Faculty Bibliography

Salvage chemotherapy and autologous stem cell transplantation (ASCT) offer the opportunity to cure eligible patients with relapsed diffuse large B-cell lymphoma (DLBCL). Epigenetic alterations such as aberrant DNA methylation patterns have been linked to chemotherapy resistance in DLBCL. Oral Azacitadine (AZA) is a hypomethylating agent that inhibits DNA methyltransferase and has provided evidence of chemotherapy sensitization in DLBCL. In this phase I trial the safety and feasibility of two dose levels of AZA were investigated in combination with standard cytotoxic chemotherapy rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in relapsed DLBCL patients who were candidates for ASCT.

BACKGROUND AND AIM/OBJECTIVE:Optimizing health and quality of life for pediatric liver transplant (LT) recipients requires balancing protection of the liver graft with overall burden of treatments on the child. Since the AASLD's 2013 guidelines, strategies for achieving this balance have evolved, with a particular focus on mitigating long-term complications. Advances include operative and intensive care strategies for reducing complications, minimizing exposure to immunosuppression and its long-term adverse effects for other organs, infection prevention with prophylaxis and vaccination, optimizing support of early nutrition and development, and improving support around transition from pediatric to adult care. This document aims to provide an evidence-based guideline to comprehensive care of pediatric LT recipients, starting at transplant and continuing as they advance to adulthood. METHODS:A multidisciplinary writing group of pediatric liver transplant experts and a medical librarian was convened by AASLD, with guidance by its Practice Guidelines Development Policy, and in collaboration with the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the American Society of Transplantation (AST). We conducted a systematic global literature review, formulated key clinical questions, and developed recommendations. Each recommendation was graded using the Oxford Centre for Evidence-Based Medicine framework and categorized by strength through a consensus voting process. CONCLUSION/CONCLUSIONS:All recommendations are based on best-available evidence and reflect expert consensus. Most of the evidence basis remains retrospective or observational data, or extrapolation from related populations. To continue improving long-term outcomes after pediatric liver transplant, multi-disciplinary, multi-center collaboration to strengthen the evidence will be essential.

BACKGROUND:Robotic Ivor-Lewis esophagectomy is increasingly adopted due to its minimally invasive approach and favorable outcomes. Anastomotic leak remains the most serious complication after esophagectomy, with reported rates of 5-18%. We describe a reinforced, stapled, single-layer, thoracic anastomosis which has resulted in no leaks in 50 consecutive patients. METHODS:We performed a retrospective review of consecutive patients who underwent robotic Ivor-Lewis esophagectomy by a two-surgeon team. RESULTS:From January 2022 to February 2026, 50 patients were included with a median age of 70 years. Indications for surgery were malignancy in 47 patients, most commonly adenocarcinoma (85.1%) and benign disease in 3 patients. Median operative time was 237 min, median actual blood loss was 35 mL and median lymph node yield was 20. R0 resection was achieved in all 47 malignant cases. Complete pathologic response (pCR) was observed in 13 out of 38 patients that received neoadjuvant therapy (34.2%). There were no conversions, and median LOS was 4 days. No anastomotic leaks were detected clinically, radiographically, or biochemically and there was no 30- or 90-day mortality. At a median follow-up of 26.8 months, 1- and 2-year overall survival rates were 88.2 and 84.6%, respectively. CONCLUSIONS:This technique, when properly executed, is reproducible, safe, and can afford R0 resection and thorough thoracic lymph node dissection, with promising results. Prospective, multicenter studies are needed to compare this approach to alternative anastomotic techniques.

BACKGROUND/UNASSIGNED:Differentiated service delivery (DSD) is increasingly available for HIV treatment. DSD has been shown to improve treatment retention, but DSD modalities incur higher costs than the clinic-based standard-of-care (SoC). We conducted a cost-effectiveness (CE) analysis to assess what DSD modalities, in what settings, would constitute an efficient use of limited HIV program resources. METHODS/UNASSIGNED:) to project HIV trends (incidence, prevalence, mortality), disability-adjusted life years (DALYs), and costs (2021 USD) arising from DSD versus SoC over 2022-2062 in four settings: South Africa, Malawi, Zambia, and a collective representation of African low- and middle-income countries (LMICs). We compared three DSD modalities: healthcare worker-managed community adherence groups (CAG), client-managed urban adherence group (UAG), and home ART delivery (HomeART). We calculated incremental cost-effectiveness ratios (ICERs) of DSD versus SoC from the health system perspective using country-specific CE thresholds, and performed one-way sensitivity analyses for key assumptions. RESULTS/UNASSIGNED:Community adherence groups (ICER: $274-$604/DALY averted) and UAG (ICER: $590-$720/DALY averted) were cost-effective for all country/model settings. HomeART was dominated by UAG in all settings. In nearly all settings, CE estimates of CAG were robust to uncertainty in DSD effectiveness (except Zambia), DSD costs, CE threshold (except South Africa), HIV-associated disability weights, and discount rates. Cost-effectiveness of UAG was highly sensitive to uncertainty in DSD effectiveness in all settings. CONCLUSIONS/UNASSIGNED:Community adherence groups and UAG can provide cost-effective alternatives to the clinic-based SoC in multiple African settings.

BACKGROUND AND AIMS/OBJECTIVE:Individuals who engage in illicit or nonmedical opioid use may have elevated risk of health and social consequences, including progression to opioid use disorder (OUD). Preventive interventions to reduce this risk are lacking. This trial tested the impact of a primary care-integrated collaborative care approach for reducing risky opioid use, defined as nonmedical use of prescription opioids or any use of illicit opioids. DESIGN/METHODS:Cluster-randomized controlled trial randomized primary care providers (PCPs) and their patients into the Subthreshold Opioid Use Disorder Prevention (STOP) intervention or enhanced usual care (EUC). SETTING/METHODS:Primary care clinics at 5 U.S. sites. PARTICIPANTS/METHODS:PCPs and their patients were recruited January 2021-May 2023. A total of 119 PCP clusters (STOP = 48, EUC = 51) and 202 patients (STOP = 88, EUC = 114) enrolled. Eligible patients were adults (≥18 years) having current risky opioid use, without moderate-severe OUD. Patient participants were majority female (63.4%), white (70.8%) and non-Hispanic (96.5%), with a mean age of 55.7 [standard deviation (SD) = 12.7] years. At baseline, 63.4% of participants had moderate-severe pain (Brief Pain Inventory) and below average physical (79.2%) and mental (62.4%) health (SF-12). INTERVENTIONS/METHODS:The STOP collaborative care intervention consisted of brief advice from the PCP about reducing risky opioid use, meetings with a clinic-embedded nurse care manager over 12 months and remote health coaching (2-6 sessions). Both groups received primary care treatment as usual and overdose risk reduction materials. MEASUREMENTS/METHODS:The primary outcome was total days of risky opioid use, recorded from 6 monthly electronic surveys. A key secondary outcome was moderate-severe OUD at 6 and 12 months. FINDINGS/RESULTS:A total of 77 (87.5%) STOP and 107 (93.9%) EUC participants completed the 6-month assessment period. The primary outcome analysis used the Intention-to-Treat sample with multiple imputations of missing data. Mean days of risky opioid use at 180 days were lower in STOP than EUC [12.2 (SD = 27.73) vs. 15.5 (SD = 32.64)]; the difference between groups adjusted for baseline risky opioid use was not statistically significant (rate ratio 0.95, 95% confidence interval = 0.52-1.74). One STOP participant (1.1%) and 13 EUC participants (11.4%) developed moderate-severe OUD at 6 months, and 3 (3.4%) STOP and 6 (5.3%) EUC participants had moderate-severe OUD at 12 months (P < 0.001). CONCLUSIONS:This cluster-randomized controlled trial did not find evidence that the STOP intervention for reducing risky opioid use produced greater reductions over 6 months compared with enhanced usual care, though fewer intervention participants progressed to moderate-severe opioid use disorder. Patients had a high burden of pain and comorbidities that may present challenges to reducing opioid use.

BACKGROUND/UNASSIGNED:The practice of living donor kidney transplantation has evolved through innovations in logistics, technology, and clinical practice. In the United States, Good Samaritan donation, a historical label exclusive to nondirected donors, now incorporates voucher-based models. METHODS/UNASSIGNED:To determine how voucher-based nondirected living kidney donation has influenced the volume and practice of Good Samaritan living kidney donation in the United States, we analyzed living donor kidney transplants from 2000 to 2024 using data from the National Kidney Registry (103 transplant centers) and the Scientific Registry of Transplant Recipients. Temporal trends were derived by linear regression. RESULTS/UNASSIGNED:We identified 4662 Good Samaritan living donor kidney transplants, defined as historical nondirected and novel voucher-based nondirected donations. Of 2131 Good Samaritan living donor kidney transplants facilitated by the National Kidney Registry, donors had a median age of 43 y, were predominantly of White race (93%), and were women (60%). Recipients had a median age of 52 y and were racially and ethnically diverse (63% White, 14% Black, and 10% Hispanic). Annual Good Samaritan donation counts in the United States increased from 17 in 2000 to 439 in 2024, corresponding to a growth rate of 14.5%. Voucher-based nondirected donations increased from 2 in 2015 to 314 in 2024, comprising 72% of all Good Samaritan donations in that year. CONCLUSIONS/UNASSIGNED:The advent of voucher-based nondirected donation correlated with growth in Good Samaritan donation volume. Given the prevalence of voucher-based donations, connecting local kidney paired donation practices to voucher-based nondirected donation may improve access to and participation in living kidney donation.