) Stabbed, cut or pierced 1 (12.5) 0 (0.0) 2 (25.0) 5 (62.5) 7 (87.5) 1 (12.5) 8 (100) Pushing from a high place 0 (0.0) 1 (50.0) 1 (50.0) 0 (0.0) 1 (50.0) 1 (50.0) 2 (100) Poisoning 0 (0.0) 1 (50.0) 0 (0.0) 1 (50.0) 1 (50.0) 1 (50.0) 2 (100) Sexual assault 0 (0.0) 0 (0.0) 1 (100) 0 (0.0) 0 (0.0) 1 (100) 1 (100) Other 0 (0.0) 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) 1 (100) Total 6 (8.0) 12 (16.0) 19 (25.3) 38 (50.7) 59 (78.7) 16 (21.3) 75 (100) Abstract 432 Table 3Association of injury location, nature and severity with age among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Age groups0 – 4 years5 – 9 years10–14 years15–17 yearsTotalChi-SquareInjury characteristicsn (%)n (%)n (%)n (%)n (%)P valueLocation of injury sustained Home/Compound 537 (34.1) 504 (32.0) 319 (20.2) 216 (13.7) 1576 (100) <0.001 Highway/road/street 85 (13.4) 196 (30.8) 190 (29.9) 165 (25.9) 636 (100) School 15 (6.4) 107 (45.9) 85 (36.5) 26 (11.2) 233 (100) Recreational area 9 (6.5) 44 (31.9) 55 (39.9) 30 (21.7) 138 (100) Workplace 1 (1.3) 4 (5.3) 19 (25.0) 52 (68.4) 76 (100) Other 6 (16.2) 11 (29.7) 12 (32.4) 8 (21.6) 37 (100) Total 653 (24.2) 866 (32.1) 680 (25.2) 497 (18.4) 2696 (100) Nature of injury Cuts, bites or open wound 328 (23.8) 506 (36.7) 314 (22.8) 230 (16.7) 1378 (100) <0.001 Bruise or superficial injury 81 (21.1) 99 (25.8) 118 (30.8) 85 (22.2) 383 (100) Fracture 48 (16.1) 101 (33.8) 112 (37.5) 38 (12.7) 299 (100) Sprain, strain or dislocation 48 (19.8) 78 (32.1) 72 (29.6) 45 (18.5) 243 (100) Internal injury 44 (35.5) 8 (6.5) 18 (14.5) 54 (43.5) 124 (100) Head Injury/Concussion 18 (21.7) 26 (31.3) 18 (21.7) 21 (25.3) 83 (100) Burns 42 (62.7) 9 (13.4) 10 (14.9) 6 (9.0) 67 (100) Other 41 (35.7) 38 (33.0) 18 (15.7) 18 (15.7) 115 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Total 652 (24.2) 865 (32.1) 680 (25.2) 497 (18.4) 2694 (100) Severity of injury No apparent injury 39 (31.2) 45 (36.0) 26 (20.8) 15 (12.0) 125 (100) <0.001 Minor 419 (25.5) 535 (32.5) 406 (24.7) 285 (17.3) 1645 (100) Moderate 171 (21.0) 262 (32.2) 225 (27.7) 155 (19.1) 813 (100) Severe 23 (20.7) 23 (20.7) 23 (20.7) 42 (37.8) 111 (100) Total 652 (24.2) 865 (32.1) 680 (25.2) 497 (18.4) 2694 (100) Abstract 432 Table 4Association of injury location, nature and severity with sex among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020SexMaleFemaleTotalChi-SquareInjury characteristicsn (%)n (%)n (%)P valueLocation of injury sustained Home/Compound 979 (62.1) 597 (37.9) 1576 (100) <0.001 Highway/road/street 421 (66.2) 215 (33.8) 636 (100) School 176 (75.5) 57 (24.5) 233 (100) Recreational area 111 (80.4) 27 (19.6) 138 (100) Workplace 62 (81.6) 14 (18.4) 76 (100) Other 29 (78.4) 8 (21.6) 37 (100) Total 1778 (65.9) 918 (34.1) 2696 (100) Nature of injury Cuts, bites or open wound 959 (69.6) 419 (30.4) 1378 (100) <0.001 Bruise or superficial injury 246 (64.2) 137 (35.8) 383 (100) Fracture 200 (66.9) 99 (33.1) 299 (100) Sprain, strain or dislocation 154 (63.4) 89 (36.6) 243 (100) Internal injury 50 (40.3) 74 (59.7) 124 (100) Head Injury/Concussion 59 (71.1) 24 (28.9) 83 (100) Burns 27 (40.3) 40 (59.7) 67 (100) Other 79 (68.7) 36 (31.3) 115 (100) Unknown 2 (100) 0 (0.0) 2 (100) Total 1776 (65.9) 918 (34.1) 2694 (100) Severity of injury No apparent injury 81 (64.8) 44 (35.2) 125 (100) 0.048 Minor 1102 (67.0) 543 (33.0) 1645 (100) Moderate 533 (65.6) 280 (34.4) 813 (100) Severe 60 (54.1) 51 (45.9) 111 (100) Total 1776 (65.9) 918 (34.1) 2694 (100) Abstract 432 Table 5Distribution of injuries by outcome and mechanism of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Outcome of injuryDischargedAdmittedTransferredDiedLAMAUnknownTotalIntent & mechanismsn (%)n (%)n (%)n (%)n (%)n (%)n (%)Unintentional Fall 787 (86.5) 65 (7.1) 53 (5.8) 0 (0.0) 4 (0.4) 1 (0.1) 910 (100) Animal/insect bite/sting 704 (96.7) 3 (0.4) 19 (2.6) 0 (0.0) 1 (0.1) 1 (0.1) 728 (100) Road traffic injury 260 (73.0) 47 (13.2) 44 (12.4) 5 (1.4) 0 (0.0) 0 (0.0) 356 (100) Injured by a blunt force 190 (94.5) 4 (2.0) 6 (3.0) 0 (0.0) 1 (0.5) 0 (0.0) 201 (100) Stabbed, cut or pierced 165 (93.8) 8 (4.5) 3 (1.7) 0 (0.0) 0 (0.0) 0 (0.0) 176 (100) Fire, burn or scald 52 (80.0) 12 (18.5) 1 (1.5) 0 (0.0) 0 (0.0) 0 (0.0) 65 (100) Poisoning 30 (57.7) 4 (7.7) 16 (30.8) 1 (1.9) 1 (1.9) 0 (0.0) 52 (100) Suffocation/choking/asphyxia 24 (66.7) 4 (11.1) 6 (16.7) 1 (2.8) 1 (2.8) 0 (0.0) 36 (100) Electrocution 7 (58.3) 2 (16.7) 2 (16.7) 1 (8.3) 0 (0.0) 0 (0.0) 12 (100) Drowning and submersion 4 (57.1) 0 (0.0) 0 (0.0) 3 (42.9) 0 (0.0) 0 (0.0) 7 (100) Other 12 (92.3) 1 (7.7) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 13 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Total 2237 (87.5) 150 (5.9) 150 (5.9) 11 (0.4) 8 (0.3) 2 (0.1) 2558 (100) Self-harm Poisoning 5 (13.2) 8 (21.1) 23 (60.5) 0 (0.0) 2 (5.3) 0 (0.0) 38 (100) Hanging 1 (8.3) 0 (0.0) 1 (8.3) 10 (83.3) 0 (0.0) 0 (0.0) 12 (100) Stabbed, cut or pierced 6 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 6 (100) Injured by blunt object 4 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 4 (100) Other 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Total 17 (27.9) 8 (13.1) 24 (39.3) 10 (16.4) 2 (3.3) 0 (0.0) 61 (100) Assault Bodily force (physical violence) 34 (79.1) 5 (11.6) 3 (7.0) 0 (0.0) 1 (2.3) 0 (0.0) 43 (100) Injured by blunt object 18 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 18 (100) Stabbed, cut or pierced 6 (75.0) 1 (12.5) 1 (12.5) 0 (0.0) 0 (0.0) 0 (0.0) 8 (100) Pushing from a high place 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Poisoning 1 (50) 0 (0.0) 1 (50.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Sexual assault 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Other 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Total 63 (84.0) 6 (8.0) 5 (6.7) 0 (0.0) 1 (1.3) 0 (0.0) 75 (100) Abstract 432 Figure 1Seasonal variation of injuries identified by the injury surveillance system over a year among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Results/ConclusionsThe total number of ED patients with injury in the study was 10,154.2,696 were patients aged <18 years. Most injuries in children were unintentional and over half of children presenting with injuries were <10 years of age. Falls, animal bites/stings and road traffic injuries accounted for nearly 75% of all injuries with some (drowning, poisonings and burns) under-represented. Over half of injuries were cuts, bites and open wounds. The next most common injury types were superficial injuries (14.2%); fractures (11.1%); sprains/dislocations (9.0%). Child mortality was 1%.This is the biggest prospective injury surveillance study in a low or middle country in recent years and supports the use of injury surveillance in Nepal for reducing child morbidity and mortality through improved data.CHILD PAPER: RESULTS SECTIONTotal number of ED patients: 33046Total number of ED patient with injury: 10154 (adult=7458 & children=2696)8.2% (n=2696) patients with injury were children aged <18 yearsHetauda hospital: 2274 (84.3%)Chure hill hospital: 422 (15.7%)
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Валиев, Всеволод Сергеевич, Денис Евгеньевич Шамаев, Рустам Равилевич Хасанов e Виталий Викторович Маланин. "ПОДВИЖНОСТЬ ТЯЖЕЛЫХ МЕТАЛЛОВ В ДОННЫХ ОТЛОЖЕНИЯХ И ОСОБЕННОСТИ ИНТЕРПРЕТАЦИИ ЕЕ ИЗМЕНЧИВОСТИ". Российский журнал прикладной экологии, n.º 2 (6 de julho de 2022): 61–67. http://dx.doi.org/10.24852/2411-7374.2022.2.61.67.
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При оценке подвижности тяжелых металлов в системе «вода – донные отложения» важно не только понимать условия и особенности фазовых переходов, но и иметь надежные критерии для их оценки и интерпретации. Среди факторов иммобилизации металлов в донных отложениях обычно рассматривают присутствие в них органического вещества и тонкодисперсных фракций и pH среды. Целью исследования явилось построение репрезентативных моделей такой взаимосвязи.
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Jihan Irbah Nadiah e Dian Filianti. "Hubungan Kualitas Audit, Komite Audit, dan Dewan Pengawas Syariah terhadap Kinerja Bank Umum Syariah di Indonesia". Jurnal Ekonomi Syariah Teori dan Terapan 9, n.º 5 (30 de setembro de 2022): 731–46. http://dx.doi.org/10.20473/vol9iss20225pp731-746.
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ABSTRAK Penelitian ini ditujukan untuk mengetahui hubungan kualitas audit, komite audit, dan Dewan Pengawas Syariah (DPS) terhadap kinerja Bank Umum Syariah di Indonesia pada tahun 2015-2020 yang diproksikan dengan ROA, baik secara parsial dan simultan. Melalui pendekatan kuantitatif dengan teknik analisis regresi data panel, hasil penelitian ini menunjukkan bahwa secara parsial, kualitas audit yang dihasilkan KAP Big 4 berpengaruh positif signifikan terhadap kinerja bank umum syariah. Pada variabel komite audit, ukuran komite audit tidak mempengaruhi kinerja bank umum syariah, sedangkan kompetensi dan frekuensi komite audit berpengaruh negatif signifikan terhadap kinerja bank umum syariah. Pada variabel DPS, ukuran dan frekuensi rapat DPS berpengaruh negatif signfikan terhadap kinerja bank umum syariah, sedangkan kompetensi DPS berpengaruh positif signifikan terhadap kinerja bank umum syariah. Secara simultan, kualitas audit, komite audit, serta DPS berpengaruh positif signifikan terhadap kinerja bank umum syariah. Penelitian ini diharapkan dapat bermanfaat bagi manajemen perusahaan, sebagai bahan pertimbangan untuk meningkatkan efektivitas peran pengawasan dalam penerapan tata kelola perusahaan agar dapat mewujudkan kinerja perusahaan menjadi lebih baik. Kata Kunci: Kualitas audit, Komite audit, Dewan Pengawas Syariah, Kinerja Bank. ABSTRACT This study aims is to find out the relationship between audit quality, audit committee, and Sharia Supervisory Board (SSB) on the performance of Islamic Commercial Banks in Indonesia in 2015-2020 as proxied by ROA, both partially and simultaneously. Through a quantitative approach with panel data regression analysis techniques, the results of the study show that partially, the audit quality produced by KAP Big 4 has a significant positive effect on the performance of Islamic commercial banks. In the audit committee variable, the size of the audit committee does not affect the performance of Islamic commercial banks, while the competence and frequency of the audit committee have a significant negative effect on the performance of Islamic commercial banks. In the DPS variable, the size and frequency of DPS meetings have a significant negative effect on the performance of Islamic commercial banks, while DPS competence has a significant positive effect on the performance of Islamic commercial banks. Simultaneously, audit quality, audit committee, and DPS have a significant positive effect on the performance of Islamic commercial banks. This research is expected to be useful for company management, as a consideration for increasing the effectiveness of the supervisory role in the implementation of corporate governance in order to realize better company performance. Keywords: Audit Quality, Audit committee, Shariah Supervisory Board, Banks performance. 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Journal of Islamic Accounting and Business Research, 11(1), 70–89. https://doi.org/10.1108/JIABR-05-2017-0069 Khalil, A., & Boulila Taktak, N. (2020). The impact of the Shariah Board’s characteristics on the financial soundness of Islamic banks. Journal of Islamic Accounting and Business Research, 11(9), 1807–1825. https://doi.org/10.1108/JIABR-08-2018-0127 Khan, I., & Zahid, S. N. (2020). The impact of Shari’ah and corporate governance on Islamic banks performance: evidence from Asia. International Journal of Islamic and Middle Eastern Finance and Management, 13(3), 483–501. https://doi.org/10.1108/IMEFM-01-2019-0003 Lassoued, M. (2018). Corporate governance and financial stability in Islamic banking. Managerial Finance, 44(5), 524–539. https://doi.org/10.1108/MF-12-2016-0370 Lestari, E., & Murtanto. (2018). Pengaruh efektivitas dewan komisaris, dan komite audit, struktur kepemilikan perusahaan, dan kualitas audit terhadap perataan laba. Jurnal Manajemen Bisnis Krisnadwipayana, 5(1), 97–116. https://doi.org/10.35137/jmbk.v5i1.81 Mansoor, M., Ellahi, N., Malik, Q. A., Attributes, B., & Bank, I. (2019). Corporate governance and credit rating: Evidence of shariah governance from pakistan. International Transaction Journal of Engineering, Management, & Applied Sciences & Technologies. 10(18), 1–11. https://doi.org/10.14456/ITJEMAST.2019.251 Merawati, E. E., & Hatta, I. H. (2014). Pengaruh pengawasan komite audit, audit internal, audit eksternal terhadap kesehatan keuangan perusahaan dan dampaknya terhadap profitabilitas (Atudi pada perusahaan asuransi dan reasuransi yang tercatat di BEI). Jurnal Akuntansi Untar, 18(3), 335–349. Mulyadi, R. (2017). Pengaruh karakteristik komite audit dan kualitas audit terhadap profitabilitas Perusahaan. Jurnal Akuntansi, 4(2), 22–35. https://doi.org/10.30656/jak.v4i2.248 Newell, R., & Wilson, G. (2002). Corporate governance: A Premium for good governance. The McKinsey Quarterly, 3(4), 20–23. Nguyen, Q. K. (2021). Oversight of bank risk-taking by audit committees and Sharia committees: conventional vs Islamic banks. Heliyon, 7(8), e07798. https://doi.org/10.1016/j.heliyon.2021.e07798 Nomran, N. M., & Haron, R. (2019). Dual board governance structure and multi-bank performance: a comparative analysis between Islamic banks in Southeast Asia and GCC countries. Corporate Governance (Bingley), 19(6), 1377–1402. https://doi.org/10.1108/CG-10-2018-0329 Nomran, N. M., Haron, R., & Hassan, R. (2018). Shari’ah supervisory board characteristics effects on Islamic banks’ performance: Evidence from Malaysia. International Journal of Bank Marketing, 36(2), 290–304. https://doi.org/10.1108/IJBM-12-2016-0197 Otoritas Jasa Keuangan. (2015). Peraturan OJK tentang Pembentukan dan Pedoman Pelaksanaan Kerja Komite Audit (Nomor 55/ POJK.04/2015). Jakarta: OJK. Otoritas Jasa Keuangan. (2020). Statistik Perbankan Syariah (Sharia Banking Statistics). Jakarta: OJK. Ramly, Z., Datuk, N., & Nordin, M. (2018). Dewan pengawasan syariah, independensi dewan, risiko komite dan pengambilan risiko bank syariah di Malaysia. Jurnal Internasional Ekonomi Dan Masalah Keuangan, 8(4), 290–300. Riandi, D., & Siregar, H. . (2011). Pengaruh penerapan good corporate governance terhadap return on asset, net profit margin, dan earning per share pada perusahaan yang terdaftar di corporate governance perception index. Jurnal Ekonom, 14(3), 127–133. Rifan, D. F., & Qintharah, Y. N. (2021). Pengaruh kualitas audit dan BOPO terhadap profitabilitas. JRAK: Jurnal Riset Akuntansi Dan Komputerisasi Akuntansi, 12(2), 55–68. http://dx.doi.org/10.33558/jrak.v12i2.2966 Rimardhani, H., Hidayat, R. R., & Dwiatmanto, D. (2016). Pengaruh mekanisme good corporate governance terhadap profitabilitas perusahaan (studi pada perusahaan bumn yang terdaftar di BEI Tahun 2012-2014). Jurnal Administrasi Bisnis, 31(1), 167-175. Rivai, V., Basir, S., Sudarto, S., & Veithzal, A. P. (2013). Commercial bank management: Manajemen perbankan dari teori ke praktik. Jakarta : PT RajaGrafindo Persada. Saeed, M. B., & Saeed, S. K. (2018). Characteristics of shariah supervisory board, corporate governance mechanisms and efficiency of Islamic banks: Evidence from listed banks in Asia. Journal of Islamic Business and Management (JIBM), 8(1), 116–138. https://doi.org/10.26501/jibm/2018.0801-008 Safieddine, A. (2009). Islamic financial institutions and corporate governance: New insights for agency theory. Corporate Governance: An International Review, 17(2), 142–158. https://doi.org/10.1111/j.1467-8683.2009.00729.x Supriyaningsih, S., & Fuad, F. (2016). The influence of audit committee characteristics on real earnings management. Jurnal Akuntansi Dan Auditing, 13(1), 61–79. https://doi.org/10.14710/jaa.13.1.61-79 Ulfa, N. (2019). Analisis pengaruh penerapan good corporate governance terhadap kinerja keuangan bank syariah mandiri tbk tahun 2010-2017. Skripsi tidak dipublikasikan. Tulungagung: UIN SATU Zraiq, M. A., & Fadzil, F. H. (2018). The impact of audit committee characteristics on firm performance: Evidence from Jordan. Scholar Journal of Applied Sciences and Research, 1(5), 39–42.
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Tidblad, Liselotte, Helga Westerlind, Bénédicte Delcoigne, Johan Askling e Saedis Saevarsdottir. "Comorbidities at diagnosis of rheumatoid arthritis: a population-based case-control study". Rheumatology, 17 de dezembro de 2020. http://dx.doi.org/10.1093/rheumatology/keaa856.
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Abstract Objectives Comorbidities contribute to the morbidity and mortality in rheumatoid arthritis (RA), and are thus important to capture and treat early. In contrast to the well-studied comorbidity risks in established RA, less is known about the comorbidity pattern up until diagnosis of RA. We therefore compared if the occurrence of defined conditions, and the overall comorbidity burden at RA diagnosis, is different from that in the general population, and if it differs between seropositive and seronegative RA. Methods Using Swedish national clinical and demographic registers, we identified new-onset RA patients (n = 11 086), and matched (1:5) to general population controls (n = 54 813). Comorbidities prior to RA diagnosis were identified in the Patient and Prescribed Drug Registers, and compared using logistic regression. Results At diagnosis of RA, respiratory (OR = 1.58, 95% CI = 1.44–1.74), endocrine (OR = 1.39, 95% CI = 1.31–1.47), and certain neurological diseases (OR = 1.73, 95% CI = 1.59–1.89) were more common in RA vs controls, with a similar pattern in seropositive and seronegative RA. In contrast, psychiatric disorders (OR = 0.87, 95% CI = 0.82–0.92) and malignancies (OR = 0.88, 95% CI = 0.79–0.97) were less commonly diagnosed in RA vs controls. The comorbidity burden was slightly higher in RA patients compared with controls (p< 0.0001). Conclusion We found several differences in comorbidity prevalence between patients with new-onset seropositive and seronegative RA compared with matched controls from the general population. These findings are important both for our understanding of the evolvement of comorbidities in established RA and for early detection of these conditions.
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"What can be impact of civil authorities’ faulty mortality registration on COVID-19 mortality count in the state of Bihar, India- Evidence from NFHS (National Family Health Survey -5)". Advance in Environmental Waste Management & Recycling 5, n.º 2 (24 de julho de 2022). http://dx.doi.org/10.33140/aewmr.05.02.09.
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Several local / global / national / international agencies have been estimating the impact of COVID-19 pandemic on mortality count in different regions. On 30 January 2020 the World Health Organization (WHO) declared COVID-19 a Public Health Emergency of International Concern (PHEIC). Death toll was only 171 on 30-01-2020 and by 31 -12- 2020, this figure increased to 1 813 188. The estimates of global deaths attributable to the COVID-19 pandemic in 2020 as published by WHO is at least 3 million, which is 1.2 million more than officially reported. Objective of this research study is to find out number of deaths in the household in the three years preceding the survey registered with the civil authorities’ with another objective of this research study is to estimate the excess mortality due to COVID-19 in a simple way to be understood by most of the readers. The total sample size was 35,834 households, 42,483 women of age 15-49 (including 6,350 women interviewed in PSUs in the state module), and 4,897 men of age 15-54 for the state of Bihar. This sample size was based on the size needed to produce reliable indicator estimates for each district. Household questionnaire regarding number of deaths in the household in the three years preceding the survey were collected and utilized to produce information in 19 languages using CAPI (Computer Assisted Personal Interviewing). This cross sectional survey study revealed that only 37.1 percent of deaths of households members due to any cause were registered with the civil authorities in the three years preceding the survey, of which 28 percent of deaths are at age 0-4, 45 percent of deaths occurred at age 25-34, and 41 percent of deaths occurred at age 35 and above (see table-1 and 2 for more details).
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KULKARNI, Kunal, Nomaan SHEIKH, Randeep AUJLA, Pip DIVALL e Joseph DIAS. "Outcomes of Unconstrained Proximal Interphalangeal Joint Arthroplasty: A Systematic Review". Journal of Hand Surgery (Asian-Pacific Volume), 31 de março de 2022, 1–13. http://dx.doi.org/10.1142/s2424835522500266.
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Background: Unconstrained pyrocarbon and metal-on-polyethylene (MoP) proximal interphalangeal (PIP) joint arthroplasty is an increasingly popular alternative to silicone implants and arthrodesis. This systematic review appraises their outcomes. Methods: Thirty studies comprising 1,324 joints (813 pyrocarbon, 511 MoP) were included. Mean patient age was 59 years (38–78) and mean follow-up period was 54 months (12–118). Results: There were mean improvements of 4.5 points (2–6.9) in pain visual analogue score, 10.5° (−26 to 58) in range of motion (ROM), 3.1 kg (−4 to 7) in grip strength, 0.6 kg (−1.5 to 2) in pinch strength and 18 points (−3 to 29) in the disabilities of the arm, shoulder and hand score, with no significant differences between implant types. ROM gains deteriorated over time. Clinical complications were frequent (23%) and significantly more common with pyrocarbon, as were radiographic complications. However, most were mild-moderate and did not necessarily correlate with negative outcomes or dissatisfaction. Overall re-operation rate was 21%, and revision rate 11%, both more frequent with pyrocarbon. Most revisions were within 24 months, beyond which survival was maintained up to 10 years. Conclusions: Unconstrained PIP joint arthroplasty is effective in improving pain scores, active ROM, grip/pinch strength and patient-reported outcome measures, particularly in patients with osteoarthritis. Results are generally maintained at least to the medium term, although gains diminish in the longer term. Complication and early revision rates are high, particularly with pyrocarbon implants. Most patients express positive attitudes to arthroplasty, with significant improvements in patient-reported outcome measures for both pyrocarbon and MoP implants. Patients with post-traumatic and inflammatory arthropathy are generally less satisfied. There is currently insufficient data to recommend one implant type over another, although the early-to-medium term results of MoP implants are promising. Prospective surveillance via small joint registries is recommended. Level of Evidence: Level III (Therapeutic)
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Kumar, Piyush. "What can be Impact of Civil Authorities’ Faulty Mortality Registration on COVID-19 Mortality Count in the State of Bihar, India- Evidence from NFHS (National Family Health Survey -5)". Public Health Open Access 6, n.º 2 (2022). http://dx.doi.org/10.23880/phoa-16000212.
Texto completo da fonteResumo:
Several local / global / national / international agencies have been estimating the impact of COVID-19 pandemic on mortality count in different regions. On 30 January 2020 the World Health Organization (WHO) declared COVID-19 a Public Health Emergency of International Concern (PHEIC). Death toll was only 171 on 30-01-2020 and by 31 -12- 2020, this figure increased to 1 813 188. The estimates of global deaths attributable to the COVID-19 pandemic in 2020 as published by WHO is at least 3 million, which is 1.2 million more than officially reported. Objective of this research study is to find out number of deaths in the household in the three years preceding the survey registered with the civil authorities’ with another objective of this research study is to estimate the excess mortality due to COVID-19 in a simple way to be understood by most of the readers. The total sample size was 35,834 households, 42,483 women of age 15-49 (including 6,350 women interviewed in PSUs in the state module), and 4,897 men of age 15-54 for the state of Bihar. This sample size was based on the size needed to produce reliable indicator estimates for each district. Household questionnaire regarding number of deaths in the household in the three years preceding the survey were collected and utilized to produce information in 19 languages using CAPI (Computer Assisted Personal Interviewing). This cross sectional survey study revealed that only 37.1 percent of deaths of households members due to any cause were registered with the civil authorities in the three years preceding the survey, of which 28 percent of deaths are at age 0-4, 45 percent of deaths occurred at age 25-34, and 41 percent of deaths occurred at age 35 and above (see table-1 and 2 for more details).
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Menis, D., F. Fiori, D. Zago, P. Cautero, L. Lesa, E. Scarpis, L. Brunelli e M. Parpinel. "Nutrient values and sustainability of omnivorous, vegetarian and vegan choices in a hospital canteen". European Journal of Public Health 33, Supplement_2 (1 de outubro de 2023). http://dx.doi.org/10.1093/eurpub/ckad160.346.
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Abstract Background A plant-based diet has a lower environmental impact than an omnivorous diet and, when balanced, may reduce the risk of certain non-communicable diseases. The aim of our work is to evaluate the nutritional profile and sustainability of omnivorous, vegan and vegetarian choices in an Italian hospital canteen. Methods We photographed the midday meals of users in the hospital canteen of Palmanova (Italy) for 5 consecutive days in September 2022. We examined the recipes provided by the canteen and divided the meal trays in omnivorous, vegan and vegetarian. For each tray we estimated the carbon and water footprint using the SU-EATABLE LIFE database and the energy and nutrient content using the Italian Food Composition Database for Epidemiological Studies. Results We analysed 228 trays (167 omnivorous, 7 vegan, 54 vegetarian). Median energy content was higher (p < 0.05) in the omnivorous trays (942 kcal/tray) than the plant-based trays (813 kcal/tray). The omnivorous trays contained more fats (42 %E) and less carbohydrates (36 %E) than the plant-based trays (fats: 35 %E; carbohydrates: 44 %E) (p < 0.05). The carbon and water footprint were higher (p < 0.05) for the omnivorous meals (1202 gCO2eq/tray, and 1370 LH2O/tray) than for the plant-based meals, which had a median value of 687 gCO2eq/tray and 907 LH2O/tray. Conclusions Vegan and vegetarian meals were more in line with the Italian dietary reference values and more sustainable than omnivorous meals. Nutrition education is needed to improve the sustainability and quality of workers’ lunches and to ensure an adequate choice of plant-based meals. Key messages • Even if plant-based meals were more sustainable and nutrionally balanced than the omnivorous ones, they were less chosen. • Improving food choices can help achieve the Sustainable Development Goals.
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Patel, Shailendra B. "Abstract 466: Stigmasterol Accumulation in ABCG8 Knockout Mice Does Not Account for Xenosterol Toxicity". Arteriosclerosis, Thrombosis, and Vascular Biology 34, suppl_1 (maio de 2014). http://dx.doi.org/10.1161/atvb.34.suppl_1.466.
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Xenosterol accumulation mice deficient in sterolin function leads to significant toxicity, with infertility, decreased body fat accumulation, macrothrombocytopenia, cardiac fibrosis and premature death1, 2. The predominant xenosterols are phytosterols derived from the diet and are a mixture of sitosterol (typically 70%), campesterol (~20%) and stigmasterol (~5-10%). Although sitosterol has been shown to have some biological effect in tissue culture, only stigmasterol has been shown to have a potent biological effect, by activating the transcriptional factor, Lxr3. To delineate whether all of the toxic biological effects were mediated by stigmasterol accumulation, we designed a diet that was supplemented with highly enriched stigmasterol (>80% purity) and fed this to Abcg8 knockout mice. Stigmasterol accumulation in the plasma and tissues was comparable to the levels observed in mice fed a mixed phytosterol-enriched diet that had been shown to result in toxicity. Over a 12-week period, both male and female Abcg8 knockout mice gained normal amounts of weight, body fat, showed no disturbances in tail-cuff measured blood pressure, and plasma analyses showed no abnormalities of platelet counts or volumes, blood glucose, plasma cholesterol, despite accumulation of stigmasterol in the plasma and tissues. Fertility testing showed no abnormalities. Gene expression analyses of livers did not show any consistent patterns, although Lxr target genes were not up-regulated. These data do not support the concept that stigmasterol accumulation, at levels of 5-10mg/dL in plasma, account for the xenosterol-mediated toxicity observed. 1. McDaniel, A.L., H.M. Alger, J.K. Sawyer, K.L. Kelley, N.D. Kock, J.M. Brown, R.E. Temel, and L.L. Rudel, Phytosterol feeding causes toxicity in ABCG5/G8 knockout mice. Am J Pathol, 2013. 182(4): p. 1131-8. 2. Solca, C., G.S. Tint, and S.B. Patel, Dietary xenosterols lead to infertility and loss of abdominal adipose tissue in sterolin-deficient mice. J Lipid Res, 2013. 54(2): p. 397-409. 3. Yang, C., L. Yu, W. Li, F. Xu, J.C. Cohen, and H.H. Hobbs, Disruption of cholesterol homeostasis by plant sterols. J. Clin. Invest., 2004. 114(6): p. 813-22.
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Pageau, Nicole, Patrice Lindsay e Mark Bayley. "Abstract WP329: A Functional Recovery Analysis of Inpatient Rehabilitation for Mild Stroke Patients". Stroke 44, suppl_1 (fevereiro de 2013). http://dx.doi.org/10.1161/str.44.suppl_1.awp329.
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Background / Purpose: Organized stroke care within the rehabilitation setting has improved functional outcomes and enable stroke patients to re-integrate within the communities. The Evidence Based Systematic Review for stroke recommends that mild stroke patients with a FIM ® > 80 could receive therapy within the community. However, in Ontario, approximately 20% of mild stroke patients continue to be admitted to inpatient rehabilitation. The purpose of this study is to identify the differences between the mild stroke patients being admitted to inpatient rehabilitation and being discharged home directly from acute care and propose a triage system for the mild stroke population. Methods: A retrospective chart audit was conducted for acute stroke discharges from two regional stroke centres in Ontario. The cohort included patients with a most responsible diagnosis of stroke and a completed AlphaFIM ® Instrument assessment. Stroke cases that had a Projected Full FIM ® score derived from the AlphaFIM ® Instrument with a score > 80, we’re stratified into two groups:discharged home and discharged to inpatient rehabilitation. Data was analyzed using a full and step wise regression model to determine which indicators impacted the discharge disposition. Results: There were 813 patients were eligible for inclusion. The mean age of participants was 72 years, and 54% were males. Overall, 33% of mild stroke patients were admitted to inpatient rehabilitation. The results of the analysis did not explain why so many mild stroke patients are admitted to inpatient rehabilitation. There was a trend toward mild stroke patients with aphasia, inattention and cognitive impairments being admitted to inpatient rehabilitation; however, this was not statistically significant. These two groups did not differ in rates of recurrent stroke or re-admission to hospital at follow-up. Conclusion: The results of this research indicates that milder stroke patients with a Projected Full FIM ® > 80 may effectively be managed in the community if appropriate rehabilitation services are available. Further research is warranted to evaluate functional outcomes of stroke patients within the community rehabilitation setting in order to determine its efficiencies.
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Rommel, Karl‐Philipp, Guillaume Bonnet, Vera Fortmeier, Lukas Stolz, Anne R. Schöber, Jennifer von Stein, Mohammad Kassar et al. "Congestion patterns in severe tricuspid regurgitation and transcatheter treatment: Insights from a multicentre registry". European Journal of Heart Failure, 4 de abril de 2024. http://dx.doi.org/10.1002/ejhf.3235.
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AbstractAimsWhile invasively determined congestion holds mechanistic and prognostic significance in acute heart failure (HF), its role in patients with tricuspid regurgitation (TR)‐related right‐ heart failure (HF) undergoing transcatheter tricuspid valve intervention (TTVI) is less well established. A comprehensive understanding of congestion patterns might aid in procedural planning, risk stratification, and the identification of patients who may benefit from adjunctive therapies before undergoing TTVI. The aim of this study was to investigate the role of congestion patterns in patients with severe TR and its implications for TTVI.Methods and resultsWithin a multicentre, international TTVI registry, 813 patients underwent right heart catheterization (RHC) prior to TTVI and were followed up to 24 months. The median age was 80 (interquartile range 76–83) years and 54% were women. Both mean right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) were associated with 2‐year mortality on Cox regression analyses with Youden index‐derived cut‐offs of 17 mmHg and 19 mmHg, respectively (p < 0.01 for all). However, RAP emerged as an independent predictor of outcomes following multivariable adjustments. Pre‐interventionally, 42% of patients were classified as euvolaemic (RAP <17 mmHg, PCWP <19 mmHg), 23% as having left‐sided congestion (RAP <17 mmHg, PCWP ≥19 mmHg), 8% as right‐sided congestion (RAP ≥17 mmHg, PCWP <19 mmHg), and 27% as bilateral congestion (RAP ≥17 mmHg, PCWP ≥19 mmHg). Patients with right‐sided or bilateral congestion had the lowest procedural success rates and shortest survival times. Congestion patterns allowed for discerning specific patient's physiology and specifying prognostic implications of right ventricular to pulmonary artery coupling surrogates.ConclusionIn this large cohort of invasively characterized patients undergoing TTVI, congestion patterns involving right‐sided congestion were associated with low procedural success and higher mortality rates after TTVI. Whether pre‐interventional reduction of right‐sided congestion can improve outcomes after TTVI should be established in dedicated studies.
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Teles, Sharon, Amanda R. Lopes e Marcelo B. Ribeiro. "Galaxy distributions as fractal systems". European Physical Journal C 82, n.º 10 (10 de outubro de 2022). http://dx.doi.org/10.1140/epjc/s10052-022-10866-0.
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AbstractThis paper discusses if large scale galaxy distribution samples containing almost one million objects can be characterized as fractal systems. The analysis performed by Teles et al. (Phys Lett B 813:136034, 2021) on the UltraVISTA DR1 survey is extended here to the SPLASH and COSMOS2015 catalogs, hence adding 750k new galaxies with measured redshifts to the studied samples. The standard $$\Lambda $$ Λ CDM cosmology having $$H_0=(70\pm 5)$$ H 0 = ( 70 ± 5 ) km/s/Mpc and number density tools required for describing these galaxy distributions as single fractal systems with dimension D are adopted. We use the luminosity distance $$d_{\scriptscriptstyle L}$$ d L , redshift distance $$d_z$$ d z and galaxy area distance (transverse comoving distance) $$d_{\scriptscriptstyle G}$$ d G as relativistic distance definitions to derive galaxy number densities in the redshift interval $$0.1\le z\le 4$$ 0.1 ≤ z ≤ 4 at volume limited subsamples defined by absolute magnitudes in the K-band. Similar to the findings of Teles et al. (2021), the results show two consecutive redshift scales where galaxy distribution data behave as single fractal structures. For $$z<1$$ z < 1 we found $$D=1.00\pm 0.12$$ D = 1.00 ± 0.12 for the SPLASH galaxies, and $$D=1,39\pm 0.19$$ D = 1 , 39 ± 0.19 for the COSMOS2015. For $$1\le z\le 4$$ 1 ≤ z ≤ 4 we respectively found $$D=0.83^{+0.36}_{-0.37}$$ D = 0 . 83 - 0.37 + 0.36 and $$D=0.54^{+0.27}_{-0.26}$$ D = 0 . 54 - 0.26 + 0.27 . These results were verified to be robust under the assumed Hubble constant uncertainty. Calculations considering blue and red galaxies subsamples in both surveys showed that the fractal dimensions of blue galaxies as basically unchanged, but the ones for the red galaxies changed mostly to smaller values, meaning that D may be seen as a more intrinsic property of the distribution of objects in the Universe, therefore allowing for the fractal dimension to be used as a tool to study different populations of galaxies. All results confirm the decades old theoretical prediction of a decrease in the fractal dimension for $$z>1$$ z > 1 .
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Patel, Shailendra B. "Abstract 667: Ergosterol or Brassicasterol Accumulations in ABCG8 Knockout Mice Do Not Account for Xenosterol Toxicity". Arteriosclerosis, Thrombosis, and Vascular Biology 34, suppl_1 (maio de 2014). http://dx.doi.org/10.1161/atvb.34.suppl_1.667.
Texto completo da fonteResumo:
Xenosterol accumulation mice deficient in sterolin function leads to significant toxicity, with infertility, decreased body fat accumulation, macrothrombocytopenia, cardiac fibrosis and premature death1,2. Although sitosterol has been shown to have some biological effect in tissue culture, only stigmasterol has been shown to have a potent biological effect, by activating the transcriptional factor, Lxr3. In patients with sitosterolemia, feeding shell-fish sterols led to accumulation of shell-fish sterols in their plasma4, suggesting any xenosterol could accumulate, if fed, to mammals deficient in Abcg5 or Abcg8. Fungi do not utilize cholesterol, but instead use ergosterol as the primary membrane sterol. To delineate whether ergosterol could accumulate in Abcg8 knockout mice, and lead to toxicity, we designed a diet that was supplemented with highly enriched ergosterol (>98% purity) and fed this to Abcg8 knockout mice. Over a 12-week period, both male and female Abcg8 knockout mice fed an ergosterol-enriched diet gained normal amounts of weight, body fat, showed no disturbances in tail-cuff measured blood pressure, and showed no abnormalities of platelet counts or volumes, blood glucose, or plasma cholesterol. Fertility testing showed no abnormalities. Dramatically, analyses of plasma from these mice showed no accumulation of ergosterol, but a dramatic increase in plasma brassicasterol, with levels reaching 80mg/dL in plasma. Gene expression analyses of livers did not show any consistent patterns, although Lxr target genes were not up-regulated. These data do not support the concept that brassicasterol accumulation, at levels of 80mg/dL in plasma, account for the xenosterol-mediated toxicity observed. Additionally, the intestine shows powerful 1st pass detoxification of ergosterol by converting it to brassicaterol by using (presumably) dehydrocholesterol Δ7 reductase enzyme and highlights the importance of intermediary metabolism enzymes as part of the defense against xenosterols. 1. McDaniel, A.L.et al Am J Pathol, 2013. 182(4): p. 1131-8. 2. Solca, C. et al J Lipid Res, 2013. 54(2): p. 397-409. 3. Yang, C.et al J. Clin. Invest., 2004. 114(6): p. 813-22. 4. Gregg, R.E.et al J. Clin. Invest., 1986. 77(6): p. 1864-72.
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Nguyen Phan, T., T. T. V. Lại, H. V. Đinh, T. Y. Đoàn, T. H. Nguyễn, T. T. H. Lê e M. Đ. Nguyễn. "P-097 Embryological and Clinical Outcomes of Microdissection testicular sperm extraction combined with Intracytoplasmic sperm injection (microTESE-ICSI) in patients with and without Klinefelter syndrome". Human Reproduction 38, Supplement_1 (1 de junho de 2023). http://dx.doi.org/10.1093/humrep/dead093.461.
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Abstract Study question This retrospective study aims to identify the embryo development and clinical outcomes in non-mosaic Klinefelter syndrome patients treated with microTESE-ICSI Summary answer Non-mosaic Klinefelter patients can retrieve their sperm using microTESE and can have their biological offsprings by combining microTESE with ICSI What is known already Klinefelter syndrome patients are classified into two main groups, namely non-mosaic Klinefelter (47, XXY) and mosaic Klinefelter (46, XY/47, XXY). To retrieve sperm from non-mosaic Klinefelter, microTESE is a crucial treatment that yields a successful rate of approximately 50%. Recent research reports that microTESE-ICSI is a treatment regime that brings a higher in-vitro fertilization (IVF) success rate for those with non-mosaic Klinefelter syndrome. However, most of the previous studies on this group focuses on sperm retrieval rate and male factors. Few studies have reported embryo development and clinical outcomes, especially, under the adjustment for female partner’s age and oocyte quantity Study design, size, duration This retrospective study was conducted to evaluate spermatozoa retrieval, embryo development, and clinical outcomes in 931 patients with microTESE treatment at Andrology and Fertility Hospital of Hanoi from 6/2019 to 9/2022. Patients were divided into two groups including 118 patients with non-mosaic Klinefelter syndrome (KS) and 813 patients without Klinefelter syndrome (non-KS). Participants/materials, setting, methods In 931 patients, 63 KS and 417 non-KS had spermatozoa retrieved from microTESE were carried out ICSI. In ICSI group, 59 KS and 319 non-KS patients whose partners were under 35 years old were selected to compare embryological and clinical outcomes. Outcomes included fertilization rate, day 3 usable embryo rate, usable blastocyst rate, pregnancy rate (positive beta-hCG test), biochemical pregnancy rate, ongoing pregnancy, and live-birth rate (calculated on the total number of IVF cycles). Main results and the role of chance Spermatozoa retrieval rate by microTESE in the KS group was 53.4% (63/118), while this rate in the non-KS group was 51.2% (417/813) (p > 0.05). The mean age of female partners was significantly lower in the KS group than in non-KS group (26.6 ± 4.0 vs. 28.0 ± 3.5; p = 0.006). The mean of mature oocytes between these two groups was similar (15.7 ± 8.1 vs 14.5 ± 7.2; p > 0.05). Fertilization rates in KS and non-KS groups were 62.7% and 65.3%, respectively. Day 3 usable embryo rate (embryo with over 6 blastomeres at day 3) in two groups was not significantly different (69% vs 69.5%, p > 0.05). Usable blastocyst rate (embryo quality is over 2BB, Gardner grading system) in the KS group (19.9%, n = 54) was significantly lower than in non-KS group (41.1%, n = 281) (p < 0.001). Pregnancy rate and biochemical pregnancy rate were 75.9% and 6.9% in KS group (n = 58), respectively. Those rates were 81.5% and 3.2% in non-KS group (n = 313), respectively. There was no significant difference in ongoing pregnancy rate between these two groups (61.1% vs 74.5%; p > 0.05). Live-birth rate in the KS group was 43.2% (16/37), while this rate in the non-KS group was 46.5% (67/145). Limitations, reasons for caution This research had limitations of a retrospective study. Male hormonal factors and baby health could not be thoroughly measured because of difficulties in contact with patients at the time of the study. Besides, day 3 top-quality embryos were directed to freeze, so usable blastocyst rate was low in this study. Wider implications of the findings These data confirmed that microTESE provides opportunities for non-mosaic Klinefelter syndrome patients to retrieve their own sperm. Combination of microTESE and ICSI is an effective treatment regimen that helps these patients to have their own usable embryos and babies. Trial registration number not applicable
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Elser, Holly, Laura W. Pappalardo, Rebecca F. Gottesman, Josef Coresh, Ramon Diaz-Arrastia, Thomas H. Mosley, Scott E. Kasner, Silvia Koton e Andrea L. C. Schneider. "Head Injury and Risk of Incident Ischemic Stroke in Community-Dwelling Adults". Stroke, 8 de maio de 2024. http://dx.doi.org/10.1161/strokeaha.123.046443.
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BACKGROUND: While stroke is a recognized short-term sequela of traumatic brain injury, evidence about long-term ischemic stroke risk after traumatic brain injury remains limited. METHODS: The Atherosclerosis Risk in Communities Study is an ongoing prospective cohort comprised of US community-dwelling adults enrolled in 1987 to 1989 followed through 2019. Head injury was defined using self-report and hospital-based diagnostic codes and was analyzed as a time-varying exposure. Incident ischemic stroke events were physician-adjudicated. We used Cox regression adjusted for sociodemographic and cardiovascular risk factors to estimate the hazard of ischemic stroke as a function of head injury. Secondary analyses explored the number and severity of head injuries; the mechanism and severity of incident ischemic stroke; and heterogeneity within subgroups defined by race, sex, and age. RESULTS: Our analysis included 12 813 participants with no prior head injury or stroke. The median follow-up age was 27.1 years (25th–75th percentile=21.1–30.5). Participants were of median age 54 years (25th–75th percentile=49–59) at baseline; 57.7% were female and 27.8% were Black. There were 2158 (16.8%) participants with at least 1 head injury and 1141 (8.9%) participants with an incident ischemic stroke during follow-up. For those with head injuries, the median age to ischemic stroke was 7.5 years (25th–75th percentile=2.2–14.0). In adjusted models, head injury was associated with an increased hazard of incident ischemic stroke (hazard ratio [HR], 1.34 [95% CI, 1.12–1.60]). We observed evidence of dose-response for the number of head injuries (1: HR, 1.16 [95% CI, 0.97–1.40]; ≥2: HR, 1.94 [95% CI, 1.39–2.71]) but not for injury severity. We observed evidence of stronger associations between head injury and more severe stroke (National Institutes of Health Stroke Scale score ≤5: HR, 1.31 [95% CI, 1.04–1.64]; National Institutes of Health Stroke Scale score 6–10: HR, 1.64 [95% CI, 1.06–2.52]; National Institutes of Health Stroke Scale score ≥11: HR, 1.80 [95% CI, 1.18–2.76]). Results were similar across stroke mechanism and within strata of race, sex, and age. CONCLUSIONS: In this community-based cohort, head injury was associated with subsequent ischemic stroke. These results suggest the importance of public health interventions aimed at preventing head injuries and primary stroke prevention among individuals with prior traumatic brain injuries.