Fatal myocardial microabscesses caused by methicillin-resistant Staphylococcus aureus in a burn patient

AbstractBacteremia- or sepsis-associated myocardial abscess is often an incidental postmortem diagnosis in patients who die of overwhelming septicemia. Myocardial abscess is more rarely the immediate cause of death as a consequence of abscess rupture or the cause of arrhythmia. We report a 66-year-old female who succumbed to sudden cardiac death with a hemodynamically stable methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, while in recovery after an accidental thermal burn. Autopsy revealed extensive myocardial abscesses and an abscess in the pineal gland. Myocardial microabscesses should be considered a rare cause of sudden cardiac death in patients with hemodynamically stable MRSA bacteremia

IL10 and IL10 receptor gene variation and outcomes after unrelated and related hematopoietic cell transplantation.

BACKGROUND: Results of a previous study with human leukocyte antigen (HLA)-identical siblings showed individual and synergistic associations of single nucleotide polymorphisms in the promoter region of the recipient's IL10 gene and the donor's IL10 receptor beta (IL-10RB) gene with development of grades III-IV acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation. METHODS: In this study of 936 patients who had unrelated donors, genotypes of single nucleotide polymorphisms in the IL10 gene and the IL-10RB gene were evaluated as correlates with outcomes after transplantation. RESULTS: We found no statistically significant associations of polymorphisms at positions -3575, -2763, -1082, and -592 of the IL10 gene or codon 238 of the IL10RB gene with severe acute GVHD, extensive chronic GVHD or nonrelapse mortality after hematopoietic cell transplantation. Among HLA-matched unrelated pairs, the patient's IL10/-592 genotype and donor's IL10RB/c238 genotype showed trends suggesting individual and combined associations with grades III-IV acute GVHD similar to those observed among patients with HLA-identical sibling donors. CONCLUSIONS: Although genetic variation in IL10 pathway affects risk of acute GVHD and non-relapse mortality in HLA-identical sibling transplants, the current results indicate that genetic variation in the IL10 pathway does not significant affect these outcomes in unrelated donor transplants suggesting that the strength of the alloimmune response in the latter exceeds the anti-inflammatory activity of IL10

Colorectal cancer in patients of advanced age is associated with increased incidence of BRAF p.V600E mutation and mismatch repair deficiency

IntroductionThe highest incidence of colorectal cancer (CRC) is in patients diagnosed at 80 years or older highlighting a need for understanding the clinical and molecular features of these tumors. Methods. In this retrospective cohort study, 544 CRCs underwent next generation sequencing and mismatch repair (MMR) evaluation. Molecular and clinical features were compared between 251 patients with traditional-onset CRC (50-69 years at diagnosis) and 60 with late-onset CRC (>80 years at diagnosis).ResultsLate-onset CRC showed a significantly higher rate of right-sided tumors (82% vs 35%), MMR deficiency (35% vs. 8%) and BRAF p.V600E mutations (35% vs. 8%) and a significantly lower rate of stage IV disease (15% vs 28%) and APC mutations (52% vs. 78%). Association of these features with advanced age was supported by stratifying patients into 6 age groups (<40, 40-49, 50-59, 60-69, 70-79 and >80 years). However, the age-related rise in MMR deficient (dMMR) CRC was only seen in the female patients with an incidence of 48% (vs. 10% in the male patient) in the >80y group. In addition, BRAF p.V600E was significantly enriched in MMR deficient CRC of advanced age (67% in late-onset CRC). Categorizing CRC by mutational profiling, late-onset CRC revealed a significantly higher rate of dMMR/BRAF+APC- (18% vs. 2.0%), dMMR/BRAF-APC- (8.3% vs. 1.2%) and MMR proficient (pMMR)/BRAF+APC- (12% vs. 4.0%) as compared to traditional-onset CRC.DiscussionIn summary, there was a higher rate of dMMR and BRAF p.V600E in late-onset CRC, independently or in combination. The higher incidence of dMMR in late-onset CRC in females is most likely predominantly driven by BRAF p.V600E induced hypermethylation. Prospective studies with treatment plans designed specifically for these older patients are warranted to improve their outcomes

Human T-Lymphotropic Virus Type Ii Infection in Vietnamese Thalassemic Patients

　　 Anti-human T-lymphotropic virus type I/II (HTLV-I/II) antibodies were screened by particle agglutination test in a total of 66 patients with thalassemia major who received multiple transfusion from paid donors at the Blood Transfusion Hematology Center of Ho Chi Minh City in South Vietnam. HTLV-II infection was confirmed in 6 patients (9.1 %) by Western blot analysis and/or polymerase chain reaction . Phylogenetic analysis revealed that long terminal repeat sequences of HTLV-II proviruses from 5 thalassemic patients in Vietnam belonged to the same phylogenetic subgroup of HTLV-IIb as those from intravenous drug abuses in North America and Europe. These data shed light on the route of introducing HTLV-II into Vietnam

Relation of an Interleukin-10 Promoter Polymorphism to Graft-Versus-Host Disease and Survival after Hematopoietic Cell Transplantation

BACKGROUND:Polymorphisms in cytokine genes can influence immune responses , inflammation, and tissue injury and may affect the outcome of hematopoietic stem-cell transplantation. METHODS:We analyzed single- nucleotide polymorphisms in the genes for interleukin-1(beta), interleukin -1-receptor antagonist, interleukin-6, interleukin-10 (IL10), and tumor necrosis factor (alpha) in 570 transplant recipients and their HLA- identical sibling donors. Genotypes were tested for an association with graft- versus-host disease (GVHD) by multivariable analysis. A second cohort of 423 transplant recipients was independently analyzed for the genotype associations identified in the first cohort. RESULTS:The recipient's IL10 promoter region genotype was significantly associated with the risk of acute GVHD in the first cohort. Analysis of all 993 transplant recipients showed that, as compared with the C/C genotype, the IL10 -592A/A genotype was associated with a decreased risk of grade III or IV acute GVHD (hazard ratio, 0.4; 95 percent confidence interval, 0.2 to 0.9; P=0.02) and death in remission (hazard ratio, 0.6; 95 percent confidence interval, 0.3 to 1.0; P=0.05). A haplotype analysis showed that the IL10 -592A allele was a specific marker for a promoter haplotype, T-C -A-T-A, defined by five polymorphisms at positions -3575, -2763, -1082, - 819, and -592, respectively. CONCLUSIONS:Among recipients of hematopoietic cells from an HLA-identical sibling, the IL10 -592A allele is a marker of a favorable outcome after transplantation