Citations

Portopulmonary hypertension (POPH), pulmonary arterial hypertension that develops in the setting of portal hypertension, has long been of significant interest to the pulmonary, cardiology, and hepatology communities. Optimal management of POPH has been challenging to define due to a lack of evidence from clinical trials regarding pulmonary arterial hypertension therapies and uncertainty regarding the role of liver transplantation (LT). Initially, the high risk of intraoperative and early post-transplant death in predominantly untreated patients with POPH tempered consideration of LT. More recently, the observation that POPH can improve, and sometimes even resolve, following LT, has led to reconsideration of the role of LT in selected patients. The first International Liver Transplantation Society (ILTS) POPH and hepatopulmonary syndrome practice guideline was a multidisciplinary consensus of expert opinions based on available evidence. Since that publication, hemodynamic definitions, management approaches, and POPH MELD exception criteria have evolved, and there have been new randomized controlled trials in POPH as well as studies regarding long-term outcomes. In order to ensure the guidelines remained current and reflected recent evidence, the original writing committee of the 2016 guidelines, leaders of the ILTS Cardiovascular Special Interest Group, and colleagues active in POPH research were invited to participate in the writing committee. In this document, approved for publication by the ILTS executive council, we provide an update to the prior guidelines with expert recommendations to guide and advance POPH management. Recommendations in these guidelines are based on expert opinion and available evidence and were agreed upon by consensus.

ABSTRACTPatients with vascular anomalies (VAs) require expert multidisciplinary care. No prior studies have characterized the sociodemographic characteristics across multiple VA centers. We collected data on 5783 patients receiving care at 20 VA centers between July 1, 2020 through December 31, 2022. Male patients were underrepresented compared to the state‐level census data at 17/20 centers. Black and Asian patients were underrepresented at 14/20 and 12/20 centers, respectively. The median distance to the hospital was 48 miles, and median age was 12.0 years. These data suggest that race, sex, age, and distance from the hospital could impede the ability to access expert VA care.

The placenta is susceptible to infection by a number of viral pathogens, including severe acute respiratory syndrome coronavirus 2, which is associated with poor fetal outcomes. The histologic pattern of injury, termed severe acute respiratory syndrome coronavirus 2 placentitis, is characterized by a triad of increased perivillous fibrin deposition, intervillous histiocytes, and trophoblast necrosis. While the etiology of massive perivillous fibrin deposition (MPVFD) is mostly unknown, previous case reports of MPVFD in association with maternal Enterovirus (ENT) suggest that a subset of these cases are a consequence of undiagnosed viral infection. We evaluated 46 placentas collected between 2011 and 2022 with a diagnosis of MPVFD (n = 41) or chronic histiocytic intervillositis (CHI; n = 4). Combining methods of pan-viral metagenomic sequencing and targeted viral PCR, we detected Enterovirus DNA in 8 of 45 (18%) MPVFD and/or CHI cases. Seven of these positive cases were from MPVFD, and 1 was associated with a CHI diagnosis. Enterovirus A species (n = 7) were commonly identified, whereas one case had Enterovirus B. Histologic evaluation of these cases, including immunohistochemical staining for CD68, demonstrated increased intervillous histiocytes in Enterovirus-positive MPVFD cases in comparison with Enterovirus -negative, as well as evidence of trophoblast necrosis. Thus, we favor the terminology Enterovirus placentitis to describe this pathology. Overall, these findings suggest that Enterovirus is an underrecognized etiology of histologic MPVFD and, possibly, CHI. Further study to evaluate the recurrence risk of Enterovirus placentitis in comparison to MPVFD may help inform future fertility planning in patients with these diagnoses.

ABSTRACT Disease Overview Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity. Diagnosis The presence of IgM monoclonal protein associated with ≥ 10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients and is found in most IgM MGUS patients. MYD88 is not required for the diagnosis. Risk Stratification Age, albumin, hemoglobin level, platelet count, β 2 microglobulin, Lactate dehydrogenase (LDH), and monoclonal IgM concentrations are characteristics that are predictive of outcomes. Risk‐Adapted Therapy Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab‐monotherapy is inferior to combination regimens. Recommended first‐line therapy can be chemoimmunotherapy or a covalent Bruton tyrosine kinase inhibitor. The preferred Mayo Clinic induction is either rituximab and bendamustine (without rituximab maintenance) or zanubrutinib. Management of Refractory Disease Bortezomib, cyclophosphamide, fludarabine, thalidomide, everolimus, pirtobrutinib, carfilzomib, lenalidomide, bendamustine, and venetoclax have all been shown to have activity in relapsed WM. Given WM's natural history, the reduction of therapy toxicity is an important part of treatment selection. Most patients succumb to causes unrelated to macroglobulinemia.

Objective Early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) differ in many respects. Here, we address the issue of possible differences in fibrillar amyloid pathology as measured by positron emission tomography (PET), which remains unresolved due to the lack of large‐scale comparative studies. Methods Three hundred ninety‐nine cognitively impaired participants younger than 65 years of age from the multicenter Longitudinal Early‐onset Alzheimer's Disease Study (LEADS) and 450 cognitively impaired participants older than 65 years from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent clinical assessment, brain magnetic resonance imaging (MRI), and amyloid PET and were included in this study. We compared amyloid PET outcomes (positivity rate based on visual read and quantified tracer uptake expressed as Centiloids [CLs]) between the 2 cohorts and studied their association with age, sex, APOE genotype, and cognition. Results The amyloid positivity rate was higher in LEADS (78%, 95% confidence interval [CI] = 74–82) than in ADNI (71%, 95% CI = 67–75, p = 0.02). Lower Mini‐Mental State Examination (MMSE) and APOE4 genotype increased the odds of amyloid positivity in both cohorts. Visually positive scans had higher CLs in LEADS (EOAD, mean = 95.3 ± 26.1) than in ADNI (LOAD, mean = 80.9 ± 36.8, p < 0.0001), predominantly in parietal cortex/precuneus, superior temporal, and frontal cortices. In amyloid‐positive patients, (1) CLs were higher in female patients in both cohorts; (2) APOE4 carriership was associated with lower CLs in EOAD, which was not observed in LOAD; and (3) correlations between CLs and MMSE scores were significantly stronger in EOAD than in LOAD. Interpretation Differences in the burden of amyloid pathology may contribute to differences in clinical and anatomic patterns in sporadic EOAD and LOAD, and have implications for optimizing therapeutic strategies in each group. ANN NEUROL 2025;98:236–248

Hypertension presents the largest modifiable public health challenge due to its high prevalence, its intimate relationship to cardiovascular diseases, and its complex pathogenesis and pathophysiology. Low awareness of blood pressure elevation and suboptimal hypertension diagnosis serve as the major hurdles in effective hypertension management. Advances in artificial intelligence in hypertension have permitted the integrative analysis of large data sets including omics, clinical (with novel sensor and wearable technologies), health-related, social, behavioral, and environmental sources, and hold transformative potential in achieving large-scale, data-driven approaches toward personalized diagnosis, treatment, and long-term management. However, although the emerging artificial intelligence science may advance the concept of precision hypertension in discovery, drug targeting and development, patient care, and management, its clinical adoption at scale today is lacking. Recognizing that clinical implementation of artificial intelligence–based solutions need evidence generation, this opinion statement examines a clinician-centric perspective of the state-of-art in using artificial intelligence in the management of hypertension and puts forward recommendations toward equitable precision hypertension care.

Abstract Objective The rapid evolution of the COVID-19 virus has led to the development of different vaccine shots, each designed to combat specific variants and enhance overall efficacy. While vaccines have been crucial in controlling the spread of the virus, they can also cause adverse events (AEs). Understanding these relationships is vital for vaccine safety monitoring and surveillance. Methods In our study, we collected data from the Vaccine Adverse Event Reporting System (VAERS) and social media platforms (Twitter and Reddit) to extract relationships between COVID-19 vaccine shots and adverse events. The dataset comprised 771 relation pairs, enabling a comprehensive analysis of adverse event patterns. We employed state-of-the-art GPT models, including GPT-3.5 and GPT-4, alongside traditional models such as Recurrent Neural Networks (RNNs) and BioBERT, to extract these relationships. Additionally, we used two sets of post-processing rules to further refine the extracted relations. Evaluation metrics including precision, recall, and F1-score were used to assess the performance of our models in extracting these relationships accurately. Results The most commonly reported AEs following the primary series of COVID-19 vaccines include arm soreness, fatigue, and headache, while the spectrum of AEs following boosters is more diverse. In relation extraction, fine-tuned GPT-3.5 with Sentence-based Relation Identification achieved the highest precision of 0.94 and a perfect recall of 1, resulting in an impressive F1 score of 0.97. Conclusion This study advances biomedical informatics by showing how large language models and deep learning models can extract relationships between vaccine shots and adverse events from VAERS and social media. These findings improve vaccine safety monitoring and clinical practice by enhancing our understanding of post-vaccination symptoms. The study sets a precedent for future research in natural language processing and biomedical informatics, with potential applications in pharmacovigilance and clinical decision-making.

BACKGROUND The articular theory of the formation of intraneural cysts has significant supporting evidence at common locations but has been less accepted at rarer sites. There have been only 5 cases in the literature documenting an intraneural ganglion cyst in the dorsal cutaneous branch of the ulnar nerve (DCBUN), with only 1 case documenting a joint connection. In this report, the authors present a second case with a proven joint connection in support of the articular theory. OBSERVATIONS The authors report the case of a 73-year-old man who developed a large intraneural ganglion cyst within the DCBUN along the palmar ulnar aspect of his left wrist. Magnetic resonance imaging demonstrated an articular connection to the distal radioulnar joint. During surgery, the intraneural ganglion cyst was resected and the articular branch was disconnected. The patient recovered and returned to work 4 weeks postoperatively. LESSONS This case further supports the articular theory as the explanation for intraneural ganglion cysts, even at unusual locations. https://thejns.org/doi/10.3171/CASE24569

BACKGROUND Degenerative cervical myelopathy (DCM) is the most common cause of adult spinal cord dysfunction. Tourette syndrome (TS) represents a rare cause of DCM that is incompletely characterized in the literature. Patients with TS might develop repetitive involuntary cervical movements that can accelerate spondylotic changes. Therefore, patients with myelopathy secondary to TS or other tic disorders might exhibit DCM symptoms at younger ages. The present study examines the surgical management of DCM secondary to TS in the literature and describes the outcomes of 3 patients who were treated for DCM secondary to TS. OBSERVATIONS In these 3 described cases, fractures led to DCM in 2 patients, while cervical spondylosis led to DCM in 1 patient, all associated with TS. Treating motor tics with medications or deep brain stimulation (DBS) provided effective tic management. All 3 patients experienced improvements in their neurological symptoms following surgery, consistent with other reports in the literature. LESSONS When treating patients with cervical myelopathy secondary to TS, the authors recommend prioritizing motor tic management prior to considering secondary interventions such as surgery. According to the authors, treating motor tics with medications or DBS provides effective tic management. This approach allows for an uncomplicated postoperative course and satisfactory relief of cervical myelopathy. https://thejns.org/doi/10.3171/CASE24751

Abstract Background Antibody responses to MF59-adjuvanted (MF59Flu) and high-dose (HDFlu) influenza vaccines have been well-characterized in older adults, yet corresponding cellular immune response data remain limited. Methods Blood samples were collected from 106 MF59Flu recipients and 112 HDFlu recipients at 4 time points: before vaccination (day 0) and on days 1, 8, and 28 postvaccination. Antibody responses were assessed in serum samples using a hemagglutination inhibition assay. Eight proinflammatory cytokines and chemokines, including IFN-α2a, IFN-γ, IP-10, MCP-1, MIP-1α, IL-1β, IL-6, and IL-8, were quantified from peripheral blood mononuclear cells using a multiplex assay. Associations between cytokine/chemokine secretion levels and antibody responses were examined, along with the effect of sex, age, body mass index (BMI), and cytomegalovirus infection status. Results Age was positively correlated with IL-8 levels on day 1 (r = 0.24, P &lt; .001) and the change in IL-8 levels from day 0 to day 1 (r = 0.16, P = .021). Notably, the change in IL-8 levels was negatively associated with day 28 hemagglutination inhibition titers (r = −0.15, P = .026). Causal mediation analysis demonstrated that IL-8 exerted significant causal mediation effects on antibody responses at both day 8 (P = .046) and day 28 (P = .0045). No significant effects of other cytokines and chemokines, vaccine type, sex, or BMI on antibody responses were observed. Conclusions Our findings underscore IL-8 as a potential mediator of antibody responses to influenza vaccination in older adults, suggesting that IL-8 inhibition could serve as a molecular intervention to improve antibody responses in this high-risk population.