Citations

Abstract Background Unresectable hepatocellular carcinoma (uHCC) is a leading cause of cancer death. FDA-approved first-line systemic therapies include atezolizumab/bevacizumab (atezo/bev) and durvalumab/tremelimumab (durva/treme); however, there is a lack of comparative data. Methods We reviewed outcomes of patients with uHCC who initiated atezo/bev or durva/treme between 2017 and 2024, across six institutions. Overall survival (OS) and time to treatment discontinuation (TTD) were analyzed using the Kaplan–Meier and Cox models, adjusting for baseline characteristics. Results Four hundred fifty-two uHCC pts were included. Median age: 68 years; 77% male; 81% white. Most common etiologies were viral hepatitis (38.9%) and metabolic dysfunction-associated steatohepatitis (19.5%). Disease progression was the primary reason for treatment discontinuation, atezo/bev (56%) and durva/treme (42%). Outcomes were not statistically significant (median OS [month, m]: 14.0 vs 14.6 [P = .66]; median TTD [m]: 4.9 vs 3.9 [P = .42] for atezo/bev vs durva/treme). Outcomes were significantly different between Child-Pugh classes (CP: A, B7, B8/9, C) respectively, median OS(m): 19.0, 6.1, 5.1, 2.0 (P < .001); median TTD(m): 6.1, 2.3, 3.0, 1.3 (P < .001). Conclusions In this real-world study of uHCC, no significant difference in clinical outcomes was observed between atezo/bev and durva/treme in the first-line setting. CP scores were a key prognostic variable with both regimens.

Background Telestroke emergency department (ED) workflow emulates that of in-person care, yet limitations of the virtual interaction may require accommodations. The optimal sequence of non-contrast head CT, cerebral CT angiogram, and decision to infuse IV thrombolytic is not defined for telestroke. Methods In this twenty-two-hospital multicenter retrospective study between 1/1/2024-12/31/2024, we characterized timing of ED CT angiograms, either bundled with the non-contrast head CT or non-bundled and performed after the IV-thrombolytic decision. The primary outcome was effect of bundling on door to needle time (DTN) when directed by telestroke. Timing of CT scans was determined by time stamps of scout images. Results In total, 5704 patients were included, with a median age of 65 years (Interquartile range, IQR 58-77) and NIHSS 8 (IQR 6-13). There were 4518 patients in the bundled group (n = 12 hospitals), with time from non-contrast CT to CTA of median 2 min (IQR 0-6 min; vs non-bundled (n = 10 hospitals): 7, 4-15 min; P = .0001). DTN was not statistically different between the groups, bundled vs not: median 47 min (IQR, 35-62 min) vs 54 min (IQR, 41-67 min, P = .21). Door in door out (DIDO) times also were unchanged (169, 117-254 vs 175, 123-247 min; P = .56). These findings, although showing no statistical difference, may have significance for clinical workflows and were consistent with the results of validation analyses conducted on individual patients. Conclusions Bundling non-contrast head CT with the CT angiogram before thrombolytic decision did not delay DTN times, trended to clinically improve times, and may be relevant for telestroke ED workflows.

Abstract Importance The addition of agents targeting critical signal mediators of cancer cell proliferation such as cyclin-dependent kinases (CDK) potentiates the efficacy of platinum chemotherapy. Objective To determine the safety and efficacy of palbociclib combined with cisplatin (cis) or carboplatin (carbo) in advanced solid malignancies Design Enrollment on dose escalation (part I) proceeded using the Bayesian adaptive design Escalation with Overdose Control (EWOC). Setting Single institution investigator initiated trial. Participants Patients with any advanced cancer after at least one prior therapy were enrolled on dose escalation to determine recommended phase II doses (RP2D). Expansion cohorts were then opened for pancreaticobiliary tract cancers. Intervention Escalating doses of palbociclib in combination with different doses of cisplatin or carboplatin. Main Outcomes and Measures Primary endpoint was objective response rate (ORR). Secondary endpoints included safety, overall survival (OS), and progression-free survival (PFS). Results We enrolled 39 patients on dose escalation (part I) and 32 additional patients on dose expansion (part II). RP2D of palbociclib 100 mg on Day 2-22 + Cisplatin (cis) 60 mg/m2 IV on Day 1 Q4W (Arm A); and palbociclib 75 mg on Day 2-22 + Carboplatin (carbo) AUC 6 IV on Day 1 Q4W (Arm B). ORR for Part I were 12.5% (Arm A) and 25% (Arm B). Median PFS and OS for dose expansion were 2.1 and 4.9 months, respectively. For PDAC, mPFS was 1.9 months (95% CI: 1.7, 2.4), and OS was 3.7 months (95% CI: 2.7, 5.7). Most common treatment-related adverse events (TRAEs—all grade %): Arm A—neutropenia (66%), thrombocytopenia (26%), nausea, fatigue, and anemia (20% each); Arm B—neutropenia (64.7%), thrombocytopenia (53%), and anemia (29%). There were no grade 4-5 TRAEs. Conclusions and Relevance The combination of palbociclib with cisplatin or carboplatin had an acceptable safety profile and clinical responses in some treatment refractory advanced cancers. There was no objective response, but about half of PDAC patients had disease stabilization. Additional efforts are needed to exploit CDK abnormalities in these patients. Clinical trial registration number: NCT02897375

ABSTRACT Traumatic brain injury (TBI), particularly among military personnel, poses significant challenges in acute management and long-term outcomes. Difficult-to-diagnose autoregulatory and inflammatory changes lead to neurocognitive impairment, anxiety, sleep disturbance, and chronic pain. To optimize readiness and test therapeutics for both diagnostic and future TBI treatments, this feasibility study introduces a novel wearable multimodal platform that integrates photoplethysmography and infra-red (IR) sensing from a camera and a wearable sensor to detect vital signs and then leverages machine learning (ML) to predict the need for acute treatment. This prospective observational study involving 28 healthy volunteers simulated a triage emergency room workflow to test sensor accuracy and mobile app functionality. The wearable device demonstrated high accuracy in pulse rate (mean error 7.3%) and oxygen saturation (mean error −1.2%) compared to standard-of-care devices. Camera-based pulse and respiratory rate, and wearable pulse, oxygen, and temperature sensing were tested in a mock triage setting to simulate activation of light-based treatment upon detection of physiological changes of concern after acute TBI. Preliminary ML models to predict hypotension and pain based on retrospective data achieved 98.4% and 93% accuracy but showed limitations in prospective real-time applications. This study provided insights to prepare for future iterations that will integrate near-IR spectroscopy to detect cerebral oximetry, and quantum dot light-emitting diodes to activate light-based treatment (photobiomodulation) from within a wearable head dressing. The findings underscore the potential of this platform to bridge critical gaps in acute TBI care through early detection and future therapeutic intervention. Further development is needed to address environmental challenges, improve accuracy across diverse populations, and refine the device for real-time clinical use. This innovative approach has the potential to revolutionize TBI care by bridging current gaps in diagnostic and therapeutic management.

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.