Artículos de revistas: "813/.54 b"

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WILLIAMS, NICOLE C. y 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 septiembre 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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Aggarwal, A., R. Gupta, R. Chatterjee, V. Negi, B. K. Das, P. Ghosh, D. Danda y 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 mayo 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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Gutiérrez Castro, Bleenis, José Luis Fernández, Federico Cassella, Andrés Wonaga y Luis Viola. "Adenoma Detection Rate at Different Age Intervals Suggests Starting Colorectal Cancer Screening at 45 Years of Age". Acta Gastroenterológica Latinoamericana 53, n.º 1 (30 de marzo de 2023): 59–67. http://dx.doi.org/10.52787/agl.v53i1.292.

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Introduction. It is uncertain whether starting screening at 45 years old would improve colorectal cancer prevention and currently available studies in adults younger than 50 years old are limited. Aim. To evaluate the adenoma detection rate at different age intervals. Materials and methods. Colonoscopies performed on adult outpatients were analyzed. Adenoma detection was recorded in the total population and in patients with screening indication. First, patients were divided into two groups: 50 years or older (group A) and younger than 50 years (group B). Then, we analyzed the different age segments: up to 44 years (group 1) 45 to 49 (group 2), 50 to 54 (group 3), and 55 or older (group 4). Results. A total of 5090 patients were included, 2877 with indication for screening. Patients were divided as follows: 3883 in group A, 1207 in group B, 811 in group 1, 396 in group 2, 749 in group 3 and 3134 in group 4. In the total population, adenoma detection was 20.5%: 23.5% in group A, 10.5% in group B (p = 0.000); 8.3% in group 1, 14.8% ingroup 2, 18.1% in group 3, and 24.8% in group 4 (group 1vs. group 2: p = 0.001, group 2 vs. group 3: p = 0.189, andgroup 3 vs. group 4: p = 0.000). In the screening population,adenoma detection was 20.5%: 21.4% in group A, 14.8%in group B (p = 0.004); 13.1% in group 1, 17.0% in group2, 16.1% in group 3, and 22.8% in group 4 (group 1 vs.group 2: p = 0.31; group 2 vs. group 3: p = 0.81; and group3 vs. group 4: p = 0.001). Conclusion. Adenoma detectionis not different between 45 to 49 and 50 to 54 years of age,and is lower below 45 years of age, which suggests startingcolorectal cancer screening at this age.

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Venkatesh, V. C., B. C. Planer, M. Schwartz, J. N. Vanderbilt, R. T. White y P. L. Ballard. "Characterization of the promoter of human pulmonary surfactant protein B gene". American Journal of Physiology-Lung Cellular and Molecular Physiology 268, n.º 4 (1 de abril de 1995): L674—L682. http://dx.doi.org/10.1152/ajplung.1995.268.4.l674.

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Pulmonary surfactant protein B (SP-B) is required for normal surfactant function and for survival at birth. To further study SP-B gene expression, we sequenced genomic clones and examined promoter activity of SP-B DNA fragments by transient transfection. A plasmid construct containing human SP-B fragment -1039/+431 linked to chloramphenicol acetyltransferase (CAT) reporter gene was readily expressed in H441 cells, which are derived from a human lung adenocarcinoma, but was < 4% as active in Hep G2, HeLa, and Calu 6 cell lines. SP-B promoter activity in H441 cells was orientation dependent and increased by linked Rous sarcoma virus (RSV) enhancer and was stronger than for thymidine kinase (tk) and RSV promoters. Deletional mapping of the 5' flanking region with exonuclease III suggested nonspecific negative (-811/-1039)- and positive (-453/-641)-control regions and a cell-specific enhancer region at -208 to -54. When a fragment from -403 to -35 base pairs (bp) was placed upstream or downstream of tkCAT, in either orientation, expression in H441 cells but not other cell lines was increased 4- to 28-fold relative to tkCAT. Deletional analysis of the 3' terminus indicated a requirement for at least 7 bp 3' of the transcription start site. Promoter activity was strongly inhibited in a dose-dependent fashion by phorbol ester, with responsiveness mapped to bp -208/-54, but was not responsive to glucocorticoid.(ABSTRACT TRUNCATED AT 250 WORDS)

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Guo, Yi-Qing, Zhen Tian y Chao Jin. "SPATIAL-DEPENDENT PROPAGATION OF COSMIC RAYS RESULTS IN SPECTRUM OF PROTON, RATIOS OF $\bar{p}/p$, B/C AND ANISOTROPY OF NUCLEI". Astrophysical Journal 819, n.º 1 (26 de febrero de 2016): 54. http://dx.doi.org/10.3847/0004-637x/819/1/54.

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Chu, Charles C., Stephanie T. Reese, Leslie O. Goodwin, Dorothy Guzowski, Alamelu Chandrasekaran, Craig Gawel, Wentian Li et al. "Is Elevated Serum IL-10 in B-CLL Associated with IL-10 Promoter Polymorphisms?." Blood 106, n.º 11 (16 de noviembre de 2005): 1198. http://dx.doi.org/10.1182/blood.v106.11.1198.1198.

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Abstract Interleukin-10 (IL-10), a cytokine that regulates inflammation, may play an important role in B-cell chronic lymphocytic leukemia (B-CLL), because of the reported association of high serum IL-10 levels with a lower prognosis of survival. Using the Bio-Plex protein array system, we confirmed that B-CLL patients exhibit higher median IL-10 levels (3.54 pg/ml, n=50) as compared to controls (1.28 pg/ml, n=33) (p<0.0001). We are in the midst of determining B-CLL VH gene mutation status and IL-10 levels. To determine if elevated IL-10 levels are due to inherent genetic polymorphisms, we examined three single nucleotide polymorphisms (SNPs) in the proximal end of the promoter region of the IL-10 gene (-1082 A/G, −819 T/C, and −592 A/C) that may affect IL-10 transcription levels. DNA from an overlapping set of 54 B-CLL patients and 48 normals was genotyped using the Transgenomic WAVE system. The difference in allele frequencies at a single locus showed no trend towards significance between groups using the Pearsons chi-square test and Odds Ratios (OR) with 95% Confidence Intervals (CI) for each SNP (-1082 (p = 0.686, OR = 1.122, CI = 0.641–1.966), −819 (p = 0.844, OR = 1.062, CI = 0.585–1.926) and −592 (p = 0.720, OR = 1.116, CI = 0.613–2.031)). B-CLL cases and normal subjects showed no significant departure from Hardy-Weinberg equilibrium in single locus genotype frequencies. Differences in single locus genotype frequencies between B-CLL cases and controls showed no significant differences for each SNP (−1082 (p = 0.600, OR = 1.366, CI = 0.425–4.389), −819 (p = 0.638, OR = 0.727, CI = 0.192–2.749), and −592 (p = 0.638, OR = 0.727, CI = 0.192–2.749)). The haplotype frequencies were calculated using maximum likelihood method based on the observed genotypes. The differences in maximum likelihood haplotype frequencies, between the B-CLL cases and controls, were insignificant (p = 0.754). The haplotype pair genotype frequency differences between the B-CLL cases and controls were also insignificant (p = 0.921). In conclusion, the allele, genotype, and haplotype frequencies of IL-10 SNPs −1082, −819, and −592 show no trend towards significance overall. This suggests that these promoter SNPs do not contribute to elevated serum IL-10 in B-CLL. However, a suggestion of association with VH gene mutation status is being further investigated with a larger sample size.

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Rocha, Sónia, Sandra Tejo, Eugénia Ferreira, Luís Trindade, Eduardo Rabadão, Nuno Marques y José Saraiva da Cunha. "Seroprevalência do Anticorpo do Vírus na Hepatite A em Viajantes Portugueses: Um Novo Paradigma". Acta Médica Portuguesa 30, n.º 7-8 (31 de agosto de 2017): 534. http://dx.doi.org/10.20344/amp.8130.

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Introduction: In Portugal, the prevalence of hepatitis A virus infection has decreased in the past decades, especially in young adults. The aim of this study was to detect the prevalence of antibody to hepatitis A virus in a population observed in our Travel Clinic.Material and Methods: Antibodies against hepatitis A, hepatitis B, hepatitis C and human immunodeficiency virus were tested using standard enzyme immunoassay in patients older than 18. The exclusion criteria were: prior vaccination for hepatitis A virus, previous diagnosis of infection with hepatitis B virus, hepatitis C virus and/or human immunodeficiency virus, foreign travelers and long-term expatriates. We applied an epidemiological survey and data was statistically analyzed with SPSS® 18.0.Results: In the 665 travelers studied, natural immunity to hepatitis A virus was present in 57.6% (n = 383). They were stratified into 8 age groups and for each one hepatitis A immunity was clarified: 5.0% (n = 1) in 18 - 25 years, 32.3% (n = 21) in 26 - 30 years, 40.9% (n = 47) in 31 - 35 years, 45.8% (n = 54) in 36 - 40 years, 68.7% (n = 79) in 41 - 45 years, 70.1% (n = 68) in 46 - 50 years, 80.8% (n = 63) in 51 - 55 years and 87.7% (n = 50) over 56 years old. In those who accepted further screening, positivity for hepatitis B core antibody was found in 0.6% (n = 3) travelers, hepatitis C virus infection in 1.1% (n = 6) and human immunodeficiency virus infection in 0.5% (n = 3) whose previous status was unknown. The most frequent travel destination was sub-Saharan Africa (72.6%; n = 483).Discussion: We found 49.1% (n = 260) travelers under 50 years old susceptible to hepatitis A virus infection and for those between 40 and 50 years, 30.7% (n = 65) still need vaccine protection.Conclusion: Across age groups there is a trend towards lower prevalence of hepatitis A virus antibody, in particular among youngsters, when compared with older Portuguese studies.

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D’Auria, Fiorella, Luciana Valvano, Luciana Rago, Teodora Statuto, Giovanni Calice, Giovanni D’Arena, Vincenzo Fusco y Pellegrino Musto. "Monoclonal B-cell lymphocytosis and prostate cancer: incidence and effects of radiotherapy". Journal of Investigative Medicine 67, n.º 4 (11 de enero de 2019): 779–82. http://dx.doi.org/10.1136/jim-2018-000902.

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Monoclonal B-cells lymphocytosis (MBL) is a benign condition that may precede chronic lymphocytic leukemia (CLL), not rarely present in peripheral blood of healthy elderly people, among which there is also a male prevalence. Though CLL has been associated with various types of solid tumors, including prostate cancer (PC), no data exist about the relationship between PC and MBL. We studied the frequency of CLL-like MBL clones in a group of 48 patients affected by PC and followed them during and after whole-pelvis radiotherapy (WPRT) treatment. We found four MBL clones (8.3%), two of which (4.2%) had a B-cell clonal count >1000 cells/µL (‘clinical MBL’). A single case (1.8%) of ‘low-count’ MBL occurred in a control group of 54 healthy males. Notably, normal B-lymphocytes were consistently affected by WPRT, while MBL clones were less radiosensitive. Our results suggest a possible association between ‘clinical’ MBL and PC and show a different impact of the radiation on monoclonal respect to normal B-cells, which could also imply a greater risk of clonal transformation.

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Hajsadeghi, Shokoufeh, Niloufar Samiei, Masoud Moradi, Maleki Majid, Ladan Kashani, Afsaneh Amani, Arezoo Salami, Melika Asefi y Negin Farsi. "Comparison of N-Terminal Pro B-Natriuretic Peptide and Echocardiographic Indices in Patients with Mitral Regurgitation". Clinical Medicine Insights: Cardiology 4 (enero de 2010): CMC.S6062. http://dx.doi.org/10.4137/cmc.s6062.

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Introduction Echocardiographic indices can form the basis of the diagnosis of systolic and diastolic left ventricular (LV) dysfunction in patients with Mitral regurgitation (MR). However, using echocardiography alone may bring us to a diagnostic dead-end. The aim of this study was to compare N-Terminal pro B-natriuretic peptide (BNP) and echocardiographic indices in patients with mitral regurgitation. Methods 2D and Doppler echocardiography and BNP serum level were obtained from 54 patients with organic mild, moderate and severe MR. Results BNP levels were increased with symptoms in patients with mitral regurgitation (NYHAI: 5.7 ± 1.1, NYHAII: 6.9 ± 1.5, NYHAIII: 8.3 ± 2 pg/ml, P < 0.001). BNP plasma level were significantly correlated with MPI (myocardial performance index) (r = 0.399, P = 0.004), and following echocardiographic indices: LVEDV (r = 0.45, P < 0.001), LVESV (r = 0.54, P < 0.001), LVEDD (r = 0.48, P < 0.001), LVESD (r = 0.54, P < 0.001), dp/dt (r = −0.32, P = 0.019) and SPAP (r = 0.4, P = 0.006). Conclusion The present study showed that BNP may be useful in patients with MR and may confirm echocardiographic indices.

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Lopes, S. R. M., N. W. S. Gormezano, R. C. Gomes, N. E. Aikawa, R. M. R. Pereira, M. T. Terreri, C. S. Magalhães et al. "Outcomes of 847 childhood-onset systemic lupus erythematosus patients in three age groups". Lupus 26, n.º 9 (29 de enero de 2017): 996–1001. http://dx.doi.org/10.1177/0961203317690616.

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Objective The objective of this study was to assess outcomes of childhood systemic lupus erythematosus (cSLE) in three different age groups evaluated at last visit: group A early-onset disease (<6 years), group B school age (≥6 and <12 years) and group C adolescent (≥12 and <18 years). Methods An observational cohort study was performed in ten pediatric rheumatology centers, including 847 cSLE patients. Results Group A had 39 (4%), B 395 (47%) and C 413 (49%). Median disease duration was significantly higher in group A compared to groups B and C (8.3 (0.1–23.4) vs 6.2 (0–17) vs 3.3 (0–14.6) years, p < 0.0001). The median Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) (0 (0–9) vs 0 (0–6) vs 0 (0–7), p = 0.065) was comparable in the three groups. Further analysis of organ/system damage revealed that frequencies of neuropsychiatric (21% vs 10% vs 7%, p = 0.007), skin (10% vs 1% vs 3%, p = 0.002) and peripheral vascular involvements (5% vs 3% vs 0.3%, p = 0.008) were more often observed in group A compared to groups B and C. Frequencies of severe cumulative lupus manifestations such as nephritis, thrombocytopenia, and autoimmune hemolytic anemia were similar in all groups ( p > 0.05). Mortality rate was significantly higher in group A compared to groups B and C (15% vs 10% vs 6%, p = 0.028). Out of 69 deaths, 33/69 (48%) occurred within the first two years after diagnosis. Infections accounted for 54/69 (78%) of the deaths and 38/54 (70%) had concomitant disease activity. Conclusions This large multicenter study provided evidence that early-onset cSLE group had distinct outcomes. This group was characterized by higher mortality rate and neuropsychiatric/vascular/skin organ damage in spite of comparable frequencies of severe cumulative lupus manifestations. We also identified that overall death in cSLE patients was an early event mainly attributed to infection associated with disease activity.

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Tumanov, Nikolay A. y Elena V. Boldyreva. "X-ray diffraction and Raman study of DL-alanine at high pressure: revision of phase transitions". Acta Crystallographica Section B Structural Science 68, n.º 4 (17 de julio de 2012): 412–23. http://dx.doi.org/10.1107/s0108768112028972.

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The effect of pressure on DL-alanine has been studied by X-ray powder diffraction (up to 8.3 GPa), single-crystal X-ray diffraction and Raman spectroscopy (up to ∼ 6 GPa). No structural phase transitions have been observed. At ∼ 1.5–2 GPa, cell parameters b and c become accidentally equal to each other, but the space-group symmetry does not change. There is no phase transition between 1.7 and 2.3 GPa, contrary to what has been reported earlier [Belo et al. (2010). Vibr. Spectrosc. 54, 107–111]. The presence of the second phase transition, which was claimed to appear within the pressure range from 6.0 to 7.3 GPa (Belo et al., 2010), is also argued. The changes in the Raman spectra have been shown to be continuous in all the pressure ranges studied.

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Zhang, L., D. J. Jacob, K. F. Boersma, D. A. Jaffe, J. R. Olson, K. W. Bowman, J. R. Worden et al. "Transpacific transport of ozone pollution and the effect of recent Asian emission increases on air quality in North America: an integrated analysis using satellite, aircraft, ozonesonde, and surface observations". Atmospheric Chemistry and Physics Discussions 8, n.º 2 (24 de abril de 2008): 8143–91. http://dx.doi.org/10.5194/acpd-8-8143-2008.

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Abstract. We use an ensemble of aircraft, satellite, sonde, and surface observations for April–May 2006 (NASA/INTEX-B aircraft campaign) to better understand the mechanisms for transpacific ozone pollution and its implications for North American air quality. The observations are interpreted with a global 3-D chemical transport model (GEOS-Chem). OMI NO2 satellite observations constrain Asian anthropogenic NOx emissions and indicate a factor of 2 increase from 2000 to 2006 in China. Satellite observations of CO from AIRS and TES indicate two major events of Asian transpacific pollution during INTEX-B. Correlation between TES CO and ozone observations shows evidence for transpacific ozone pollution. The semi-permanent Pacific High and Aleutian Low cause splitting of transpacific pollution plumes over the Northeast Pacific. The northern branch circulates around the Aleutian Low and has little impact on North America. The southern branch circulates around the Pacific High and impacts western North America. Both aircraft measurements and model results show sustained ozone production driven by peroxyacetylnitrate (PAN) decomposition in the southern branch, roughly doubling the transpacific influence from ozone produced in the Asian boundary layer. Model simulation of ozone observations at Mt. Bachelor Observatory in Oregon (2.7 km altitude) indicates a mean Asian ozone pollution contribution of 9±3 ppbv to the mean observed concentration of 54 ppbv, reflecting mostly an enhancement in background ozone rather than episodic Asian plumes. Asian pollution enhanced surface ozone concentrations by 5–7 ppbv over western North America in spring 2006. The 2000–2006 rise in Asian anthropogenic emissions increased the influence by 1–2 ppbv.

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HARIRAM, UPASANA y RONALD LABBÉ. "Spore Prevalence and Toxigenicity of Bacillus cereus and Bacillus thuringiensis Isolates from U.S. Retail Spices". Journal of Food Protection 78, n.º 3 (1 de marzo de 2015): 590–96. http://dx.doi.org/10.4315/0362-028x.jfp-14-380.

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Recent incidents of foodborne illness associated with spices as the vehicle of transmission prompted this examination of U.S. retail spices with regard to Bacillus cereus. This study focused on the levels of aerobic-mesophilic spore-forming bacteria and B cereus spores associated with 247 retail spices purchased from five states in the United States. Samples contained a wide range of aerobic-mesophilic bacterial spore counts (< 200 to 8.3 × 107 CFU/g), with 19.1% of samples at levels above 105 CFU/g. For examples, paprika, allspice, peppercorns, and mixed spices had high levels of aerobic spores (>107 CFU/g). Using a novel chromogenic agar, B. cereus and B. thuringiensis spores were isolated from 77 (31%) and 11 (4%) samples, respectively. Levels of B. cereus were <3 to 1,600 MPN/g. Eighty-eight percent of B. cereus isolates and 91%of B. thuringiensis isolates possessed at least one type of enterotoxin gene: HBL (hemolysin BL) or nonhemolytic enterotoxin (NHE). None of the 88 isolates obtained in this study possessed the emetic toxin gene (ces). Using commercially available immunological toxin detection kits, the toxigenicity of the isolates was confirmed. The NHE enterotoxin was expressed in 98% of B. cereus and 91% of B. thuringiensis isolates that possessed the responsible gene. HBL enterotoxin was detected in 87% of B. cereus and 100% of B. thuringiensis PCR-positive isolates. Fifty-two percent of B. cereus and 54% of B. thuringiensis isolates produced both enterotoxins. Ninety-seven percent of B. cereus isolates grew at 12°C, although only two isolates grew well at 9°C. The ability of these spice isolates to form spores, produce diarrheal toxins, and grow at moderately abusive temperatures makes retail spices an important potential vehicle for foodborne illness caused by B. cereus strains, in particular those that produce diarrheal toxins.

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Kobayashi, Hiroki, Yoshihiro Nakamura, Masanori Abe, Isao Kurihara, Hiroshi Itoh, Takamasa Ichijo, Yoshiyu Takeda et al. "Effect of cosyntropin during adrenal venous sampling on subtype of primary aldosteronism: analysis of surgical outcome". European Journal of Endocrinology 182, n.º 3 (marzo de 2020): 265–73. http://dx.doi.org/10.1530/eje-19-0860.

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Objectives We investigated the clinical significance of ACTH stimulation during adrenal venous sampling (AVS) by surgical outcome of primary aldosteronism (PA). Design Multicenter retrospective study by Japan PA study. Method We allocated 314 patients with both basal and ACTH-stimulated AVS data who underwent adrenalectomy to three groups: basal lateralization index (LI) ≥2 with ACTH-stimulated LI ≥4 on the ipsilateral side (Unilateral (U) to U group, n = 245); basal LI <2 with ACTH-stimulated LI ≥4 (Bilateral (B) to U group, n = 15); and basal LI ≥2 with ACTH-stimulated LI <4 (U to B group, n = 54). We compared surgical outcomes among the groups using the Primary Aldosteronism Surgical Outcome (PASO) criteria. Results Compared with U to U group, U to B group had poor clinical and biochemical outcomes and low rates of adrenal adenoma as pathological findings (P = 0.044, 0.006, and 0.048, respectively), although there were no significant differences between U to U and B to U groups. All patients in U to B group with clinical and biochemical benefits, however, had adrenal adenoma as pathological findings and could be well differentiated from those with poor surgical outcomes via basal LI (>8.3), but not ACTH-stimulated LI. These results were similar even when we defined each group based on a cut-off value of 4 for basal LI. Conclusions Although PA patients in U to B group had worse surgical outcomes than did those in U to U group, basal LI could discriminate among patients with better surgical outcomes in U to B group.

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Biganzoli, L., H. Cortes-Funes, C. Thomssen, K. I. Pritchard, J. Pierga, A. Kupp, S. Borstnar y I. Smith. "Tolerability and efficacy of first-line bevacizumab (B) plus chemotherapy (CT) in elderly patients with advanced breast cancer (aBC): Subpopulation analysis of the MO19391 study". Journal of Clinical Oncology 27, n.º 15_suppl (20 de mayo de 2009): 1032. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.1032.

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1032 Background: Limited data exist on the efficacy and safety of biological agents in elderly patients with aBC. This is essentially due to the lack of studies specifically targeting the older population and to strict inclusion criteria in clinical trials. B significantly improved the efficacy of 1st-line taxane therapy in two large, randomized phase III trials, E2100 and AVADO. Methods: In study MO19391, 1st-line B 10mg/kg q2w or 15mg/kg q3w + CT (primarily but not exclusively taxane monotherapy) was investigated in a broader, large aBC patient population, with the aim of understanding safety and efficacy in patients seen in routine clinical practice, including elderly patients. Results: A total of 2,027 patients were enrolled. Median age was 54 years (range 21–93); 359 patients (17.7%) were aged ≥65 years and 169 (8.3%) were ≥70 years. Baseline characteristics and safety and efficacy results according to age are shown below (Table). Conclusions: Treatment with B is feasible in elderly patients. Hypertension was the only grade 3 B-related side effect reported more frequently in the older than in the younger cohort. Efficacy was similar in the two subgroups. These results suggest that the combination of B with 1st-line CT shows a similar therapeutic index regardless of age. Data on compliance according to the different CT regimens, the impact of comorbidities on safety, and analyses in the subgroup of patients ≥70 years will be presented. [Table: see text] [Table: see text]

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Reinson, Tina, Christopher D. Byrne, Janisha Patel, Magdy El-Gohary y Michael Moore. "Transient elastography in patients at risk of liver fibrosis in primary care: a follow-up study over 54 months". BJGP Open 5, n.º 6 (2021): BJGPO.2021.0145. http://dx.doi.org/10.3399/bjgpo.2021.0145.

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BackgroundLiver fibrosis assessment services using transient elastography are growing in primary care. These services identify patients requiring specialist referral for liver fibrosis, and provide an opportunity for recommending lifestyle change. However, there are uncertainties regarding service design, effectiveness of advice given, and frequency of follow-up.AimTo assess the following: (a) effectiveness of standard care lifestyle advice for weight management and alcohol consumption; (b) uptake for liver rescan; and (c) usefulness of a 4.5-year time interval of rescanning in monitoring progression of liver fibrosis.Design & settingAnalysis of patient outcomes 4.5 years after the first ‘liver service’ attendance that included transient elastography in five GP practices in Southampton, UK.MethodOutcomes included weight, alcohol consumption, rescan uptake, time interval between scans, and change in liver fibrosis stage.ResultsA total of 401 participants were recontacted. Mean standard deviation (± SD) weight loss was 1.2 kg±8.4 kg (P = 0.005); Alcohol Use Disorders Identification Test (AUDIT) grade increased by 7.8% (P ≤0.001). A total of n = 116/401 participants were eligible for liver rescanning and n = 59/116 (50.9%) agreed to undergo rescanning. Mean ± SD time interval between scans was 53.6±3.4 months. Liver fibrosis progressed from mild (≥6.0 kPa–8.1 kPa) to significant fibrosis (8.2 kPa–9.6 kPa) in 3.4% of patients; from mild to advanced fibrosis (9.7 kPa–13.5 kPa) and cirrhosis (≥13.6 kPa) in 15.3% of patients, and did not progress in 81.3%. No baseline factors were independently associated with liver fibrosis progression at follow-up.ConclusionRescan recall attendance and adherence to lifestyle changes needs improving. Optimum time interval between scans remains uncertain. After a mean interval of 53.6 months between scans, and with no specific predictors indicated, a substantial minority (18.7%) experienced a deterioration in fibrosis grade.

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Nazir, Mashal, Rahman Ullah, Aqsa Saleema, Nisar Ahmed, Javaid Sajjad Hashmi, Muhammad Tariq Khan y Ibrahim Shujjah. "Compare Short Term Post-Operative Complication of Laparoscopic Transabdominal Preperitoneal (TAPP) and Lichtenstein’s Tension Free Hernia Repair". Pakistan Journal of Medical and Health Sciences 16, n.º 8 (30 de agosto de 2022): 859–61. http://dx.doi.org/10.53350/pjmhs22168859.

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Objective: To compare short term post-operative complication of laparoscopic transabdominal preperitoneal (TAPP) and Lichtenstein’s tension free hernia repair. Study Design: Randomized clinical trial. Place & Duration of Study: Surgical Unit of Khyber Teaching Hospital (KTH) Peshawar during the period of 6 months from 1st January, 2020 to 30 June, 2021. Material and Methods: In this study 492 cases of inguinal Hernia with 246 in each group. For group A, laparoscopic TAPP repair were performed with 10cmx 15cm polyprophlene mesh (prolene-Ethicon) and were fixed with tackers (Protack 5mm fixation device - covidien). For Group B Lichtenstein’s repair were performed through supra inguinal incision, using 10cmx 15 cm polypropylene mesh (prolene- ethicon). Then the patients were monitored for short term post-operation complication post-operatively. Results: Our study shows that in Group A(Laparoscopic TAPP) mean age was 42 years with SD ± 8.13 and in Group (Lichtenstein repair) mean age was 45 years with SD ± 8.13. In Group A (Laparoscopic TAPP) 99% patients were male and 1% patients were female while in Group B (Lichtenstein repair) 99% patients were male and 1% patients were female. In Group A(Laparoscopic TAPP), urinary retention was 5(2%), hematoma was 5(2%), surgical site infection was 10(00%), Ischemic orchitis was 2(1%), seroma was 20(8%) While in Group B (Lichtenstein repair). urinary retention was 25(10%), hematoma was 39(16%), surgical site infection was 66(27%), Ischemic orchitis was 5(2%), seroma was 54(22%). Conclusion: Frequency of short term post operative complication are higher in Lichtenstein’s tension free hernia repair as compare to laparoscopic transabdominal preperitoneal (TAPP) group. Keywords: Short Term, Post-Operative Complication, Laparoscopic Transabdominal Preperitoneal (TAPP), Lichtenstein’s Tension Free, Hernia Repair.

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Harnett, P., M. Buck, P. Beale, A. Goldrick, S. Allan, B. Fitzharris, P. De Souza et al. "Phase II study of gemcitabine and oxaliplatin in patients with recurrent ovarian cancer: an Australian and New Zealand Gynaecological Oncology Group study". International Journal of Gynecologic Cancer 17, n.º 2 (2007): 359–66. http://dx.doi.org/10.1111/j.1525-1438.2007.00763.x.

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Gemcitabine and oxaliplatin have shown single-agent activity in relapsed ovarian cancer. This combination was used to determine response rates, time-to-event efficacy measures, and toxicity in patients with recurrent ovarian cancer. Patients with prior platinum-based chemotherapy who had measurable lesions and/or elevated CA-125 levels were identified as group A (platinum-refractory/platinum-resistant patients) and group B (platinum-sensitive patients). All patients received gemcitabine 1000 mg/m2 on days 1 and 8 and oxaliplatin 130 mg/m2 on day 8 every 21 days for up to eight cycles. Seventy-five patients (21 in group A and 54 in group B), with a median age of 58 years (range, 37–78), were enrolled. A median of six cycles (range, 1–8) was administered. By intent-to-treat analysis, 15 patients with measurable disease achieved partial response for an overall best response rate of 20.0% (9.5% in group A and 24.1% in group B). CA-125 response was observed in 48.4% patients (30.0% in group A and 57.1% in group B). Median time to progressive disease was 7.1 months (95% CI, 5.6–9.0 months) with 5.0 months in group A and 8.3 months in group B. Median overall survival was 17.8 months (95% CI, 12.9–21.3 months) with 9.2 months for group A and 20.0 months for group B. Major grade 3/4 toxicities were neutropenia (61.3%), leukopenia (24.0%), nausea (16.0%), and vomiting (22.7%). We conclude that the combination of oxaliplatin and gemcitabine is active in patients with recurrent ovarian cancer, but the regimen is unsatisfactory for further study due to modest response and relatively high toxicity.

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Intragumtornchai, Tanin, Udomsak Bunworasate, Thanyaphong Na Nakorn y Ponlapat Rojnuckarin. "Alemtuzumab in Combination with CHOP and ESHAP as First-Line Treatment in Peripheral T-Cell Lymphoma." Blood 108, n.º 11 (16 de noviembre de 2006): 4740. http://dx.doi.org/10.1182/blood.v108.11.4740.4740.

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Abstract Patients diagnosed with peripheral T-cell lymphomas (PTCL) generally had a poorer prognosis compared to B-cell non-Hodgkin’s lymphomas. With conventional treatment, the 5-year overall and failure-free survivals (OS and FFS) were 36% and 23%, respectively (Vose et al, Blood2005;106:abstract 811). Between February 2005 and January 2006, 13 consecutive patients newly diagnosed with PTCL (5, extranodal nasal NK/T-cell lymphoma, 4 subcutaneous panniculitis-like, 3 PTCL, unspecified and 1 enteropathy type) were enrolled. The median age was 44 years (range, 21–56) and male:female was 1.6:1. Fifty-four percent had stage III/IV, 31%, PS 2–3, 69%, B-symptoms, 15%, bulky disease, 46%, > 1 extranodal site, 38%, elevated serum LDH and 39%, aaIPI 2–3. Twenty-three percent had thrombocytopenia. Patients were treated with alemtuzumab 30 mg. sc. D1-3 of cycle 1–5 plus CHOP (day 1 of cycle 1, 3, 5) and ESHAP (day 1 of cycle 2, 4, 6) at 28-day intervals. Valacyclovir 500 mg tid and trimethoprim/sulfamethoxazole were given for prophylaxis of CMV and Pneumocystis carinii infection, respectively. Of the evaluable 10 patients, complete remission was obtained in 8 patients, 1 had partial remission and 1 had CNS progression while on treatment. Infection was a major adverse complication: 54% had CMV reactivation (1 had CMV disease), 54%, febrile neutropenia and 15%, tuberculosis. With a median follow-up time of 8 months, the 2-year OS and FFS were 75% (95%CI, 41–92) and 48% (95%CI, 14–76), respectively. From the standpoint of this result, alemtuzumab in combination with CHOP and ESHAP is an effective front-line therapy for patients newly diagnosed with PTCL.

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Vose, J., P. Bierman, G. Bociek, F. Loberiza, C. Enke, J. Hankins y J. Armitage. "Radioimmunotherapy with 131-I tositumomab enhanced survival in good prognosis relapsed and high-risk diffuse large B-cell lymphoma (DLBCL) patients receiving high-dose chemotherapy and autologous stem cell transplantation". Journal of Clinical Oncology 25, n.º 18_suppl (20 de junio de 2007): 8013. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.8013.

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8013 Background: The 5-year overall survival (OS) for pts with relapsed chemosensitive DLBCL with standard transplantation is approximately 40–50%. We previously piloted the addition of standard outpatient radioimmunotherapy (RIT) with 131-I tositumomab to the transplant regimen for patients with relapsed chemoresistant NHL. This phase I study demonstrated a 3 yr OS of 55% in these poor prognosis patients (JCO 23: 461–467, 2005). The current study is a follow-up phase II study in good prognosis relapsed and high risk DLBCL patients using 131-I tositumomab with BEAM (BCNU, etoposide, cytarabine, and melphalan) followed by an autologous stem cell transplant. Methods: Forty patients were accrued to the study between 2000–2005. The patients had a median age of 54 yrs (26–75) and all had a diagnosis of DLBCL. The patients had a median of two prior chemotherapies before transplant and 88% had received prior Rituximab. All patients had chemotherapy sensitive disease at the time of stem cell transplant. Following stem cell collection, all patients received a stem cell preparative regimen of 75 cGy total body dose of 131-I tositumomab (dosimetric dose day -19 and therapeutic day -12) followed by a standard BEAM transplant regimen. Autologous unpurged stem cells were infused on day 0. The median time of follow-up of the survivors is 28 months (3–68). Results: Seventy eight percent of the patients had a complete remission following the transplant. The 3 year progression free survival (PFS) is 70% (95% CI - 48 - 84%) and the 3 year OS is 81% (95% CI - 61 - 91%). The entire transplant can be delivered on an outpatient basis. No increased toxicity compared to a similar cohort receiving BEAM alone could be detected. Conclusions: The addition of 131-I tositumomab to BEAM and autologous stem cell transplant for relapsed or high-risk chemosensitive DLBCL produces a 3-yr OS of 81% without excess toxicity. This compares favorably to historical controls. This regimen is currently being tested in a phase III trial in the BMT/CTN of Rituximab/BEAM vs. 131-I tositumomab/BEAM in patients with relapsed chemosensitive DLBCL. No significant financial relationships to disclose.

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Zhou, Caicun, Yi-Long Wu, Gongyan Chen, Xiaoqing Liu, Yunzhong Zhu, Shun Lu, Jifeng Feng et al. "BEYOND: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study of First-Line Carboplatin/Paclitaxel Plus Bevacizumab or Placebo in Chinese Patients With Advanced or Recurrent Nonsquamous Non–Small-Cell Lung Cancer". Journal of Clinical Oncology 33, n.º 19 (1 de julio de 2015): 2197–204. http://dx.doi.org/10.1200/jco.2014.59.4424.

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Purpose The phase III BEYOND trial was undertaken to confirm in a Chinese patient population the efficacy seen with first-line bevacizumab plus platinum doublet chemotherapy in globally conducted studies. Patients and Methods Patients age ≥ 18 years with locally advanced, metastatic, or recurrent advanced nonsquamous non–small-cell lung cancer (NSCLC) were randomly assigned to receive carboplatin (area under the curve, 6) intravenously and paclitaxel (175 mg/m2) intravenously (CP) on day 1 of each 3-week cycle, for ≤ six cycles, plus placebo (Pl+CP) or bevacizumab (B+CP) 15 mg/kg intravenously, on day 1 of each cycle, until progression, unacceptable toxicity, or death. The primary end point was progression-free survival (PFS); secondary end points were objective response rate, overall survival, exploratory biomarkers, safety. Results A total of 276 patients were randomly assigned, 138 to each arm. PFS was prolonged with B+CP versus Pl+CP (median, 9.2 v 6.5 months, respectively; hazard ratio [HR], 0.40; 95% CI, 0.29 to 0.54; P < .001). Objective response rate was improved with B+CP compared with Pl+CP (54% v 26%, respectively). Overall survival was also prolonged with B+CP compared with Pl+CP (median, 24.3 v 17.7 months, respectively; HR, 0.68; 95% CI, 0.50 to 0.93; P = .0154). Median PFS was 12.4 months with B+CP and 7.9 months with Pl+CP (HR, 0.27; 95% CI, 0.12 to 0.63) in EGFR mutation–positive tumors and 8.3 and 5.6 months, respectively (HR, 0.33; 95% CI, 0.21 to 0.53), in wild-type tumors. Safety was similar to previous studies of B+CP in NSCLC; no new safety signals were observed. Conclusion The addition to bevacizumab to carboplatin/paclitaxel was well tolerated and resulted in a clinically meaningful treatment benefit in Chinese patients with advanced nonsquamous NSCLC.

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Kambhampati, Swetha, Kelly Bauer, Jimmy Hwang, Andrea Grace Bocobo, John Dozier Gordan y Robin Kate Kelley. "Nivolumab in advanced hepatocellular carcinoma (HCC) and Child Pugh B (CPB) cirrhosis: Safety and clinical outcomes in a retrospective case series." Journal of Clinical Oncology 36, n.º 4_suppl (1 de febrero de 2018): 496. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.496.

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496 Background: HCC patients (pts) with Child Pugh B (CPB) cirrhosis have poor prognosis and limited treatment (Tx) options. Nivolumab demonstrated durable responses and acceptable safety in Child Pugh A (CPA) HCC in the CheckMate-040 trial with rates of hepatotoxicity similar to non-HCC populations. The safety and efficacy of nivolumab has not been established in pts with CPB cirrhosis. Methods: Design: Retrospective case series with IRB approval. Key eligibility: HCC with CPB cirrhosis; treated with nivolumab as standard Tx; enrolled in the UCSF Hepatobiliary Tissue Bank and Registry. Study endpoints: Safety during nivolumab Tx including all-cause grade(Gr) ≥ 3 adverse events (AE), serious AE (SAE), any grade immune-related (ir)AE, and systemic steroid (SS) requirement; clinical outcomes including time on Tx (TOT) with nivolumab and overall survival (OS). Results: Thirteen pts were included: male 77%; Asian 38%, white 54%; median age 66 (range: 26-86); HCV Ab+ 31%, HBsAg+ 23%; BCLC B/C 31%/69%; median Child-Pugh score 8; median prior systemic Tx 1 (range: 0-6); prior sorafenib 69%, median duration on prior sorafenib 137 days (range 10-341). The Table depicts safety outcomes on nivolumab. Median TOT on nivolumab: 44 days (95% CI: 32, 98) (range: 17-811+). Median OS from start of nivolumab: 119 days (95% CI: 40, 247) (range: 40-811+). Best response of at least stable disease occurred in 3/13 (23%) of patients, including prolonged stable disease (SD) for 6+ months and complete response (CR) for 24+ months on nivolumab (1 pt each). Conclusions: CPB HCC pts treated with nivolumab experienced high rates of all-cause Gr ≥ 3 AE and SAE and short OS, similar to prior studies in CPB HCC. Rates of irAE attributed to nivolumab were similar to rates reported in CheckMate-040 CPA population, without unexpected AE. A subset of pts experienced prolonged stable disease and CR. Nivolumab warrants further study in CPB HCC.[Table: see text]

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., Ibrahim, Farhana Ahmad, Anila Farhat, Nayab Butt, Muhammad Attique Sadiq y Abid Rafiq Chaudhry Md. "Ondansetron vs Domperidone in the Treatment of Vomiting in Children with Acute Diarrhea: A Randomized, Double-Blind Study". Pakistan Journal of Medical and Health Sciences 16, n.º 1 (30 de enero de 2022): 944–47. http://dx.doi.org/10.53350/pjmhs22161944.

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Objective: The aim of this study is to compare the efficacy of oral ondansetron with oral domperidone in reducing vomiting in children with acute diarrhea. Study Design: Randomized control trial Place and Duration:The study was conducted atChildren Medical Center (CMC) / Dr Habibun Nabi Children Hospital, Airport Road Mingora Swat and Paediatrics department of Central Park Teaching Hospital, Lahore during the period fromJanuary 2020 to September 2020. Methods: Total one hundred and fifty children with ages 1-7 years were presented in this study. Children had diarrhea and vomiting from the last 24-48 hours. Informed written consent was taken from guardians for detailed demographics age, sex, weight, height and residency were calculated. Children were equally split into two groups. Group A received 0.15 mg/kg oral ondansetron with 75 children and group B received 0.5 mg/kg oral domperidone with 75 patients. Post treatment blockage of vomiting was observed after 12-24 hours. SPSS 24.0 version was used to analyze all data. Results: Majority of the patients were males 45 (60%) in group A and 42 (56%) in group B while rest were females 30 (40%) in group A and 33 (44%) in group B. Mean age of the patients in group A was 4.3 ±2.17 years and in group B mean age was 3.08±6.88 years. Mean weight of the patients were 15.07±8.23 kg and 15.02±3.09 kg in group A and B respectively. In group A mean height was 98.07±11.14 cm and in group B mean height was 97.67±18.24 cm. After 12 hours vomiting stopped in group A was 61 (81.3%) and 54 (72%) patients in group B. Efficacy after 24 hours were significantly higher among patients of group A in 69 (92%) children as compared to group B in 60 (80%) cases with p value < 0.05. Conclusion: In this study we concluded that for reducing vomiting in children with acute diarrhea use of oral ondansetron was effective and useful as compared to oral domperidone. Keywords: Acute Diarrhea, Ondansetron, Domperidone, Vomiting

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Neubauer, Aljoscha, Susanne Guthoff-Hagen, Jacob Menzler, Carsten Schwenke, Markus Rueckert y Axel Boehnke. "VP46 German Claims Data In Rare Disease HTA: Diffuse Large B-cell Lymphoma". International Journal of Technology Assessment in Health Care 35, S1 (2019): 87. http://dx.doi.org/10.1017/s0266462319003143.

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IntroductionIn rare disease areas representative data are scarce. Routine sick fund claims data provide a meaningful and reliable base for the in- and outpatient treatment landscape. This real-world data (RWE) from Germany was used to describe treatment patterns for Diffuse Large B-cell Lymphoma (DLBCL), the most frequent and aggressive non-Hodgkin lymphoma type in adults.MethodsClaims data from several sick funds of 4.8 Million insured were analyzed. Diagnosis of non-follicular Lymphoma (C83) was confirmed in 2.178 patients, DLBCL (C83.3) in 819 patients. The analysis was age- and gender-adjusted, observational period was 2014 and 2015. Treatments were analyzed for hospitalization and medication based on ATC-Code, Pharma Central Number and coded diagnoses (per ICD).ResultsMean age of DLBCL patients was 60.3 years, with two peaks at 50-54 and 70-74 years. Total costs for patients with DLBCL averaged 25.048 EUR versus 1.259 EUR in healthy insured. Charlson comorbidity index (CCI) of 4.58 indicates clinical relevance and severity. Comorbidities included several psychiatric diagnoses such as depression in every fifth patient. Mean 3.2 hospitalizations with average 31.5 hospital days were observed in DLBCL patients. Forty-seven percent of patients during observational time-frame did not receive oncological treatment, including relapsed / refractory patients. Only few patients received stem cell transplantation (2.6 percent) or radiation (3.9 percent). Most pharmacological treatments were Rituximab (RTX) + CHOP (57 percent), followed by RTX mono therapy (25 percent) or RTX in combination with Bendamustine (8 percent).ConclusionsDespite limitations in sick fund claims analyses, these provide a reasonable database for rare diseases. They allow standard treatment pathway- and longitudinal analyses. All DLBCL patients frequently required hospitalization and generated significant costs. A high unmet medical need exists for treatments other than palliative care, especially for a tolerable and effective outpatient therapy in elderly relapsed / refractory DLBCL.

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Murai, Kazunori, Shugo Kowata, Akiko Abo, Tatsuo Oyake, Shigeki Ito y Yoji Ishida. "Hepatotoxicity During Eltrombopag Administration Might Be Due to Necrosis of Hepatocytes". Blood 118, n.º 21 (18 de noviembre de 2011): 2228. http://dx.doi.org/10.1182/blood.v118.21.2228.2228.

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Abstract Abstract 2228 Background: Eltrombopag is an oral thrombopoietin receptor agonist for the treatment of immune thrombocytopenic patients who are refractory to the medications including corticosteroid. In RAISE study (The Lancet 2011: 377; 393–402), 79% patients in the eltrombopag group responded to treatment at least once during the study. However, 7% of eltrombopag-treated patients had increase of alanine aminotransferase (ALT) concentration and 4% of total bilirubin. The mechanism of eltrombopag-induced hepatobiliary toxicity remains unknown. In this study, we evaluated the effects of eltrombopag on hepatocytes using HepG2, human hepatocellular carcinoma cell line. Method: Cell proliferation was analyzed by MTT assay. Analysis of apoptosis/necrosis was analyzed by flow cytometry assay using Annexin V and propium iodide (PI) (Annexin-/PI-, viable cells; Annexin+/PI-, early apoptosis cells; Annexin+/PI+, late apoptosis and necrosis cells; Annexin-/PI+, late necrosis cells). Reduced glutathione was measured by DTNB colorimetric method. Murine hepatoma cell line Hepa 1–6 and murine normal liver derived cell line NCTC clone 1469 were also used in this study. Results: HepG2 was incubated with eltrombopag for 72 hrs and then MTT assay was performed. Figure 1a showed the growth inhibition curve of HepG2. HepG2 growth was suppressed by eltrombopag in a dose dependent manner (Figure 1a: without NAC, 12.5 μM 44.3 ± 8.7 %). In the addition of N-acetylcysteine (NAC) canceled the inhibitory effect (Figure 1a: with NAC 10mM: 60.4 ± 22.3 % at 12.5μM eltrombopag, p<0.05). To investigate whether this suppression was due to apoptosis or necrosis, we used PI/ Annexin V assay using flow cytometry. Figure 1b showed that each cell fraction after 72 hrs incubation with eltrombopag. PI positive and PI negative fraction was markedly increased (0μM: 0.7 ± 0.4%, 12.5 μM: 8.0 ± 6.0% p<0.01, 25μM: 39.6 ± 12.2% p<0.001). To confirm that the inhibitory effects of eltrombopag might be due to necrosis, we used IM-54, which is inhibitory molecule against oxidative stress induced necrosis, in MTT assay and PI/ Annexin V assay. As shown in Figure 2 a and 2 b, IM-54 canceled the inhibitory effects of eltrombopag in MTT assay (IM-54 0μM: 18.3 ± 7.5 %, IM-54 10 μM: 33.9 ± 10.6 % at eltrombopag 25μM, p<0.01) and PI/Annexin V assay (IM-54 0μM: 48.3 ± 12.4 %, IM-54: 10 μM 74.2 ± 8.3 % in PI/Annexin V double negative fraction at eltrombopag 25μM, p<0.01). The addition of Caspase-Inhibitor III (Boc-D-FMK) did not cancel the growth inhibition by eltrombopag in MTT assey. We measured GSH concentration of HepG2 cells. After the treatment of eltrombopag for 72 hrs, GSH decreased at 12.5μM of eltrpmbopag, however IM-54 restored the GSH concentration (83 mM at IM-54 0μM and eltrombopag 0 μM, IM-54 0 μM: 42.0 mM and IM-54 10μM: 83.3 mM at eltrombopag 12.5μM). Similar data were obtained in the study using Hepa 1–6 and NCTC clone 1469. Conclusion: Basic structure of eltrombopag is similar to that of 3-bipheyl-carboxylic acid, which is a strong oxidizing agent. Taken together, eltrombopag have an oxidative stress on hepatocytes to result in hepatotoxicity. Disclosures: No relevant conflicts of interest to declare.

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Petrova, Penka, Alexander Arsov, Ivan Ivanov, Lidia Tsigoriyna y Kaloyan Petrov. "New Exopolysaccharides Produced by Bacillus licheniformis 24 Display Substrate-Dependent Content and Antioxidant Activity". Microorganisms 9, n.º 10 (10 de octubre de 2021): 2127. http://dx.doi.org/10.3390/microorganisms9102127.

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Bacillus licheniformis is a soil bacterium with many industrial applications. In addition to enzymes, platform chemicals, antibiotics and phytohormones, the species produces exopolysaccharides (EPSs) of various biological activities. This study revealed that Bulgarian isolate B. licheniformis 24 produced EPSs consisting of galactose, glucose and mannose with substrate-dependent ratio. From glucose, B. licheniformis 24 secreted EPS1, consisting of 54% galactose, 39% glucose and 7% mannose. From fructose, the strain formed EPS2, containing 51% glucose, 30% mannose and 19% galactose. Batch cultivation in flasks yielded 2.2–2.6 g/L EPS1 and 1.90–2.11 g/L EPS2. Four to five times higher yields of EPS were obtained from both substrates during batch and fed-batch processes in a fermenter at 37.8 °C, pH 6.2 and aeration 3.68 vvm. The batch process with 200 g/L of starting substrates received 9.64 g/L EPS1 and 6.29 g/L EPS2, reaching maximum values at the 33rd and 24th h, respectively. Fed-batch fermentation resulted in the highest yields, 12.61 g/L EPS1 and 7.03 g/L EPS2. In all processes, EPSs were produced only in the exponential growth phase. Both EPSs exhibited antioxidant activity, but EPS2 was much more potent in this regard, reaching 811 μM Vitamin C Equivalent Antioxidant Capacity (versus 135 μM for EPS1). EPS1 displayed antibacterial activity against a non-O1 strain of Vibrio cholerae.

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Minoda, S., R. Sada, S. Matsushita, Y. Nakayama, H. Akebo, Y. Tsugihashi, H. Ishimaru y K. Hatta. "POS0516 REDEFINING THE CLINICAL AND LABORATORY FEATURES OF RHEUMATIC PLEURAL EFFUSION: A 30-CASE SERIES". Annals of the Rheumatic Diseases 80, Suppl 1 (19 de mayo de 2021): 492.1–492. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1197.

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Background:Rheumatoid pleural effusion (RPE) is a common extra-articular complication in patients with rheumatoid arthritis (RA). Previous studies have shown that RPE usually occurs in middle-aged men with rheumatoid factor (RF)-positive RA. RPE usually has features of pleural fluid acidosis, high lactate dehydrogenase (LDH) levels, and very low glucose levels(1). However, to the best of our knowledge, these findings were based on very few case series and reports, and most of these reports were published by the early 2000s(1, 2).Objectives:To investigate the clinical and laboratory characteristics and typical clinical courses of patients with RPE in a single centre of Japan since the beginning of the 21st century.Methods:Medical records of RPE patients were retrospectively reviewed between May 2006 and September 2020. RPE was identified by fulfilling these five conditions: (1) confirmation of the RA diagnosis; (2) having an exudative pleural effusion according to Light’s criteria; (3) negative results of pleural fluid culture; (4) negative results of pleural fluid cytology; and (5) exclusion of a parapneumonic effusion or empyema defined as no antibiotic use or ineffectiveness of antibiotics during the clinical course. Patients were divided into two groups according to their age at diagnosis: <60 years (Group A) and ≥60 years (Group B).Results:A total of 30 cases of RPE were included in the study. The median age was 71 years (interquartile range [IQR], 66–78 years). Of these patients, 16 (53%) were women. The median disease duration of RA was 98 months (IQR, 8–162 months). The two groups comprised six patients aged <60 years old and 24 patients ≥60 years. The median age was 54 years (IQR, 49–56 years) in Group A and 74 years (IQR, 69–78 years) in Group B. The median disease duration of RA was longer in Group B than that in Group A (132 vs. 3 months, p=0.008). Compared with Group A, Group B had fewer patients with fever (14% vs. 83%, p=0.003), and had lower serum C-reactive protein levels (3.3 vs. 11.1 mg/dL, p=0.03). Moreover, Group B was more likely to show mild inflammatory pleural fluids with higher pH (7.5 vs. 7.2, p=0.005) and lower LDH levels (155 vs. 1810 IU/L, p=0.046). Corticosteroids were started or increased in five (83%) and nine (38%) patients, and biologic disease-modifying anti-rheumatic drugs were started in one (17%) and two (8%) patients in groups A and B, respectively. One patient (16%) died within 5-years in Group A, and seven patients (29%) died in Group B.Conclusion:In contrast to previous studies, RPE was seen in older patients as well as middle-aged adults, and the pleural fluid analysis in older patients with RPE showed milder inflammation than the middle-aged patients.References:[1]Balbir-Gurman A, et al. Semin Arthritis Rheum. 2006 Jun; 35(6): 368-78.[2]Faurschou P, et al. Thorax. 1985 May; 40(5): 371-5.Table 1.Comparison of clinical and laboratory findings between Group A and Group B.Group A (n=6)Group B (n=24)P valueAge (years)54 [49-56]74 [69-78]Female2 (n=6, 33.3)14 (n=24, 58.3)0.38Disease duration of RA (months)3 [1-9]132 [44-199]0.008Fever ≥37.0°C5 (n=6, 83.3)3 (n=22, 13.6)0.003SerumCRP (mg/dL)11.1 [5.6-1.4]3.3 [0.9-10.5]0.03 RF (IU/mL)100 [19-816]63 [23-193]0.95 Anti-CCP ab positive5 (n=6, 83.3)12 (n=15, 80)1.00Pleural fluid analysispH7.2 [7.2-7.2]7.5 [7.4-7.5]0.005LDH (IU/L)1810 [594-2932]155 [123-346]0.046Glu (mg/dL)59 [10-123]105 [91-122]0.42Tp (g/dL)5.1 [4.9-5.6]4.6 [3.6-5.2]0.21Number of cells (/μL)5235 [3353-9300]3300 [1490-5008]0.27 Glu/serum Glu0.41 [0.09-0.99]1.05 [0.85-1.15]0.71Started or increased CS5 (n=6, 83.3)9 (n=24, 37.5)0.18Started bDMARDs1 (n=6, 16.6)2 (n=24, 8.3)0.50Died within 5 years1 (n=6, 16.6)7 (n=24, 29.1)1.00Data are median [interquartile range], or number (total number, percent).Abbreviations: RA, rheumatoid arthritis; CRP, C-reactive protein; RF, rheumatoid factor; Anti-CCP ab, anti-cyclic citrullinated peptide antibodies; LDH, lactate dehydrogenase; Glu, glucose; Tp, total protein; CS, corticosteroid; bDMARDs, biologic disease-modifying anti-rheumatic drugsDisclosure of Interests:None declared

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Fazzio, Luis E., Nicolas Yacachury, Walter R. Galvan, Elias Peruzzo, Ricardo O. Sánchez y Eduardo J. Gimeno. "Impact of ivermectin-resistant gastrointestinal nematodes in feedlot cattle in Argentina". Pesquisa Veterinária Brasileira 32, n.º 5 (mayo de 2012): 419–23. http://dx.doi.org/10.1590/s0100-736x2012000500010.

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The aim was to evaluate for 75 days the impact on production of the remaining burden of ivermectin (IVM)-resistant parasites in naturally infected feedlot calves. The herds came from tick-infested areas of cattle breeding where the systematic use of IVM to control tick increases the gastrointestinal parasites resistant to this drug. This investigation was carried out in two commercial feedlots in Buenos Aires province. In feedlot A, two groups of 35 animal each received IVM 1% and the other received ricobendazole (RBZ) 10% respectively. The same was done in feedlot B. On day 0, two groups of 35 animals were made in feedlots A and B. Fecal samples were taken on days 0, 22, 54 and 75 pos-treatment (PT), and body weight was registered, from each animal. Fecal samples were processed for individual count of eggs per gram (EPG) and pooled fecal culture was carried out for identification of the parasite genus in each sampling. Fecal egg count reduction test (FECR) was calculated on day 22 PT. The study design used was a totally randomized block, with commercial feedlot and sex as block variables. For data analysis, a mixed model of the SAS statistical program was used. The FECR average on day 22 was 28.4% in the IVM group, and 94,2 % in the RBZ group . From this date on, significant differences in EPG were kept until day 54. EPG counts were only equal near the end of the trial, on day 75 (p=0.16). In both commercial feedlots, especially in the IVM group, Cooperia spp. was the most prevalent parasite in the fecal cultures. Significant differences in weight (P<0.01) on post-treatment day 75 was found between the average weight in the RBZ and the IVM group (246 vs. 238 kg respectively), what means a difference of 8.3% in gains. The importance for production in the antiparasite failure treatment in commercial feedlots was demonstrated, and the need of pos-treatment controls to evaluate the efficacy of the antiparasitic administered is emphasized.

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Thu, Le Thi Arm, Michael J. Dibley, Vo Van Nho, Lennox Archibald, William R. Jarvis y Annette H. Sohn. "Reduction in Surgical Site Infections in Neurosurgical Patients Associated With a Bedside Hand Hygiene Program in Vietnam". Infection Control & Hospital Epidemiology 28, n.º 05 (mayo de 2007): 583–88. http://dx.doi.org/10.1086/516661.

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Objective. We conducted an intervention study to assess the impact of the use of an alcohol-chlorhexidine-based hand sanitizer on surgical site infection (SSI) rates among neurosurgical patients in Ho Chi Minh City, Vietnam. Design. A quasi-experimental study with an untreated control group and assessment of neurosurgical patients admitted to 2 neurosurgical wards at Cho Ray Hospital between July 11 and August 15, 2000 (before the intervention), and July 14 and August 18, 2001 (after the intervention). A hand sanitizer with 70% isopropyl alcohol and 0.5% Chlorhexidine gluconate was introduced, and healthcare workers were trained in its use on ward A in September 2000. No intervention was made in ward B. Centers for Disease Control and Prevention definitions of SSI were used. Patient SSI data were collected on standardized forms and were analyzed using Stata software (Stata). Results. A total of 786 patients were enrolled: 377 in the period before intervention (156 in ward A and 221 in ward B) and 409 in the period after intervention (159 in ward A and 250 in ward B). On ward A after the intervention, the SSI rate was reduced by 54% (from 8.3% to 3.8%; P = .09), and more than half of superficial SSIs were eliminated (7 of 13 vs 0 of 6 in ward B; P = .007). On ward B, the SSI rate increased by 22% (from 7.2% to 9.2%; P = .8). In patients without SSI, the median postoperative length of stay and the duration of antimicrobial use were reduced on ward A (both from 8 to 6 days; P <.001) but not on ward B. Conclusions. Our study demonstrates that introduction of a hand sanitizer can both reduce SSI rates in neurosurgical patients, with particular impact on superficial SSIs, and reduce the overall postoperative length of stay and the duration of antimicrobial use. Hand hygiene programs in developing countries are likely to reduce SSI rates and improve patient outcomes.

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Daly, Hafedh. "Diagnosis and Management of Acute Limb Ischemia". Angiology & Vascular Surgery 7, n.º 2 (2 de junio de 2022): 1–6. http://dx.doi.org/10.24966/avs-7397/100089.

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Introduction: Acute limb ischemia is considered as a life threatening disease .After twelve hours of ischemia, chances of saving the ischemic limb are lower (78%), with higher mortality (31%) as well. Methods: A total of 54 patients who underwent surgery for acute non traumatic limb ischemia between January 2013 and December 2020 were retrospectively reviewed. Results: We included 30 women and 24 men; median age was 69 years. Twenty patients (37%) were presented with upper limb ischemia, where as 34 patients (63%) with lower limb ischemia. Mean delay between the onset of symptoms and hospital admission of upper limb ischemia was 22 hours, 35% of Patients were diagnosed at the stage IIA of Rutherford classification, while 65% were diagnosed at the stage of II B. Lower limb ischemia patients were admitted after 28.5 hours, 64.8% of patients were diagnosed at the stage of II A of Rutherford, while 32.3% were diagnosed at the stage of II B of Rutherford. Revascularization of all ischemic upper limbs (100%) and the majority of ischemic lower limbs (94.1%) were carried out through endovascular thromboembolectomy with Fogarty ballooncathete. Meanlength of hospitalstaywas 8.3 days for upper limb ischemia cases ; while lower limb ischemia patients required 9.2 days of mean hospitalstay. We report a total of 4 deaths (7.4%). Conclusion: Acute limb ischemia remains a challenging entity for clinicians with significant risk of patient limbloss and mortality. Prompt diagnosis, anticoagulation, and timely revascularization are crucial to minimize the risk of limbloss.

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Roick, Julia, Peter Esser, Beate Hornemann, Anja Mehnert y Jochen Ernst. "Warum gerade ich? – Subjektive Krankheitsursachen und Zusammenhänge zu sozialen Faktoren und wahrgenommener Stigmatisierung bei Brust-, Prostata-, Darm- und Lungenkrebspatienten". PPmP - Psychotherapie · Psychosomatik · Medizinische Psychologie 70, n.º 01 (3 de abril de 2019): 22–31. http://dx.doi.org/10.1055/a-0851-6758.

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Zusammenfassung Hintergrund Subjektive Krankheitsursachen gehen vielfach mit Selbstbeschuldigung und Schamgefühlen einher. Diese psychosozialen Belastungen können durch mögliche Stigmatisierungserfahrungen verstärkt werden. Die vorliegende Studie untersucht Annahmen zu subjektiven Krankheitsursachen von Krebspatienten und prüft Zusammenhänge mit sozialen Faktoren und dem Grad erlebter Stigmatisierung. Methoden Im Rahmen einer bizentrischen Studie wurden 858 Patienten mit Brust-, Darm-, Lungen oder Prostatakrebs quantitativ befragt, von denen 815 in die Berechnungen eingingen. Subjektive Krankheitsursachen wurden durch ein Fragenset aus 17 Items mit den wichtigsten Ursachen von Krebserkrankungen erhoben und Stigmatisierung anhand der SIS-D (Social Impact Scale) erfasst. Die Daten werden uni- und multivariat ausgewertet. Ergebnisse Das Durchschnittsalter liegt bei 60 Jahren, 54% sind männlich. Die Mehrheit der Patienten (95%) führt multiple Krankheitsursachen an. Umwelt wird von allen Entitäten als der wichtigste Einflussfaktor bewertet (M=3,0). Schuld/Strafe Gottes und Ansteckung wird am wenigsten Einfluss beigemessen (M=1,1). Ursachen, die auf den Lebensstil zurückzuführen sind, korrelieren nicht höher mit stigmatisierenden Aussagen als externe Ursachenannahmen (r=0,07–0,38). Patienten mit höherem Einkommen sehen weniger psychosoziale Faktoren (Beta=− 0,051 bis −0,086), Rauchen (Beta=− 0,087) und Schuld/Strafe Gottes (Beta=− 0,023) als Ursache ihrer Erkrankung. Je niedriger die Bildung, desto mehr Einfluss wird der Ansteckung (Beta=− 0,019) als Ursache beigemessen. Schlussfolgerung Tatsächliche Krebsursachen und -risiken werden nur teilweise als solche eingeschätzt (z. B. Ernährung), während andere unterschätzt werden (z. B. Alkohol). Zukünftige Interventionen zur Aufklärung über Krebsursachen sollten v. a. Patienten mit niedriger Bildung fokussieren.

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Dorofieieva, O. E., K. S. Yarymbash, O. A. Glinyana, Yu V. Syomych y I. T. Skrypchenko. "Rehabilitation diagnosis of patients with mine-explosive wounds of the lower leg based on the international classification of functioning, disability and health". Medicni perspektivi 28, n.º 2 (30 de junio de 2023): 143–49. http://dx.doi.org/10.26641/2307-0404.2023.2.283384.

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Mine-explosive wounds at the level of the lower leg are accompanied by significant functional disorders, leading to long-term disability, and in some cases – to disability. The introduction at the state level of the document of the International Classification of Functioning, Disabilities and Health (ICF) in the treatment and rehabilitation process of medical institutions, necessitates its detailed study and application for making a rehabilitation diagnosis of patients. The aim of this study is to improve the process of rehabilitation diagnosis of patients with mine-explosive wounds of the lower leg based on the International Classification of Functioning, Disability and Health. The study involved 54 people, the average age of the subjects was 37±4.2 years, 80% of them were men, 20% were women. In the course of the clinical and instrumental methods of examination of patients with mine-explosive wounds at the level of the lower leg, the assessment of categories according to the ICF revealed disorders at the level of structure: functions: s 75010 bones of lower leg, s 75012 muscles of lower leg, s 75013 ligaments and fasciae of lower leg, s 8104 skin of lower extremity; b 28015 pain in the lower limb, b 4550 general physical endurance, b 7101 mobility of several joints, b 7351 muscle tone of one limb, b 770 function of the stereotype of walking, b 7800 sensation of muscular stiffness, b 810 protective function of skin; activities: d 4104 standing position, d 4106 moving the center of gravity of the body, d 4501 walking long distances, d 465 moving using technical means, d 5100 washing body parts, d 5102 wiping and drying, d 5402 putting on footwear, d 5403 taking off footwear, d 5702 self-health support, d 850 well-paid work, d 920 recreation and leisure, e 1151 assistive products and technologies for personal everyday use, e 310 close relatives, e 355 professional health care workers. Mine-blast injuries of the shin cause impairments at the structural level, but the majority of impairments in patients were found at the level of function, activity, and participation, which significantly affected their quality of life.

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Grant, Conor, Sarah O'Connell, Darren Lillis, Anne Moriarty, Ian Fitzgerald, Linda Dalby, Ciaran Bannan et al. "Opt-out screening for HIV, hepatitis B and hepatitis C: observational study of screening acceptance, yield and treatment outcomes". Emergency Medicine Journal 37, n.º 2 (5 de diciembre de 2019): 102–5. http://dx.doi.org/10.1136/emermed-2019-208637.

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BackgroundWe initiated an emergency department (ED) opt-out screening programme for HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) at our hospital in Dublin, Ireland. The objective of this study was to determine screening acceptance, yield and the impact on follow-up care.MethodsFrom July 2015 through June 2018, ED patients who underwent phlebotomy and could consent to testing were tested for HIV, HBV and HCV using an opt-out approach. We examined acceptance of screening, linkage to care, treatment and viral suppression using screening programme data and electronic health records. The duration of follow-up ranged from 1 to 36 months.ResultsOver the 36-month study period, there were 140 550 ED patient visits, of whom 88 854 (63.2%, 95% CI 63.0% to 63.5%) underwent phlebotomy and 54 817 (61.7%, 95% CI 61.4% to 62.0%) accepted screening for HIV, HBV and HCV, representing 41 535 individual patients. 2202 of these patients had a positive test result. Of these, 267 (12.1%, 95% CI 10.8% to 13.6%) were newly diagnosed with an infection and 1762 (80.0%, 95% CI 78.3% to 81.7%) had known diagnoses. There were 38 new HIV, 47 new HBV and 182 new HCV diagnoses. 81.5% (95% CI 74.9% to 87.0%) of known patients who were not linked were relinked to care after screening. Of the new diagnoses, 86.2% (95% CI 80.4 to 90.8%) were linked to care.ConclusionAlthough high proportions of patients had known diagnoses, our programme was able to identify many new infected patients and link them to care, as well as relink patients with known diagnoses who had been lost to follow-up.

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Okuno, Scott, William J. Maples, Michelle R. Mahoney, Tom Fitch, James Stewart, Paula M. Fracasso, Michael Kraut, David S. Ettinger, Fitzroy Dawkins y Charles Erlichman. "Evaluation of Epothilone B Analog in Advanced Soft Tissue Sarcoma: A Phase II Study of the Phase II Consortium". Journal of Clinical Oncology 23, n.º 13 (1 de mayo de 2005): 3069–73. http://dx.doi.org/10.1200/jco.2005.00.372.

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Purpose Epothilones are a new class of nontaxane tubulin polymerization agents that have activity in taxane-resistant tumors. Epothilone B (BMS-247550) is a semisynthetic analog of the natural product epothilone B. This study was performed to determine the activity of BMS-247550 in patients with soft tissue sarcomas (STSs) who had not received prior chemotherapy for metastatic disease. Patients and Methods Patients with measurable, advanced, or metastatic STS with no prior chemotherapy for metastatic disease were treated with BMS-2457550 50 mg/m2 intravenously during 1 hour every 21 days. All responses were confirmed 4 weeks later. Results Thirty-one patients (median age, 54 years; range, 19 to 78 years; 48% female) were entered onto the trial and were assessable for response. All but one patient had an Eastern Cooperative Oncology Group performance score of 0% or 1%, and 39% had received prior adjuvant chemotherapy. Mean follow-up was 22 months, with a confirmed response rate of 6% (95% CI, 0% to 17%). Median time to progression was 4.5 months (95% CI, 1.9 to 8.3 months), and 1 year progression-free survival was 17% (95% CI, 8% to 38%). Median survival was 16.4 months, with a 1-year survival of 61% (95% CI, 46% to 81%). Toxicity was mainly hematologic, with eight of 31 (26%) patients experiencing grade 3 to 4 leukopenia; 15 of 31 patients (48%) experienced grade 3 to 4 neutropenia. The grade 3 to 4 nonhematologic toxicities included neuropathies (26%), myalgia (13%), and fatigue (10%). Conclusion BMS-247550 has limited activity against STSs when given in this dose and schedule. The clinical toxicity is similar to that of taxanes.

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Sartori, Giulio, Filippo Spriano, Luciano Cascione, Chiara Tarantelli, Alberto J. Arribas, Luca Aresu, Davide Rossi, Giovanna Damia, Massimo Broggini y Francesco Bertoni. "Abstract B170: The in vitro anti-tumor activity of the multi-kinase inhibitor nemtabrutinib (ARQ-531, MK-1026) is seen across multiple B-cell lymphoma subtypes, only partially overlapping with what achieved by single BTK inhibition". Molecular Cancer Therapeutics 22, n.º 12_Supplement (1 de diciembre de 2023): B170. http://dx.doi.org/10.1158/1535-7163.targ-23-b170.

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Abstract Background. Nemtabrutinib is a reversible, ATP competitive tyrosine kinase inhibitor of BTK and of several other kinases, including LYN and MEK1 (Reiff et al, Cancer Discov 2018). Nemtabrutinib has shown preclinical and clinical activity in chronic lymphocytic leukemia (CLL), also against tumors bearing mutations affecting the C481 amino acid of BTK (Reiff et al, Cancer Discov 2018; Eradat et al, ICML 2023), which is commonly mutated in patients treated with 1st and 2nd generation inhibitors such as ibrutinib, acalabrutinib, zanubrutinib (Thompson & Tam, Blood 2023). Based on these data, a phase 3 trial is comparing the drug against chemo-immunotherapy in untreated-CLL patients (NCT05624554). Phase 1/2 studies are currently exploring nemtabrutinib in various B-cell lymphomas as single-agent (NCT05673460, NCT04728893) and combined with the ROR1-targeting antibody drug conjugate zilovertamab vedotin (NCT05458297). Due to the ability of nemtabrutinib to block multiple kinases, we exposed a large series of lymphoma cell lines to nemtabrutinib to understand the lymphomas that might most benefit. Methods. Nemtabrutinib (MedChemExpress) was assessed for its anti-proliferative activity at 72h across 54 cell lines, comprising germinal-center B-cell like (GCB) DLBCL (n.=18), activated B-cell like (ABC) DLBCL (n.=8), mantle cell lymphoma (MCL) (n.=10), marginal zone lymphoma (MZL) (n.=6), CLL (n.=2), plus other two derived from B- and eight from T-cell (n.=8) lymphomas. Results. The median IC50 for nemtabrutinib was 1.4 µM (95%CI, 0.8-2.3 µM) across all 54 lymphoma cell lines tested. Higher activity was found in B (median-IC50, 1.1 µM) compared to T (median IC50, 22.6 µM) cell lymphomas. Strong anti-lymphoma activity was observed in CLL cell lines (median IC50, 389 nM), MCL (median IC50, 627 nM), in one primary mediastinal B cell lymphoma (815 nM) and one canine diffuse large B-cell lymphoma cell line (389 nM). No difference was seen between ABC (median IC50, 1 µM) and GCB (median IC50, 1.2 µM) DLBCL. In DLBCL, nemtabrutinib anti-tumor activity was not affected by the presence of inactive TP53, BCL2 and/or MYC translocations. Taking advantage of publicly available ibrutinib data, we observed that nemtabrutinib and the 1st generation BTK inhibitor behaved similarly across 45 lymphoma cell lines (Pearson correlation r=0.5, P=0.001), especially in MCL (r=0.8, P=0.005) and ABC-DLBCL (r=0.75, P=0.039), but not in GCB-DLBCL, in which only nemtabrutinib was active. Further analyses integrating baseline transcriptome and mutational data are underway. Conclusions. Nemtabrutinib showed anti-tumor activity across B-cell lymphomas, higher in some histotypes (including MCL, CLL). The pattern of anti-tumor activity was only partially overlapping by what achieved by the BTK inhibitor ibrutinib: while MCL and ABC-DLBCL responded similarly, activity in GCB-DLBCL was seen only with nemtabrutinib. Citation Format: Giulio Sartori, Filippo Spriano, Luciano Cascione, Chiara Tarantelli, Alberto J. Arribas, Luca Aresu, Davide Rossi, Giovanna Damia, Massimo Broggini, Francesco Bertoni. The in vitro anti-tumor activity of the multi-kinase inhibitor nemtabrutinib (ARQ-531, MK-1026) is seen across multiple B-cell lymphoma subtypes, only partially overlapping with what achieved by single BTK inhibition [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B170.

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Kedra, Joanna, Raphaele Seror, Philippe Dieudé, Arnaud Constantin, Eric Toussirot, Elias Kfoury, Charles Masson et al. "Lymphoma complicating rheumatoid arthritis: results from a French case–control study". RMD Open 7, n.º 3 (septiembre de 2021): e001698. http://dx.doi.org/10.1136/rmdopen-2021-001698.

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Objectives To study the characteristics of B-cell non-Hodgkin’s lymphoma (NHL) or Hodgkin lymphoma complicating rheumatoid arthritis (RA) and to identify RA-related factors associated with their occurrence. Methods A multicentre case–control study was performed in France. Cases were patients with RA fulfilling ACR-EULAR 2010 criteria in whom B-cell NHL or Hodgkin lymphoma developed after the diagnosis of RA. For each case, 2 controls were assigned at random from the ESPOIR cohort and were matched on age at lymphoma diagnosis (cases)/age at the 10-year follow-up visit in the cohort (controls). Case and control characteristics were compared to identify parameters associated with the occurrence of lymphoma. Results 54 cases were included and matched to 108 controls. Lymphomas were mostly diffuse large B-cell lymphoma (DLBCL, n=27, 50.0%). On immunochemistry, 4 of 27 (14.8%) lymphoma cases were positive for Epstein-Barr virus. On univariate analysis, factors associated with the occurrence of lymphoma were male sex (OR 3.3, 95% CI 1.7 to 6.7), positivity for ACPA (OR 5.1, 95% CI 2.0 to 15.7) and rheumatoid factor (OR 3.9, 95% CI 1.6 to 12.2), and erosions on radiographs (OR 3.8, 95% CI 1.7 to 8.3) and DAS28 (OR 2.0, 95% CI 1.5 to 2.7), both at the time of matching. Methotrexate, TNF blockers and a number of previous biologics were not associated with the occurrence of lymphoma. On multivariable analysis, erosions and DAS28 remained significantly associated with increased risk of lymphoma. Conclusion Lymphomas complicating RA are mostly DLBCL. Risk of lymphoma in patients with RA was increased with markers of disease activity and severity, which supports the paradigm of a continuum between autoimmunity and lymphomagenesis in RA.

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Atwill, E. R., B. Hoar, M. das Graças Cabral Pereira, K. W. Tate, F. Rulofson y G. Nader. "Improved Quantitative Estimates of Low Environmental Loading and Sporadic Periparturient Shedding of Cryptosporidium parvum in Adult Beef Cattle". Applied and Environmental Microbiology 69, n.º 8 (agosto de 2003): 4604–10. http://dx.doi.org/10.1128/aem.69.8.4604-4610.2003.

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ABSTRACT Our primary goal was to generate an accurate estimate of the daily environmental loading rate of Cryptosporidium parvum oocysts for adult beef cattle, using immunomagnetic separation coupled with direct immunofluorescence microscopy for a highly sensitive diagnostic assay. An additional goal was to measure the prevalence and intensity of fecal shedding of C. parvum oocysts in pre- and postparturient cows as an indicator of their potential to infect young calves. This diagnostic method could detect with a ≥90% probability oocyst concentrations as low as 3.2 oocysts g of feces−1, with a 54% probability of detecting just one oocyst g of feces−1. Using this diagnostic method, the overall apparent prevalence of adult beef cattle testing positive for C. parvum was 7.1% (17 of 240), with 8.3 and 5.8% of cattle shedding oocysts during the pre- and postcalving periods, respectively. The mean intensity of oocyst shedding for test-positive cattle was 3.38 oocysts g of feces−1. The estimated environmental loading rate of C. parvum ranged from 3,900 to 9,200 oocysts cow−1 day−1, which is substantially less than a previous estimate of 1.7 × 105 oocysts cow−1 day−1 (range of 7.7 × 104 to 2.3 × 105 oocysts cow−1 day−1) (B. Hoar, E. R. Atwill, and T. B. Farver, Quant. Microbiol. 2:21-36, 2000). Use of this highly sensitive assay functioned to detect a greater proportion of low-intensity shedders in our population of cattle, which reduced the estimated mean intensity of shedding and thereby reduced the associated environmental loading rate compared to those of previous studies.

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Ragg, J. C. "Film compression bandage". Phlebologie 44, n.º 05 (septiembre de 2015): 249–55. http://dx.doi.org/10.12687/phleb2276-5-2015.

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SummaryPurpose: Textile compression stockings or bandages are limited in comfort; they do not allow uninterrupted wearing. A novel elastic film bandage was evaluated regarding practicability, patient comfort and effect on vein regression. Main endpoint was the frequency of symptomatic inflammatory reactions.Methods: In a comparative pilot study, a compression film bandage (CFB, investigational) comprising an elastic, self-adhesive breathable polymer film of d <20 µm was continuously worn for 14 d after foam sclero-therapy. Inclusion: 62 patients (26–68 y.) frequently doing sports and taking daily showers, 90 legs with superficial varicosities, 5–12 mm ø (MW: 7.3 mm), randomized to A) CFB + medical compression stocking (MCS), B) MCS alone, C) CFB alone. Follow-up examinations including ultrasound and photography were performed after 2, 4 and 8 weeks.Results: Continuous wearing time of 14 days was completed in 57/60 cases with CFB (95.0 %, A+C), while 3/60 (5.0 %) finished wearing after 8–10 d. There were no adverse skin reactions except minor irritations at the upper edge (n = 2). Vein diameters were reduced within 14 days by 29–54 % (mean: 43.5 %) in group A, 16–44% (mean: 39.1 %) in group B, and 24–50 % (mean: 37.3 %) in group C. Symptomatic inflammation, indu-ration or discolouration was observed within 28 days in 5/60 cases (8.3 %) when using CFB (A, C) versus 19/30 (63.3%) related to stocking compression (B). Comfort was rated by the patients 6.6 (A), 4.3 (B) and 9.2 (C) on a 10 degree scale. This difference was statistically highly significant (p <0.01).Conclusions: The film bandage is an effective and safe compression modality. For superficial varicosities the adhesive bond to the skin seems to be relevant additional to the elastic properties. The device significantly improves vein regression of foam-treated superficial varicosities when combined with compression stockings or even as stand-alone modality. Continuous wearing for two weeks is well tolerated. The bandage may also offer an alternative for patients not tolerating textile compression media, or during summer.

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Lee, Sang-Ho, H. Yener Erken y Junseok Bae. "Percutaneous Transforaminal Endoscopic Lumbar Interbody Fusion: Clinical and Radiological Results of Mean 46-Month Follow-Up". BioMed Research International 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/3731983.

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Background. Spinal fusion has been shown to be the preferred surgical option to reduce pain, recover function, and increase quality of life in the treatment of a variety of lumbar spinal disorders. The main goal of the present study is to report our clinical experience and results of percutaneous transforaminal endoscopic lumbar interbody fusion (PELIF) applications using the expandable spacer in a single institution.Methods. We performed a retrospective review of 18 patients with >12-month follow-up who had been operated on PELIF using expandable spacer from 2001 to 2007. Their clinical and radiological data were collected and analyzed.Results. The mean follow-up period was 46 months. The mean DH before the surgery was 8.3 mm which improved to 11.4 mm at the early postoperative period and regressed to 9.3 mm at the last follow-up visit. The VAS-B, VAS-L, and ODI scores at the last follow-up showed a 54%, 72%, and 69% improvement from the preoperative period, respectively.Conclusions. The presented PELIF technique with the expandable spacer seems to be a promising surgical technique for the treatment of a variety of lumbar spinal disorders. Conversely, radiological results including disc space subsidence make the stand-alone application of the expandable spacer debatable.

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Choi, Gwang-Jun, Ji Young Park, Joon-Sik Choi, Bitna Kim, Sae Rom Choi, Dong Sub Kim, Ji-Man Kang et al. "724. Neurologic Complications in Hospitalized Pediatric Patients with Influenza Infection, A Multicenter Retrospective Study in Korea". Open Forum Infectious Diseases 5, suppl_1 (noviembre de 2018): S260. http://dx.doi.org/10.1093/ofid/ofy210.731.

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Abstract Background The aim of the study was to evaluate the incidence and characteristics of influenza associated neurologic complications (IANCs) in hospitalized pediatric patients in Korea. Methods We performed retrospective review of hospitalized cases of confirmed influenza infection from October 2010 to April 2017. Patient’s data were collected from three referral hospitals in different regions of the country. Results A total 2,002 laboratory confirmed influenza cases were identified. The median age was 3.3 years old (range 0.0–18.9 years) and 1,003 patients were male (54%). Influenza A was diagnosed in 1,357 cases (68%), influenza B in 624 (31%) and both influenza A and B in 21 (1%). Other combined respiratory virus infection was detected in 104 (5.2%) cases. Out of 2,002 cases, IANCs were identified in 167 cases (8.3%); influenza virus A was detected in 116 (69.4%), B in 50 (29.9%) and both A and B in one case (0.6%). Of 167 cases with IANCs, 25 patients (15%) had underlying neurologic diseases. Eleven patients (11/167, 6.5%) had combined respiratory viral infection (Rhinovirus = 5; respiratory syncytial virus = 3; coronavirus = 2; and bocavirus = 1). The most common diagnosis was a simple febrile seizure (112/167, 67.1%), followed by other seizures (26/167, 15.6%), encephalopathy/encephalitis (17/167, 10.2%), meningitis (7/167, 4.2%), meningism (4/167, 2.4%) and acute ataxia (1/167, 0.6%). In two patients with encephalitis/meningitis, one patient had influenza A and the other patient had influenza B detected by PCR in cerebrospinal fluid. Most of the patients were fully recovered (162/167, 97%) and no neurologic complication occurred in patients who had only initial manifestation of simple febrile seizure. Ten patients (10/167, 6.0%) required hospitalization in intensive care unit. Three patients (3/167, 1.8%) died of encephalopathy (n = 1) and combined encephalopathy/myocarditis (n = 2). Pre-existing neurologic disease was a risk factor of IANCs with an odds ratio of 3.94 (95% confidence interval 2.37 to 6.56, P < 0.0001). Conclusion IANCs is not rare and may cause serious outcome including death. Clinicians should be aware of the increased risk for IANCs in certain patients with neurologic diseases. Disclosures All authors: No reported disclosures.

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Kim, Jee Hung, Soong June Bae, Sung Gwe Ahn, Jeonghee Lim, Min Hwan Kim, Gun Min Kim, Joo Hyuk Sohn y Joon Jeong. "Abstract PO5-02-09: Discordance of the PAM50 intrinsic subtypes with the immunohistochemistry-based subtypes in HER2-negative early breast cancer treated with neoadjuvant chemotherapy". Cancer Research 84, n.º 9_Supplement (2 de mayo de 2024): PO5–02–09—PO5–02–09. http://dx.doi.org/10.1158/1538-7445.sabcs23-po5-02-09.

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Abstract Background The PAM50 (Prosigna Breast Cancer Gene Signature Assay) can be used to assess the expression levels of 50 genes in early breast cancer biopsies, including formalin-fixed paraffin-embedded (FFPE) tissue from human epidermal growth factor receptor 2 (HER2)-negative patients. However, there is currently no practical molecular assay for intrinsic subtype in real-world practice that addresses the problems of cost and run-time. Methods In the phase 2 HER2E-PAM/PAMILIA study (NCT04817540), we prospectively analyzed molecular subtyping through the PAM50 test in low HER2 (HER2 IHC 1+ or 2+ SISH-) breast cancer patients. PAM50 intrinsic subtypes were determined according to 50 cancer genes using the NanoString nCounter Analysis System. This study was originally designed to determine whether adding HER2-targeted treatment in HER2 enriched molecular subtype increases the pathologic complete rate (pCR). We aimed to analyze the discordance between immunohistochemistry (IHC)-based surrogate subtyping of pre- & post-operative tissues and PAM50 intrinsic subtypes, and to assess the pCR according to the discordance. Results In a total 82 patients, the proportions of HR+/HER2- and triple negative breast cancer (TNBC) in the preoperative tissue were 85.4% (n=70) and 14.6% (n=12), respectively. According to PAM50 intrinsic subtypes, 11.0% (n=9) were basal, 8.5% (n=7) were HER2-enriched, 34.1% (n=28) were luminal A, 36.6% (n=30) were luminal B, and 3.7% (n=3) were normal-like type. In total, 32 patients (41.5%) were discordant between IHC-based preoperative subtype and PAM50 intrinsic subtype. Among the 70 patients with HR+/HER2-, non-luminal A, B type was found in 12.9% with basal-like, 8.6% with HER2-enriched, and 4.3% with normal-like type, respectively. Of 12 TNBC patients, 83.3% were luminal A, B type, and 8.3% were HER2-enriched. In the other hands, 6 patients (13.0%) were discordant between IHC-based post-operative subtype and PAM50 intrinsic subtype. Among the 40 patients with HR+/HER2- postoperative subtype, non-luminal A, B type was found in 2.5% with basal-like, 2.5% with HER2-enriched, and 5.0% with normal-like type, respectively. Of 6 TNBC postoperative patients, 16.7% were normal-like. Most received anthracycline- and taxane-based neoadjuvant chemotherapy. During data analysis (June 2023), 54 cases underwent surgery after neoadjuvant chemotherapy. 4 of 54 patients (7.4%) achieved a pCR, of which one was HER2-enriched, one was luminal B-like, and two were basal-like PAM50 intrinsic subtype. However, discordance of IHC based subtype with intrinsic subtype was not considerable and was not correlated with pCR. Conclusion A substantial portion of patients showed discrepancy between preoperative and postoperative IHC subtype and PAM50 intrinsic subtype in our study. Citation Format: Jee Hung Kim, Soong June Bae, Sung Gwe Ahn, Jeonghee Lim, Min Hwan Kim, Gun Min Kim, Joo Hyuk Sohn, Joon Jeong. Discordance of the PAM50 intrinsic subtypes with the immunohistochemistry-based subtypes in HER2-negative early breast cancer treated with neoadjuvant chemotherapy [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 PO5-02-09.

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Валиев, Всеволод Сергеевич, Денис Евгеньевич Шамаев, Рустам Равилевич Хасанов y Виталий Викторович Маланин. "ПОДВИЖНОСТЬ ТЯЖЕЛЫХ МЕТАЛЛОВ В ДОННЫХ ОТЛОЖЕНИЯХ И ОСОБЕННОСТИ ИНТЕРПРЕТАЦИИ ЕЕ ИЗМЕНЧИВОСТИ". Российский журнал прикладной экологии, n.º 2 (6 de julio 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. Список литературы Бреховских В.Ф. Тяжёлые металлы в донных отложениях Нижней Волги и дельты реки // Вода: химия и экология. 2010. №2. С. 2‒10. Даувальтер В.А. Геоэкология донных отложений озер. Мурманск: МГТУ, 2012. 242 с. Добровольский В.В. Роль гуминовых кислот в формировании миграционных массопотоков тяжелых металлов // Почвоведение. 2004. №1. С. 32‒39. Садчиков А.П. Структурные показатели бактерий и детрита в пресных водоемах (методические аспекты) // Материалы по флоре и фауне Республики Башкортостан / Сборник статей. Вып. XII. Уфа: РИЦ БашГУ, 2016. C. 37‒42. Кочарян А.Г., Веницианов Е.В., Сафронова Н.С., Серенькая Е.П. Сезонные изменения форм нахождения тяжёлых металлов в донных отложениях Куйбышевского водохранилища // Водные ресурсы. 2003. Т. 30, №4. С. 443‒451. Толкачёв Г.Ю. Сравнительная характеристика содержания и форм существования микроэлементов в донных отложениях различных районов р. Волга // Международный научно-исследовательский журнал. 2017. №3. С. 85‒89. Толкачёв Г.Ю. Тяжёлые металлы в системе «вода–донные отложения». Saarbrucken: LAP LAMBERT Academic Publishing, 2012. 98 с. Balls P.W. The partition of trace metals between dissolved and particulate phases in European coastal waters: A compilation of field data and comparison with laboratory studies // Netherlands journal of sea research. 1989. Vol. 23, iss. 1. Р. 7–14. Bantan R.A., Al-Dubai T.A., Al-Zubieri A.G. Geo-environmental assessment of heavy metals in the bottom sediments of the Southern Corniche of Jeddah, Saudi Arabia // Marine pollution bulletin. 2020. Vol. 161(Pt A). 111721. doi: 10.1016/j.marpolbul.2020.111721 Baran A., Mierzwa-Hersztek M., Gondek K., Tarnawski M., Szara M. The influence of the quantity and quality of sediment organic matter on the potential mobility and toxicity of trace elements in bottom sediment // Environmental geochemistry and health. 2019. Vol. 41. Р. 2893‒2910. doi: 10.1007/s10653-019-00359-7 Chen J., Gu B., Royer G.B., Burgos R.W. The roles of natural organic matter in chemical and microbial reduction of ferric ion // The science of total environment. 2003. Vol. 307, iss. 1‒3. P. 167‒178 р. doi: 10.1016/S0048-9697(02)00538-7 Horowitz A.J. A primer on trace metal-sediment chemistry. Alexandria, 1985. 67 p. Steell K.F., Wagner G.H. Trace metal relationships in bottom sediments of freshwater stream the Buffalo River, Arkansas. J. Sediment Petrol. 1975. Vol. 45. №1. P. 310–319. Hutchins C.M., Teasdale P.R., Lee J., Simpson S.L. The effect of manipulating sediment pH on the porewater chemistry of copper- and zinc-spiked sediments // Chemosphere. 2007. Vol. 69, №7. Р. 1089‒1099. doi: 10.1016/j.chemosphere.2007.04.029 Jabłońska-Czapla M., Nocoń K., Szopa S., Łyko A. Impact of the Pb and Zn ore mining industry on the pollution of the Biała Przemsza River, Poland // Environmental monitoring and assessment. 2016. Vol. 188, №5. Р. 262. doi: 10.1007/s10661-016-5233-3 Joshua E.O., Oyebanjo O.A. Grain-size and heavy mineral analysis of River Osun sediments // Australian journal of basic and applied science. 2010. №4(3). P. 498‒501. Kulbat E., Sokołowska A. Methods of assessment of metal contamination in bottom sediments (Case study: Straszyn Lake, Poland) // Archives of environmental contamination and toxicology. 2019. Vol. 77, №4. Р. 605‒618. doi: 10.1007/s00244-019-00662-5 MacDonald D.D., Ingersoll C.G., Berger T.A. Development and evaluation of consensus-based quality guidelines for freshwater ecosystem // Archives of environmental contamination and toxicology. 2000. Vol. 39. Р. 20‒31. Martínez-Santos M., Probst A., García-García J., Ruiz-Romera E. Influence of anthropogenic inputs and a high-magnitude flood event on metal contamination pattern in surface bottom sediments from the Deba River urban catchment // The science of total environment. 2015. Vol. 514. P. 10–25. Michalski R., Kostecki M., Kernert J., Pecyna P. Time and spatial variability in concentrations of selected metals and their species in water and bottom sediments of Dzierżno Duże (Poland) // Journal of environmental science and health. Part A. Toxic/Hazardous substances & environmental engineering. 2019. Vol. 54, №8. Р. 728‒735. doi: 10.1080/10934529.2019.1592530 Ming L., Jingbo C., Xueshi S., Zhizhou H., Dejiang F. Accumulation and transformation of heavy metals in surface sediments from the Yangtze River estuary to the East China Sea shelf // Environmental pollution. 2019. Vol. 245. P. 111‒121. doi: 10.1016/j.envpol.2018.10.128 Steell K.F., Wagner G.H. Trace metal relationships in bottom sediments of freshwater stream the Buffalo River, Arkansas // Journal of sedimentary petrology. 1975. Vol. 45, №1. P. 310–319. Vasiliev O.F., Papina T.S., Pozdnjakov Sh.R. Suspended sediment and associated mercury transport – the case study on the Katun River // Proc. 4 Int. Symp. on river sedimentation. Beijing. China: IRTCES, 1990. P. 155–162. Vodyanitskii Y., Vlasov D. Integrated assessment of affinity to chemical fractions and environmental pollution with heavy metals: a new approach based on sequential extraction results // International journal of environmental research and public health. 2021. Vol. 10, №18(16). Р. 8458. doi: 10.3390/ijerph18168458 Wasserman J., Oliveira F., Bidarra M. Cu and Fe associated with humic acids in sediments of a tropical coastal lagoon // Organic geochemistry. 2003. Vol. 28. P. 813–822. Wolter K. Bacterial in corporation of organic substances released by natural phytoplankton population // Marine ecology progress series. 1982. Vol. 17, №3. Р. 287‒295. Wu G.H., Cao S.S., Chen S.R., Cao F.T. Accumulation and remobilization of metals in superficial sediments in Tianjin, China // Environmental monitoring and assessment. 2011. Vol. 173, №1‒4. Р. 917‒928. doi: 10.1007/s10661-010-1434-3 Xun X., Qingliang Z., Mingsong W., Jing D., Weixian Z. Biodegradation of organic matter and anodic microbial communities analysis in sediment microbial fuel cells with/without Fe(III) oxide addition // Bioresource technology. 2017. Vol. 225. P. 402‒408. doi: 10.1016/j.biortech.2016.11.126 Yanqi Z., Ying Y., Rongkun D., Sobkowiak L., Xinyi W., Lizhi X. Adsorption and migration of heavy metals between sediments and overlying water in the Xinhe River in central China // Water science and technology. 2021. Vol. 84, №5. Р. 1257‒1269. doi: 10.2166/wst.2021.314

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Oliveira, Ana Tereza Ramos de, Lísia Marcílio Rabelo, Adelson Dias Costa y Ines Lessa. "Características da demanda por tomografia computadorizada crânio-encefálica motivos e custos dos exames". Arquivos de Neuro-Psiquiatria 50, n.º 1 (marzo de 1992): 91–98. http://dx.doi.org/10.1590/s0004-282x1992000100016.

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Foram levantadas as 2860 tomografias computadorizadas crânio-encefálicas (TCCE) feitas em um dos três serviços da cidade do Salvador, Brasil, sendo: caracterizados o perfil do usuário e a procedência da demanda; analisados os motivos dos exames e os custos com TCCE normais e anormais. Foram constatadas frequências altas de exames normais: (a) para o sexo feminino (66,0%) e até os 54 anos (73,0%), neste sexo (variação de exames normais entre 65 e 80%); (b) para o sexo masculino nos grupos <15, 25-34 e 35-44 anos (64,7%); (c) para solicitações efetuadas pelos convênios (65,3%); (d) pelos seguintes motivos, para homens e mulheres respectivamente: cefaléias (81,3 e 87,5%); desmaios/tonturas (79,3 e 78,6%); convulsões (67,3 e 70%); retardo do desenvolvimento psicomotor (72,0 e 67,7%); «distúrbios endócrinos» (75,0% em cada sexo). Proporções altas de exames anormais foram observadas pelos seguintes motivos e para homens e mulheres, respectivamente: síndrome demencial (91,7 e 83,3%); acidentes vasculares encefálicos (85,1 e 73,7%); doenças infecciosas (76,5 e 78,6%); suspeitas de tumor (65,8 e 55,4%); e traumatismo crâ-nioencefálico, 63,6% no sexo masculino. No total, os custos com as TCC normais corresponderam a US$ 565,255 e com as anormais, US$ 381,247; para os convênios, os custos com TCC normais foram 2,2 vezes superiores ao INAMPS e 2,8 vezes superiores àqueles da medicina privada.

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Hassan, Neelma, Suleman Khan, Maha Abdulla Alwaili, Wedad Saeed Al-Qahtani, Farman Ullah, Taj Muhammad, Hussain Ahmad y Hanif Ullah. "Sero-prevalence and Associated Complications of Hepatitis B Virus Infected Patients of Khyber Pakhtunkhwa". Pakistan Journal of Medical and Health Sciences 15, n.º 12 (30 de diciembre de 2021): 3789–94. http://dx.doi.org/10.53350/pjmhs2115123789.

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Background: Hepatitis B infection is among the most significant public health challenge worldwide. The prevalence of HBV infection is common among most populations in Peshawar, including pregnant women. Objective: The present study aims to estimate the prevalence and complications associated with clinical parameters and risk factors in patients with HBV. Methodology: A total 150 patients were reported and subjected to Enzyme linked assay (ELISA) for HBeAg test and HBs-Ag by immunochromaticgraphic assay (ICT). RT-PCR assay was used for detection of HBV DNA load. A study designed Performa was used for face-to-face interview to collect data from the study participants. Results: According to our study, highest prevalence was found in Peshawar 34% and the second highest prevalence in Waziristan 20.2%. The results showed highest prevalence in male (54%) than female (46%) and amongst female patients, 10% were pregnant. According to patient’s age, the highest prevalence was found group 26-35 years 34.2% and lowest prevalence was <= 15 years 2.6%. In our study patients were reported on the base of antigen were 94 (62.7%) of patients with HBsAg positive and 56 HBeAg positive (37.3%). Among total patients, 5.3% were co-infected with HCV and no patients were observed co-infected with HDV or HIV. In current study, the prevalence of family affected on the base of relation was found with 21.3%, amongst these 9.3% (spouse affected), 2.7% (mother affected), sibling affected patients (4%) and children affected (5.3%) were observed. The data showed patients with normal ALT 81.3% and 18.7% with elevated and the patients 9.4% and 90.6% found with elevated and normal creatinine level respectively. The normal bilirubin (93.3%), raised bilirubin (6.7%), normal ultrasound (83.7%) and 16.3% dysfunction ultrasound were reported in patients after antiviral drugs treatment. The study surveyed 64% and 36% patients reported under tenofovir and entecavir treatment with different duration and 36%. The less mortality rate of patients leading HBV infection was reported 1.3% in this study due to renal failure and diabetics. Conclusion: The male are more exposed to the environment and that is why highest frequency infected as compared to the female. The main reason of high HBV prevalence was less awareness in people and highest prevalence on the base of family history in spouse because may close contact. Keywords: HBV,Elisa, ICT, virus , antviral

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Kindler, H. L., D. Niedzwiecki, D. Hollis, E. Oraefo, D. Schrag, H. Hurwitz, H. L. McLeod, M. F. Mulcahy, R. L. Schilsky y R. M. Goldberg. "A double-blind, placebo-controlled, randomized phase III trial of gemcitabine (G) plus bevacizumab (B) versus gemcitabine plus placebo (P) in patients (pts) with advanced pancreatic cancer (PC): A preliminary analysis of Cancer and Leukemia Group B (CALGB". Journal of Clinical Oncology 25, n.º 18_suppl (20 de junio de 2007): 4508. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.4508.

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4508 Background: In a phase II trial in 52 PC pts, GB yielded a 21% response rate and a median survival of 8.8 months (mo) (Kindler, JCO 2005). These data led CALGB to conduct a phase III trial of GB vs. GP in advanced PC pts. Methods: This randomized trial was double-blind, placebo-controlled. Eligible pts had no prior therapy for advanced disease, PS 0–2, no tumor invasion of adjacent organs, no increased bleeding risk. Primary endpoint: overall survival (OS). Stratification: PS (0/1 or 2), disease extent (locally advanced or metastatic), prior radiation (RT) (yes/no). Statistics: 90% power to detect a difference in median OS of 6 vs. 8.1 mo. Treatment: Pts received G 1,000 mg/m2 over 30 minutes days (D) 1, 8, 15 Q28D; B 10 mg/kg or P D 1, 15 Q28D. CT scans: Q2 cycles. Results: 602 pts enrolled 6/30/04–4/14/06. Based on a protocol-specified interim analysis with 64% of information on OS, the CALGB Data Safety Monitoring Board released study data in 6/06 because a futility boundary was crossed. Pts on treatment were notified and unblinded. Pt characteristics (302GB/300GP): male 58%/51%; median age 63.8/65.0; PS 2 9%/9%; stage IV 85%/84%; prior RT 11%/11%. Median follow-up: 11.3/11.7 mo. As of 12/22/06, 436 pts (224/212) have died (93% of total expected deaths at planned final analysis). Median OS 5.7/6.0 mo (95% CI: 4.9, 6.5/5.0, 6.9). Median failure-free survival 4.8/4.3 mo (95% CI: 4.3, 5.7/3.8, 5.6). Response (includes unconfirmed responses): complete (CR) 1.9%/3.0%; partial (PR) 11.2%/8.3%, stable disease (SD) 40.7%/35.7%. Disease control rate (CR/PR/SD) 54%/47%. 525 pts (268/257) are currently evaluable for toxicity. Median cycles 3.5/3.1 (p=0.09). Total mg/m2 G received 9095/8334 (p=0.22). Grade ¾ toxicity (%pts GB/GP): neutropenia 33%/30%; anemia 5%/8%; thrombocytopenia 12%/12%; hypertension 8%/2%; perforation 0.4%/0%; GI bleed 3%/2%; CVA 2%/2%; proteinuria 4%/1%; venous thrombosis 9%/9%. Conclusion: The addition of B to G does not improve survival in advanced PC. [Table: see text]

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Al-Maghrabi, Jaudah, Lada Vorobyova, A. Toi, William Chapman, Maria Zielenska y Jeremy A. Squire. "Identification of Numerical Chromosomal Changes Detected by Interphase Fluorescence In Situ Hybridization in High-Grade Prostate Intraepithelial Neoplasia as a Predictor of Carcinoma". Archives of Pathology & Laboratory Medicine 126, n.º 2 (1 de febrero de 2002): 165–69. http://dx.doi.org/10.5858/2002-126-0165-ionccd.

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Abstract Context.—High-grade prostate intraepithelial neoplasia (HPIN) is the most likely precursor of prostate cancer. The condition of many patients with a diagnosis of HPIN in prostate needle core biopsy could, if left untreated, progress to invasive cancer. Currently there is no available clinical, immunohistochemical, or morphologic criteria that are predictive of this progression. Objective.—To determine whether chromosomal instability in these precursor lesions could increase their predictive value for cancer detection. Design.—Dual-color interphase fluorescence in situ hybridization analysis was performed on archived prostate needle core biopsies from 54 patients with initial diagnosis of isolated HPIN and follow-up of 3 years or more. We used commercially available centromere probes for chromosomes 4, 7, 8, and 10. We had interpretable results in 44 patients as follows: (1) group A: 24 HPIN patients with persistent HPIN and/or benign lesions in the follow-up biopsies, and (2) group B: 20 HPIN patients with progression to prostate carcinoma. Results.—Twenty-five percent of the patients in group B displayed numeric chromosomal aberrations. Only 8.3% of the patients from group A had chromosomal abnormalities (P = .1). The observed overall chromosomal changes in HPIN were higher than those in normal or hyperplastic epithelium, with a statistically significant difference (P < .05). All aberrations were detected in the form of chromosomal gain. Overall, the commonest aberration was gain of chromosome 8, followed by gains of chromosomes 7 and 10. Conclusion.—These results indicated that although no single numeric chromosomal abnormality could be assigned as a predictor of HPIN progression to carcinoma, the overall level of numeric chromosomal abnormalities shows a trend of elevation in HPIN patients whose condition subsequently progressed to carcinoma.

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Fowler, Nathan H., Ranjana H. Advani, Jeff Sharman, Sonali M. Smith, Jesse McGreivy, Lori Kunkel, Vina Troung, Cathy Zhou y Thomas E. Boyd. "The Bruton's Tyrosine Kinase Inhibitor Ibrutinib (PCI-32765) Is Active and Tolerated in Relapsed Follicular Lymphoma". Blood 120, n.º 21 (16 de noviembre de 2012): 156. http://dx.doi.org/10.1182/blood.v120.21.156.156.

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Abstract Abstract 156 Background Bruton's tyrosine kinase (BTK) is a central mediator of B-cell receptor (BCR) signaling and is essential for normal B-cell development. Subtypes of non-Hodgkins lymphoma (NHL) may be dependent on chronic activation of the BCR pathway and primary follicular lymphoma (FL) cells have been found to maintain enhanced signaling when compared to normal B-cells (Irish JM, et al. Blood 2006; 108: 3135). Ibrutinib is an orally administered, covalently-bound inhibitor of BTK which induces apoptosis and inhibits cellular migration and adhesion in malignant B-cells. Based on promising preclinical data in B-cell malignancies, a phase I study was conducted to test the safety, tolerability, pharmacokinetics, and pharmacodynamics of ibrutinib in relapsed NHL. We report the long-term tolerability and sustained activity of ibrutinib in FL patients in this study with extended follow-up. Methods Adult patients with relapsed or refractory B-cell lymphoma were eligible for trial entry and 16 patients with FL were enrolled in this Phase I study. Ibrutinib was administered orally with dose escalation according to protocol-defined dose-limiting toxicities (DLT) to define a maximum tolerated dose (MTD) or until 3 dose levels above attainment of full BTK occupancy. A 28-day on/7-day off (intermittent) schedule was evaluated in 5 cohorts (1.25–12.5 mg/kg PO qd) and a once daily oral dose (without a drug holiday) in 2 cohorts (8.3 mg/kg and 560-mg fixed dose). Patients were evaluable for safety if they received study drug. Efficacy was evaluated in all patients who received 2.5 mg/kg or higher (which achieves full BTK occupancy) and had one on-study imaging assessment. Efficacy was also analyzed at higher doses to determine if there was improved efficacy. Responses were assessed every 2 months using the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Results Median age 60 (41–71), equal numbers of males and females, median time from diagnosis 54 months (19–186), median number of prior therapies 3 (1–5) including: stem cell transplantation (6%), alkylators (88%), anthracyclines (56%), nucleoside analogs (19%), and rituximab (100%). FLIPI scores at baseline: low risk = 19%, intermediate risk = 37%, high risk = 44%. Treatment-emergent AEs occurring in ≥ 25% included: diarrhea (50%), fatigue (44%), nausea (38%), cough (31%) and myalgia (25%). Observed grade 3 AEs included: anemia, anxiety, hypersensitivity, hypokalemia, hypophosphatemia, decreased neutrophil count, non-cardiac chest pain, pancytopenia, pneumonia and vomiting (one event each). A Grade 4 hypokalemia occurred and was considered to be related to study drug by the investigator. One case of myelodysplastic syndrome occurred 29 days after the last dose of ibrutinib in a patient with pre-existing anemia and multiple lines of prior treatment and was considered to be unrelated by the investigator. One patient in the 2.5 mg/kg/day intermittent cohort experienced DLTs of grade 2 neutropenia resulting in the ibrutinib dose being held > 7 days and a grade 4 hypokalemia. One patient in the 8.3 mg/kg/day intermittent cohort experienced a Grade 3 hypersensitivity reaction. No DLTs were observed in the 12.5 mg/kg/day cohort and the MTD was not reached. In the 16 patients with FL, 11 patients received ibrutinib at 2.5 mg/kg or higher and were evaluable for efficacy (2 patients at 2.5 mg/kg, 1 at 5 mg/kg, 3 at 8.3 mg/kg intermittent, 3 at 12.5 mg/kg, 2 at 8.3 mg/kg continuous dosing). Median time on ibrutinib was 7 months (0–29). Overall response rate (ORR) 54.5% (3 CRs, 3 PRs), duration of response (DOR) 12.3 months, median PFS 13.4 months. In the 9 patients who received ibrutinib at 5 mg/kg or higher, the median time on ibrutinib, ORR and DOR were similar to the efficacy in the 11 patients. However, there was a slight trend toward improved PFS of 19.6 months; 2 patients are still responding to ibrutinib at 25 and 29 months. Conclusions The BTK inhibitor ibrutinib (PCI-32765) is well tolerated and active in patients with relapsed FL. Based upon drug occupancy and clinical responses, a dose of 5 mg/kg/day or above is recommended for phase II studies. Extended dosing did not appear to increase toxicity and response rates improved with continued treatment in some patients. Phase II studies with ibrutinib in FL are planned. Disclosures: Advani: Pharmacyclics, Inc: Research Funding. Sharman:Celgene: Consultancy; Pharmacyclics: Honoraria; Calistoga: Honoraria; Portola pharmaceuticals: Consultancy. McGreivy:pharmacyclics: Employment. Kunkel:Pharmacyclics: Employment, Equity Ownership. Troung:Pharmacyclics, Inc: Employment, Equity Ownership. Zhou:Pharmacyclics, Inc.: Employment, Equity Ownership.

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48

Sullivan, M. P. y I. Ramirez. "Curability of Burkitt's lymphoma with high-dose cyclophosphamide-high-dose methotrexate therapy and intrathecal chemoprophylaxis." Journal of Clinical Oncology 3, n.º 5 (mayo de 1985): 627–36. http://dx.doi.org/10.1200/jco.1985.3.5.627.

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Twenty-four children with Burkitt's lymphoma were treated beginning May 1976 with a regimen alternating high doses of cyclophosphamide and methotrexate in induction and consolidation; only high doses of methotrexate were used in the maintenance phase. Throughout therapy, which was planned for 54 weeks, intrathecal chemoprophylaxis using methotrexate, cytosine arabinoside, and hydrocortisone was coordinated with the high-dose methotrexate infusion therapy to provide CNS chemoprophylaxis that maintained therapeutic methotrexate spinal fluid levels (greater than 10(-6) mol/L) for approximately 60 hours. Twenty-two (92%) of the 24 children attained complete remission; two (8.3%) patients attained only partial remission, failing therapy. Two children died of infection while in complete remission; two children relapsed on therapy. Actual survival is 75%; the median follow-up time is 38+ months (range, 1 1/2+ to 84+ months). Relapses correlated with Murphy disease stage as follows: stage I--0/3, stage II--2/7, stage III--2/10, and stage IV--0/2. Serious side effects and toxicities of chemotherapy occurred in ten patients (metabolic disturbances after rapid tumor lysis, two; infectious and/or febrile episodes following cyclophosphamide therapy, three; methotrexate side effects, four; and complications of intrathecal therapy, one). Results of this therapy are similar to those of the best regimens that have been reported. Treatment has been adapted for use in Burkitt's lymphoma by the Pediatric Oncology Group; the responsiveness of other B cell lymphomas of childhood to this treatment is also being determined.

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49

Abrisqueta, Pau, Francesc Bosch, Marta Aymerich, Eva Gine, Carol Moreno, Maria Rozman, Neus Villamor, Elias Campo, Ciril Rozman y Emili Montserrat. "Changes in the Natural History, Treatment Modalities, and Survival Patterns in Patients with Chronic Lymphocytic Leukemia (CLL) from 1980 to 2008. The Hospital Clinic of Barcelona Experience". Blood 112, n.º 11 (16 de noviembre de 2008): 48. http://dx.doi.org/10.1182/blood.v112.11.48.48.

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Abstract Whether recent advances in the understanding and treatment of CLL are changing referral patterns of patients with this disease to specialized centers and their outcome is largely unknown. We analyzed demographics, disease characteristics, treatments administered, and survival over a period of 28 years in a series of 900 patients with CLL separated in three different cohorts based on the year of referral (table). As shown in the table, one of the main differences observed over the years relies on the stage of the disease, with most patients being currently seen in early phase of the disease, reflecting an earlier diagnosis because of analyses performed for routine reasons. In contrast, no differences were observed in patients’ age over the years, in agreement with the stable incidence of CLL in different age groups (SEER). No differences were detected in the proportion of patients developing autoimmune cytopenias, Richter’s syndrome or second neoplasias (data not shown). Not unexpectedly, since 1990 most patients receive purine analogs-based therapies. Importantly, the increasing proportion of patients who remain alive in each time period not only reflects an earlier diagnosis but also improvement in clinical management. Thus, median survivals of patients < 65 with Binet B or C disease are 3.9 yrs (1980–1989), 7.5 yrs (1990–1999) and not reached (2000 onwards), and the proportion of patients alive at 5 years in the same periods of time are 43%, 63% and 72% (figure). Unfortunately survival of patients > 65 yrs has not improved (median survival around 5.5 years across the three groups). Also, survival of patients in early stage (Binet A) has remained basically unchanged. From this large, single-institution study it can be concluded that the outcome of patients with CLL has been steadily improving since 1980. Nevertheless, the most significant progress has been made in younger patients with advanced disease, which constitute a small proportion of subjects with CLL. Besides to improving the outcome of these patients, future efforts should be aimed at prolonging survival of all patients, irrespectively of their age, and seeking the cure for the disease. 1980–1989 1990–1999 > 2000 P Number 254 388 258 Age (yrs). 67 (24–88) 66 (28–96) 67 (34–94) NS < 65 yrs (%) 43 46 45 > 65 yrs (%) 57 54 55 Males (%) 55 55 60 NS Binet A (%) 65 75 85 <0.001 Binet B (%) 22 16 10 Binet C (%) 13 9 5 Blood lymphocyte count (per μL) 46 (37–54) 30 (24–33) 19 (16–22) <0.001 Hb (g/dL) 14 (13–15) 14 (13–15) 15 (14–16) NS Platelets (per μL) 190 (181–199) 183 (177–190) 202 (194–211) 0.002 LDH increased (%) 22 12 9 <0.001 ECOG > 2 (%) 1.2 1.9 0 NS Treatment No treated (%) 59 37 60 <0.001 No PA (%) 84 44 26 <0.001 PA (%) 10 19 11 PA + other cytotoxics (%) 5 34 33 Rit.+ PA in comb. (%) 1 3 30 Alive (%) 21 37 81 Alive at 5-yrs (%) 65 (59–71) 70 (65–75) 77 (70–84) Overall median s. (yrs) 8.3 (7–10) 8.3 (8–9) > 8 NS PA = Purine analogs; Rit. = Rituximab

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50

Rodríguez-Abreu, Delvys, Maximillian Hochmair, Byoung Chul Cho, Tibor Csőszi, Talia Shentzer Kutiel, Veronika Müller, Myung-Ju Ahn et al. "Abstract CT253: Results from KEYNOTE-B99: Phase 2 study of first-line (1L) pembrolizumab (pembro) plus investigational agents and chemotherapy (chemo) for extensive-stage small-cell lung cancer (ES-SCLC)". Cancer Research 84, n.º 7_Supplement (5 de abril de 2024): CT253. http://dx.doi.org/10.1158/1538-7445.am2024-ct253.

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Abstract Background: ES-SCLC is an aggressive cancer with substantial mortality. Current 1L treatments include anti-PD-(L)1 + etoposide-platinum chemo (EP), but with minimal improvements in OS vs chemo. In the phase 3 KEYNOTE-604 study, pembro + EP significantly improved PFS (P = 0.0023) but not OS vs placebo + EP; ORR was also improved (71% vs 62%). We present data from the phase 2 KEYNOTE-B99 study (NCT04924101) of 1L pembro + investigational agents (MK-4830, anti-ILT4; boserolimab, anti-CD27; or lenvatinib), and EP for ES-SCLC. Methods: In this open-label platform study, patients (pts) were aged ≥18 y with previously untreated histologically or cytologically confirmed stage IV ES-SCLC (per AJCC v8) and ECOG PS 0 or 1. Pts were randomized 1:1:1 to receive MK-4830 800 mg Q3W (35 cycles; arm A), boserolimab 30 mg Q6W (18 cycles; arm B), or lenvatinib 8 mg (induction)/20 mg (maintenance) QD (arm C). All pts received pembro 200 mg Q3W (35 cycles) + etoposide 100 mg/m2 Q3W and cisplatin 75 mg/m2 Q3W or carboplatin AUC 5 mg/mL/min Q3W (4 cycles). Primary endpoints were ORR and PFS at 6 mo, both assessed per RECIST v1.1 by BICR. Secondary endpoints included DOR, PFS, OS, and safety. Results: 122 pts received ≥1 dose of study treatment (arm A, 43; B, 41; C, 38). At data cutoff (Sep 15, 2023), median follow-up was 14.1 (range, 6.1-25.7) mo. ORR was 65%, 71%, and 74% in arms A, B, and C, respectively; median DOR was 6.8, 4.7, and 7.1 mo. 6-mo PFS rates were 45%, 38%, and 54%, respectively (Table). AEs (any cause) occurred in 98% of pts in arm A and all pts in arms B and C; most commonly neutropenia and anemia. Serious AEs occurred in 30%, 37%, and 55%; grade ≥3 AEs in 86%, 83%, and 87% of pts; and grade 5 AEs in 5%, 7%, and 21%, respectively. Conclusions: 1L ES-SCLC treatment with pembro + EP and MK-4830, boserolimab, or lenvatinib was associated with similar antitumor activity as in KEYNOTE-604 with pembro + EP. No new safety signals were identified. TABLE 1. NAND Group A MK-4830 + Pembro + EP(n = 43) Group B boserolimab + Pembro + EP(n = 41) Group C Lenvatinib + Pembro + EP(n = 38) ORR (95% CI), % 65.1 (49.1-79.0) 70.7 (54.5-83.9) 73.7 (56.9-86.6) Median DOR (range), mo 6.8 (2.4-13.9) 4.7 (1.4+ to 16.4+) 7.1 (1.8 to 18.4+) PFS - 6-mo PFS rate (95% CI), % 45.2 (29.9-59.4) 37.8 (22.7-52.7) 54.2 (35.8-69.4) - Median PFS (95% CI), mo 5.5 (4.2-8.3) 5.5 (4.0-6.7) 7.2 (5.4-NR) Median OS (95% CI), mo 15.5 (8.3-NR) NR (13.2-NR) 15.8 (7.2-NR) ‘+’, no PD at the time of last disease assessment. NR, not reached. Citation Format: Delvys Rodríguez-Abreu, Maximillian Hochmair, Byoung Chul Cho, Tibor Csőszi, Talia Shentzer Kutiel, Veronika Müller, Myung-Ju Ahn, Dariusz Kowalski, Michele Maio, Vladimir Moiseyenko, Alejandro Navarro, Jianxin Niu, Andrea S. Fung, Carolin Lips, Heng Zhou, Bin Zhao, Humberto Lara-Guerra, Nir Peled. Results from KEYNOTE-B99: Phase 2 study of first-line (1L) pembrolizumab (pembro) plus investigational agents and chemotherapy (chemo) for extensive-stage small-cell lung cancer (ES-SCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT253.

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