Hardening of Additive Manufactured 316L Stainless Steel by Using Bimodal Powder Containing Nanoscale Fraction

The particle size distribution significantly affects the material properties of the additively manufactured parts. In this work, the influence of bimodal powder containing nano- and micro-scale particles on microstructure and materials properties is studied. Moreover, to study the effect of the protective atmosphere, the test samples were additively manufactured from 316L stainless steel powder in argon and nitrogen. The samples fabricated from the bimodal powder demonstrate a finer subgrain structure, regardless of protective atmospheres and an increase in the Vickers microhardness, which is in accordance with the Hall-Petch relation. The porosity analysis revealed the deterioration in the quality of as-built parts due to the poor powder flowability. The surface roughness of fabricated samples was the same regardless of the powder feedstock materials used and protective atmospheres. The results suggest that the improvement of mechanical properties is achieved by adding a nano-dispersed fraction, which dramatically increases the total surface area, thereby contributing to the nitrogen absorption by the material.     

Preoperative versus intraoperative diagnosis of hiatal hernia in bariatric population

BackgroundHiatal hernia is frequently encountered intraoperatively during bariatric surgery. There is scarce research pertaining to the diagnostic accuracy of a preoperative diagnostic modality in comparison to intraoperative diagnosis, along with patient characteristics and related factors contributing to hiatal hernia.ObjectiveTo identify the prevalence and associations of hiatal hernia in the bariatric patient population, we compared the diagnostic accuracy of upper gastrointestinal series and esophagogastroduodenoscopy with the intraoperative findings across various patient characteristics.SettingMetabolic and Bariatric Surgery Accreditation and Quality Improvement Program, Teaching Hospital, New York, USA.MethodsRetrospective study of patients from 2015 to 2018 who met National Institutes of Health criteria for bariatric surgery.ResultsThere were 1094 patients included (135 males, 959 females), with an age range of 18 to 74 years. The diagnostic accuracy was determined by a sensitivity of 64.71% (95% confidence interval [CI] .55–.70), specificity of 74.38% (95% CI .71–.70), positive predictive value of 29.86% (95% CI .24–.30), negative predictive value of 92.59% (95%CI .89–90), likelihood ratio of 2.526, and P value < .0001 for esophagogastroduodenoscopy; a sensitivity of 14.02% (95% CI .08–0), specificity of 98.23% (95% CI .96–.90), positive predictive value of 71.43% (95% CI .50–.80), negative predictive value of 78.35% (95% CI .74–.80), likelihood ratio 7.921, and P value < .0001 were used for upper gastrointestinal series. Hiatal hernia with age <60 years was 17.09% versus 48.44% at >60 years (P < .0001). Hiatal hernia incidence was 17% in Hispanics, 22.5% in Caucasians, and 23.10% in blacks.ConclusionThe prevalence of hiatal hernia is 18.92%. There is strong association between hiatal hernia and age and ethnicity and no association based on sex and body mass index. The diagnostic accuracy of upper gastrointestinal series is very low compared with that of esophagogastroduodenoscopy for hiatal hernia. Preoperative diagnosis of hiatal hernia in the bariatric population is not required based on our study. Not only does it lessen the economic burden, patient wait time, and discomfort of an additional study, but preoperative diagnosis does not change, alter, or aid in the intraoperative management of hiatal hernia considering the suboptimal accuracy of preoperative diagnostics, thus deeming them unwarranted.     

Proposed rituximab biosimilar BCD-020 versus reference rituximab for treatment of patients with indolent non-Hodgkin lymphomas: An international multicenter randomized trial

BCD-020 is a proposed rituximab biosimilar, which has shown high similarity to rituximab in quality and nonclinical studies in vitro and in vivo. International multicenter clinical trial was conducted to compare efficacy and safety of BCD-020 and reference rituximab in adult (older than 18 years) patients with indolent lymphomas (follicular lymphoma grade 1-2, splenic marginal zone lymphoma, and nodal marginal zone lymphoma). Pharmacokinetics, pharmacodynamics, and immunogenicity were also studied. Patients with no previous biologic treatment for lymphoma were randomly assigned 1:1 to receive BCD-020 or comparator 375 mg/m² for 4 weeks. Primary study outcome was day 50 overall response rate defined as complete or partial remission. Equivalence range was −20% to 20% for 95% CI for overall response rates difference. Secondary outcomes included adverse events, pharmacokinetics, pharmacodynamics, and immunogenicity. One hundred seventy-four patients were enrolled, 89 in BCD-020 arm and 85 in comparator arm. The overall response rate was 44.71% in BCD-020 arm and 41.89% in comparator arm. Limits of 95% confidence interval (CI) for difference of overall response rates between arms were (−12.62%-18.24%) showing equivalent efficacy. Sixty-one (68.54%) and 59 (69.41%) patients had at least one adverse event in BCD-020 arm or comparator arm, respectively. No unexpected adverse reactions were reported. Antidrug antibodies with no neutralizing activity were detected in two patients in comparator arm on day 14 further declining below detection threshold. Rituximab concentrations had equivalent pattern after intravenous administration of both drugs. Both drugs caused depletion of B-cells without significant influence on other blood cell lineages. In this study, we showed equivalent efficacy of BCD-020 and reference rituximab when used in patients with CD20-positive indolent lymphomas. We also confirmed pharmacokinetic equivalence of BCD-020 and reference rituximab. Safety profile, pharmacodynamics, and immunogenicity of BCD-020 were also comparable with those of reference rituximab.     

Ticagrelor Versus Clopidogrel in Patients With STEMI Treated With Fibrinolysis: TREAT Trial

BackgroundThe efficacy of ticagrelor in the long-term post–ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain.ObjectivesThe purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy.MethodsThis international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months.ResultsThe combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups.ConclusionAmong patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088)     

Dynamic Graft-versus-Host Disease-Free,Relapse-Free Survival: Multistate Modeling of the Morbidity and Mortality of Allotransplantation

Graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) represents complete, ideal recovery after allogeneic hematopoietic cell transplantation (HCT). However, as originally proposed, this composite endpoint does not account for the possibility that HCT complications may improve after treatment. To more accurately estimate survival with response to GVHD and relapse after HCT, we developed a dynamic multistate GRFS (dGRFS) model with outcomes data from 949 patients undergoing their first allogeneic HCT for hematologic malignancy at the University of Minnesota. Because some patients were successfully treated for GVHD and relapse, dGRFS was higher than the originally defined time-to-event GRFS at 1 year (37.0 versus 27.6%) through 4 years (37.4% versus 22.2%). Mean survival without failure events was .52 years (95% confidence interval, .45 to .58 year) greater in dGRFS compared with the originally defined GRFS. Patient age (P< .001), disease risk (P < .001), conditioning intensity (P = .007), and donor type (P = .003) all significantly influenced dGRFS. The multistate model of dGRFS closely estimates the continuing and prevalent severe morbidity and mortality of allogeneic HCT. To serve the greater HCT community in more accurately modeling recovery from transplantation, we provide our R code for determination of dGRFS with annotations in Supplementary Materials.     

Reduced-Intensity Conditioning Followed by Related and Unrelated Allografts for Hematologic Malignancies: Expanded Analysis and Long-Term Follow-Up

Reduced-intensity conditioning (RIC) extends the curative potential of allogeneic hematopoietic cell transplantation (HCT) to patients with hematologic malignancies unable to withstand myeloablative conditioning. We prospectively analyzed the outcomes of 292 consecutive patients, median age 58 years (range, 19 to 75) with hematologic malignancies treated with a uniform RIC regimen of cyclophosphamide, fludarabine, and total body irradiation (200 cGy) with or without antithymocyte globulin and cyclosporine and mycophenolate mofetil graft-versus-host disease (GVHD) prophylaxis followed by allogeneic HCT at the University of Minnesota from 2002 to 6. Probability of 5-year overall survival was 78% for patients with indolent non-Hodgkin lymphoma, 53% for chronic myelogenous leukemia, 55% for Hodgkin lymphoma, 40% for acute myelogenous leukemia, 37% for myelodysplastic syndrome, 29% for myeloma, and 14% for myeloproliferative neoplasms. Corresponding outcomes for relapse were 0%, 13%, 53%, 37%, 39%, 75%, and 29%, respectively. Disease risk index (DRI) predicted both survival and relapse with superior survival (64%) and lowest relapse (16%) in those with low risk score compared with 24% survival and 57% relapse in those with high/very-high risk scores. Recipient cytomegalovirus (CMV)-positive serostatus was protective from relapse with the lowest rates in those also receiving a CMV-positive donor graft (29%). The cumulative incidence of 2-year nonrelapse mortality was 26% and was lowest in those receiving a matched sibling graft at 21%, with low (21%) or intermediate (18%) HCT-specific comorbidity index, and was similar across age groups. The incidence of grades II to IV acute GVHD was 43% and grades III to IV 27%; the highest rates were found in those receiving an unrelated donor (URD) peripheral blood stem cell (PBSC) graft, at 50%. Chronic GVHD at 1 year was 36%.Future approaches incorporating alternative GVHD prophylaxis, particularly for URD PBSC grafts, and targeted post-transplant antineoplastic therapies for those with high DRI are indicated to improve these outcomes.