Hooversmidt0493

In contrast, in both HH mouse models and HH patients, the lack of hepcidin expression protects neutrophils from toxic iron accumulation. Moreover, systemic iron overload correlated with a surprising neutrophil priming and resulted in a more powerful oxidative burst. Indeed, important factors in neutrophil priming and activation, such as tumor necrosis factor α (TNF-α), VCAM-1, and ICAM-1 are increased in the plasma of HH patients and are associated with an increase in HH neutrophil phagocytosis capacity and a decrease in L-selectin surface expression. This is the first study to characterize neutrophil iron homeostasis and associated functions in patients with HH.Transfusion-related acute lung injury (TRALI) remains a leading cause of transfusion-related deaths. In most cases, anti-leukocyte antibodies in the transfusion product trigger TRALI, but not all anti-leukocyte antibodies cause TRALI. It has been shown that the anti-major histocompatibility complex (MHC) class I antibody 34-1-2S (anti-H-2Kd) causes TRALI in BALB/c mice (MHC class I haplotype H-2Kd), whereas SF1.1.10 (anti-H-2Kd) does not. In C57BL/6 mice (MHC class I haplotype H-2Kb), TRALI only occurs when anti-MHC class I antibody AF6-88.5.5.3 (anti-H-2Kb) is administered together with a high dose of 34-1-2S. It remains unknown which specific antibody characteristics are responsible for eliciting TRALI. We therefore investigated several biological and structural features of 34-1-2S compared with other anti-MHC class I antibodies, which on their own do not cause TRALI SF1.1.10 and AF6-88.5.5.3. No substantial differences were observed between the TRALI-causing 34-1-2S and the TRALI-resistant SF1.1.10 regarding binding affinity to H-2Kd. Regarding binding affinity to H-2Kb, only AF6-88.5.5.3 potently bound to H-2Kb, whereas 34-1-2S exhibited weak but significant cross-reactivity. Furthermore, the binding affinity to FcγRs as well as the Fc glycan composition seemed to be similar for all antibodies. Similar Fc glycosylation profiles were also observed for human TRALI-causing donor anti-HLA antibodies compared with human anti-HLA antibodies from control donors. 34-1-2S, however, displayed superior complement activation capacity, which was fully Fc dependent and not significantly dependent on Fc glycosylation. We conclude that TRALI induction is not correlated with Fab- and Fc-binding affinities for antigen and FcγRs, respectively, nor with the composition of Fc glycans; but increased Fc-mediated complement activation is correlated with TRALI induction.In 2017, an updated European LeukemiaNet (ELN) risk classification was published allocating patients with acute myeloid leukemia (AML) to 3 risk groups on the basis of certain cytogenetic and molecular aberrations. To date, studies of the prognostic significance of the ELN2017 risk classification in the context of an allogeneic hematopoietic stem cell transplantation (HSCT) are lacking. We performed risk stratification according to the ELN2017 classification in 234 patients with AML who underwent allogeneic HSCT as a consolidation therapy. In our cohort, the risk of 39.7% of the patients was classified as favorable, that of 12.8% as intermediate, and that of 47.4% as adverse. In the context of allogeneic HSCT, the assignment to the 3 ELN2017 risk groups retained its prognostic significance, with patients with favorable risk having the best prognosis and those with adverse risk having the worst one. Subgroup analyses showed that patients with a monosomal karyotype or TP53 mutation had considerably increased relapse rates, even in the adverse-risk group. When we analyzed the impact of digital droplet PCR-based measurable residual disease (MRD) before allogeneic HSCT, MRD+ patients had impaired prognoses, with cumulative incidence of relapse and overall survival comparable to those of patients classified as having an ELN2017 adverse genetic risk. This study is the first to demonstrate that the ELN2017 classification distinguishes the 3 risk groups with significantly distinct prognoses, even after allogeneic HSCT, and emphasizes the dismal prognosis of patients with AML with TP53 mutations, monosomal karyotype, or MRD positivity after allogeneic HSCT.Because of high relapse rates with rituximab combinations, there is an unmet need for new therapeutic agents for treatment of indolent B-cell non-Hodgkin lymphoma (iNHL) or follicular lymphoma (FL). In previous trials, ofatumumab in combination with chemotherapy showed good results in relapsed/refractory FL pretreated with rituximab. This phase 3 trial evaluated the efficacy and safety of single-agent ofatumumab vs single-agent rituximab in rituximab-sensitive relapsed FL that relapsed at least 6 months after completing the last prior treatment with single-agent rituximab or a rituximab-containing regimen. Patients were randomized 11 to receive either ofatumumab (1000 mg) or rituximab (375 mg/m2) every week for 4 weeks for the induction phase, followed by once every 2 months for 4 additional doses. The primary endpoint, progression-free survival (PFS) and secondary endpoints, overall response rate (ORR) and overall survival (OS), were evaluated. Overall, 438 patients were assigned to receive ofatumumab (n = 219) and rituximab (n = 219). Baseline characteristics were similar in both arms. The independent review committee assessed whether median PFS was shorter in the ofatumumab arm than in the rituximab arm (16.33 vs 21.29 months), with no significant difference (hazard ratio, 1.15; 95% confidence interval, 0.89-1.49; P = .29) and also showed a lower ORR (50%) compared with the rituximab arm (66%). At the time of analysis, data were not matured for OS results. The number of grade >3 adverse events was higher in the ofatumumab arm (37%) than the rituximab arm (28%). selleck inhibitor Ofatumumab showed no superiority over rituximab in patients with FL who had relapsed after a rituximab-containing therapy. This study was registered at www.clinicaltrials.gov as #NCT01200589.

Children who sustain moderate to large surface area burns present in a hypermetabolic state with increased caloric and protein requirements. A policy was implemented at our institution in 2017 to initiate enteral nutrition (EN) in pediatric burn patients within four hours of admission. We hypothesize that early EN (initiated within 4 hours of admission) is more beneficial than late EN (initiated ≥ 4 hours from admission) for pediatric burn patients and is associated with decreased rates of pneumonia, increased calorie and protein intake, fewer feeding complications, a shorter Intensive Care Unit (ICU) length of stay (LOS), and a reduced hospital LOS.

Children who sustained a total body surface area (TBSA) burn injury ≥ 10% between 2011 and 2018 were identified in a prospectively maintained burn registry at Children's Hospital Colorado. Patients were stratified into two groups for comparison early EN and late EN.

We identified 132 pediatric burn patients who met inclusion criteria, and most (60%) were male.