Citations

Abstract Few prospective benchmark studies exist to characterize the evolving contemporary real-world practice for peripheral T-cell lymphoma (PTCL). We report the patterns of first-line care and outcomes for 720 patients with systemic PTCL enrolled in 2 related prospective cohort studies, Lymphoma Epidemiology of Outcomes (LEO) from 2015 to 2020 and Molecular Epidemiology Resource (MER) from 2002 to 2015, both followed to 2024. The primary end points were event-free survival (EFS) and overall survival (OS) using Kaplan-Meier estimator and Cox regression model. Secondary end points included correlations of clinical and treatment factors with survival. The most common induction regimens were CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) based (70%), given as CHOP (36%), CHOP plus etoposide (23%), or CHOP-like plus novel agents (11.5%, including 5% BV-CHP [brentuximab plus cyclophosphamide, doxorubicin, and prednisone]). Consolidative autologous stem cell transplant was performed in 102 patients (14%). Within nodal PTCL, EFS and OS were adversely associated with International Prognostic Index 2 to 5, prognostic index for T-cell lymphoma score 1 to 4, and non–anaplastic large-cell lymphoma (ALCL) subtypes. Within LEO, which captured increasing first-line etoposide and brentuximab vedotin, adding etoposide to CHOP was associated with better OS in anaplastic lymphoma kinase-negative ALCL. BV-CHP showed a trend toward OS improvement in ALCL. Patients failing EFS6 and EFS24 had 5-year subsequent OS of 12% and 17%, respectively. The inferior outcomes in non-ALCL subtypes and patients failing EFS6 and EFS24 highlight unmet needs with CHOP-based induction, where clinical trials with targeted therapy should be prioritized. This trial was registered at www.clinicaltrials.gov as NCT02736357.

Abstract INTRODUCTION The locus coeruleus (LC) degenerates early in Alzheimer's disease (AD). However, the extent of rostrocaudal degeneration across clinicopathologic heterogeneity remains underexplored in AD. METHODS Using digital pathology, we quantified LC neuronal density and area at three neuroanatomic levels in a large AD series. RESULTS Analysis of neuropathologic AD subtypes revealed greater middle LC vulnerability in hippocampal sparing AD compared to typical and limbic predominant AD. Regression analyses identified distinct predictor variables associated with the degeneration of rostral and middle LC. Age at onset predicted 24% of the variability in rostral LC neuronal density, whereas Braak stage, brain weight, Lewy body disease, and age at onset accounted for 15% of the variability in middle LC. Analyses of clinical presentations revealed lower rostral LC neuronal density in non‐amnestic compared to amnestic AD cases. DISCUSSION These insights demonstrate greater LC degeneration in atypical clinicopathologic forms of AD, including hippocampal sparing, young‐onset, and non‐amnestic presentations.

ABSTRACT Atraumatic and localized drug delivery to the vascular endothelium remains a critical unmet need in interventional medicine, with major implications for arterial and venous disease management. Here, we present EndoBot, an untethered elastic millirobot designed to enable endothelial‐safe, soft‐contact operation, under physiologic blood flow. EndoBot is magnetically actuated and navigates along the vessel lumen through curved, non‐uniform geometries while maintaining ultra‐low radial contact pressures (<1 kPa), far below endothelial injury thresholds. We demonstrate stable locomotion, with intrinsically compliant mechanics within a defined safety envelope under arterial and venous hemodynamics in phantom vessels, ex vivo human umbilical veins, and an in vivo rat inferior vena cava, without detectable vessel damage. EndoBot is compatible with standard vascular sheaths for wireless deployment and retrieval and is controlled under clinical fluoroscopic guidance using a human‐scale magnetic manipulation platform. Blood compatibility testing confirms safety, with minimal hemolysis and no increased coagulation tendency during navigation. For localized therapy, EndoBot employs a gentle endoluminal painting strategy, transferring a washout‐resistant drug depot directly onto the vessel lumen. By combining atraumatic mobility, clinical deployability, and localized drug deposition, EndoBot establishes a translationally viable platform for developingmaintenance‐oriented endovascular therapies, supporting prevention of restonosis, thrombosis and inflammatory remodeling following intervention.

Abstract Background Women with advanced chronic kidney disease (CKD) encounter reproductive health challenges, including reduced fertility, menstrual irregularity, and sexual dysfunction. This study examined changes in sex hormones in patients with CKD, their correlation with sexual function, and changes after transplant. Methods This study recruited women aged 18–51 years with CKD stages 3b-5 from outpatient clinics and dialysis units. Exclusion criteria included active pregnancy, menopause, prior hysterectomy/bilateral oophorectomy, or use of hormonal contraceptives/therapy. Data were collected at enrollment and at 6 months post-transplant. Results Thirty-eight subjects met eligibility criteria and enrolled in the trial (8 in CKD stage 3b, 10 in CKD stage 4, and 20 in CKD stage 5/5D). Sexual dysfunction (25/38, 65.8%), defined as total female sexual function index score &lt; 26.55, and menstrual irregularities (17/38, 44.7%) were common, with abnormal elevation of luteinizing hormone present in the follicular phase in the majority of patients. There was a significant negative association between total female sexual function index score and prolactin (β = -0.26, P = 0.03) and dehydroepiandrosterone sulfate (β = -0.07, P = 0.01) after adjusting for age. After transplant, there was also a significant improvement in both prolactin and dehydroepiandrosterone sulfate levels, although sexual dysfunction persisted. Conclusions This study highlights the complex interplay between advanced CKD, reproductive endocrinology, and sexual health. Significant hormonal dysregulation and associated reproductive challenges were observed. The prominent role of dehydroepiandrosterone sulfate in sexual dysfunction among women with CKD requires further study.

Objective: Auditory nerve monitoring through electrically evoked compound action potentials (eCAP) can be used to assess cochlear neural integrity during vestibular schwannoma (VS) resection. Herein, we report on 5 cochlear implant (CI) patients who underwent VS resection with present eCAP responses both intraoperatively and postoperatively. Patients either did not perceive any sound through their CI or rapidly adapted to electrical stimulation, suggesting that the presence of eCAP does not guarantee auditory nerve function in patients with VS resection. Patients: Five patients who underwent simultaneous VS translabyrinthine resection and cochlear implantation. Interventions: Simultaneous cochlear implantation and translabyrinthine microsurgical VS resection. Main outcome measure: Electrically evoked compound action potential. Results: All patients had eCAP responses present during their VS resection and for at least 50 days post-surgery. Three of the 5 patients did not perceive any sound with their cochlear implant. This shows that the presence of an eCAP alone does not guarantee a functional auditory nerve or auditory perception. The other 2 patients could hear non-speech sounds, but these sounds quickly became inaudible, indicating that their auditory nerve lacked the ability to integrate the electrical stimulus over time. Conclusions: The presence of an eCAP response does not guarantee auditory sensation through a CI. Although eCAP measurements provide insight into the function of the distal end of the nerve, it does not ascertain integrity or function of the larger auditory nerve pathway. Therefore, eCAPs should not be used in isolation to monitor auditory nerve function during VS resection.

OBJECTIVES: The overall goal of this work is to discuss the various topics associated with critical care advanced practice provider (APP) postgraduate training programs and provide resources for new, developing and existing programs. DESIGN: Three rounds of voting until consensus achieved. SETTING: Electronic surveys, followed by virtual meeting. SUBJECTS: Critical care APPs, physicians, a pharmacist, and a nurse were also included to ensure multidisciplinary representation. All subjects resided and practiced in the United States with a history of education scholarship or post-graduate training leadership. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The workgroup included 14 APPs (ten nurse practitioners and four physician associates), three physicians, one pharmacist, and one registered nurse from 14 institutions across the United States. The workgroup identified six areas of concentration: administration, audience, program structure, curriculum, procedural competence, and accreditation. A survey was generated and employed in three rounds. The first two rounds of voting were completed anonymously, the third round was completed as a live meeting until consensus recommendations, defined as 75% agreement or more, were achieved. CONCLUSIONS: Expert consensus was used to generate consensus recommendations for critical care postgraduate training programs based upon 3 rounds of voting.

Background: Cardiac CT acquired during the acute stroke imaging protocol is an emerging diagnostic modality to detect cardiac thrombi. We aimed to determine its diagnostic yield in a large, international, multicenter study. Methods: We performed an individual patient data meta-analysis by pooling prospective and retrospective observational data of patients with acute ischemic stroke (AIS) who underwent cardiac CT (ECG-gated or non-ECG-gated) as part of the acute imaging protocol between May 2018 and June 2024. We excluded patients with a TIA or stroke mimic. The primary outcome was the proportion of patients with a cardiac thrombus detected on cardiac CT. Secondary outcomes were additional scan time and radiation dose, comparison of yield with echocardiography, and 90-day mortality and recurrent ischemic stroke rates. Results: We included 3940 patients from 4 hospitals (median age 74 [IQR 63-82], 58.0% male, median NIHSS 6 [IQR 3-12], median time onset to hospital arrival 100 minutes [IQR 62-185]). Atrial fibrillation at baseline was present in 23.1% patients, and 29.6% had a large vessel occlusion. Cardiac CT was non-diagnostic in 17 (0.4%) patients. In total, cardiac CT detected 254 cardiac thrombi in 243/3923 (6.2%) patients. Thrombi were located in the left atrial appendage (n=193), left atrium (n=19), and left ventricle (n=42). Of 95/243 (39.1%) patients with a cardiac thrombus that underwent echocardiography (median interval cardiac CT-echocardiography: 2 days), transthoracic echocardiography detected a thrombus in 18/92 (19.6%) patients and transesophageal echocardiography in 2/5 (40.0%) patients. The diagnostic yield in patients that underwent both modalities was higher for cardiac CT (OR 7.5 [CI 4.0-15.3], p<0.001). Median additional scan time was 6 minutes (IQR 5-7) for ECG-gated and 17 seconds (IQR 15-63) for non-ECG-gated cardiac CT. Median additional radiation dose was 5.4mSv (IQR 3.0-7.6). Patients with a cardiac thrombus on cardiac CT had higher 90-day mortality than those without a thrombus (33.3% vs 14.6%, p<0.001). We found no difference in 90-day recurrent stroke rate (5.4% vs 4.4%, p=0.50). Conclusion: Routine cardiac CT performed during the acute stroke imaging protocol detects a cardiac thrombus in 1 out of 16 patients with AIS, with a 7-times higher yield than routine echocardiography. Mortality rate was doubled in patients with a cardiac thrombus, but 90-day stroke recurrence risk did not differ.

Background: The rate of intracardiac thrombus detection in the hyperacute phase of stroke varies from 5% to 12% between studies. Our aim was to compare the thrombus detection rate between ECG-gated and non-ECG-gated cardiac CT protocols in acute stroke patients, using data from a large, international, multicentre registry. Methods: We conducted an individual patient data meta-analysis by pooling prospective and retrospective observational data from stroke patients assessed at four comprehensive stroke centres who underwent either ECG-gated or non-ECG-gated cardiac CT (extended CT angiography or two-phase non-ECG-gated cardiac CT) as part of the acute stroke imaging protocol between May 2018 and June 2024. The primary outcome was the proportion of patients with a cardiac thrombus in gated vs non gated techniques. Results: Of 3,940 patients, 1,474 (37.4%) underwent ECG-gated and 2,466 (62.6%) non-ECG-gated cardiac CT. Patients in the ECG-gated group were younger (median age 72 [IQR 62–81] vs. 74 [IQR 64–82] years, p = 0.000) and had a lower NIHSS at baseline (median 5 [IQR 2–12] vs. 6 [IQR 3–13], p < 0.00). There was a higher rate of thrombus detection with ECG-gated CT compared to non-gated CT (7.5% vs. 5.5%, p = 0.011. The association remained significant after adjusting for age, sex, baseline NIHSS score, and baseline atrial fibrillation (adjusted OR 1.87, 95% CI 1.42–2.47, p = 0.000). ECG-gated CT was associated with lower radiation dose (3.6 vs. 6.3 mSv, p = 0.000) but longer acquisition time (5.8 vs. 0.28 min, p = 0.000). Conclusion: ECG-gated cardiac CT has a higher detection rate for intracardiac thrombus detection compared to non-ECG-gated CT in patients with acute ischemic stroke.

BACKGROUND There is a paucity of literature investigating the use of liposomal bupivacaine (LB) in a dermatologic surgery setting. OBJECTIVE To identify the treatment characteristics and adverse events, including Local Anesthetic System Toxicity (LAST), in patients receiving perioperative LB. MATERIALS AND METHODS A retrospective chart review was performed at a single institution using an institutional database and key words “Exparel” or “liposomal bupivacaine.” Patients ≥18 years old who received perioperative LB to the surgical site and surrounding skin were included. RESULTS A total of 140 LB administrations and 129 patients were included. Liposomal bupivacaine was used most often in the setting of excisions ( n = 88, 62.9%) and Mohs micrographic surgery ( n = 49, 35%), with hidradenitis suppurativa ( n = 77, 55%) and cutaneous neoplasms ( n = 56, 40%) the most frequent diagnoses. The median postoperative area and length were 23.6 cm 2 and 15.4 cm, respectively. The median LB dosage was 20 mL (range 1.5–20). There were no adverse events in 134 out of 136 patients of LB administration (98.5%). There were 2 reports (1.5%) of nausea on POD1 while these patients were taking opioids. CONCLUSION Liposomal bupivacaine should be considered for postoperative analgesia in patients undergoing dermatologic surgery because it is well tolerated and efficacious. The authors observed no cases of LAST.

ABSTRACT Background Previous studies have shown an increased prevalence of eosinophilic gastrointestinal disease (EGID) in pediatric liver and heart transplant recipients. However, EGID after other solid organ and bone marrow transplantations has not been extensively evaluated. Aims The purpose of this study is to determine relationships between subsets of EGID with different solid organ and bone marrow transplants in pediatric patients. Methods We performed a single‐center retrospective chart review of pediatric patients with transplant and EGID between 2007 and 2023. For comparison between transplant groups, ANOVA was used for statistical analysis of continuous variables, and Fisher's exact test was used for categorical variables. Results There were 30 patients with EGID (eosinophilic esophagitis [EoE] = 21; eosinophilic gastritis [EoG] = 4; EoE + EoG = 3; EoE + eosinophilic colitis [EoC] = 1; eosinophilic duodenitis [EoD] = 1) and history of transplant (liver = 15; heart = 9; bone marrow = 3; multivisceral liver + small bowel + pancreas = 2; kidney = 1). When comparing the transplant groups, there was a significant difference in EoE + EoG incidence ( p = 0.011), specifically, EoE + EoG was present in 2 (100%) multivisceral and in 1/15 (7%) liver transplant patients. A statistically significant difference in the presence of gastroesophageal reflux (GER) and oral allergy syndrome between groups was noted ( p = 0.036, p = 0.033). There was no significant difference in the symptoms leading to EGID work‐up: incidence; morphologic features; achievement of histologic remission; medications; or family history of atopy between groups. Conclusion This retrospective biopsy‐confirmed cohort demonstrates that EGID subtype varies by transplant type, with higher rates of EoE + EoG in multivisceral recipients. Findings are exploratory and hypothesis‐generating; larger multicenter studies including more non‐liver and non‐heart transplant patients are needed.