Citations

Background. The adoption of technical variant grafts has expanded the donor pool for pediatric liver transplantation, but it also poses a risk of portal vein thrombosis (PVT). This study evaluated risk and prognostic factors of PVT in children undergoing liver transplantation with technical variant grafts. Methods. A total of 3137 pediatric patients from 19 centers were included: 470 received split/reduced deceased donor grafts and 2667 received living donor grafts. Multivariable logistic regression was used to identify risk factors, whereas time-dependent Cox models were used to assess the impact on survival. Results. PVT occurred in 102 patients (3.3%) and was associated with increased mortality (adjusted hazard ratio, 2.86; 95% confidence interval [CI], 1.13-7.25; P = 0.027) and graft loss (adjusted hazard ratio, 9.97; 95% CI, 4.90-20.3; P < 0.001). Risk factors included younger age, lower weight, higher Pediatric End-Stage Liver Disease score, longer cold ischemia and operation times, higher graft-to-recipient weight ratio, increased red blood cell transfusions, and biliary atresia. After adjusting for center, lower weight (odds ratio, 0.84 per kg; 95% CI, 0.71-1.00; P = 0.047) and biliary atresia (odds ratio, 2.34; 95% CI, 1.10-5.00; P = 0.027) remained predictors. Five-year patient (88.4% versus 93.1%) and graft survival (82.7% versus 96.3%) were significantly inferior in patients with PVT. Conclusions. Low-weight children with biliary atresia constituted a high-risk group, highlighting the necessity for early detection and management.

Rural populations are underrepresented in cognitive impairment research and have limited resources for education about brain and cognitive health, Alzheimer's disease and related dementias, or caregiving. As our Outreach, Recruitment, and Engagement team aimed to expand activities into more rural communities, we also wanted to better understand the characteristics of the communities surrounding our center and gain insight into the social exposome of the areas. The goal of the manuscript is to reflect on our experience and share measures that were useful in this effort, which can be further enriched and adjusted by other outreach teams.

ABSTRACT The enteric nervous system (ENS) is a complex peripheral neural network that coordinates gastrointestinal motility through highly organized synaptic communication. Although tissue-resident muscularis macrophages (MMs) closely associate with enteric neurons, whether they regulate enteric synaptic organization remains unknown. In the central nervous system (CNS), microglia sculpt neural circuits through complement-dependent synaptic remodeling, raising the possibility that analogous neuroimmune mechanisms operate in the gut. Here, we identify a previously unrecognized role for C1qa□ MMs in regulating enteric synaptic homeostasis and gastrointestinal motility. Using macrophage-specific constitutive and inducible C1qa deletion models, single-cell RNA sequencing, enteric synaptosome proteomics, physiology, and advanced imaging, we demonstrate that loss of MMs-derived C1qa increases enteric synaptic density without altering neuronal numbers. C1qa deficiency induced broad transcriptional changes in enteric neurons and macrophages, including altered synapse-associated, lysosomal, and endocytic programs. Proteomic analysis revealed that enteric synapses share a conserved molecular architecture with brain synapses while exhibiting distinct gastrointestinal-specific complement-associated synaptic networks enriched for structural and receptor-localization pathways. Functionally, macrophage-specific C1qa deletion altered excitatory and inhibitory enteric neurotransmission, enhanced cholinergic signaling, reduced nitrergic responses, and accelerated gastrointestinal transit, while smooth muscle responsiveness remained preserved. C1qa□ MMs displayed transcriptional and functional features consistent with a phagocytic synapse-remodeling phenotype, including enrichment of complement, lysosomal, and engulfment pathways. Loss of C1qa impaired macrophage phagocytic activity both in vitro and in vivo and was associated with synapse accumulation and altered macrophage morphology. Importantly, inducible deletion of C1qa in adulthood recapitulated the synaptic and motility phenotypes, demonstrating that C1qa□ MMs continuously regulate enteric synaptic organization beyond development. Together, these findings identify a complement-dependent neuroimmune mechanism that regulates enteric circuit organization and gut motility, establishing MMs as active modulators of adult ENS synaptic homeostasis. Abstract Figure

ABSTRACT Background While guidelines state that patients with NCCN favorable intermediate risk (FIR) prostate cancer (PCa) may consider active surveillance (AS), there is a relative lack of longer term follow up data informing AS inclusion criteria of patients with Grade Group (GG) 2 prostate cancer in the MRI era. Here we evaluate patient outcomes from a MRI‐screened AS‐eligible cohort of FIR GG2 PCa receiving radical prostatectomy (RP). Methods Patients with prostate MRI, NCCN FIR GG2 PCa (PSA < 10 ng/mL, ≤ cT2a, < 50% core positivity), and no prior treatments who underwent RP from 2015 to 2023 were included from a prospectively maintained prostatectomy registry. Primary outcomes were adverse pathologic features (APF) at RP (GG3‐5, ≥ pT3a, or pN1) and biochemical recurrence (BCR). Logistic regression and Cox regression identified factors associated with APF at RP and time to BCR, respectively. Results Of 522 patients, 110 (21%) had APF at RP and 45 (9%) developed BCR with median follow up 2.4 years (IQR 1.3–2.8). On multivariable logistic regression, % Gleason pattern 4 (%GP4, %GP4 > 25% OR 2.14, 95% CI 1.28–3.58, p = 0.004) was independently associated with APF. On multivariable Cox regression for time to BCR, PSAD (HR 1.06, 95% CI 1.04–1.09, p < 0.001) and positive surgical margins (HR 1.06, 95% CI 1.09–3.78, p = 0.03) were independently associated with BCR. PIRADS, % core positivity, and specimen involvement were associated with neither APF nor BCR. Conclusions % Gleason pattern 4 > 25% and PSAD are the primary factors associated with adverse outcomes and should be considered for patients with FIR GG2 PCa considering active surveillance. PIRADS and measures of biopsy cancer volume were not associated with APF or BCR. These results may inform patient selection for active surveillance among patients with FIR GG2 PCa.

ABSTRACT Traumatic defects of the helical rim caused by human bites present significant reconstructive challenges because of tissue loss, infection risk, and the need to preserve auricular contour and symmetry. We report a 27‐year‐old man who presented with a middle‐third defect of the left helical rim following necrosis of an initially sutured avulsed flap caused by a human bite injury. After discussion of reconstructive options, including chondrocutaneous advancement and staged flap procedures, a single‐stage modified postauricular flap without skin grafting was selected to preserve ear size and minimize donor‐site morbidity. The flap was successfully inset with restoration of the helical contour, and postoperative follow‐up demonstrated stable healing, preserved auricular shape, and high patient satisfaction without complications. This case highlights that a single‐stage modified postauricular flap is a reliable and patient‐centered option for reconstruction of traumatic helical rim defects following human bite injuries.

Abstract Interstitial lung disease (ILD) is a chronic, irreversible condition that is challenging to diagnose due to subtle symptoms and limitations of conventional tools. Noninvasive lung sound analysis using phonopulmography offers a promising alternative. This study evaluated the feasibility of a deep learning model for distinguishing normal and pathological lung sounds in ILD. Lung sound recordings were collected from 12 subjects (6 healthy, 6 ILD) and segmented beat-to-beat using simultaneously acquired ECG and phonopulmography, yielding 2,280 segments. Mel-frequency cepstral coefficients (MFCCs; 13 per segment) were extracted, and a one-dimensional CNN-based You Only Listen Once (YOLO) model was trained for segment classification. Evaluation used Leave-One-Out Cross-Validation, with patient-level classification by aggregating segment predictions via majority vote. On the test set (190 segments per class), the model achieved an average segment-level accuracy of 0.738 ± 0.087 and mean AUC of 0.850 ± 0.062. Precision, recall, and F1-score were 0.775 ± 0.148, 0.755 ± 0.183, and 0.738 ± 0.089, respectively. These preliminary results suggest that beat-level MFCCs with a 1D CNN-based YOLO model enable accurate segment- and patient-level classification. This feasibility study highlights the potential of AI-assisted auscultation for noninvasive monitoring and clinical decision support in ILD management, pending further validation in larger cohorts.

Background Despite consistent epidemiological evidence identifying smoking as a risk factor for medication-overuse headache (MOH), the mechanisms underlying this association remain incompletely elucidated. The aim of this work was to explore the relationship between the severity of analgesic dependence, headache-related disability, nicotine dependence, psychological distress, and addiction-related personality traits in patients with MOH. Methods This multicenter cross-sectional study was conducted on 442 patients with primary headache disorders. Participants underwent structured face-to-face interviews and were asked to fill out the following questionnaires: Headache Impact Test–6 (HIT-6), Severity of Dependence Scale (SDS), Depression Anxiety Stress Scales-12 (DASS-12), and Substance Use Risk Profile Scale (SURPS). Smoking status was documented for all participants. Current smokers were asked to complete Fagerström Test for Nicotine Dependence questionnaire (FTND). Results This study included 442 patients with primary headache disorders, of whom 150 had MOH and 292 did not. Patients with MOH (n = 150) reported significantly higher monthly headache days (MHD), acute medication days (AMD), HIT-6, DASS-12, and SURPS scores than those without MOH (n = 292) (all P-values < 0.001). Smoking prevalence and FTND scores were significantly higher among MOH patients than those without MOH (all P-values < 0.001). Smokers demonstrated higher MHD, AMD, prevalence of MOH, DASS-12, and SURPS scores than non-smokers (all P-values < 0.05). Among smokers, FTND correlated positively with MHD, AMD, HIT-6, DASS-12, and SURPS (all P-values < 0.001). In patients with MOH, SDS scores showed positive correlations with AMD, HIT-6, DASS-12, and SURPS (all P-values < 0.05). Conclusion Severity of dependence on analgesics in patients with MOH is strongly associated with headache burden, nicotine dependence, psychological distress, and addiction-related personality traits.

Background: Liver transplantation (LT) remains the definitive treatment for end-stage liver disease; however, post-LT outcomes may differ depending on underlying disease etiology. Our study aimed to compare post-LT outcomes between alcoholic and non-alcoholic steatohepatitis (NASH)-related liver transplant recipients in the United States. Methods: A retrospective cohort study was conducted using the TriNetX Research Network. Adult liver transplant recipients (≥18 years) were categorized into two mutually exclusive cohorts: alcoholic liver disease and NASH-related liver disease. Propensity score matching (1:1) was performed to balance baseline characteristics. Clinical outcomes were assessed. Comparative analyses included risk ratios, risk differences, odds ratios, Kaplan–Meier survival analysis, and hazard ratios with log-rank testing. Results: Compared with NASH recipients, alcoholic LT recipients had a significantly higher risk of rejection (14.5% vs. 12.1%; RR 1.195, 95% CI 1.076–1.327; p = 0.001) and hepatic encephalopathy (14.3% vs. 8.3%; RR 1.720, 95% CI 1.526–1.938; p < 0.001). Acute kidney injury was also more frequent in the alcoholic cohort (47.3% vs. 43.6%; RR 1.084, 95% CI 1.036–1.133; p < 0.001). In contrast, sepsis (15.6% vs. 18.0%; RR 0.869, 95% CI 0.794–0.952; p = 0.003) and CKD (46.1% vs. 51.1%; RR 0.901, 95% CI 0.863–0.939; p < 0.001) occurred less frequently in alcoholic LT patients. No significant differences were observed for liver transplant failure or ascites. Kaplan–Meier analyses demonstrated significantly lower rejection-free survival (HR 1.241, p < 0.001), higher hepatic encephalopathy (HR 1.808, p < 0.001), increased AKI risk (HR 1.150, p < 0.001) and higher all-cause mortality in the alcoholic cohort (HR 1.106, p = 0.031). Conclusions: In this large real-world matched cohort study, alcoholic LT recipients demonstrated higher risks of complications and all-cause mortality compared with NASH LT recipients.

Background: Perianal Crohn’s disease (PCD) is a severe and disabling phenotype of Crohn’s disease that often requires multidisciplinary medical and surgical management. Although ustekinumab (UST) and vedolizumab (VDZ) are widely used after antitumor necrosis factor (anti-TNF) failure, direct comparative data specifically in PCD remain limited. Methods: We conducted a multicenter, retrospective cohort study using the TriNetX US Collaborative Network to compare the effectiveness of UST versus VDZ in adults (18 y or older) with PCD between January 2017 and May 2023. Outcomes were perianal-specific clinical events, including definitive fistula surgery, incision and drainage, diversion procedures, and antibiotic use (metronidazole or ciprofloxacin), assessed at 1 and 2 years after biological initiation. Propensity score matching (PSM) (1:1) was performed to balance baseline variables. Time-to-event analyses were conducted in the matched population using Kaplan–Meier methods, and hazard ratios (HRs) were estimated using Cox proportional hazards models within the matched cohorts. Results: A total of 2936 patients were identified before PSM: 1997 patients in the UST group and 939 patients in the VDZ group. After PSM, 936 patients were included in each cohort. In the matched cohorts, UST was associated with significantly lower risk of definitive perianal fistula surgery (HR: 0.66, 95% CI: 0.50-0.89; P <0.01), and composite surgical events (HR: 0.70, 95% CI: 0.54-0.87; P <0.01) compared with VDZ at 1 year. Rates of antibiotic use, incision and drainage of perianal abscess, and diversion procedures were numerically lower but not statistically significant. At 2 years, these findings persisted, with significantly lower cumulative incidence of definitive perianal fistula surgery (HR: 0.78, 95% CI: 0.61-0.90; P =0.03), composite surgical events (HR: 0.81, 95% CI: 0.69-0.90; P <0.01), and antibiotic use (HR: 0.86, 95% CI: 0.75-0.93; P =0.04) in the UST cohort compared with VDZ. Rates of incision and drainage and diversion procedures remained similar between groups. Conclusion: In this large real-world cohort, UST was associated with lower risks of perianal surgical interventions at one and two years and reduced antibiotic utilization at two years compared with VDZ in patients with PCD. These findings highlight meaningful differences in real-world effectiveness between therapies and support the need for prospective studies to further evaluate comparative effectiveness in this population.