Citations

Background: Timely intervention and effective control of Alzheimer’s disease (AD) have been shown to limit memory loss and preserve cognitive function and the ability to perform simple activities in older adults. In addition, magnetic resonance imaging (MRI) scans are one of the most common and effective methods for early detection of AD. With the rapid development of deep learning (DL) algorithms, AD detection based on deep learning has wide applications. Methods: In this research, we have developed an AD detection method based on three-dimensional (3D) convolutional neural networks (CNNs) for 3D MRI images, which can achieve strong accuracy when compared with traditional 3D CNN models. The proposed model has four main blocks, and the multi-layer fusion functionality of each block was used to improve the efficiency of the proposed model. The performance of the proposed model was compared with three different pre-trained 3D CNN architectures (i.e., 3D ResNet-18, 3D InceptionResNet-v2, and 3D Efficientnet-b2) in both tasks of multi-/binary-class classification of AD. Results: Our model achieved impressive classification results of 91.4% for binary-class as well as 80.6% for multi-class classification on the Open Access Series of Imaging Studies (OASIS) database. Conclusions: Such results serve to demonstrate that multi-stage feature fusion of 3D CNN is an effective solution to improve the accuracy of diagnosis of AD with 3D MRI, thus enabling earlier and more accurate diagnosis.

Abstract Hepatocellular carcinoma (HCC) mortality is increasing globally, partly due to the growing prevalence of nonviral liver diseases. Genome‐wide association studies (GWAS) have identified genetic variants associated with HCC development. Leveraging GWAS summary statistics and linkage disequilibrium score regression (LDSR), we investigated disease co‐development with hepatitis C virus‐negative (HCV‐negative) HCC to provide unique insights into HCC etiology and prioritize relationships for further causal inquiry. We utilized the LDSR statistical framework to estimate the genetic correlation and heritability between HCV‐negative HCC with 901 epidemiologic, behavioral, and clinical traits from the United Kingdom Biobank (UKBB). First, we set the threshold for observed scale heritability of each trait at 0.02 to ensure reliable inferences with adequate study power. Next, we observed significant positive genetic correlations between HCV‐negative HCC and blood‐based biomarkers of liver injury (ALT, GGT) and allostatic load (including glycated hemoglobin, blood pressure, and total albumin). We also identified a positive genetic correlation between HCV‐negative HCC and diseases associated with metabolic dysfunction‐associated steatotic liver disease (MASLD), including diabetes, hypertension, chronic ischemic heart disease, and others. Taken together, our results help to identify polygenic and pleiotropic signals related to different phenotypic traits associated with HCC and support further exploration of the predictive power of blood‐based biomarkers identified in this study for inferring HCC development among HCV‐negative individuals.

Objectives: Current standard of care after a First-Time patellar instability event is non-operative management, with exceptions for patients with osteochondral fracture or loose body requiring immediate surgical intervention, patients with significant pathoanatomy, or contralateral patellar instability. For recurrent patellar instability, there is controversy as to when isolated medial patellofemoral ligament reconstruction (MPFL-R) is enough. The purpose of this study is to determine (1) the comparative outcomes of isolated MPFL-R after first-time patellar instability (FTPI) and recurrent patellar instability (RPI) and (2) the impact of osteochondral injury on outcomes after surgical treatment of FTPI. Methods: A prospective, multicenter cohort study (JUPITER: Justifying Patellar Instability Treatment by Results) database was queried for patients who underwent patellar stabilization surgery (PSS) between December 2016 and September 2022. Patients were included if they underwent a medial patellofemoral ligament reconstruction (MPFL-R) for FTPI or RPI. Those with less than 2 years of clinical follow-up, revision PSS, or concomitant bony procedures at the time of MPFL-R were excluded. Independent t-tests were performed to compare means for continuous variables, and chi-squared tests were performed to compare frequency for categorical variables, between groups. Results: A total of 739 patients met inclusion criteria with a mean age of 15.6 ± 3.3 years, and 59.9% female sex. FTPI occurred in 216 (27.2%) patients, and of these 104 (48.1%) sustained an operative chondral or osteochondral lesion. Those with FTPI had a significantly greater trochlear depth (2.9 mm vs. 2.6 mm; P = .048), but a significantly lower rate of pathological trochlear bump > 5 mm (52.3% vs. 67.8%; P = .008) than those with RPI (Table 1). Among the FTPI cohort, those with treatment of a chondral lesion were less likely to have patella alta (Caton-Deschamps Index > 1.3) (14.9% vs. 41.3%, P = .006), and less frequently had a mild or severe J-sign (25.0% vs. 42.7%, p = .016) than those without a chondral intervention (Table 2). Postoperatively, there were no differences with rates of recurrent instability (8.3% vs. 12.3%; P = .130) or return to sport (90.4% vs. 94.5%; P = .182) between FTPI and RPI, respectively (Table 3). There were no differences with rates of recurrent instability (7.6% vs. 9.1%; P = .807) or return to sport (89.1% vs. 91.7%; P = .755) between those with or without a chondral intervention, respectively (Table 4). Conclusions: This study demonstrates no difference in rates of recurrent post-operative instability between FTPI and RPI with rates consistent with the current literature. MPFL reconstruction remains as a durable surgical treatment option for patients presenting with either FTPI or RPI with relatively low rates of recurrent instability. In this patient population, patella alta was found to be protective of osteochondral injury which is also consistent with existing literature. Continued, long-term investigation is needed to understand outcomes for First-Time patellar instability and to better define the indications for surgical interventions in this population.

Normothermic machine perfusion (NMP) enables preservation and functional assessment of liver allografts, improving outcomes, particularly in marginal organs. However, the TransMedics Organ Care System (OCS) permits only single hepatic artery (HA) cannulation, limiting its use in grafts with variant arterial anatomy. Arterial reconstruction before NMP may overcome this limitation and expand the pool of grafts eligible for perfusion. We conducted a retrospective single-center cohort study of adult liver transplants utilizing OCS from January 2022 to September 2024. Allografts with variant hepatic artery anatomy requiring arterial reconstruction before NMP initiation were identified. Postoperative outcomes, including vascular and biliary complications, were compared between reconstructed and non-reconstructed grafts. Among 541 OCS-preserved grafts, 74 (13.7%) underwent arterial reconstruction. Compared with non-reconstructed grafts, reconstructed grafts had longer cross-clamp to cannulation time (2.8 vs. 2.4 h, p <0.001), but similar rates of early allograft dysfunction (23.0% vs. 20.8%, p =0.65), ischemic cholangiopathy (4.1% vs. 4.1%, p =1.00), and primary nonfunction (0.0% vs. 0.4%, p =1.00). Early (2.7% vs. 0.2%, p =0.05) and late hepatic artery thrombosis (HAT) (4.1% vs. 2.1%, p =0.40) were infrequent and not significantly different between non-reconstructed and reconstructed groups, respectively. Hepatic artery stenosis occurred more often in reconstructed grafts (12.2% vs. 4.1%, p =0.008), though most cases were managed with interventional radiology or surgical revision. Only one reconstructed graft required retransplantation due to vascular complications. Arterial reconstruction before NMP is safe and feasible, enabling successful perfusion and transplantation of liver allografts with variant HA anatomy. These findings support the broader application of NMP in anatomically complex donor livers.

ABSTRACT Objectives To characterize practice patterns and outcomes in the management of low‐ and intermediate‐grade salivary gland carcinoma prior to the existence of treatment guidelines. Methods Analysis of a registry of patients who underwent parotid and submandibular gland resections for low‐and intermediate‐grade carcinomas between 2010 and 2019. Results Of all 786 patients included in the study, 726 (92%) had preoperative imaging and 653 (83%) had preoperative biopsy. Of the 729 patients with parotid gland cancer, the majority underwent superficial ( n = 384, 53%) or total ( n = 254, 35%) parotidectomy. In patients with facial nerve preservation, total parotidectomy was associated with a significant increase in transient facial weakness (72/177 (41%) vs. 82/311 (26%), RR 0.65, 95% CI 0.50–0.84, p < 0.05) and permanent facial nerve weakness (23/176 (13%) vs. 16/301 (5%), RR 0.41, 95% CI 0.22–0.75, p < 0.05) compared to superficial parotidectomy. Adjuvant radiation therapy ( RT ) was delivered to 285 (36%) patients. The proportion of patients receiving adjuvant RT declined significantly over the time period from 2015 to 2019 compared to 2010 to 2014 at 162/504 (32%) and 123/282 (44%), respectively ( RR 0.74, 95% CI 0.61–0.89, p < 0.05). When comparing the time periods from 2015 to 2019 and 2010 to 2014, there was no significant difference in local control rates ( RR 0.52, 95% CI 0.26–1.04, p = 0.06) or regional control rates ( RR 0.75, 95% CI 0.26–2.13, p = 0.58). Conclusions Management of low‐ and intermediate‐grade salivary cancer from 2010 to 2019 was variable, which is expected given the rarity and heterogeneity of the disease and the lack of treatment guidelines prior to 2021. Most patients with parotid malignancies underwent superficial or total parotidectomy. The extent of parotidectomy had an impact on facial nerve function outcomes. Delivery of adjuvant radiation trended down with time. The data presented here will support dissemination of the guidelines and provide data that could inform future trials. Level of Evidence 2b.

AbstractBackgroundVEXAS syndrome is an autoinflammatory disease caused by somatic UBA1 mutations on the X chromosome, predominantly affecting men.ObjectiveTo characterize VEXAS syndrome in women and to compare the features of VEXAS syndrome between sexes.MethodsWe conducted an international, multicenter study, including 12 women and 301 men with genetically confirmed VEXAS syndrome. Data were collected using a standardized case report form. Bone marrow analyses and molecular investigations were performed locally.ResultsClinical features, age at onset, UBA1 mutation type, variant allele frequency, and mortality were comparable between sexes. Acquired X monosomy was found in 6/8 tested women. Additional clonal mutations were present in 3/5 tested women. Three additional UBA1‐mutated women without typical inflammation are described separately.ConclusionVEXAS syndrome affects women with clinical features similar to men, supporting the need for UBA1 testing in women with compatible presentations. X monosomy is common but not universal, suggesting alternative pathogenic mechanisms.