Citations

Abstract There are no studies directly comparing the efficacy of bendamustine with rituximab (BR) as induction therapy followed by maintenance rituximab (Rm) against rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) followed by Rm in previously untreated, older, transplant-ineligible patients with mantle cell lymphoma (MCL). The objective of this international study was to retrospectively compare the efficacy of these two treatment regimens by pooling and comparing a clinical trial cohort with a population-based cohort. 140 patients treated with R-CHOP and 112 patients treated with BR were evaluable for the analysis of the primary endpoint progression-free survival (PFS). Patients receiving R-CHOP had a more favorable risk profile. Median PFS for the R-CHOP group was 3.93 years (95% CI: 2.79–5.30) and for the BR group 2.88 years (95% CI: 1.84–4.61, p-value = 0.12). The Hazard ratio of PFS of R-CHOP vs. BR adjusted for MIPI score was 0.80 (95% CI: 0.57–1.13, p-value = 0.2) and adjusted for MIPI score, Ki67 and cytology was 0.85 (95% CI: 0.51–1.40, p-value = 0.52). These data indicate that there was no difference regarding the efficacy between R-CHOP + Rm and BR + Rm for previously untreated, older patients with MCL.

Introduction: Medical students experience high levels of stress, burnout, depression, suicidal ideation, and compassion fatigue. Mindfulness interventions in this population have demonstrated improvement in psychological outcomes. However, it is unclear if these improvements are maintained. Evaluation of changes in lifestyle behaviors may provide insight into factors that sustain improvements. Specific aims of this study were to (1) assess feasibility and acceptability of an innovative, virtual program involving experiential learning, social support, and motivational interviewing; and (2) evaluate preliminary healthy lifestyle behaviors and psychological outcomes from preprogram to postprogram and 4-week follow-up. Methods: We used a mixed-methods approach to investigate feasibility, acceptability, and effects of the virtual program using validated measures and open-ended questions. Participants were 20 first- and second-year medical students at one Midwestern US medical college who participated between October 2020 and December 2020. Participants were enrolled in one of two groups for the 8-week program via Webex. Participants completed surveys at preprogram, postprogram, and 4-week follow-up. They also completed weekly home practice assessments. Results: Nineteen of 20 participants completed the program (95% retention rate). All participants attended six or more sessions. Repeated measures analysis of variance revealed that participants had significant improvements in healthy lifestyle behaviors, burnout, self-compassion, and stress across time. Results were supported by qualitative themes of increased social support, wellness skills, and overall positive experiences. Conclusion: Findings suggest that the virtual program was feasible and acceptable to medical students, and improved healthy lifestyle behaviors and psychological outcomes that were maintained or increased at 4-week follow-up.

Background Vedolizumab is an anti-α4β7 integrin antibody used to treat moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD). This post hoc analysis of patient-reported outcomes (PROs) from the VISIBLE 1 (NCT02611830) and 2 (NCT02611817) phase 3 studies evaluated onset of treatment effect on patient-reported symptoms during 6-week vedolizumab induction. Methods Patient-reported stool frequency (SF) and rectal bleeding (RB) (UC Mayo score), and SF and abdominal pain (AP) in CD were collected via electronic diary from VISIBLE patients receiving one or more open-label intravenous (IV) vedolizumab induction doses (weeks 0 and 2). PRO data were analyzed using descriptive statistics. Results Data from 994 patients (UC 383, CD 611) showed mean ratings for all PROs declined consistently week-on-week from baseline through week 6, with early onset of improvement. By week 2, 22% of patients with UC reported RB improvement (≥1-point reduction in RB subscore, 7-day mean), rising to 45% by week 6. By week 6, 18% of patients with UC achieved SF improvement (SF subscore 0; 21% antitumor necrosis factor alpha [anti-TNFα] naive, 13% anti-TNFα experienced). SF improvement in patients with CD (reduction of ≥3 stools, 7-day mean) was achieved by 32% at week 6 (34% anti-TNFα naive, 30% anti-TNFα experienced). Fewer patients with CD reported severe/moderate AP at week 6 (5.1%/28.5%) than baseline (14.6%/61.5%). SF decline appeared greater and faster for anti-TNFα-naive vs. anti-TNFα-experienced patients (UC and CD). Conclusion Results indicate early onset of patient-reported UC and CD symptom improvement during vedolizumab IV induction in VISIBLE 1 and 2.

Abstract Background Alcohol consumption behaviors and alcohol use disorder risk and presentation differ by sex, and these complex traits are associated with blood concentrations of the steroid sex hormones, testosterone and estradiol, and their regulatory binding proteins, sex hormone binding globulin (SHBG) and albumin. Genetic variation is associated with alcohol consumption and alcohol use disorder, as well as levels of steroid sex hormones and their binding proteins. Methods To assess the contribution of genetic factors to previously described phenotypic associations between alcohol-use traits and sex-hormone levels, we estimated genetic correlations (rg) using summary statistics from prior published, large sample size genome-wide association studies (GWAS) of alcohol consumption, alcohol dependence, testosterone, estradiol, SHBG, and albumin. Results For alcohol consumption, we observed positive genetic correlation (i.e. genetic effects in the same direction) with total testosterone in males (rg = 0.084, p = 0.007) and trends toward positive genetic correlation with bioavailable testosterone (rg = 0.060, p = 0.084) and SHBG in males (rg = 0.056, p = 0.086) and with albumin in a sex-combined cohort (rg = 0.082, p = 0.015); however in females, we observed positive genetic correlation with SHBG (rg = 0.089, p = 0.004) and a trend toward negative genetic correlation (i.e. genetic effects in opposite directions) with bioavailable testosterone (rg = -0.064, p = 0.032). For alcohol dependence, we observed a trend toward negative genetic correlation with total testosterone in females (rg = -0.106, p = 0.024) and positive genetic correlation with BMI-adjusted SHBG in males (rg = 0.119, p = 0.017). Several of these genetic correlations differed between females and males and were not in the same direction as the corresponding phenotypic associations. Conclusions Findings suggest that shared genetic effects may contribute to positive associations of alcohol consumption with albumin in both sexes, as well as positive associations between alcohol consumption and bioavailable testosterone and between alcohol dependence and SHBG in males. However, relative contributions of heritable and environmental factors to associations between alcohol-use traits and sex-hormone levels may differ by sex, with genetic factors contributing more in males and environmental factors contributing more in females.

Abstract Performing bedside procedures requires knowledge, reasoning, physical adeptness, and self-confidence; however, no consensus on a specific, comprehensive strategy for bedside procedure training and implementation is available. Bedside procedure training and credentialing processes across large institutions may vary among departments and specialties, leading to variable standards, creating an environment that lacks consistent accountability, and making quality improvement difficult. In this Scholarly Perspective, the authors describe a standardized bedside procedure training and certification process for graduate medical education with a common, institution-wide educational framework for teaching and assessing the following 7 important bedside procedures: paracentesis; thoracentesis; central venous catheterization; arterial catheterization; bladder catheterization or Foley catheterization; lumbar puncture; and nasogastric, orogastric, and nasoenteric tube placement. The proposed framework is a 4-stage process that includes 1 preparatory learning stage with simulation practice for knowledge acquisition and 3 clinical stages to guide learners from low-risk to high-risk practice and from high to low supervision. The pilot rollout took place at Henry Ford Hospital from December 2020 to July 2021 for 165 residents in the emergency medicine and/or internal medicine residency programs. The program was fully implemented institution-wide in July 2021. Assessment strategies encompass critical action checklists to confirm procedural understanding and a global rating scale to measure performance quality. A major aim of the bedside procedure training and certification was to standardize assessments so that physician trainers from multiple specialties could train, assess, and supervise any participating trainee, regardless of discipline. The authors list considerations revealed from the pilot rollout regarding electronic tracking systems and several benefits and implementation challenges to establishing institution-wide standards. The proposed framework was assembled by a multidisciplinary physician task force and will assist other institutions in adopting best approaches for training physicians in performing these critically important and difficult-to-perform procedures.

Single-cell analyses of viral infections reveal heterogeneity that is not detected by traditional population-level studies. This study applies drop-based microfluidics to investigate the dynamics of herpes simplex virus type 1 (HSV-1) infection of neurons at the single-cell level. We used micrometer-scale Matrigel beads, termed microgels, to culture individual murine superior cervical ganglia (SCG) neurons or epithelial cells. Microgel-cultured cells are encapsulated in individual media-in-oil droplets with a dual–fluorescent reporter HSV-1, enabling real-time observation of viral gene expression and replication. Infection within drops revealed that the kinetics of initial viral gene expression and replication were dependent on the inoculating dose. Notably, increasing inoculating doses led to earlier onset of viral gene expression and more frequent productive viral replication. These observations provide crucial insights into the complexity of HSV-1 infection in neurons and emphasize the importance of studying single-cell outcomes of viral infection. These techniques for cell culture and infection in drops provide a foundation for future virology and neurobiology investigations.