Citations

Abstract Background Surgical resection without visible or residual microscopic disease (R0 resection) is known as the optimal path to cure localized pancreatic cancer (PDAC). Neoadjuvant therapy (NAT) is used to improve R0 resection rates; however, the optimal regimen is unclear. We assessed the safety and efficacy of peri-operative gemcitabine/nab-paclitaxel (GEM/NAB) and pre-operative stereotactic body radiotherapy (SBRT) in patients with resectable (R-PDAC) and borderline resectable PDAC (BR-PDAC). Patients and Methods This was a prospective, multicenter single arm phase 2 study in patients with R-PDAC and BR-PDAC. Patients received three cycles of GEM/NAB prior to SBRT followed by surgery and three cycles of adjuvant GEM/NAB. Primary endpoint was R0 surgical resection rate in each cohort. Secondary endpoints included safety and overall survival (OS). Results Eighty-six patients consented and following radiologic screening, 49 were enrolled into two cohorts: R-PDAC (n = 20) and BR-PDAC (n = 29) between June 2016 and April 2021. Seventy percent of R-PDAC (14/20) and 55.2% of BR-PDAC patients (16/29) completed all NAT. Eleven R-PDAC (55.0%) and 11 BR-PDAC patients (37.9%) underwent surgical resection. Nine R-PDAC (45.0%) and 9 BR-PDAC patients (31.0%) had R0 resections. The median OS for R-PDAC and BR-PDAC patients with R0 resections was 22 months (95% CI: 17.7 months-NA) and 39 months (95%CI: 13.21 months-NA), respectively. Conclusion While the trial failed to meet one of its primary objectives as only 45% of R-PDAC patients had an R0 resection, the objective of 30% R0 resection for the BR-PDAC group was met. NAT should be part of current therapeutic strategies for BR-PDAC; however, our trial does not answer what is the best NAT for BR-PDAC. Trial Registration NCT02723331

Abstract Background Recent clinical trial evidence supports broader use of partial oral therapy (POT) for infective endocarditis (IE), yet real-world uptake in the U.S. has not been investigated. Methods Adult infectious diseases (ID) physician members of the Infectious Diseases Society of America Emerging Infections Network were surveyed in April–May 2025. A 10-item instrument captured frequency of POT, organism-specific influence, decision factors, barriers, and facilitators. Results Among 1531 members, 516 (34%) responded; 452 (88%) of them managed IE. POT was uncommon: 16% never used, 53% used in ≤10% of cases, and only 10% used in >25% of patients. Frequent POT rose with caseload (23% in physicians treating >50 IE cases year vs ≤9% in lower-volume groups, P < .001) and with fewer years in clinical practice (13% in <5 yrs vs 5% in ≥25 yrs, P = .013). Comfort with POT depended on the pathogen: 66% were comfortable switching for Streptococcus spp., 52% for Gram-negative bacilli, 19% for methicillin-resistant Staphylococcus aureus. Three quarters of those who used POT finished with a single agent. In people who inject drugs, 34% of physicians often or always considered an oral regimen. Availability of an active oral agent (75%) and the pathogen involved (69%) were the leading decision drivers; principal barriers were fear of relapse (72%), adherence concerns (53%), and insufficient evidence (48%). Respondents most desired clearer guidelines (75%) and additional data (71%). Conclusions U.S. adult ID physicians adopt POT for IE sparingly. Updated IE treatment guidelines, additional clinical trial data, and broader access to complex outpatient antimicrobial therapy services may facilitate wider adoption.

BACKGROUND. We developed a prospective, multicenter “registry” to evaluate the effect of extracorporeal photopheresis for lung transplant recipients who develop chronic lung allograft dysfunction (CLAD) with the bronchiolitis obliterans syndrome (BOS) phenotype (CLAD/BOS) and who are refractory to conventional standard-of-care therapy. METHODS. Data from 258 lung transplant recipients enrolled in the Registry between April 2015 and April 2022 were included in this analysis. All recorded parameters (eg, demographics), including forced expiratory volume in 1 s (FEV1) measurements and indices (FEV1% baseline, FEV1 rate of decline) at several time periods, were included in multivariate linear/logistic and Kaplan-Meier analyses to evaluate potential associations with survival. RESULTS. Mortality at 6 and 12 mo after CLAD/BOS diagnosis was 5% and 14%, whereas mortality at 6 and 12 mo after enrollment was 15% and 26%, respectively. The primary cause of death in the cohort was respiratory failure or graft failure (74%). Rate of FEV1 decline (log) at enrollment was independently associated with survival (log days) from CLAD/BOS diagnosis and enrollment (r = 0.55 and r = 0.3, respectively). The rates of FEV1 decline among survivors were lower (–77 ± 89 mL/mo) compared with nonsurvivors (–148 ± 155 mL/mo) at 6 mo after enrollment (P = 0.0001). CONCLUSIONS. The rate of FEV1 decline quantified using at least 5 FEV1 measurements is a robust surrogate outcome. We plan to use these findings to revise our randomized controlled trial to facilitate risk adjustment using FEV1 rate of decline strata at enrollment and as a scientifically valid surrogate for outcome.

Abstract Foramen of Winslow hernia is a rare subtype of internal hernias, accounting for ⁓8% of all internal hernia cases. Its nonspecific clinical presentation often delays diagnosis, with ˂10% identified preoperatively. With advances in minimally invasive techniques, robotic-assisted surgery has emerged as a safe and precise method for managing complex intra-abdominal pathology. A 70-year-old male presented with an acute abdomen. He was hemodynamically stable, and computed tomography imaging suggested an internal hernia. Robotic-assisted abdominal exploration revealed a segment of colon herniated through the foramen of Winslow. The colon was carefully reduced without complications. A piece of omentum was placed into the defect, and the retracted gall bladder naturally positioned itself within the foramen, potentially minimizing the risk of recurrence. The patient recovered uneventfully and discharged on postoperative day one. To our knowledge, this is the first documented case of foramen of Winslow hernia repair using a robotic-assisted approach.

Abstract Objectives To develop a volume of interest (VOI) imaging technique in multi-detector-row helical CT to reduce radiation dose or improve image quality within the VOI. Methods A deep-learning method based on a residual U-Net architecture, named VOI-Net, was developed to correct truncation artifacts in VOI helical CT. Three patient cases, a chest CT of interstitial lung disease and 2 abdominopelvic CT of liver tumour, were used for evaluation through simulation. Results VOI-Net effectively corrected truncation artifacts (root mean square error [RMSE] of 5.97 ± 2.98 Hounsfield Units [HU] for chest, 3.12 ± 1.93 HU, and 3.71 ± 1.87 HU for liver). Radiation dose was reduced by 71% without sacrificing image quality within a 10-cm diameter VOI, compared to a full scan field of view (FOV) of 50 cm. With the same total energy deposited as in a full FOV scan, image quality within the VOI matched that at 350% higher radiation dose. A radiologist confirmed improved lesion conspicuity and visibility of small linear reticulations associated with ground-glass opacity and liver tumour. Conclusions Focusing radiation on the VOI and using VOI-Net in a helical scan, total radiation can be reduced or higher image quality equivalent to those at higher doses in standard full FOV scan can be achieved within the VOI. Advances in knowledge A targeted helical VOI imaging technique enabled by a deep-learning-based artifact correction method improves image quality within the VOI without increasing radiation dose.

Purpose: To determine the factors associated with compliance with recommended intravitreal injections (IVIs) for retinal diseases among out-of-pocket, insured, and fully subsidized (non-paying) patients. Methods: This retrospective observational hospital-based study included patients recommended for IVI in at least one eye between November 2011 and May 2022. Three cohorts of patients were assessed: out-of-pocket payers, insured, and those fully subsidized (non-paying) by the hospital. The main outcome measure was the compliance rate, defined as the proportion of patients receiving an injection after one was recommended. The impact on the visual outcome in each cohort was a secondary outcome. Results: Overall, 50,408 IVI were recommended for at least one eye and were included in the analyses. Male patients were more common (66.72%), and the mean age was 55.36 ± 16.39 years. The overall compliance rate with the first recommended injection was 51.37%, which increased and eventually stabilized with subsequent recommendations to approximately 80% (range: 77.48%–82.93%). Insured patients had a higher compliance rate with the first recommendation compared to the non-insured (100% vs. 49.84%; P < 0.000 01 ), and non-paying patients had a higher compliance rate after the first recommendation compared to paying patients (62.51% vs. 48.66%; P < 0.000 01 ). Patients with insurance achieved a better visual outcome at the last follow-up compared to other cohorts. Conclusion: Insured patients have a much higher compliance rate with recommended IVIs compared to out-of-pocket or non-paying patients. The high non-compliance rate among non-paying patients suggests that factors other than the direct cost of the injections may impact compliance with recommended treatment.

Abstract Glutamine dependence of cancer cells reduces local glutamine availability, which hinders antitumor T-cell functionality and facilitates immune evasion. We thus speculated that glutamine deprivation might be limiting efficacy of chimeric antigen receptor (CAR) T-cell therapies in patients with cancer. We have seen that antigen-specific T cells are unable to proliferate or produce interferon gamma (IFN-γ) in response to antigen stimulation when glutamine concentration is limited. Using multiple myeloma (MM) as a glutamine-dependent disease model, we found that murine CAR T cells selectively targeting B-cell maturation antigen (Bcma) in MM cells were sensitive to glutamine deprivation. However, CAR T cells engineered to increase glutamine uptake by expression of the glutamine transporter Asct2 exhibited enhanced proliferation and responsiveness to antigen stimulation, increased production of IFN-γ, and heightened cytotoxic activity, even under conditions of low glutamine concentration. Mechanistically, Asct2 overexpression reprogrammed the metabolic fitness of CAR T cells by upregulating the mechanistic target of rapamycin complex 1 gene signature, modifying the solute carrier transporter repertoire, and improving both basal oxygen consumption rate and glycolytic function, thereby enhancing CAR T-cell persistence in vivo. Accordingly, expression of Asct2 increased the efficacy of Bcma-CAR T cells in syngeneic and genetically engineered mouse models of MM, which prolonged mouse survival. In patients, higher-level expression of ASCT2 by MM cells predicted poor outcome to combined immunotherapy and BCMA-CAR T-cell therapy. Our results indicate that reprogramming glutamine metabolism may enhance antitumor CAR T-cell functionality in MM. This approach may also be effective for other cancers that depend on glutamine as a key energy source and metabolic hallmark.

Background: An extended trochanteric osteotomy (ETO) is commonly used to improve exposure and facilitate femoral component removal in revision total hip arthroplasty (THA). An additional medial corticotomy may be used in conjunction with an ETO to correct a femoral deformity, particularly varus remodeling in association with a failed femoral component. This study evaluated the outcomes of combining an ETO with a medial corticotomy in revision THA, with emphasis on implant fixation, femoral alignment, bone union, and clinical outcomes. Methods: Of the 612 ETOs performed between 2003 and 2013, 13 patients (9 men and 4 women) underwent ETO combined with a medial corticotomy to correct varus remodeling, representing 2% of all ETOs during that period. The average follow-up was 8 ± 3.5 years. The mean age at surgery was 67 ± 13.5 years. The mean body mass index was 32 ± 7.7 kg/m 2 . Radiographs were reviewed to measure preoperative and postoperative femoral deformity, time to consolidation, and femoral fixation. Clinical outcomes were evaluated using the Harris Hip Score (HHS). Results: All patients had preoperative varus femoral deformity (mean 16.3° ± 5.7°). The mean postoperative alignment was 4.3 ± 1.6° varus achieving an average correction of 12° (95% CI −15.7 to −8.3, p < 0.0001). Both the ETO and the medial corticotomy consolidated in 10 of 11 patients (91%) with available 1-year radiographs at a mean of 11 ± 7.7 months. The mean HHS improved significantly from 42 preoperatively to 82 at 5-year follow-up (p = 0.0002). Complications related to the ETO and corticotomy occurred in 4 patients (30%), including 1 intraoperative fracture, 1 postoperative greater trochanteric fracture, 1 nonunion of the medial corticotomy, and 1 postoperative wound-hematoma. All femoral components remained well fixed at final follow-up. Conclusion: The combination of ETO and medial corticotomy in revision THA effectively corrected femoral alignment in patients with a preoperative varus deformity and was associated with significant functional improvement at the final follow-up. Level of Evidence: Level IV . See Instructions for Authors for a complete description of levels of evidence.