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Histone deacetylase inhibitors (HDACi) are active agents for peripheral T-cell lymphoma (PTCL). Anecdotally angioimmunoblastic T-cell lymphoma (AITL) appears to respond better than PTCL-not otherwise specified (NOS) to HDACi. The new World Health Organization classification shows that a subgroup of PTCL carries similarities in phenotype and gene expression profiling to AITL, comparable to T follicular helper (TFH) cells. The disease might behave similarly to AITL when treated with HDACi. We analyzed 127 patients with AITL or PTCL-NOS treated with HDACi at relapse as a single agent or in combination. We re-reviewed the pathology of all PTCL-NOS to identify the TFH phenotype. Patients received HDACi at relapse as a single agent in 97 cases (76%, 59 TFH, 38 non-TFH) or in combination in 30 cases (24%, 18 TFH, 12 non-TFH) including duvelisib, lenalidomide, lenalidomide plus carfilzomib, and pralatrexate. https://www.selleckchem.com/products/AZD2281(Olaparib).html Seven PTCL-NOS had TFH phenotype; 2 PTCL-NOS were reclassified as AITL. Overall response rate (ORR) was 56.5% (28.9% complete response [CR]) in TFH and 29.4% (19.6% CR) in non-TFH phenotype patients (P = .0035), with TFH phenotype being an independent predictor of ORR (P = .009). Sixteen patients sufficiently responded to HDACi or HDACi in combination with another agent to proceed directly to allogeneic transplantation; 1 of 16 responded to donor lymphocyte infusion (12 TFH, 4 non-TFH). Our results, although retrospective, support that HDACi, as a single agent or in combination, may have superior activity in TFH-PTCL compared with non-TFH PTCL. This differential efficacy could help inform subtype-specific therapy and guide interpretation of HDACi trials.Anticoagulant treatment of pediatric central venous catheter-related venous thromboembolism (CVC-VTE) has not been specifically evaluated. In EINSTEIN-Jr, 500 children with any VTE received rivaroxaban or standard anticoagulants. A predefined analysis of the CVC-VTE cohort was performed. Children with CVC-VTE (age, birth to 17 years) were administered rivaroxaban or standard anticoagulants during the 1-month (children less then 2 years) or 3-month (all other children) study period. Predefined outcomes were recurrent VTE, change in thrombotic burden on repeat imaging, and bleeding. Predictors for continuation of anticoagulant therapy beyond the study period were evaluated. One hundred twenty-six children with symptomatic (n = 76, 60%) or asymptomatic (n = 50, 40%) CVC-VTE received either rivaroxaban (n = 90) or standard anticoagulants (n = 36). There was no recurrent VTE (0%; 95% confidence interval [CI], 0.0%-2.8%). Three children had the principal safety outcome none had major bleeding and 3 children had clinically relevant nonmajor bleeding (2.4%; 95% CI, 0.7%-6.5%), all in the rivaroxaban arm. Complete or partial vein recanalization occurred in 57 (55%) and 38 (37%) of 103 evaluable children, respectively. Results were similar for symptomatic and asymptomatic CVC-VTE. Continuation of anticoagulant therapy beyond the study period occurred in 61 (48%) of children and was associated with residual VTE but only in children less then 2 years (odds ratio [OR], 20.9; P = .003) and continued CVC use (OR, 6.7; P = .002). Anticoagulant therapy appeared safe and efficacious and was associated with reduced clot burden in most children with symptomatic or asymptomatic CVC-VTE. Residual VTE and continued CVC use were associated with extended anticoagulation. This trial was registered at www.clinicaltrials.gov as #NCT02234843. In Integrated Community Case Management (iCCM), village health workers (VHW) assess and treat malaria, pneumonia and diarrhea using a clinical algorithm. Study objectives included 1) Compare VHWs' performance on case scenario exercises to record review data; 2) assess impact of formal education on performance in the case scenario exercises. 36 VHWs in Bugoye Subcounty, Uganda completed the case scenarios exercise, which included video case scenarios and brief oral case vignettes, between July 2017 and February 2018. We obtained clinical records for all iCCM encounters in the same time period. In the video case scenarios, 45% of mock patients received all correct management steps (including all recommended education), while 94% received all critical management steps. Based on the level of data available from record review, 74% of patients in the record review dataset received overall correct management compared to 94% in the video case scenarios. In the case scenarios, VHWs with primary school education performed similarly to those with some or all secondary school education. The case scenarios produced higher estimates of quality of care than record review. VHWs often omitted recommended health education topics in the case scenarios. Level of formal education did not appear to influence performance in the case scenarios. The case scenarios produced higher estimates of quality of care than record review. VHWs often omitted recommended health education topics in the case scenarios. Level of formal education did not appear to influence performance in the case scenarios.Stressors like metals or antibiotics can affect bacterial community permissiveness for plasmid uptake, but there is little knowledge about long-term effects of such stressors on the evolution of community permissiveness. We assessed the effect of more than 90 years of soil Cu contamination on bacterial community permissiveness (i.e. uptake ability) toward a gfp-tagged IncP-1 plasmid (pKJK5) introduced via an Escherichia coli donor. Plasmid transfer events from the donor to the recipient soil bacterial community were quantified and transconjugants were subsequently isolated by fluorescence activated cell sorting and identified by 16S rRNA gene amplicon sequencing. Transfer frequency of plasmid pKJK5 was reduced in bacterial communities extracted from highly Cu contaminated (4526 mg kg-1) soil compared to corresponding communities extracted from moderately (458 mg kg-1) Cu contaminated soil and a low Cu reference soil (15 mg kg-1). The taxonomic composition of the transconjugal pools showed remarkable similarities irrespective of the degree of soil Cu contamination and despite contrasting compositions of the extracted recipient communities and the original soil communities.
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