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1
Abbasi, S., and A. Honaramooz. "305 OPTIMIZING DONOR AND RECIPIENT FACTORS IN XENOGRAFTING OF TESTIS TISSUE." Reproduction, Fertility and Development 22, no. 1 (2010): 308. http://dx.doi.org/10.1071/rdv22n1ab305.
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Grafting of donor mammalian testis tissue into recipient mice allows completion of spermatogenesis in the grafted tissue and therefore can serve as a new option for preservation of male germ line. For testis tissue xenografting, castrated male nude mice typically serve as recipients, each receiving 8 testis tissue fragments; however, no study has comprehensively investigated donor and recipient factors. The objective of this study was to determine the effects of strain of immunodeficient recipient mouse (nude v. SCID), gonadal status (intact v. gonadectomized), and gender (male v. female) on the outcome of testis tissue xenografting. A secondary objective was to determine the optimal number of testis tissue fragments per mouse most suitable for xenografting. Testis parenchyma from newborn piglets were cut into small fragments (5 mg each) and grafted under the back skin of different groups of immunodeficient mice. In Experiment 1, 8 groups of mice (n = 7/group) served as recipients: castrated male nude, intact male nude, ovariectomized female nude, intact female nude, castrated male SCID, intact male SCID, ovariectomized female SCID, and intact female SCID. In Experiment 2, 4 groups of mice (n = 10/group) served as recipients of 2, 4, 8, or 16 testis tissue fragments per mouse. Recipient mice were sacrificed 8 months after grafting and the weight of the grafts and vesicular glands (male mice) were compared among groups by analysis of variance. In Experiment 1, mouse gonadal status (intact v. gonadectomized) did not affect the total graft weight (P > 0.05), but both the recipient mouse strain (nude v. SCID) and gender (male v. female) affected the total graft weight (2460 ± 320.9, 1420 ± 290.0, 758 ± 156.7, and 2780 ± 297.4, mean ± SEM, P < 0.0001 for SCID, nude, female, and male mice, respectively). In Experiment 2, the total graft weight was highest in the group of mice receiving 8 testis tissue fragments (192 ± 76.1, 695 ± 96.5, 2443 ± 338.8, and 1458 ± 305.4, mean ± SEM, P < 0.0001 for 2, 4, 8, or 16 fragment groups, respectively). These results collectively indicate that male SCID mice receiving 8 testis tissue fragments provide optimized conditions for the recovery of largest grafts. Research was supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Saskatchewan Health Research Foundation (SHRF) to A. Honaramooz and scholarships from the Western College of Veterinary Medicine and the International Peace Scholarship to S. Abbasi.
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Salwa, Dian Fatimatus, Nurjaya, Muhammad Yusuf Wibowo, Dwi Prasojo, and Nisrina Hasna’ Nabil. "Bioethanol Production from Breadnut (Artocarpus Camansi) Rind Waste as a Sustainable Energy Source." IOP Conference Series: Earth and Environmental Science 1105, no. 1 (December 1, 2022): 012010. http://dx.doi.org/10.1088/1755-1315/1105/1/012010.
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Abstract Global energy consumption of fossil fuels which is expected to rise by about 177 quadrillion British thermal units (BTU). The scarcity of oil and fossil fuels along with the demand for energy needs can be overcome by switching to renewable and environmentally friendly energy. Biofuels can be an alternative energy and provide a clean green environment. Breadfruit peel waste is high in carbohydrates and sugar so have potential to be optimized into bioethanol. This research aims to determine the effect of variations in yeast mass and fermentation time on the bioethanol content of breadfruit rind through the distillation process. This study applies the fermentation method with variations (PI: 8 grams 72 hours), (P2: 10 grams 72 hours), (P3: 8 grams 96 hours), and (P4: 10 grams 96 hours). Then, the ethanol content was tested with Perkin Elmer Clarus 580 (GC) Perkin Elmer HS Turbo Matrix 40 (headspace sampler). The optimum results were found in the variation of yeast mass of 8 grams and fermentation time of 96 hours, with the resulting ethanol content of 339.8 mg/L at simplo and 338.08 mg/L at the time of duplication or an average of 338.94 mg/L.
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Casoinic, F., D. Sampelean, Anca D. Buzoianu, N. Hancu, and Dorina Baston. "Serum Levels of Oxidative Stress Markers in Patients with Type 2 Diabetes Mellitus and Non-alcoholic Steatohepatitis." Romanian Journal of Internal Medicine 54, no. 4 (December 1, 2016): 228–36. http://dx.doi.org/10.1515/rjim-2016-0035.
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Abstract Introduction. Oxidative stress is one of the key mechanisms responsible for disease progression in non-alcoholic fatty liver disease. The aim of this study was to evaluate the serum levels of oxidative stress markers in patients with type 2 diabetes mellitus (DMT2) and non-alcoholic steatohepatitis (NASH) and test their relationships with clinical and biochemical patient characteristics, compared to patients with DMT2 without non-alcoholic fatty liver disease (NAFLD), and controls. Materials and methods. In all, 60 consecutive patients with DMT2 and NASH, 55 with DMT2 without NAFLD, and 50 age-and-gender-matched healthy subjects participated in the study. The serum levels of protein carbonyls and 8-isoprostane were determined by ELISA methods, while the serum levels of malondialdehyde (MDA) were detected by means of the spectrophotometric method. Clinical, demographic, and laboratory parameters were examined for all the subjects included in the study. Multivariate logistic regression was used to test the independent predictive factors in the relationships investigated here. Results. Patients with DMT2 and NASH displayed significantly higher serum levels of protein carbonyls (1.112 ± 0.42 nmol/dL), MDA (6.181 ± 1.81 ng/mL), and 8-isoprostane (338.6 ± 98.5 pg/mL) compared to patients with DMT2 without NAFLD, and controls. Results of multivariate logistic regression analyses indicate that in patients with DMT2 and NASH, the serum levels of oxidative stress markers were independently and positively associated with: HbA1c, duration of diabetes, the UKPDS cardiovascular risk score (for protein carbonyls); age, LDL-cholesterol (for 8-isoprostane); and triglycerides serum levels (for MDA). Conclusions. Our findings indicate that the process of oxidative stress tends to increase in patients with DMT2 and NASH, compared to patients with DMT2 without NAFLD, and controls. This evidence suggests that an antioxidant therapy might prove useful in the treatment of patients with DMT2 and NASH.
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Manohar, Murli, Thomas E. Goetz, Beth Saupe, Elizabeth Hutchens, and Elizabeth Coney. "Thyroid, renal, and splanchnic circulation in horses at rest and during short-term exercise." American Journal of Veterinary Research 56, no. 10 (October 1, 1995): 1356–61. http://dx.doi.org/10.2460/ajvr.1995.56.10.1356.
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SUMMARY Using radionuclide-labeled 15-μm-diameter microspheres injected into the left ventricle, we examined blood flow to the thyroid gland, adrenal glands, kidneys, and various gastrointestinal tract tissues in 9 healthy horses while they were standing quietly (rest) and during exercise at 2 work intensities (8 and 13 m/s). Hemodynamic measurements were made during steady-state conditions, as judged by the stability of heart rate as well as aortic, pulmonary, and right atrial pressures. The similarity of blood flow values for the left and the right kidneys during each of the 3 conditions indicated adequate mixing of microspheres with blood. In standing horses, of all tissues examined, the thyroid gland had the highest blood flow (1,655.2 ± 338.5 ml/min/100 g)—being about threefold that in the kidneys. Adrenal blood flow, by contrast, was only 25% of that in the kidneys (589.5 ± 50.4 ml/min/100 g). Among the gastrointestinal tract tissues, glandular stomach and pancreas had the highest blood flows (214.3 ± 21.6 and 197.6 ± 23.4 ml/min/100 g, respectively). Small intestinal perfusion was not different from that in the ventral colon and cecum, but their values exceeded those for the dorsal and small colons. Exercise at 8 and 13 m/s caused significant increase in adrenal blood flow as vascular resistance decreased significantly. In the kidneys, blood flow was only insignificantly affected during exercise at 8 m/s, but at 13 m/s there was a profound reduction in renal blood flow as intense renal vasoconstriction occurred. Vasoconstriction also caused thyroid and pancreatic blood flow to decrease significantly at both levels of exertion. Significant vasoconstriction occurring in all gastrointestional tract tissues at 8 and 13 m/s caused blood flow to be diverted away from these vascular beds. Thus, our data indicated that renal, adrenal, and splanchnic organ/tissue blood flow responses of strenuously exercising horses closely resemble those described for exercising ponies.
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Ling, C. D., R. L. Withers, A. D. Rae, S. Schmid, and J. G. Thompson. "Antiferroelectric modulations in Sb2WO6 and Sb2MoO6." Acta Crystallographica Section B Structural Science 52, no. 4 (August 1, 1996): 610–15. http://dx.doi.org/10.1107/s0108768196003813.
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The structure of Sb2WO6 [Mr = 523.4, triclinic, F{\bar 1}, a = 11.132 (1), b = 9.896 (4), c = 18.482 (7) Å, α = 90.20 (4), β 96.87 (8), γ = 90.21 (5)°, Dx = 6.88 g cm−3, Z = 16, Mo Kα, λ = 0.7107 Å, μ = 338.5 cm−1, F(000) = 3536] has been refined as an enlarged 2a × 2b × 2c F-centred superstructure of the previously reported structure [Castro, Millan, Enjalbert, Snoeck & Galy (1994). Mat. Res. Bull. 29, 871–879] refined in the space group P1. The re-refinement follows the observation, initially by TEM, of satellite reflections at G± ½(111)*, where G represents a reflection of the P1 reciprocal lattice. A final value of 0.040 for R 1 = Σ h ||F obs(h)| − |F calc(h)||/Σ h ||F obs(h)| was obtained for 3316 merged reflections with I(h) > 3σ[I(h)], compared with R 1 = 0.12 for the previous refinement. The refined structure is described in terms of an antiferroelectric modulation of a P121/a1 underlying parent structure in the original setting. Twinning of the crystal was successfully modelled in the refinement. Synthesis of the previously unknown phase Sb2MoO6 [Mr = 435.5, triclinic, F{\bar 1}, a = 10.758 (1), b = 9.673 (2), c = 17.57 (1) Å, α = 90.00 (5), β = 96.98 (3), γ = 90.05 (2)°, Z = 16, Dx = 4.97 g cm−3] is also reported, along with evidence for its isostructuralism with Sb2WO6.
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Andrýs, Ctirad, Oldřich Pozler, Jan Krejsek, Václav Derner, Marcela Drahošová, and Otakar Kopecký. "Serum Soluble Adhesion Molecules (sICAM-1, sVCAM-1 and sE-Selectin) in Healthy School Aged Children and Adults." Acta Medica (Hradec Kralove, Czech Republic) 43, no. 3 (2000): 103–6. http://dx.doi.org/10.14712/18059694.2019.121.
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The aim of this study was to map normal levels of serum soluble isoforms of adhesion molecules in relation to age and sex in the group of school-aged children. sICAM-1, sVCAM-1 and sE-selectin were determined in the group of 158 normal children subdivided into two subgroups; 6-10 years (68 children, median age 8 years) and 11-15 years (90 children, median age 12 years) and in 70 normal adult blood donors (25 females and 45 males, median age 46 years). The levels of sICAM-1 and sE-selectin fell down significantly over the age range 6-15 years, while the level of sVCAM-1 was remained. Age-related normal ranges were established using correlation analysis and were expressed as the 5%-95% percentiles intervals: sICAM-1 206.8-486.8 ng/ml, sE-selectin 36.7-153.2 ng/ml in the group of 6-10 years old children, sICAM-1 184.1-354.0 ng/ml, sE-selectin 29.9-114.1 ng/ml in group of 11-15 years old children. The levels of sVCAM-1 were 359.6-822.0 ng/ml and were constant within the examined age interval from 6 to 15 years. The influence of sex was also assayed and it was not statistically significant in any age category tested. Normal ranges of sICAM-1 (60.2-218.4 ng/ml), sE-selectin (8.3-116.9 ng/ml) and sVCAM-1 (338.0-1148.0 ng/ml) were established for adult population of healthy blood donors using the same methods.
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Moraes, Mariana Jucá, Erick Fonseca de Castilho, Júlio Cesar de Carvalho Balieiro, Alberto Carlos de Campos Bernardi, Andréa do Nascimento Barreto, Lívia Ferreira Pinho, Giovanna Galhardo Ramos, Gabriela Novais Azevedo, Letícia Krügner Zanetti, and Alexandre Rossetto Garcia. "Differences in the Behavioral Parameters of Young Zebu and Composite Bulls Kept on Non-Forested or in Integrated Crop–Livestock–Forestry Systems." Animals 14, no. 6 (March 19, 2024): 944. http://dx.doi.org/10.3390/ani14060944.
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The behavior of ruminants can influence their productive efficiency. The aim of this study was to evaluate the behavior of young zebu and composite bulls kept in pasture production systems, either in a crop-livestock-forest integration or without afforestation. The work was carried out in São Carlos, Brazil (21°57′42″ S, 47°50′28″ W), in a high-altitude tropical climate, from March to July, 2022. Forty young bulls were evaluated, being 20 Nelore (Bos indicus) (342.5 ± 36.6 kg BW; 16.9 ± 1.8 months) and 20 Canchim (5/8 Bos taurus × 3/8 Bos indicus) (338.4 ± 39.8 kg BW; 19.1 ± 1.9 months), equally distributed in full-sun (FS) and integrated crop–livestock–forestry (ICLF) production systems. Behavior was monitored uninterruptedly by an acoustic sensor and accelerometer attached to a collar, and complemented by direct visual assessment, in two one-day campaigns per month. Serum cortisol concentration was assessed monthly. Statistical analyses were conducted using a general linear model at a 5% significance level (SAS, version 9.4). The ICLF system had a milder microclimate and favored thermal comfort. Natural shading influenced grazing, resting, and rumination time. The Canchim bulls were more active when moving and grazing (p < 0.05), even at the hottest times of the day. In turn, the Nelore bulls spent more time resting at all times (p < 0.001), which was shown to be an adaptive strategy in response to environmental stimuli. The Canchim bulls had a longer rumination time than the Nelore bulls (p < 0.001), due to their longer grazing time. The frequency of water and mineral mixture intake did not differ between genotypes, regardless of the production system (p > 0.05). There was no difference in the serum cortisol concentrations of the Nelore and Canchim bulls kept in FS or ICLF (p = 0.082). Thus, young bulls of the different genotypes showed different behaviors, regardless of whether they were kept on pasture without afforestation or in an integrated crop–livestock–forestry system.
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Viscuse, Paul Vincent, Miao Zhang, Jingjing Liu, Rebecca Slack Tidwell, Sumit Kumar Subudhi, Amado J. Zurita, Paul Gettys Corn, et al. "Linking the Aggressive Variant Prostate Cancer (AVPC) molecular signature (-ms) to androgen indifference in a prospective clinical trial." Journal of Clinical Oncology 38, no. 6_suppl (February 20, 2020): 156. http://dx.doi.org/10.1200/jco.2020.38.6_suppl.156.
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156 Background: AVPC are morphologically heterogeneous tumors that share clinical features with the rare, virulent, androgen-indifferent and platinum-sensitive, small cell histologic variant. The AVPC-ms is composed of ≥2 defects in TP53, RB1 and PTEN, is detectable in »30% of advanced prostate cancers and predicts for benefit from platinum combinations (Corn et al. Lancet Oncol, 2019). Preclinical studies link the AVPC-ms with androgen indifference, but a prospective clinical association with decreased sensitivity to androgen signaling inhibitors is lacking. Methods: In a phase II trial (NCT02703623), men with metastatic castration resistant prostate cancer (mCRPC) treated with abiraterone and apalutamide were classified at week 8 as having a ‘satisfactory’ decline in PSA (≥ 50% from baseline) and CTC (≤5/7.5mL) or ‘unsatisfactory’. Pretreatment biopsies were obtained for immunohistochemistry (IHC) for TP53, RB1 and PTEN and RNA sequencing. Results: 198 men were registered. 59 (31.5%) of 187 evaluable had ‘unsatisfactory’ marker declines. Age, race/ethnicity, and baseline ECOG, PSA and LDH were similar between the groups. Men in the ‘unsatisfactory’ group had higher median total alkaline phosphatase (120 vs. 86; p=0.002), bone-specific alkaline phosphatase (21 vs. 16; p=0.01), CTC (9 vs. 1; p<0.001), and urine n-telopeptides (338.5 vs 182.5; p=0.003) levels. Unsupervised clustering of RNA profiles from 45 tumor biopsies revealed two distinct clusters. The top enriched gene set (FDR q-val<0.000) included ‘epithelial mesenchymal transition’, ‘E2F targets’ and ‘G2M checkpoint’ genes in one (n=18) and ‘androgen response’ in another (n=27) cluster. Six (33.3%) and 9 (33.3%) of the samples respectively belonged to patients in the ‘unsatisfactory’ decline group. IHC and RNA sequencing of the remaining samples are ongoing. Conclusions: Signaling pathways associated with androgen indifference can be identified in the tumor biopsies of men with early mCRPC, prior to exposure to secondary androgen signaling inhibitors. Their association with the AVPC-ms and patient outcomes will be presented. If confirmed, these markers could be used to inform therapy selection. Clinical trial information: NCT02703623.
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Thorn, Ross L., and James S. Drouillard. "PSVI-5 Extruded blend of Nannochloropsis oculata microalgae and flaxseed and its effects on ruminal fermentation and nutrient digestion." Journal of Animal Science 102, Supplement_2 (May 1, 2024): 340–41. http://dx.doi.org/10.1093/jas/skae102.389.
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Abstract Omega-3 fatty acids are essential nutrients for mammals, and are required for cellular growth and synthesis of numerous cellular signaling molecules. NBO3 Technologies, LLC (Manhattan, KS) has developed an omega-3 supplement consisting of an extruded blend of flaxseed and Nannochloropsis oculata microalgae (GreatOplus; GOP). Our objective was to evaluate effects of GOP on dry matter intake (DMI), water intake (WI), ruminal metabolism, and apparent total tract nutrient disappearance in cannulated Holstein steers (n = 11; initial body weight 586.4 ± 49.7 kg). Treatments consisted of backgrounding diets (40% roughage, 60% concentrate) containing 0% (CON) or 10% GOP (dry basis). Feed and water intake were recorded using an Insentec Roughage and Water monitoring system (Hokofarm Group; Emmeloord, The Netherlands). Steers were utilized in a cross-over design with two 19-d periods. Each period consisted of a 15-d adaptation phase and a 4-d collection phase. Ruminal contents, duodenal digesta, and feces were collected at 8-h intervals for 4 d starting at 1000 h on d 16. The sampling schedule was advanced by 2 h with each subsequent sampling day, thus generating a 24-h profile at 2-h intervals post-feeding over the 4-d sampling phase. Titanium dioxide (15 g) was dispensed directly into the rumen of each steer 15 min before feeding and to estimate apparent ruminal flow and fecal excretion of nutrients. There was a Treatment X Day interaction for DMI (P < 0.001); DMI was greater for steers fed GOP some of the days during the adaptation phase compared with steers fed the control diet, but intakes were similar during the collection phase. Ruminal fluid pH, ruminal ammonia concentration, and WI were not affected by treatment (P > 0.10). As expected, ruminal outflows of total fatty acids (195.6 vs 338.1 g/d for CON and GOP, respectively) and α-linolenic acid (ALA; 1.6 vs 6.3 g/d, respectively) were greater for steers fed GOP compared with steers fed CON (P < 0.05); however, ruminal disappearance (i.e., biohydrogenation) of ALA was extensive, with only 8% and 4.7% of ALA intake exiting the rumen for CON and GOP, respectively. Apparent total tract digestion of organic matter was not impacted by diet (P > 0.20; 78.1 and 76.8% for CON and GOP, respectively). Supplementing an extruded blend of flaxseed and microalgae can effectively increase the amount of α-linolenic acid available for absorption in the small intestine, but overall recovery of dietary α-linolenic acid is relatively low due to extensive biohydrogenation by microbes within the rumen.
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Prokina, V. Е., А. А. Ansheles, A. V. Tarasov, A. S. Ametov, and V. B. Sergienko. "The Role of Scintigraphy and Hybrid Single-Photon Emission Tomography in Comparison with Laboratory Data in a Comprehensive Examination of Patients with Secondary Hyperparathyroidism." Journal of radiology and nuclear medicine 103, no. 1-3 (July 7, 2022): 15–29. http://dx.doi.org/10.20862/0042-4676-2022-103-1-3-15-29.
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Objective: to estimate the possibilities and determine the diagnostic value of scintigraphy and single-photon emission computed tomography combined with computed tomography (SPECT/CT) in the assessment of the functional state of parathyroids in comparison with laboratory data in patients with secondary hyperparathyroidism (SHPT). Material and methods. The study consistently included 64 patients with the established diagnosis of SHPT due to the acquired vitamin D deficiency or with terminal chronic kidney disease (CKD), with the presence of ultrasound data and laboratory tests of calcium-phosphoric exchange indicators. Neck and mediastum nuclear study with 99mTc-methoxy-isobutyl-isonitrile (MIBI) was performed in the planar two-phase scintigraphy mode according to the standard protocol with an estimation of parathyroid visualization intensity, as well as in SPECT/CT performed 1 hour after MIBI injection. Results. In the group of patients with CKD as a cause of SHPT (n = 14), the most pronounced increase of parathyroid hormone (PTH) level (210.8 ± 103.0 vs. 107.0 ± 40.2 pg/ml in patients with vitamin D deficiency (n = 50, p < 0.001)) and phosphorus (mean 1.39 ± 0.51 mmol/l), as well as excess of normal levels of alkaline phosphatase (407.7 ± 338.1 units/l) were noted. In patients with vitamin D deficiency, impaired parathyroids according to SPECT/CT data was visualized in 8 % of cases, and in patients with CKD in 14.3 %. No significant differences in the mean levels of vitamin D in patients with (n = 46) and without (n = 4) modified parathyroids according to scintigraphy were detected: 26.06 ± 13.19 vs. 25.82 ± 18.80 ng/ml, respectively (p = 0.97). Differences in PTH and calcium levels were not observed: 91.3 ± 39.2 vs. 89.2 ± 29.5 pg/ml (p = 0.90), 2.53 ± 0.21 vs. 2.58 ± 0,15 mmol/l (p = 0.64), respectively. Conclusion. The neck SPECT/CT is a key method of topical imaging of impaired parathyroids in preoperative preparation of patients with SHPT caused by CKD. The method may have a diagnostic value in treatment-resistant patients with vitamin D deficiency and upper-normal PTH and calcium levels in terms of detection of the nodular form of parathyroid hyperplasia. The implementation of SPECT/CT after 1 hour after MIBI injection increases the sensitivity of the study.
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Labarca, Gonzalo, Jose Luis Che, Mario Henriquez-beltran, Fernando Saldias, Eva Retamal, Joaquin Nieto, Daniel Perez-chada, et al. "0725 Phenotyping Obstructive Sleep Apnea in Latin American Women: The Latin American Sleep Network (LATAM Sleep Net)." SLEEP 47, Supplement_1 (April 20, 2024): A310. http://dx.doi.org/10.1093/sleep/zsae067.0725.
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Abstract Introduction Obstructive Sleep Apnea (OSA) is a major cardiovascular risk factor and has worse health outcomes. Novel OSA-driven metrics have been associated with worse outcomes. However, data on women from unrepresentative groups, such as the Hispanic/Latino population outside the USA, is scant. This study aims to quantitatively describe the clinical and novel OSA-driven phenotypes among women from Latin America. Methods We performed a prospective, multicenter study including women with suspected OSA from 18 sleep clinics in 8 countries (Argentina, Bolivia, Chile, Colombia, Costa Rica, Mexico, Peru, and Uruguay). We extracted the raw data from the baseline sleep study from October 2022 to December 2023. To determine 1). Sleep Apnea Specific hypoxic burden (SASHB) is defined as the total area under respiratory event-related desaturation curves; 2) Specific Heart Rate Response (ΔHR), defined as the difference between a maximum heart rate during a subject-specific search window and an event-related minimum heart rate; 3) Ventilatory burden, defined as the event-specific area under the ventilation signal, identified by amplitude changes in the nasal pressure signal; and 4) Desaturation sensitivity (i.e., the tendency to desaturate) was defined as a hypoxic burden divided by a ventilatory burden. Results A total of 318 women were included 26% non-OSA, 38% mild OSA, and 36% moderate to severe OSA). The average AHI3% was 16.5 ev/hr, SASHB was 43.4%min/hr; VB was 244.3 %eupnea*min/h; ΔHR was 8.2 bpm, and the desaturation sensitivity was 0.16. Among OSA patients, the AHI3% was 21.78 ev/hr; SASHB was 57.8 %min/hr; VB was 338.1 %eupnea*min/h; ΔHR was 8.14 bpm, and the desaturation sensitivity was 0.18. Based on high SASHB (≥ 60%min/hr) or high ΔHR (≥ 10 bpm), 19% and 26% of the sample are at risk of worse cardiovascular outcomes, respectively, and 7.4% of the sample reported both criteria associated with adverse outcomes. Conclusion Among OSA women from Latin America, OSA-physiologically driven metrics are reproducible and similar to previous publications. Further studies are needed to fully understand the clinical utility of these metrics in clinical practice. Study register ISRCTN11936746. Support (if any) The Chest /AASM (7868 ); NIH(1R21HL161766-01); SRS (07-SRG-22); Universidad de Concepcion(2022000589)
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He, Qiang, Chenrui Wu, Long Pan, Jiachu Li, Yin Zhou, Hongxiang Cao, Ruirui Sun, Junjie Huang, Yongchen Wang, and Ping Huang. "Hepatic artery infusion chemotherapy combined with donafenib and camrelizumab in patients with unresectable hepatocellular carcinoma presenting portal vein tumor thrombus: A prospective, single-arm study." Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): e16134-e16134. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e16134.
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e16134 Background: Rational and effective treatment strategies for patients with unresectable hepatocellular carcinoma (uHCC) presenting portal vein tumor thrombus (PVTT) are lacking, and hepatic artery infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors and immune checkpoint inhibitors could be an effective therapy. Herein, we evaluated the efficacy and safety of HAIC combined with donafenib and camrelizumab in patients with uHCC presenting PVTT. Methods: This prospective, single-arm, single-center study enrolled patients with uHCC presenting PVTT (distant metastases were allowed), BCLC stage C, Child-Pugh scores ≤ 7, ECOG PS ≤1, and no previous local or systemic treatment. Patients received mFOLFOX6-HAIC (every 3 weeks, no more than 6 cycles), followed by peroral donafenib (200 mg BID every day) and intravenous camrelizumab (200 mg every 3 weeks). The primary endpoint was the objective response rate (ORR; per RECIST1.1 and mRECIST). Secondary endpoints included surgical conversion rate, disease control rate, progression-free survival (PFS), overall survival (OS), duration of response, and safety. Results: Between November 2021 and September 2022, we enrolled 15 eligible patients with a median age of 53 years (range, 36-76), including 12 (80%) males. Considering enrolled patients, 14 (93.3%) were HBV+, 13(86.7%) presented with PVTT invasion into the main portal vein, Child-Pugh scores 5/6/7: 9/5/1, ECOG PS 0/1: 10/5, median tumor size was 8.4 cm (range, 5.2-13.6), and 5 (33.3%) had extrahepatic metastases. The median number of HAIC procedures was 5 (range, 1-6). The median follow-up time was 338.0 days (95% CI, 298.7-377.4). Considering the 15 evaluable patients (completed at least one cycle of treatment), the ORR was 66.7% (10/15) according to RECIST 1.1, with 0 complete response (CR) and 10 partial responses (PR). According to mRECIST, the ORR was 73.3% (11/15), with 2 CR and 9 PR. Three patients (20%) became eligible for surgical resection, with one undergoing surgical resection (two refused surgery for financial reasons). Median PFS and OS were insufficient. All 15 (100%) patients experienced treatment-related adverse events (TRAEs). Common TRAEs included hand-and-foot skin reaction (HFSR; 93.3%), abdominal pain (73.3%), hypoalbuminemia (60.0%), platelet count decreased (60.0%), nausea (60%), aspartate aminotransferase increased (53.3%), and vomiting (53.3%). Grade 3/4 TRAEs included platelet count decreased (13.3%), HFSR (13.3%), hepatic function abnormal (6.7%), and ascites (6.7%). No grade 5 TRAEs were observed. TRAEs led to drug reduction in 8 patients (53.3%). Conclusions: HAIC combined with donafenib and camrelizumab afforded promising efficacy and safety in patients with uHCC presenting PVTT. Longer follow-up is required for further evaluation. Clinical trial information: ChiCTR2100051714 .
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Touma, Z., B. Hoskin, C. Atkinson, D. Bell, O. Massey, J. H. Lofland, P. Berry, C. Karyekar, and K. Costenbader. "THU0246 DIAGNOSTIC CLUSTER PROFILING OF PATIENTS IN A REAL-WORLD DATA SET WITH SYSTEMIC LUPUS ERYTHEMATOSUS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 350.2–350. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5865.
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Background:Previous systemic lupus erythematosus (SLE) studies have identified potential clusters of SLE clinical manifestations post diagnosis.Objectives:To describe the presentation of SLE at diagnosis across different cohorts of patients and describe management and outcomes after diagnosis within clusters.Methods:Cross-sectional study of 263 rheumatologists in the US and EU5. Data were collected from the Adelphi Real World 2015 Lupus Disease Specific Programme. Rheumatologists completed patient record forms (PRFs) for the next 5 prospectively consulting SLE patients; these patients completed patient self-completion (PSC) forms describing how SLE affected them. PRF data includes patient’s characteristics and management history. PSCs focused on similar data collection, including patient reported outcome measures on the humanistic burden. Age at diagnosis, symptoms at diagnosis, organ involvement at diagnosis, and severity at diagnosis were used as covariates in a latent cluster analysis.Results:Data were extracted from 1376 PRFs. Cluster analysis resulted in up to 6 clusters, and disease understanding led to the selection of a 4-cluster solution.Cluster 1 displayed the mildest disease, characterised by joint involvement, while cluster 2 displayed more skin involvement in conjunction with joint. Cluster 3 were characterised by renal involvement and cluster 4 had skin and joint involvement, but also high constitutional and haematological involvement at diagnosis (Table 1).Table 1Cluster analysisClustersOrgan involvement at diagnosis, n (%)Overall(n=1304)1(n=210)2(n=493)3(n=162)4(n=439)p-valueMusculoskeletal1145 (87.8)174 (82.9)444 (90.1)134 (82.7)393 (89.5)0.0065Mucocutaneous898 (68.9)5 (2.4)397 (80.5)95 (58.6)401 (91.3)<0.0001Neuropsychiatric87 (6.7)19 (9.0)9 (1.8)16 (9.9)43 (9.8)<0.0001Cardiorespiratory176 (13.5)36 (17.1)14 (2.8)22 (13.6)104 (23.7)<0.0001Gastrointestinal44 (3.4)8 (3.0)14 (2.8)8 (4.9)14 (3.2)0.6115Opthalmic47 (3.6)020 (4.1)10 (6.2)17 (3.9)0.0102Renal213 (16.6)15 (7.1)9 (1.8)162 (100)27 (6.2)<0.0001Constitutional425 (32.6)45 (21.4)89 (18.1)55 (34.0)236 (53.8)<0.0001Haematological452 (34.7)64 (30.5)22 (4.5)80 (49.4(286 (65.1)<0.0001Severity at diagnosis, n (%)Mild209 (16.0)55 (26.2)99 (20.1)1 (0.6)54 (12.3)<0.0001Moderate806 (61.8)122 (58.1)324 (65.7)75 (46.3)285 (64.9)Severe289 (22.2)33 (15.7)70 (14.2)86 (53.1)100 (22.8)Significant between-cluster differences were observed when comparing outcomes; cluster 4 have been diagnosed longest (mean weeks diagnosed 354.6 v. 1: 232.6, 2: 228.7, 3: 338.2, p<0.0001). Cluster 3 consulted more in the last 12 months (mean number of visits 7.9 vs. 1: 5.7, 2: 6.3, 4: 7.6).Significant differences were also observed between clusters in relation to current treatment proportions: corticosteroid (highest cluster 3: 78.4%), immunosuppressant (highest cluster 3: 75.3%), biologic DMARD (highest cluster 4: 17.8%) and antidepressant (highest cluster 4: 4.1%).Conclusion:This study demonstrates the heterogeneity of SLE at diagnosis and highlights four distinct presentations of the disease at diagnosis. Significant proportions of patients present with advanced disease, these clusters go on to present the greatest burden demonstrating the need for better diagnostic tools and novel earlier intervention.Study funded by Johnson and Johnson.Disclosure of Interests:Zahi Touma Consultant of: Consultant for Janssen, Ben Hoskin Consultant of: Consultant for Janssen, Christian Atkinson Consultant of: Consultant for Janssen, David Bell Consultant of: Janssen, Olivia Massey Consultant of: Janssen, Jennifer H. Lofland Employee of: Janssen, Pamela Berry Employee of: Janssen, Chetan Karyekar Shareholder of: Johnson & Johnson, Consultant of: Janssen, Employee of: Janssen Global Services, LLC. Previously, Novartis, Bristol-Myers Squibb, and Abbott Labs., Karen Costenbader Grant/research support from: Merck, Consultant of: Astra-Zeneca
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Chang, Hung, Hsiao-Wen Kao, Ming-Chung Kuo, Jin-Hou Wu, Ying-Jung Huang, Ting-Yu Huang, Tung-Huei Lin, and Lee-Yung Shih. "Genetic Evolution from Chronic Myeloproliferative Neoplasms to Acute Myeloid Leukemia: An Analysis of Forty-Six Paired Samples." Blood 142, Supplement 1 (November 28, 2023): 3155. http://dx.doi.org/10.1182/blood-2023-182624.
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Background: Secondary acute myeloid leukemia (sAML) may arise from chronic myeloproliferative neoplasm (MPN). The genetic evolution pattern may be understood by paired sample analysis. Knowledge of genetic change in MPN/sAML is still limited and more extensive studies should be done. Patients and Methods: Forty-six paired samples (27 males) at diagnosis of MPN (12 polycythemia vera, 6 essential thrombocythemia, 25 primary myelofibrosis and 3 MPN-unclassified) and sAML transformation were available. Mutational analyses of 27 genes ( JAK2V617F, CALR, MPL, ASXL1, IDH1, IDH2, TET2, DNMT3A, EZH2, SRSF2, U2AF1, SF3B1, ZRSR2, SMC1, STAG2, SMC3, RUNX1, SETBP1, IKZF1, WT1, K-RAS, N-RAS, C-CBL, TP53, RAD21, BCOR and BCORL1) were performed. Mutations and their variant allele frequencies (VAF) were measured by next generation sequencing. Results: At baseline (MPN), the mutation number was 2 (maximal 5). Forty-five samples harbored driver gene mutations (31 JAK2V617F, 13 CALR and 1 MPL). Twenty-eight samples harbored at least one epigenetic regulator mutations (11 TET2, 8 DNMT3A,7 ASXL1, 5 EZH2, 2 IDH2, 1 IDH1). Twelve samples harbored spliceosome mutations which were mutually exclusive (6 SRSF2, 3 SF3B1, 2 U2AF1 1 ZRSR2). Other mutations were RUNX1, BCORL1 (n=2 each), CBL and BCOR (n=1 each). In sAML, the median mutation number was 3 (maximal 7). Loss of mutation was found for JAK2V617F (9/31), TET2 (1/11) and SRSF2 (1/6). Acquisition was most common for RUNX1 (n=9), followed by TP53, ASXL1 (n=5 each), K-RAS (n=4) , ZRSR2, STAG2 (n=3 each). The median number of acquired mutation was 1 (maximal 5). The frequencies of gene mutations are summarized in Figure 1A. The baseline VAF of JAK2V617F was high (>35%) in 80.6% (25/31). In progression to sAML, VAF was constant in 29.0% (9/31, VAF changes <10%), increased in 20.0% (9/31, increased VAF> 10%), decreased in 41.9% (13/31, decreased VAF>10%) (Figure 1B). The baseline VAF in CALR mutation was high (>35%) in 91.3% (12/13). VAF remained stable in 76.9% (10/13), and loss of CALR mutation was not observed (Figure 1B). TET2 mutations tended to be stable (7/16), but clonal expansion (5/16 of all mutation events at MPN), or acquisition (n=2) could be found during transformation to sAML. DNMT3A mutations remained stable (5/8), exhibited clonal expansion (2/8), or acquisition (n=1) in sAML progression. ASXL1 mutations remained stable (6/7), with clonal expansion (1/7), or acquisition (n=5) during MPN/sAML progression. All EZH2 mutants had clonal expansion (5/5) and one acquired in sAML (Figure 1B). We found that CALR mutationwas often the founding clone with high VAF at MPN phase, stable clone during sAML, and might acquire mutations in signaling pathways (1 CBL, 1 KRAS), epigenetic regulators (2 ASXL1, 1 IDH2), transcription factors (2 RUNX1, 1 BCOR), spliceosome (2 ZRSR2, 1 SF3B1), and cohesin complex (1 STAG2). JAK2 mutationwas often preceded by other ancestral mutations such as TET2, ASXL1, DNMT3A, EZH2, IDH2, SRSF2 or ZRSR2. During evolution, leukemia arose from non- JAK2 mutated clones with mutations in EZH2, DNMT3A, RUNX1, EZH2, SETBP1, or acquisition of TP53, SF3B1, BCOR and STAG2 mutations) in sAML. In outcome, the median time from MPN to sAML was 82 (range 3.7 to 338.5) months. Female gender, loss of JAK2V617F, presence of U2AF1 and absence of IDH1 were associated with shorter time to sAML transformation. No other genetic mutation in our gene panel or the number of mutations harbored by patients in our cohort had significant impact on time to sAML. Marked increase of VAF was observed for JAK2 (7/22) , DNMT3A (1/7) , IDH1 (2/3), IDH2 (1/3), TET2 (3/10) , EZH2 (4/5), C-CBL (1/1) and SRSF2 (1/4). Marked decrease of VAF was observed for JAK2 (4/22), MPL (1/1), DNMT3A (1/7) , ASXL1 (1/8), SF3B1 (2/3), SRSF2 (1/4) and U2AF1 (1/2). Multiple mutational clones were detected for TET2 (two clones in 4 samples and 3 clones in 1). Clonal expansion and reduction were observed in two pairs of samples upon sAML transformation. Conclusions: At the MPN stage, most patients had driver mutations with frequent co-mutations of epigenetic modifier or spliceosome genes. CALR mutant clones were stable while for JAK2, sAML often arose from clones without JAK2V617F which acquired RUNX1, TP53, ASXL1 and K-RAS. Research funding:Ministryof Science and Technology Council,Taiwan (NSTC 112-2314-B-182-055) and Ministry of Health and Welfare, Taiwan (112-TDU-B-222-124001)
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Family, Leila, Su-Jau Yang, Zandra Klippel, Yanli Li, John H. Page, Roberto Rodriguez, and Chun Chao. "Risk of Febrile Neutropenia (FN) in Select Myelosuppressive Chemotherapy Regimens." Blood 126, no. 23 (December 3, 2015): 3257. http://dx.doi.org/10.1182/blood.v126.23.3257.3257.
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Abstract Introduction Febrile neutropenia (FN) is a serious adverse effect of myelosuppressive chemotherapy, which often results in hospitalization and chemotherapy dose modification. FN risk depends on patient characteristics and chemotherapy regimen risk. Understanding the FN risk associated with individual chemotherapy regimens can help guide the use of prophylactic granulocyte colony-stimulating factor (G-CSF) and patient monitoring. To this end, the NCCN has classified regimens into high (≥20%), intermediate (10%-20%), or low (<10%) FN risk based primarily on clinical trial data. However, even for the same regimen, the FN risk is often higher in clinical practice than in clinical trials. In this study, we assessed the FN risk associated with several regimens for which FN risk has not been determined or has shown substantial variability outside of a clinical trial setting, using data from Kaiser Permanente Southern California (KPSC), a large, community-based practice. Methods Included were patients diagnosed with incident non-Hodgkin's lymphoma (NHL), breast cancer (BC), or multiple myeloma (MM) between 2008 and 2013 at KPSC who initiated the following chemotherapy regimens: bendamustine ± rituximab for NHL; docetaxel, carboplatin, and trastuzumab (TCH) or docetaxel and cyclophosphamide (TC) for BC; or Q4W lenalidomide 25 mg/dexamethasone for MM. Bendamustine ± rituximab, TCH, and lenalidomide are not classified by NCCN; TC is classified as intermediate FN risk but has shown considerable variability of FN incidence when used in clinical practice. Data on cancer diagnosis, chemotherapy use, G-CSF use, neutrophil count, and infections were obtained from KPSC's electronic medical records to estimate the incidence proportions of FN and grade 3 and 4 neutropenia. FN was defined as (1) hospitalization with absolute neutrophil count (ANC) <1000/µL or (2) hospitalization with primary or secondary diagnosis codes of neutropenia (ICD-9 288.0x) and fever (ICD-9 780.6), diagnosis code for bacterial/fungal infection, or antibiotic use. Grade 3 neutropenia was defined as ANC ≥500/µL to <1000/µL; grade 4 neutropenia as ANC <500/µL. Patients who received prophylactic G-CSF within 5 days of chemotherapy initiation were excluded from analysis. Results Overall, 40 (12%) NHL patients; 149 (24%) and 340 (28%) BC patients who received TCH and TC, respectively; and 0 (0%) MM patients were excluded due to prophylactic G-CSF. Over the first 6 cycles of bendamustine (median 338.4 mg/m2) ± rituximab for NHL patients (n = 307), 7.2% experienced FN, 4.2% grade 3 neutropenia, and 17.6% grade 4 neutropenia. Over the first 6 cycles of TCH for BC patients (n = 462), 24.2% experienced FN, 10.6% grade 3 neutropenia, and 44.6% grade 4 neutropenia. Over the first 6 cycles of TC for BC patients (n = 859), 20.5% experienced FN, 9.5% grade 3 neutropenia, and 37.5% grade 4 neutropenia. Over the first 4 cycles of lenalidomide/dexamethasone for MM patients (n = 186), 3.8% experienced FN, 5.9% grade 3 neutropenia, and 18.3% grade 4 neutropenia (Table 1). Conclusions Using NCCN criteria, bendamustine ± rituximab for NHL and lenalidomide/dexamethasone for MM would be classified as low-FN-risk regimens (<10%). By contrast, BC regimens TCH and TC would be classified as high-FN-risk regimens (>20%) based on our data. These results could help inform prophylactic G-CSF use for the selected regimens in clinical practice. Table 1. Number and Incidence Proportion of Neutropenic Outcomes Overall and by Cycle Cancer: Regimen Cycle Patients n FN Events n (%) Grade 3 Neutropenia Events n (%) Grade 4 Neutropenia Events n (%) NHL: Bendamustine ± rituximab Overall 307 22 (7.2) 13 (4.2) 54 (17.6) 1 307 12 (3.9) 5 (1.6) 28 (9.1) 2 225 3 (1.3) 4 (1.8) 21 (9.3) 3 173 2 (1.2) 4 (2.3) 15 (8.7) 4 130 2 (1.5) 4 (3.1) 10 (7.7) 5 92 4 (4.4) 4 (4.4) 8 (8.7) 6 69 2 (2.9) 2 (2.9) 0 (0) BC: TCH Overall 462 112 (24.2) 49 (10.6) 206 (44.6) 1 462 70 (15.2) 39 (8.4) 138 (29.9) 2 326 13 (4.0) 15 (4.6) 42 (12.9) 3 282 17 (6.0) 9 (3.2) 39 (13.8) 4 247 6 (2.4) 8 (3.2) 31 (12.6) 5 199 4 (2.0) 6 (3.0) 25 (12.6) 6 169 8 (4.7) 3 (1.8) 12 (7.1) BC: TC Overall 859 176 (20.5) 82 (9.5) 322 (37.5) 1 859 126 (14.7) 51 (5.9) 266 (30.9) 2 649 21 (3.2) 42 (6.5) 82 (12.6) 3 571 19 (3.3) 23 (4.0) 62 (10.9) 4 511 14 (2.7) 22 (4.3) 45 (8.8) 5 94 1 (1.1) 3 (3.2) 9 (9.6) 6 84 2 (2.4) 1 (1.2) 2 (2.4) MM: Lenalidomide / dexamethasone Overall 186 7 (3.8) 11 (5.9) 34 (18.3) 1 186 2 (1.1) 8 (4.3) 17 (9.1) 2 101 3 (3.0) 5 (5.0) 14 (13.9) 3 63 2 (3.2) 2 (3.2) 8 (12.7) 4 37 0 (0) 0 (0) 4 (10.8) Disclosures Family: Amgen Inc.: Research Funding. Klippel:Amgen Inc.: Employment, Equity Ownership. Li:Amgen Inc.: Employment, Equity Ownership. Page:Amgen Inc.: Employment, Equity Ownership.
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Hirano, Y., H. Kosugiyama, K. Hattori, and D. Kihira. "AB0898 IMPACT OF BIOLOGICAL AGENTS, ORAL GLUCOCORTICOIDS, OR BOTH ON THE EFFICACY OF DAILY TERIPARATIDE TREATMENT FOR OSTEOPOROSIS IN PATIENTS WITH RHEUMATOID ARTHRITIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1752.2–1753. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4200.
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Background:Daily teriparatide (dTP) strongly affects bone metabolism in patients with rheumatoid arthritis (RA), resulting in increased bone mineral density (BMD). We reported the 2-year results of dTP treatment for osteoporosis (OP) in patients with RA in EULAR2014 [1]. Drugs affecting bone metabolism, such as biological agents (BIOs) and glucocorticoids (GCs), are frequently administered to patients with RA in addition to dTP in daily clinical practice. Although dTP increases bone turnover, BIOs reduce osteoclast activity and GCs decrease bone turnover. We reported the effects of GCs or BIOs on the efficacy of dTP in EULAR2015 [2]. The present retrospective study investigated the effects of GCs or BIOs on the efficacy of dTP in patients with RA using a larger patient cohort.Objectives:To evaluate the effects of BIOs, GCs, or both on the efficacy of dTP treatment for OP in patients with RA.Methods:The study included 56 female patients who had completed 2 years of dTP treatment. We separated these patients into four groups according to their treatment regimen at dTP initiation: B(−)G(−),included patients who did not receive BIOs or GCs (n = 14); B(+)G(−), included patients treated only with BIOs (n = 8); B(−)G(+), included patients treated only with GCs (n = 24); and B(+)G(+),included patients treated with both BIOs and GCs (n = 10). We determined baseline (BL) characteristics, % changes in BMD in the lumbar spine (LS) and total hip (TH) from BL to 24 months, and % changes in serum bone turnover markers (BTMs), such as BAP, P1NP, NTX, and TRACP-5b, from BL to 6 months after dTP initiation. Dunnett’s test was used for comparisons between B(−)G(−) and other groups.Results:The mean ages of the B(−)G(−), B(+)G(−), B(−)G(+), and B(+)G(+) groups at BL were 70.0, 65.5, 69.6, and 71.5 years, whereas the mean duration of RA in these groups were 15.4, 20.8, 69.9, and 71.5 years, respectively. Furthermore, the mean baseline DAS28-CRP levels in these groups were 2.8, 2.2, 2.8, and 2.3. The mean LS-BMD (g/cm2) at BL were 0.795, 0.819, 0.826, and 0.853, whereas the mean TH-BMD at BL were 0.619, 0.570, 0.601, and 0.629, respectively. The mean % changes in LS-BMD at 24 months were 15.5%, 12.7%, 11.9%, and 8.1%, respectively (Fig 1A). There were no significant differences between B(−)G(−) and other groups. The mean % changes in TH-BMD at 24 months in the B(−)G(−), B(+)G(−), B(−)G(+), and B(+)G(+) groups were 6.4%, 5.3%, 4.4%, and 1.5%, respectively (Fig 1B) A significant difference was observed between the B(−)G(−) and B(+)G(+) groups (p = 0.03). The % changes in BTMs in the B(−)G(−), B(+)G(−), B(−)G(+), and B(+)G(+) groups were as follows: BAP, 90.5%, 44.0%, 29.5%, and 87.7%; P1NP, 374.1%, 338.2%, 225.9%, and 640.0%; NTX, 75.2%, 106.6%, 42.5%, and 80.5%; and TRACP-5b, 75.8%, 43.85, 20.4%, and 122.3%, respectively. No significant differences were observed in the changes in BTMs among the groups.Conclusion:This study suggested that concomitant use of BIOs and GCs inhibited the increase in BMD induced by dTP treatment in patients with RA, particularly TH-BMD. Although BTM analysis revealed no statistical significance, GCs tended to decrease the % change in BTMs.References:[1]Hirano et al. Ann Rheum Dis 2014: 73 (Suppl 2): 166[2]Hirano et al. Ann Rheum Dis 2015: 74 (Suppl 2): 528Disclosure of Interests:Yuji Hirano Speakers bureau: Tanabe-Mitsubishi, Pfizer, Eisai, Abbie, Chugai, Bristol-Meyers, Jansen, Astellas, UCB, Eli-Lilly, Asahikasei, Daiichi-Sankyo, Amgen, Hironobu Kosugiyama: None declared, Kyosuke Hattori: None declared, Daisuke Kihira: None declared
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Indran, Tishya, Grigorios T. Gerotziafas, Jawed Fareed, and Andrew Spencer. "Malignant Clonal Cell Proliferation in Multiple Myeloma and the Hypercoagulable State." Blood 136, Supplement 1 (November 5, 2020): 23–24. http://dx.doi.org/10.1182/blood-2020-142781.
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Introduction: The malignant clonal cell proliferation in multiple myeloma (MM) results in significant immune dysregulation through clonal specific T cell expansion, elevated levels of CD4+ CD25+FOXP3+ T regulator cells, downregulation of NK cells, high levels of IL-6 and activation of immunosuppressive tumour associated macrophages (TAM) . However, the mechanisms underlying the hypercoagulable state in MM and predisposing to venous thromboembolic (VTE) complications is unclear. Confounding disease factors is the use of immunomodulatory drugs (IMiDs) such as Lenalidomide, Thalidomide and Pomalidomide causing ubiquitination and degradation of the Ikaros Family Zinc Finger Protein (IKZF)1 and 3 by cereblon which also contributes to the prothrombotic effect despite thromboprophylaxis. Aims: The aim of this study was to analyse the changes in the coagulation profile and plasma cell disease burden with treatment, including Lenalidomide, in patients with MM to help define potential underlying mechanisms for hypercoagulability and thrombosis. Methods: Coagulation profiles and disease markers were retrospectively analysed in 16 MM patients receiving treatment with Daratumumab, Lenalidomide and Dexamethasone (DRd) at The Alfred Hospital, Melbourne from April 2019 to August 2020. Patients enrolled were transplant eligible with MM that was refractory to initial induction therapy with Velcade, Cyclophosphamide and Dexamethasone (VCD). This study was approved by The Alfred Hospital ethics committee. Statistical analysis was performed using descriptive statistics and the Wilcoxon Sign Rank Test to compare the median coagulation profiles and disease markers after 1-2 cycles of DRd and 3-4 cycles of DRd. Biomarkers included Prothrombin Time (PT), Partial Thromboplastin Time (PTT), Fibrinogen, Thrombin Clotting Time (TCT), serum paraprotein (SPEP) and serum free light chain (SFLC) with a p value of <0.05 indicating statistical significance. Results: A total 7 patients had coagulation profiles at the two time points i) post 1-2 cycles and ii) post 3-4 cycles of DRd (Table 1). 9 patients had coagulation profiles only after 3-4 cycles of DRd. A separate analysis was performed using Wilcoxon Sign Rank with imputed median differences to allow the inclusion of the 9 additional patients subsequently increasing the sample size to a total of 16 (Table 2). All patients were on anticoagulation with aspirin (n=14), rivaroxaban (n=1) or clopidogrel (n=1) at the time of the analysis. The analysis showed a statistically significant reduction in PT from median 13.6s (11.9-16.6) to 12.7s (11.7-14.1) with 3-4 cycles DRd in both analysis (p=0.006 and p= 0.027). Fibrinogen levels reduced from median of 5.4 g/L (2.8-8) to 3.98 g/L (2.3- 5.1) after 3-4 cycles (p=0.001). TCT increased after 3-4 cycles of DRd (p=0.005). Serum paraprotein demonstrated statistically significant reduction from 10.8g/L (6 -13) to 7.6 g/L (2-13) after 3-4 cycles (p=0.007). Serum free light chain assay also demonstrated reduction in median values from 82.8mg/L (8.1 - 415.7) to 54.6mg/L (0.8 - 338.6) but was not statistically significant (p=0.084). Discussion: All the patients in this study either responded to treatment or had stable disease after treatment with DRd. The data demonstrate a coagulation response to treatment. The median fibrinogen level that was above the upper limit of normal declined on treatment, the TCT increased and the PT decreased, all coinciding with the statistically significant decline in paraprotein level. A larger study is required to confirm these findings. However, this study has demonstrated that the hypercoagulable state in MM improves with disease response. Disclosures Spencer: Roche: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Pharmamar: Other; Secura Bio: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Servier: Consultancy, Other: Grant/Research Support; Janssen: Consultancy, Honoraria, Other: Grant/Research Support, Speakers Bureau; Haemalogix: Consultancy, Honoraria, Other: Grant/Research Support; BMS: Honoraria, Other: Grant/Research Support, Research Funding, Speakers Bureau; TheraMyc: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Grant/Research Support; Takeda: Honoraria, Other, Speakers Bureau; Antegene: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Other: Grant/Research Support.
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Chapin, John C., Katrina Piskorski, Stephen J. Eyler, Richard J. H. Smith, and Jeffrey Laurence. "The Alternate Complement Pathway in Thrombotic Thrombocytopenic Purpura." Blood 120, no. 21 (November 16, 2012): 3342. http://dx.doi.org/10.1182/blood.v120.21.3342.3342.
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Abstract Abstract 3342 The thrombotic microangiopathies (TMA) thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS) involve progressive microvascular thrombi, endothelial cell (EC) injury, vascular ischemia, and severe end-organ damage. Acquired TTP is often associated with autoantibody-mediated suppression of the ADAMTS13 vWF cleaving protease, causing vWF multimer accumulation and platelet aggregation. aHUS is associated with dysregulation of the alternate complement pathway through mutation in and/or autoantibodies against, complement regulatory proteins. It is responsive to the anti-C5 mAb eculizumab. TTP, by contrast, usually responds to plasma exchange, but in the refractory setting there are few effective treatments. We hypothesized that dysregulation of the alternate complement pathway represents a susceptibility factor for EC injury in at least a subset of TTP patients. Our objective was to identify the degree of complement dysregulation in acute TTP vs. other TMAs in vivo, and correlate these data with (1) the ability of plasma from acute TTP and aHUS patients to induce apoptotic injury in primary human microvascular EC in vitro and (2) the potential of eculizumab to block this injury. Plasmas from acute TMA patients (TTP n=12, malignancy-associated aHUS n=6, ticlopidine-associated TTP n=4, systemic Degos disease n=1), and healthy controls (n=4) were collected at time of presentation. Samples were assayed for terminal complement components sC5b-9 (MAC, membrane attack complex) and C5a by ELISA. Genomic DNA was isolated from these plasmas and amplified by standard DNA PCR, followed by semi-nested PCR using primers designed around the exon sequences of complement factor H (CFH), complement factor I (CFI) and MCP (CD46) known to be mutated in 60–80% of aHUS cases. Amplicons were sequenced and correlated with a database of previously reported mutations and SNPs with varying degrees of functional significance in the complement regulatory pathway. In our in vitro model for plasma-mediated EC injury, primary human dermal microvascular ECs were starved in medium lacking EC growth factors and then incubated for 18–24 hours with 1–2% plasma (v/v) in the presence or absence of pharmacologic levels of anti-C5 mAb (100–250μg/ml). Apoptosis was assessed by ELISA-based quantification of cytoplasmic histone-associated DNA fragments from cell lysate and propidium iodide labeling with construction of DNA histograms and assessment of A0 peaks by flow cytometry. We found significantly elevated plasma levels of C5a in all subsets of patients with TMAs compared to control plasma (42.8 ng/ml +/− 6.2 vs. 32 ng/ml +/− 6.8; p=0.014). We also found markedly elevated levels sC5b-9 in these TMAs compared to controls (1852.0 ng/ml +/− 1169.8 vs 598.8 +/− 338.7; p=0.012). Little variation was seen in TTP vs. aHUS and other TMAs, regardless of ADAMTS13 status. Complement mutations in CFH and CFI were identified in 14 (66.7%) of TMA patients: 41.6% TTP, 60% malignancy-aHUS, 100% ticlopidine TTP. In terms of interference with TMA plasma-induced MVEC apoptosis in vitro, EC injury was blocked by anti-C5 mAb eculizumab in 8 of 19 cases (5 TTP, 2 aHUS, 1 Degos). Correlation of sensitivity to plasma-mediated EC apoptosis and blockade with eculizumab with levels of terminal complement components, presence of complement regulatory factor mutations, levels of ADAMTS13 activity, and anti-ADAMTS13 antibody titers are underway. We conclude that dysregulation of the alternate complement pathway may represent a susceptibility factor in the pathophysiology of many TMAs, not only aHUS. Blockade of C5 may offer a therapeutic avenue for some patients with refractory TTP. Indeed, in a recent report our group noted the rescue of a patient with classic TTP, including ADAMTS13 activity <5% and anti-ADAMTS13 IgG, refractory to plasma exchange and a variety of immune suppressive regimens, utilizing eculizumab (Chapin J, et al. Brit J Hematol, 2012). Defining this subset, and the potential for clinical response to anti-C5 therapy, will involve exploration of other complement and complement regulatory factor mutations and autoantibodies. Disclosures: Off Label Use: Eculizumab is not FDA approved for use in the treatment of TTP. Laurence:Alexion Pharmaceuticals: Consultancy, Speakers Bureau.
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Maruna, P., J. Lindner, and KM Kubzová. "Leptin and leptin soluble receptor changes after pulmonary endarterectomy: relations to cortisol and cytokine network." Physiological Research, 2009, 569–76. http://dx.doi.org/10.33549/physiolres.931523.
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Leptin is a hormone that regulates food intake. During inflammatory status, leptin may contribute to the anorexia and cachexia of infection. Pulmonary endarterectomy was used as a model of non-infectious cytokine network hyperstimulation. Leptin and soluble leptin receptor (SLR) were compared with evolution of cortisol and inflammatory cytokines in twenty-two patients with chronic thromboembolic pulmonary hypertension treated with pulmonary endarterectomy using cardiopulmonary bypass (CBP) and deep hypothermic circulatory arrest (DHCA). Leptin, SLR, cortisol, IL-1β, IL-6, IL-8, and TNFα concentrations in arterial blood were measured before/after sternotomy, last DHCA, separation from bypass, 12, 18, 24, 36, and 48 h after sternotomy. Mean duration of CPB was 338.2 min.; mean circulatory arrest time 39.9 min. The initial decline of leptin, SLR, TNFα, IL-6, and IL-8 was followed by an increase culminating 6- 24 h after sternotomy. Leptin peak levels were detected 24 h after sternotomy (28.0 ng/ml, 21.9-37.6). IL-6 culminated after separation from CPB, IL-8 was highest 12 h after sternotomy. Leptin concentrations correlated with IL-6 (r=0.82), and TNFα (r=0.73). Large cardiovascular surgery caused a significant increase in serum leptin, indicating its acute regulation by stress factors. This effect may be secondary to the inflammatory response mediated via cytokine stimulation. Correlation between leptin and IL-6 indicates the role of IL-6 in leptin induction.
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Gilbo, Nicholas, Joris Blondeel, Tine Wylin, Veerle Heedfeld, Ina Jochmans, Jacques Pirenne, Hannelie Korf, and Diethard Monbaliu. "The dynamics of cytokine release during 24 hours continuous normothermic machine perfusion liver preservation: An explorative porcine study." Artificial Organs, January 25, 2024. http://dx.doi.org/10.1111/aor.14717.
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AbstractBackgroundNormothermic machine perfusion (NMP) has been proposed to preserve liver grafts in a less pro‐inflammatory environment. However, the effect of NMP on liver inflammation remains unclear. Therefore, we aimed at characterizing the inflammatory response during continuous NMP with a comprehensive investigation of cytokine release during perfusion.MethodsTen porcine livers underwent either 24 h NMP or whole blood‐based NMP (WB‐NMP) immediately after procurement. WB‐NMP was used as a positive control to mimic early post‐reperfusion inflammation. High mobility group box‐1 (HMGB1), interleukin 1‐beta (IL‐1beta), tumor necrosis factor‐alpha (TNFalpha), interleukin 6 (IL‐6), 8 (IL‐8), and 10 (IL‐10), transforming growth factor‐beta (TGFbeta), aspartate transferase (AST), and hyaluronic acid were measured in the perfusate. The area under the curve (AUC) of their perfusate concentration was compared between groups. Median (IQR) is given.ResultsThe AUC of HMGB1 and IL‐1beta was similar between groups. Compared to WB‐NMP, NMP inhibited the release of TNFalpha [NMP: 20275 (18402–32 152), WB‐NMP: 242100 (203511–244 238); p = 0.01], IL‐6 [NMP: 1206 (338.9–1686), WB‐NMP: 8444 (7359–10 087); p = 0.03], and IL‐8 [NMP: 1635 (106.90–2130), WB‐NMP: 3951 (3090–4116); p = 0.008]. The release of TGFbeta remained unchanged but IL‐10 release was lower in NMP [1612 (1313–1916), WB‐NMP: 5591 (4312–6421); p = 0.01]. The ratios TGFbeta:TNFalpha and IL‐10:TNFalpha were significantly higher in the NMP than in the WB‐NMP group. Importantly, the AUC of AST was significantly lower during NMP [1960 (1950–2893)] than WB‐NMP [6812 (6370–7916); p = 0.02].ConclusionsContinuous NMP leads to the release of detectable levels of cytokines with a slow, linear increase over time and a shift toward anti‐inflammatory signaling.
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Klopsch, Christian, Dario Furlani, Ralf Gäbel, Klaus Wagner, Weiwei Wang, Lee-lee Ong, Wenzhong Li, et al. "Abstract 1063: Intracardiac Injection of Epoetin-α Upregulates Stem Cell Chemoattractant Gene Expression In a Rat Myocardial Infarction Model." Circulation 116, suppl_16 (October 16, 2007). http://dx.doi.org/10.1161/circ.116.suppl_16.ii_212-d.
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Emerging evidence suggests that Erythropoietin (EPO) protects the myocardium from ischemic injury and promotes beneficial remodelling. However, the role of EPO and its receptor (EPO-R) in mediating cardiac regeneration remains unclear. We hypothese that stem cell homing and proliferation modulated by EPO could contribute to its cardio-protective effects. Epoetin-α (3000 U/kg) was injected along the infarction border after the induction of a rat myocardial infarction (MI) by permanent ligation of the left descending coronary artery. At six weeks after MI, cardiac function was measured by pressure-volume loops in left and right ventricles. Infarction size, angiogenesis and pathologic effects were evaluated. Gene expressions of EPO-R, SDF-1α, CXCR-4, c-kit, eNOS, TNF-α, IL-8, Integrin-β and CdK4 were analyzed by RT-PCR at different time points of the first week (24h, 48h, 96h and 7 days). We found EPO treatment improved left ventricular function both at baseline levels and under Dobutamine stress (tau, cardiac output, stroke work, ejection fraction, dp/dt maximum and minimum, n=11–14, p<0.05) and decreased right ventricular wall stress (maximum and endsystolic pressure, n=5– 8, p<0.05). Infarction size was reduced from 27.8±3.4% to 20.1±2.8% (n=6 – 8, p<0.01). Capillary density was increased from 257.7±24.5 to 338.5±35.9 (vessels per square mm, n=6 – 8, p<0.05). Mortality was decreased from 29.0% to 22.2% (n=53– 69). EPO-R was down regulated in infarcted, peri-infarcted and non infarcted areas at all time points (n=7, p<0.05). Cardiac SDF-1α, CXCR-4 and eNOS gene expressions were increased at 24 hours. C-kit was up regulated significantly at 48 hours compared to 24 hours in the EPO treated hearts. In untreated hearts, c-kit expression remained constant. Proinflammatory cytokines (TNF-β, IL-8 and Integrin-γ) were down regulated. Cell cycle re-entry marker (CdK4) was increased at 24 hours in non infarcted zones. In conclusion, we demonstrate intramyocardium Epoetin-α injection induces an earlier up regulation of stem cell chemoattractants, reduces inflammation, enhances angiogenesis and restores heart function after MI.
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Zhong, Hua, Qingqing Dong, Qing Cun, Guangyu He, Yijin Tao, Keyao Song, Yunqing Lu, Qin Zhu, Xi Chen, and Qin Chen. "Peripapillary vessel density correlates with visual field mean sensitivity in highly myopic eyes." Journal of Translational Medicine 20, no. 1 (March 10, 2022). http://dx.doi.org/10.1186/s12967-022-03323-9.
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Abstract Purpose To identify the global and regional distribution of peripapillary vessel density (pVD) and try to find out the relationships between pVD and the visual field mean sensitivity (VFMS) in healthy myopic eyes. Design Prospective cross-sectional study. Methods Two hundred and twenty-two participants (393 eyes) with myopia (myopic refractive error < − 0.5 diopters) from two clinical centers were recruited in this study and were divided into 4 groups according to the spherical equivalent (SE): Group1:− 0.5D ≥ SE > − 6.00D, Group2: − 6.00D ≥ SE > − 8.00D, Group3:− 8.00D ≥ SE > − 10.00D, Group4:SE ≤ -10.00D.The pVD assessed with optical coherence tomography angiography (OCTA) was quantified in 8 sectors. Peripapillary retinal nerve fibre layer (pRNFL) imaging was performed with SD-OCT. Visual field (VF) tests were performed with the 30-2 SITA standard program on the Humphrey 750i Visual Field Analyzer and were grouped into 8 regions that matched the structure. Results The pRNFL had no significant difference in all groups (p = 0.422). The average pVD were significantly lower in group 4 (47.61 ± 6.58) than in group 2 and 3 (51.49 ± 3.21, 50.48 ± 3.43 respectively) (p < 0.05). While both pVD in group2 and 3 were statistically lower than group1 (52.77 ± 2.86). The average VFMS was significantly lower in group 4 (901.85 ± 386.54) than other three groups (1169.15 ± 328.94, 1081.77 ± 338.83, 1076.89 ± 358.18, for group1,2,3 respectively). The pVD and VFMS were positively correlated in group3 (r = 0.184) and group4 (r = 0.476) (p < 0.05). Linear regression analysis demonstrated that VFMS were positively associated with pVD especially in temporal and nasal quadrants in myopic eyes. Conclusions The pVD shows a significant positive correlation with VFMS in highly myopic eyes with SE ≤ − 8.00D. We suggest that pVD measurement by OCTA could be a sensitive and useful method for monitoring myopic functional change.
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Abba, Abba Bello, Abdulrahman Lado, Muhammad Auwal Hussaini, and Fatima Zahra Buhari. "Weed Competition and Performance of Sorghum and Groundnut Intercrop as Influenced by Row Orientation and Arrangement." Bhartiya Krishi Anusandhan Patrika, Of (June 11, 2024). http://dx.doi.org/10.18805/bkap717.
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Background: Intercropping and row arrangement represent a dynamic frontier of research and practical application, influencing resource allocation, weed competition and overall crop productivity in a modern agro ecosystem. This study aimed to investigate the impact of row orientation and arrangement on weed competition and crop performance within the Sudan savannah ecology of Nigeria during the 2018 rainy season. Methods: A field experiment was conducted at BUK (Latitude 11°58'N and Longitude 8°25'E) and Minjibir (Latitude 12.14590N and Longitude 0.866'4850E), utilizing two orientations (East-West and North-South) and seven sorghum: groundnut row arrangements (1:1, 1:2, 2:1, 2:2, 3:3, 2:4 and 4:2). A randomized complete block design with three replications was used, with simultaneous cultivation of SAMSORG 40 sorghum and SAMNUT 24 groundnut varieties. Result: The 2:1 row arrangement exhibited the lowest weed density (23.2 and 31.1 m-2) and dry weight (408.6 and 438.2 kg ha-1). East-West orientation reduced weed density by 24.5% at BUK and 20.8% at Minjibir. North-South row orientation significantly increased sorghum grain yield by 17.7% and reduced groundnut kernel yield by 9.37%. Higher sorghum yield (699.6 and 773. 7 Kg ha-1) was observed with 2:1 whereas the 1:2 arrangement yielded more groundnut kernels (329.2 and 338.1 kg ha-1). East-West orientation and the 2:1 row arrangement suppressed weed growth and recorded higher yields.
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Luu, Van Ai, and Tam Vo. "CLINICAL CHARACTERISTICS AND DETERMINE THE CONCENTRATIONS OF AUTOBODIES AND CYTOKINES IN PATIENTS WITH RHEUMATOID ARTHRITIS." Journal of Medicine and Pharmacy, January 2015, 86–92. http://dx.doi.org/10.34071/jmp.2014.6.12.
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Background: Rheumatoid arthritis is an autoimmune disease with complex pathophysiological mechanisms, in which cytokines plays an important role. Currently, based on the understanding of the cytokines, the treatment of rheumatoid arthritis with biological agents had changed the course of the disease. Objectives: Study the clinical characteristics and determine the concentrations of autoantibodies (RF, Anti CCP) and cytokines (IL-1α,IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, VEGF, IFN-γ, TNF-α, MCP1, EGF) in patients with rheumatoid arthritis, simultaneously, evaluate the correlation between the cytokines concentrations and levels of autoantibodies in patients with rheumatoid arthritis treated at Cho Ray Hospital.Subjects and Methods: Descriptive cross-sectional study conducted in 76 patients with rheumatoid arthritis treated at Cho Ray Hospital form June 2013 to April 2014.Results: - Clinical and laboratory characteristics: The most common clinical manifestations are arthritis (98.7%), symmetry joint damage (96.1%), morning stiffness over 1 hour (90.8%). Subcutaneous nodule is accounted for 3.9%. The most common joints involved in rheumatoid arthritis are wrist (93.4%), MCP and knee (90.8%), PIP (76.3%) and ankle (67.1%), the least common is the hip (14.5%). The percentage of autoantibodies and cytokines: rheumatoid arthritis patients with positive results of anti – CCP is accounted for 86%. rheumatoid arthritis patients with increased IL-1α concentrations is accounted for 40,8%; increased IL-1β concentration in 48.7%; increased IL-2 concentration in 32,9%; increased IL-4 concentration in 86%; increased IL-6 concentration in 100%; increased IL-8 concentration in 39,5%; increased IL-10 concentration in 81,6%; increased VEGF concentration in 51,3%; increased IFN-γ concentration in 67,1%; increased TNF-α concentration in 61,8%; increased MCP1 concentration in 30,3%; increased EGF concentration in 39,43%. The average concentrations of cytolines in rheumatoid arthritis patients is as followings: IL-1α (57.36 ± 196.43), IL-1β (123.77± 532.51), Il-2 (279.93 ± 945.04), IL-4(279.93 ± 945.04), IL-6(91.35 ± 170.52), IL-8(270.84 ± 445.45), IL-10(134.58 ± 496.14), VEGF(638.87 ± 540.18), IFN-γ(136.43 ± 338.68), TNF-α(106.27 ± 265.57), MCP1(292.34 ± 265.52), EGF(152.62 ± 123.64).RF is correlated with IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IFN-γ, and TNF-α. Anti – CCP is correlated with IL-1α, IL-6. Key words: Rheumatoid arthritis, cytokines
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"Influence of Comorbidities on Hospital Mortality and Healthcare Utilization in Hospitalized Chronic Obstructive Pulmonary Disease Patients." Journal of the Medical Association of Thailand 103, no. 7 (July 15, 2020). http://dx.doi.org/10.35755/jmedassocthai.2020.07.11054.
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Background: Comorbidities of chronic obstructive pulmonary disease (COPD) are associated with both increased short-term and long-term mortality. However, information on regarding the influence of comorbidities on hospital mortality and healthcare utilization remain limited. Objective: To evaluate the influence of COPD and comorbidities associated with increased risk of hospital mortality and healthcare utilization. Materials and Methods: A retrospective cohort study was performed on COPD patients admitted to the Chiang Mai University Hospital between 2007 and 2013. Logistic regression was performed to identify independent comorbidities that increased the risk of hospital mortality and influenced healthcare utilization. Results: The present study involved 739 COPD patients with 1,099 visits. The hospital mortality rate was 12.3%. The comorbidities associated with increased hospital mortality were depression (odds ratio [OR] 8.61, 95% confidence interval [CI] 1.66 to 43.95, p=0.010), atrial fibrillation (OR 2.37, 95% CI 1.33 to 4.21, p=0.003), and coronary artery disease (OR 1.85, 95% CI 1.03 to 3.32, p=0.04). The comorbidities were also associated with increased hospital length of stay [7 (3 to 12) versus 5 (3 to 8) days, p=0.001], mechanical ventilation days [5 (2 to 13) versus 3 (2 to 6) days, p=0.029], and total hospital costs [915.1 (401.2 to 2,258.4) versus 562.1 (338.1 to 1,372.9) USD, p=0.010]. In addition, comorbidities were associated with increased hospital mortality (one and two comorbidities: OR 2.06, 95% CI 1.24 to 3.43, p=0.005 and OR 5.47, 95% CI 2.07 to 14.47, p=0.001, respectively). Conclusion: The COPD comorbidities, which are depression, atrial fibrillation, and coronary artery disease, were associated with increased hospital mortality and healthcare utilization. Keywords: COPD, Comorbidity, Mortality, Healthcare utilization
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Pacheco, Ana, Balázs Soós, Edina Lempel, Imre Simon, Péter Maróti, Stephan Christian Möhlhenrich, and József Szalma. "The effect of individual drilling sleeves on the precision of coronectomy tooth sections. An in vitro 3D-printed jaw model experiment." Clinical Oral Investigations, October 3, 2023. http://dx.doi.org/10.1007/s00784-023-05289-4.
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Abstract Objectives The aim of this in vitro study was to evaluate the effect of a 3D-printed drill sleeve (DS) on the precision and duration of coronectomy sections. Materials and methods Thirty-six trainees and oral surgeons performed 72 coronectomy cuts in a 3D-printed, entirely symmetric mandible model. Coronectomy was performed freehand (FH) on one side and with a DS on the other side. The occurrence of “too superficial” (≥ 4 mm unprepared lingual tooth tissue) and “too deep” (drilling ≥ 1 mm deeper as tooth contour) cuts and sectioning times were registered. Results In 7 cases, the sections were “too deep” with FH, while none with DS (OR: 18.56; 95%CI: 1.02–338.5; p = 0.048). The deviation between virtually planned and real cut depths was significantly greater in the FH group (1.91 ± 1.62 mm) than in DS group (1.21 ± 0.72 mm) (p < 0.001). A total of 18 “too superficial” buccolingual sections occurred with FH, while 8 cases with DS (OR: 3.50; 95%CI: 1.26–9.72; p = 0.016). Suboptimal sections did not correlate with experience (p = 0.983; p = 0.697). Shortest, suboptimal drillings were most frequently seen distolingually (OR: 6.76; 95% CI: 1.57–29.07; p = 0.01). In the inexperienced group, sectioning time was significantly longer with FH (158.95 ± 125.61 s vs. 106.92 ± 100.79 s; p = 0.038). Conclusions The DS effectively reduced tooth sectioning times by less experienced colleagues. Independently from the level of experience, the use of DS obviated the need for any preparation outside the lingual tooth contour and significantly decreased the occurrence of “too superficial” cuts, leaving thinner unprepared residual tooth tissue lingually. Clinical relevance Coronectomy sections may result in lingual hard and soft tissue injury with the possibility of damaging the lingual nerve. The precision of the buccolingual depth-control can be improved, while surgical time can be reduced when applying a drilling sleeve.
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Teoh, Zhi Yi, Amy Yee‐Hui Then, Jol Ern Ng, Sui Hyang Kuit, Fairul Izmal Jamal Hisne, and Louisa Shobhini Ponnampalam. "Movement, ranging patterns and habitat use of Indo‐Pacific humpback dolphins (Sousa chinensis) in the Langkawi Archipelago and adjacent Perlis‐Kedah coastal waters, Malaysia." Aquatic Conservation: Marine and Freshwater Ecosystems, August 18, 2023. http://dx.doi.org/10.1002/aqc.4002.
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Abstract1. Studies on the ranging patterns and habitat use of Indo‐Pacific humpback dolphins (Sousa chinensis) in Southeast Asia are scarce but essential to inform conservation and management of a species known to be susceptible to anthropogenic pressures.2. This study is the first to investigate the long‐term movement, range sizes and habitat use of humpback dolphins in the Langkawi Archipelago and adjacent Perlis‐Kedah mainland coast of Malaysia using boat‐based photo‐identification surveys conducted between 2010 and 2020.3. A total of 669 humpback dolphin individuals were identified, making it one of the largest photo‐ID catalogues within their geographic range. Lagged identification rates suggested that some individuals maintained long‐term site fidelity in the study area.4. Low transition probabilities and 194 photo‐identification matches revealed humpback dolphins moved minimally between Langkawi and the adjacent Perlis‐Kedah mainland; however, most southward dolphin movements did not extend beyond Kuala Jerlun in northern Kedah.5. The mean range sizes estimated for 16 regularly sighted individuals through minimum convex polygon and kernel density estimate 95% utilization distribution were significantly different, at 338.2 ± 183.8 and 75.6 ± 28.6 km2, respectively.6. Most individual and population core areas (i.e. kernel density estimate 50% utilization distribution) overlapped with core feeding and nursery grounds in shallow coastal and estuarine waters (i.e. <10 m deep and <1.3 km from the coastline).7. Dolphin range size and spatial use patterns were probably linked to prey distribution and availability (i.e. influenced by environmental factors such as habitat features) and social groupings and dynamics.8. These findings inform science‐based recommendations for habitat management, including implementing restricted areas from coastal development, vessel speed‐limit zones and boating codes‐of‐conduct, to minimize anthropogenic impacts and support sustainable coastal development in the binational Satun‐Langkawi Important Marine Mammal Area.
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Bunnell, Kristen L., Manjunath P. Pai, Monica Sikka, Susan C. Bleasdale, Eric Wenzler, Larry H. Danziger, and Keith A. Rodvold. "Pharmacokinetics of Telavancin at Fixed Doses in Normal-Body-Weight and Obese (Classes I, II, and III) Adult Subjects." Antimicrobial Agents and Chemotherapy 62, no. 4 (January 8, 2018). http://dx.doi.org/10.1128/aac.02475-17.
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ABSTRACT A recommended total-body-weight (TBW) dosing strategy for telavancin may not be optimal in obese patients. The primary objective of this study was to characterize and compare the pharmacokinetics (PK) of telavancin across four body size groups: normal to overweight and obese classes I, II, and III. Healthy adult subjects ( n = 32) received a single, weight-stratified, fixed dose of 500 mg ( n = 4), 750 mg ( n = 8), or 1,000 mg ( n = 20) of telavancin. Noncompartmental PK analyses revealed that subjects with a body mass index (BMI) of ≥40 kg/m 2 had a higher volume of distribution (16.24 ± 2.7 liters) than subjects with a BMI of <30 kg/m 2 (11.71 ± 2.6 liters). The observed area under the concentration-time curve from time zero to infinity (AUC 0–∞ ) ranged from 338.1 to 867.3 mg · h/liter, with the lowest exposures being in subjects who received 500 mg. AUC 0–∞ values were similar among obese subjects who received 1,000 mg. A two-compartment population PK model best described the plasma concentration-time profile of telavancin when adjusted body weight (ABW) was included as a predictive covariate. Fixed doses of 750 mg and 1,000 mg had similar target attainment probabilities for efficacy as doses of 10 mg/kg of body weight based on ABW and TBW, respectively. However, the probability of achieving a target area under the concentration-time curve from time zero to 24 h of ≥763 mg · h/liter in association with acute kidney injury was highest (19.7%) with TBW-simulated dosing and lowest (0.4%) at the 750-mg dose. These results suggest that a fixed dose of 750 mg is a safe and effective alternative to telavancin doses based on TBW or ABW for the treatment of obese patients with normal renal function and Staphylococcus aureus infections. (This study has been registered at ClinicalTrials.gov under identifier NCT02753855.)
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Raza, Muhammad Ali, Hassan Shehryar Yasin, Hina Gul, Ruijun Qin, Atta Mohi Ud Din, Muhammad Hayder Bin Khalid, Sajad Hussain, et al. "Maize/soybean strip intercropping produces higher crop yields and saves water under semi-arid conditions." Frontiers in Plant Science 13 (November 1, 2022). http://dx.doi.org/10.3389/fpls.2022.1006720.
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Sustainable increases in crop production require efficient use of resources, and intercropping can improve water use efficiency and land productivity at reduced inputs. Thus, in a three-year field experiment, the performance of maize/soybean strip intercropping system differing with maize plant density (6 maize plants m-2, low, D1; 8 maize plants m-2, medium, D2; and 10 maize plants m-2, high, D3) was evaluated in comparison with sole maize or soybean cropping system. Results revealed that among all intercropping treatments, D2 had a significantly higher total leaf area index (maize LAI + soybean LAI; 8.2), total dry matter production (maize dry matter + soybean dry matter; 361.5 g plant-1), and total grain yield (maize grain yield + soybean grain yield; 10122.5 kg ha-1) than D1 and D3, and also higher than sole maize (4.8, 338.7 g plant-1, and 9553.7 kg ha-1) and sole soybean (4.6, 64.8 g plant-1, and 1559.5 kg ha-1). The intercropped maize was more efficient in utilizing the radiation and water, with a radiation use efficiency of 3.5, 5.2, and 4.3 g MJ-1 and water use efficiency of 14.3, 16.2, and 13.3 kg ha-1 mm-1, while that of intercropped soybean was 2.5, 2.1, and 1.8 g MJ-1 and 2.1, 1.9, and 1.5 kg ha-1 mm-1 in D1, D2, and D3, respectively. In intercropping, the land and water equivalent ratios ranged from 1.22 to 1.55, demonstrating that it is a sustainable strategy to improve land and water use efficiencies; this maximization is likely associated with the species complementarities for radiation, water, and land in time and space, which resulted in part from competition avoidance responses that maximize the economic profit (e. g., 1300 US $ ha-1 in D2) over sole maize (798 US $ ha-1) or sole soybean (703 US $ ha-1). Overall, these results indicate that optimizing strip intercropping systems can save 20–50% of water and land, especially under the present scenario of limited resources and climate change. However, further research is required to fully understand the resource capture mechanisms of intercrops in intercropping.
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Syafruddin, Syafruddin, Tongku Nizwan Siregar, Sri Wahyuni, Gholib Gholib, Ilfa Liyandara Chairunnisa Pulungan, and Muchsalmina Muchsalmina. "Transplantation of Aceh cattle ovary into the uterus of pseudopregnant local rabbits: Effect of post-transplant stress on uterine histopathology and ovarian follicle dynamics." Veterinary World, March 2023, 500–508. http://dx.doi.org/10.14202/vetworld.2023.500-508.
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Background and Aim: The increase in the levels of the cortisol hormone caused by the stress conditions generated by an ovary transplantation procedure can damage the uterus of the transplant recipient as well as the transplanted ovaries. This study aimed to analyze the histopathological changes that occur in the uterine horn of pseudopregnant local rabbits (recipients), as well as the ovarian follicular integrity of the donor Aceh cattle after transplantation. Materials and Methods: After 30 days of adaptation, all rabbits were divided into three treatment groups: R1 (the group of rabbits that underwent ovarian transplantation for 3 days, n = 5), R2 (the group of rabbits that underwent ovarian transplantation for 5 days, n = 5), and R3 (the group of rabbits that underwent ovarian transplantation for 7 days, n = 5). Pseudopregnancy induction was performed using the pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) methods. The rabbits were injected with 100 IU of PMSG intramuscularly, followed by an injection of 75 IU of hCG intravenously 3 days later. Ovarian transplantation was performed on day 8 (day 0 was the day of hCG injection). The concentration of cortisol hormone metabolites was measured from fecal samples using an enzyme-linked immunosorbent assay technique. The uterus and ovaries were collected for histopathological and follicular dynamics examination after the transplantation process was completed. Results: The mean cortisol levels (ng/g) recorded before versus after the transplant in the R1, R2, and R3 groups were 146.23 ± 17.60 versus 338.84 ± 302.79, 128.97 ± 81.56 versus 174.79 ± 101.70, and 124.88 ± 43.61 versus 321.91 ± 221.63 (p < 0.05), respectively. The examination of the histopathological appearance of the uterus revealed edema in the uterine lumen, hyperemia and hemorrhage in the endometrium, necrosis of the epithelium, and infiltration of inflammatory cells. Hemorrhage and hyperemia were severe and filled the endometrium in the R1 compared with the R2 and R3 animals. Ovarian follicle development occurred in all treatment groups, although some histopathological features were observed. The number of tertiary follicles in R1, R2, and R3 animals was 24.67 ± 7.37, 20.67 ± 7.57, and 9.67 ± 3.79 (p < 0.05), respectively. Conclusion: Based on the results of this study, it can be concluded that the transplantation of ovaries from Aceh cattle into pseudopregnant local rabbits triggered an increase in the levels of the cortisol hormone and uterine histological changes; however, follicles were still detected at various stages of development in the transplanted Aceh cattle ovaries. The results of this study are valuable for clinicians and researchers because they provide information regarding an alternative in vivo ovarian preservation technique using pseudopregnant rabbits. Keywords: cortisol, ovarian, transplantation.