Westermannboyle9667
Interestingly, we detected the deletion in both the patient and her mother. A sister of the mother, who carried the same germline PIGB mutation but without this microdeletion involving TM2D3 and TARSL2, did not have a PNH clone or CN-LOH. In conclusion, we describe PNH caused by CN-LOH of a germline heterozygous PIGB mutation in a patient and her mother and hypothesize that the 70-kbp microdeletion may have contributed to the PNH clone in both.There are limited data regarding the combined value of the pretransplant Deauville score (DS) from a positron emission tomography scan and clinical risk factors in patients with relapsed/refractory aggressive non-Hodgkin lymphoma (NHL). We performed a retrospective analysis to assess the prognostic role of pretransplant DS in patients with relapsed/refractory aggressive NHL who underwent salvage chemotherapy and autologous stem cell transplantation (ASCT). We identified 174 eligible patients between January 2013 and March 2019. In multivariable analysis, pretransplant DS, B symptoms, and secondary International Prognostic Index (sIPI) were independent risk factors for event-free survival (EFS). These variables were used to derive an integrated risk score that categorized 166 patients with available information for all risk factors into 3 groups low (n = 92; 55.4%), intermediate (n = 48; 28.9%), and high (n = 26; 15.7%). The new prognostic index showed a strong association with EFS (low-risk vs intermediate-risk hazard ratio [HR], 3.94; 95% confidence interval [CI], 2.16-7.17; P less then .001; low-risk vs high-risk HR, 10.83; 95% CI, 5.81-20.19; P less then .001) and outperformed models based on clinical risk factors or DS alone. These results were validated in 60 patients from an independent external cohort (low-risk vs intermediate-risk HR, 4.04; 95% CI, 1.51-10.82; P = .005; low-risk vs high-risk HR, 10.49; 95% CI, 4.11-26.73; P less then .001). We propose and validate a new prognostic index that risk-stratifies patients undergoing salvage chemotherapy followed by ASCT, thereby identifying patients at high risk for posttransplant treatment failure.BK polyomavirus (BKPyV) infection is a major complication of hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT). Treatment options are limited, poorly effective, and have significant toxicities. Cellular therapy using T cells directed against BKPyV is an emerging therapy, and we report efficacy in controlling BKPyV-associated disease in highly immunocompromised patients. Virus-specific T cells (VSTs) against BKPyV were manufactured using either blood from the patient's stem cell donor (donor-derived VSTs) or from unrelated donors (third-party VSTs). VSTs were used to treat BKPyV in 38 HSCT recipients and 3 SOT recipients between June 2017 and December 2019. Overall response rate was 86% in patients treated for BK viremia, 100% in patients treated for hemorrhagic cystitis, and 87% in patients treated for both BK viremia and hemorrhagic cystitis. No infusional toxicity, de novo graft-versus-host disease, or rejection of the organ occurred attributable to the VST infusion. BKPyV-specific immune responses were demonstrated by interferon-γ production by peripheral blood mononuclear cells postinfusion in response to BKPyV antigens. VSTs are a safe and potentially effective strategy to treat BKPyV and associated symptoms in recipients of HSCT and SOT. Cellular therapy should be considered for all patients with BKPyV and underlying immune suppression at risk of complications. This trial was registered at www.clinicaltrials.gov as #NCT02532452.The prevalence of deoxynivalenol (DON) is a concern for swine producers, and although there has been extensive research into the effects of DON in pigs, focus has been in young pigs and/or in short-term studies. The objective of the study was to determine the effect of long-term exposure to DON-contaminated diets in finisher pigs. A total of 200 pigs (76.6 ± 3.9 kg initial weight) were group housed (five pigs per pen; n = 10 pens/treatment) in a 6-wk trial. Pigs were fed a wheat-barley-soybean meal-based control (CONT) diet with no DON or the basal diet in which clean wheat was replaced by DON-contaminated wheat and wheat screenings to provide DON content of 1, 3, or 5 ppm (DON1, DON3, and DON5, respectively). Individual BW and pen feed intake were recorded weekly to calculate average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (GF). Blood was collected on days 0, 14, and 43 and analyzed for indicators of liver and kidney health. Nitrogen (N)-balance was conducted immediately following the growth performance period to determine the effect of DON on nutrient utilization. Blood and urine samples collected during N balance were analyzed for DON content. selleck kinase inhibitor Feeding DON reduced (P 1 ppm DON.
The 2017 hypertension guidelines lowered systolic blood pressure goals to <130mm Hg and re-defined resistant hypertension. We investigated if these changes alter the cardiovascular benefits demonstrated by combining a calcium channel blocker, rather than hydrochlorthiazide, with an angiotensin converting enzyme inhibitor.
In this post hoc analysis of the ACCOMPLISH trial (n=11,506), we compared the primary composite outcome (cardiovascular death, myocardial infarction, stroke, hospitalization for angina, resuscitation after sudden cardiac death, and coronary revascularization) between the 2 combination-treatment limbs in patients achieving a systolic blood pressure ≤130mm Hg and those with "apparent resistant hypertension" (prescribed ≥4 antihypertensive medications).
Among study patients, 5221 (45.4%) achieved a systolic blood pressure ≤130mm Hg. There were fewer primary endpoints in the amlodipine/benazepril (9.2%) versus the hydrochlorothiazide/benazepril (10.9%) limb (adjusted hazard ratio 0.83; 95% confidence interval, 0.70 to 0.99). There were also fewer primary endpoints in the amlodipine/benazepril (12.8%) versus the hydrochlorothiazide/benazepril (15.2%) limb (n=4451, 38.7%) among patients with apparent resistant hypertension (hazard ratio 0.81, 95% confidence interval, 0.70-0.95). Most individual outcomes did not significantly differ between treatment limbs, given reduced power, but many trended to favor amlodipine/benazepril.
Combination therapy adding a calcium channel blocker, rather than hydrochlorothiazide, to an angiotensin converting enzyme inhibitor was more effective in preventing composite cardiovascular events even in hypertensive patients achieving aggressive systolic blood pressure targets as well as in those with apparent resistant hypertension. Our findings add support that most patients, including those following contemporary clinical guidelines, will benefit from this combination.
ClinicalTrials.gov, NCT00170950.
ClinicalTrials.gov, NCT00170950.