Providing 0.1 Full-Time Equivalent (FTE) Support to Fellowship Core Faculty Improves Faculty Involvement in Fellowship Education and Recruitment.

In 2022, the American Council for Graduate Medical Education (ACGME) recommended that core faculty (CF) in medical subspecialty fellowships receive at least 0.1 full-time equivalent (FTE) salary support, with plans to enforce compliance in July 2023. After early feedback raised concerns about potential unintended consequences, ACGME deferred enforcement to July 2024. Hence, there is an urgent need to understand the ramifications of providing FTE support for CF. In 2020, the Yale hematology and medical oncology (HO) fellowship program began providing 0.1 FTE support to all CF. Perceptions regarding this were assessed via surveys distributed to all CF in 2021 and 2022 and to all HO fellows in 2021. The vast majority (83.3%) of CF survey respondents reported improved job satisfaction and an increased sense of involvement in the fellowship program as a result of the new 0.1 FTE-supported CF program. Most CF increased attendance at fellowship conferences, devoted more time to mentorship, and increased participation in recruitment. In free text comments, CF respondents described that providing 0.1 FTE support made them "feel rewarded," gave them "a sense of commitment" to the fellowship, and helped "offset clinical requirements." HO fellows reported "a positive impact" of the new program with faculty being "more present at lectures." The median number of times faculty were available to interview fellowship applicants rose markedly after introduction of the program. The FTE-supported CF program was viewed enthusiastically by fellows and faculty, resulting in increased CF involvement in fellowship education and recruitment.

High-Grade B-Cell Lymphoma, Not Otherwise Specified: CNS Involvement and Outcomes in a Multi-Institutional Series.

Little is known about the central nervous system (CNS) risk in high-grade B-cell lymphoma, not otherwise specified (HGBL, NOS). Hence, we sought to describe the rates of baseline CNS involvement, risk of CNS recurrence after primary therapy, and management strategies in HGBL, NOS. In this multicenter retrospective study, we included 160 adults with newly diagnosed HGBL, NOS treated between 2016 and 2021 at 20 US institutions. Eleven patients (7%) had baseline CNS involvement at diagnosis (leptomeningeal=6, parenchymal=4, and both=1). Baseline CNS involvement was significantly associated only with MYC rearrangement (OR=3.5) and testicular (in men) or female pelvic (in women) involvement (OR=8.1). There was no significant difference in survival outcomes between HGBL, NOS patients with (median PFS=4 years) or without (median PFS=2.4 years) baseline CNS involvement (p=0.45). The cumulative incidence of CNS recurrence at 3 years was 11%. Patients with baseline CNS involvement were at the highest risk (48.5% versus 8% for those without baseline CNS involvement) and were excluded from the risk factors analysis for CNS recurrence. The risk for CNS recurrence was significantly associated with blood or bone marrow involvement, CD5 expression, non-GCB subtype, and DEL phenotype, however, high CNS-IPI was not. The prognosis of relapsed HGBL, NOS was poor, regardless of whether recurrence was systemic or limited to the CNS, and with currently available salvage strategies, including autologous transplantation and CAR T-cell modalities, almost all patients with CNS recurrence ultimately succumbed to their disease. These patients represent an unmet need and should be prioritized for experimental approaches.

Warm autoantibodies mimicking alloantibodies: Three cases of autoantibodies with unusual antigenic specificity.

OBJECTIVES: We describe 3 cases of red blood cell (RBC) autoantibodies with unusual apparent antigenic specificity and discuss the testing methodology and implications of these findings. METHODS: All immunohematologic testing, including ABO and RhD typing, antibody detection and identification, RBC antigen phenotyping and genotyping, direct antiglobulin tests, and elution studies were performed using standardized and validated methods and reagents. RESULTS: Three patients were found to have autoantibodies, which were originally presumed to be alloantibodies. Case 1 was a 60-year-old man with autoanti-Jka following babesiosis; case 2 was a 79-year-old woman with an autoanti-f; and case 3 was a 28-year-old pregnant woman with an autoanti-S. Cases 1 and 2 required RBC transfusions, which were performed with Jka-negative and f-positive RBC units, respectively. No transfusion reactions were reported, and the hemoglobin responded appropriately in both cases. CONCLUSIONS: These 3 cases complement the minimal literature regarding warm autoantibodies with unusual antigenic specificity and their potential to mediate clinically significant hemolysis. There are only rare reports of warm autoantibodies with specificity for non-Rh antigens, and prior authors have suggested that autoantibodies with mimicking specificity are usually detected only serologically; in contrast, 2 of the 3 patients herein experienced autoimmune hemolytic anemia.

High-grade B-cell lymphoma, not otherwise specified: a multi-institutional retrospective study.

In this multi-institutional retrospective study, we examined the characteristics and outcomes of 160 patients with high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS)-a rare category defined by high-grade morphologic features and lack of MYC rearrangements with BCL2 and/or BCL6 rearrangements ("double hit"). Our results show that HGBL-NOS tumors are heterogeneous: 83% of patients had a germinal center B-cell immunophenotype, 37% a dual-expressor immunophenotype (MYC and BCL2 expression), 28% MYC rearrangement, 13% BCL2 rearrangement, and 11% BCL6 rearrangement. Most patients presented with stage IV disease, a high serum lactate dehydrogenase, and other high-risk clinical factors. Most frequent first-line regimens included dose-adjusted cyclophosphamide, doxorubicin, vincristine, and etoposide, with rituximab and prednisone (DA-EPOCH-R; 43%); rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 33%); or other intensive chemotherapy programs. We found no significant differences in the rates of complete response (CR), progression-free survival (PFS), or overall survival (OS) between these chemotherapy regimens. CR was attained by 69% of patients. PFS at 2 years was 55.2% and OS was 68.1%. In a multivariable model, the main prognostic factors for PFS and OS were poor performance status, lactate dehydrogenase >3 × upper limit of normal, and a dual-expressor immunophenotype. Age >60 years or presence of MYC rearrangement were not prognostic, but patients with TP53 alterations had a dismal PFS. Presence of MYC rearrangement was not predictive of better PFS in patients treated with DA-EPOCH-R vs R-CHOP. Improvements in the diagnostic criteria and therapeutic approaches beyond dose-intense chemotherapy are needed to overcome the unfavorable prognosis of patients with HGBL-NOS.

Predictive factors and outcomes for ibrutinib in relapsed/refractory marginal zone lymphoma: a multicenter cohort study.

Ibrutinib is effective in the treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL) with an overall response rate (ORR) of 48%. However, factors associated with response (or lack thereof) to ibrutinib in R/R MZL in clinical practice are largely unknown. To answer this question, we performed a multicenter (25 US centers) cohort study and divided the study population into three groups: "ibrutinib responders"-patients who achieved complete or partial response (CR/PR) to ibrutinib; "stable disease (SD)"; and "primary progressors (PP)"-patients with progression of disease as their best response to ibrutinib. One hundred and nineteen patients met the eligibility criteria with 58%/17% ORR/CR, 29% with SD, and 13% with PP. The median PFS and OS were 29 and 71.4 months, respectively, with no difference in PFS or OS based on the ibrutinib line of therapy or type of therapy before ibrutinib. Patients with complex cytogenetics had an inferior PFS (HR = 3.08, 95% CI 1.23-7.67, p = 0.02), while those with both complex cytogenetics (HR = 3.00, 95% CI 1.03-8.68, p = 0.04) and PP (HR = 13.94, 95% CI 5.17-37.62, p < 0.001) had inferior OS. Only primary refractory disease to first-line therapy predicted a higher probability of PP to ibrutinib (RR = 3.77, 95% CI 1.15-12.33, p = 0.03). In this largest study to date evaluating outcomes of R/R MZL treated with ibrutinib, we show that patients with primary refractory disease and those with PP on ibrutinib are very high-risk subsets and need to be prioritized for experimental therapies.

Colonizing multidrug-resistant bacteria and the longitudinal evolution of the intestinal microbiome after liver transplantation.

Infections by multidrug-resistant bacteria (MDRB) remain a leading cause of morbidity and mortality after liver transplantation (LT). Gut dysbiosis characteristic of end-stage liver disease may predispose patients to intestinal MDRB colonization and infection, in turn exacerbating dysbiosis. However, relationships between MDRB colonization and dysbiosis after LT remain unclear. We prospectively recruited 177 adult patients undergoing LT at a single tertiary care center. 16 S V3-V4 rRNA sequencing was performed on 723 fecal samples collected pre-LT and periodically until one-year post-LT to test whether MDRB colonization was associated with decreased microbiome diversity. In multivariate linear mixed-effect models, MDRB colonization predicts reduced Shannon α-diversity, after controlling for underlying liver disease, antibiotic exposures, and clinical complications. Importantly, pre-LT microbial markers predict subsequent colonization by MDRB. Our results suggest MDRB colonization as a major, previously unrecognized, marker of persistent dysbiosis. Therapeutic approaches accounting for microbial and clinical factors are needed to address post-transplant microbiome health.

Therapeutic Options for Aggressive T-Cell Lymphomas.

T-cell lymphomas (TCL) are a rare, heterogeneous group of non-Hodgkin lymphomas associated with very poor prognosis with standard cytotoxic chemotherapy. Epigenetic-based therapy, such as with histone deacetylase inhibitors, was initially discovered to be efficacious in TCL. In recent years, our understanding of the mechanisms driving T-cell lymphomagenesis has validated the use of epigenetic-based drugs and has also led to the development of novel agents with promising efficacy in pre-clinical and early clinical trials. These new treatments play upon the prominent existence of epigenetic and immune dysfunction present in T-cell lymphomas. With these advances, novel therapeutic regimens combining traditional chemotherapy as well as epigenetic and/or immunotherapy serve as promising future treatment options for TCL. In this review, we discuss the traditional methods of treatment for TCL as well as novel agents and combinations that will likely change the treatment paradigms resulting in better clinical outcomes.

Illness Perceptions, Medication Beliefs, and Adherence to Antiretrovirals and Medications for Comorbidities in Adults With HIV Infection and Hypertension or Chronic Kidney Disease.

BACKGROUND: Mortality in patients with HIV infection is increasingly due to comorbid medical conditions. Research on how adherence to medications for comorbidities relates to antiretroviral (ARV) medication adherence and how interrelations between illness perceptions and medication beliefs about HIV and comorbidities affect medication adherence is needed to inform adherence interventions. METHODS: HIV-infected adults with hypertension (HTN) (n = 151) or chronic kidney disease (CKD; n = 41) were recruited from ambulatory practices at an academic medical center. Illness perceptions and medication beliefs about HIV and HTN or CKD were assessed and adherence to one ARV medication and one medication for either HTN or CKD was electronically monitored for 10 weeks. RESULTS: Rates of taking, dosing, and timing adherence to ARV medication did not differ from adherence to medication for HTN or CKD, with the exception that patients were more adherent to the timing of their ARV (78%) than to the timing of their antihypertensive (68%; P = 0.01). Patients viewed HIV as better understood, more chronic, having more negative consequences, and eliciting more emotions, compared with HTN. Patients viewed ARVs as more necessary than medication for HTN or CKD. Having a realistic view of the efficacy of ARVs (r = -0.20; P < 0.05) and a high level of perceived HIV understanding (r = 0.21; P < 0.05) correlated with better ARV adherence. CONCLUSIONS: Patients with HIV showed similar rates of adherence to ARVs as to medications for comorbidities, despite perceiving HIV as more threatening and ARVs as more important. This can be used in adapting existing interventions for ARV adherence to encompass adherence to medications for comorbid conditions.