Citations

Abstract Objective To describe the presenting symptoms, treatment regimens, and outcomes associated with oropharyngeal adenoid cystic carcinoma. Data Sources Ovid MEDLINE(R), Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, and Scopus via Elsevier. Review Methods This review followed the Preferred Reporting Items for Systematic Reviews and Meta‐analyses. A medical librarian conducted the literature search using controlled vocabulary and keywords, with investigator input. Eligible articles were clinical trials and observational studies reporting on clinical features, treatment, or outcomes for oropharyngeal adenoid cystic carcinoma. Results Our search identified 233 unique citations, with 44 articles included covering 195 patients. The female‐to‐male ratio was 1.7:1, and the base of the tongue was the most common subsite (73%). Presenting symptoms were mainly pain/discomfort (n = 31), followed by a palpable mass (n = 19) and dysphagia (n = 12). At diagnosis, 22.3% (29 patients) had positive lymph nodes. Treatment was primarily surgical (n = 102), with definitive radiation therapy used in 58 cases. Disease progression was noted in 86 patients, 36% (n = 31) of whom developed distant metastases—primarily to the lungs (n = 26). Long‐term outcomes (n = 76) showed 3‐ and 5‐year overall survival rates of 71.5% to 100% and 47.6% to 79.0%, and disease‐free survival rates of 54.7% to 70.0% and 21.9% to 44.0%, respectively. Conclusion Among patients with available data, oropharyngeal adenoid cystic carcinoma appeared more common in women and has a predilection for the base of the tongue. However, this finding should be interpreted with caution, given the high proportion of missing data. These tumors appear to carry a higher risk for nodal metastases and may lead to poor outcomes.

Abstract Background Immunosuppression (IS) is required in AAV-mediated gene therapy to maximize safety and efficacy, in part to mitigate potential hepatotoxicity and prevent immune-mediated loss of transgene expression. However, prolonged IS increases the risk of complications, including infections. MYBPC3-associated HCM patients have limited treatment options. MyPEAK-1 is a first-in-human trial to assess the safety and efficacy of TN-201, a gene replacement therapy, which was designed to address the underlying genetic cause of MYBPC3-associated HCM in symptomatic adults. Objective To describe the safety and refinement of the IS regimen and monitoring used during the dosing of Cohorts 1 and 2 in the MyPEAK-1 trial. Methods The dose-escalation study utilized two cohorts (n=3 each) receiving 3E13 vg/kg (Cohort 1) or 6E13 vg/kg (Cohort 2) of TN-201 as a single IV infusion. All patients received prophylactic prednisone (starting at 1 mg/kg, maximum 80 or 60 mg/day) and sirolimus (target trough level of 4–8 ng/mL). Prednisone was tapered over several weeks, with variable timing depending on safety laboratory results. The dose of prednisone and timing of sirolimus were adjusted to reduce IS burden in Cohort 2. Specifically, sirolimus was initiated earlier (Day -7 vs Day -3) and the maximum starting dose of prednisone was reduced (from 80 to 60 mg/day). Monitoring frequency was increased to weekly throughout the course of IS. An independent data safety monitoring board provided safety oversight. Results All six patients successfully completed the IS regimen. TN-201 was generally well-tolerated at both dose levels (follow-up >52 weeks and >12 weeks in Cohort 1 and 2, respectively). Adjustments to the IS regimen and monitoring during Cohort 1 facilitated a significantly shorter course of IS in Cohort 2, with a mean duration of prednisone use of 256 vs 81 days. Despite receiving a higher dose of TN-201, peak transaminase levels, reflecting liver inflammation, were lower in Cohort 2 than Cohort 1. There was no clinical TMA in either cohort. Mean sirolimus trough levels remained consistent between groups (7.2 vs 7.4 ng/mL). Increases in MyBP-C protein, decreases in circulating cardiac biomarkers, and a reduction in LV hypertrophy were observed during follow up. Conclusion Standardized adjustments to the prophylactic immunosuppressive regimen in the MyPEAK-1 trial successfully managed the immunogenicity of AAV9-based gene therapy. Cohort 2 patients required lower cumulative corticosteroid doses without compromising safety or cardiac transduction. These refinements enabled lower cumulative steroid exposure and shorter IS durations in the higher-dose cohort. These results suggest that individualized, protocol-driven IS is effective in controlling the immune response to TN-201 while supporting transgene expression, paving the way for continued investigation of this gene therapy clinical investigation in MYBPC3-associated HCM population.Corticosteroid duration and daily doseFor image description, please refer to the figure legend and surrounding text.

Abstract Introduction In the latest ESC Guidelines for the diagnosis and treatment of heart failure, NTproBNP has been recognized as substantial laboratory diagnostic marker. N-terminal pro-B-type natriuretic peptide is a stable degradation product of the active B-type natriuretic peptide, that is produced mainly by cardiomyocytes in response to stretching impulse. Despite being a great diagnostic marker of heart failure, the levels of NTproBNP vary depending on cardiac and non-cardiac conditions. Aim We wanted to evaluate what are the variables that correlate the most with NTproBNP levels in our population of hospitalized patients with heart failure and reduced ejection fraction (HFrEF). Methods We evaluated medical histories of 245 HFrEF patients hospitalized from March 2023 until November 2024. We focused our analysis on parameters related to the most common comorbidities – coronary disease, anemia, sideropenia, chronic kidney disease (CKD), atrial fibrillation (AF), chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM). We collected both numerical (NTproBNP, hemoglobin concentration, estimated glomerular filtration rate - eGFR, serum Fe) and categorical data (the presence of the comorbidity). For statistical analysis we used Spearman’s Rank correlation test and Mann Whitney U test. Results In our patient population (n=245, males 65.53%, mean age 68.48+-10.4 years), out of all analyzed variables, the strongest negative correlation was found between NTproBNP levels and eGFR (rho -0.3989, p<0.01), followed by serum Fe (rho – 0.3791, p<0.01) and hemoglobin concentration (rho -0.3417, p<0.01). There was statistically significant difference of NTproBNP levels in groups with the presence of selected comorbidities - CKD, anemia, coronary disease, COPD and right heart failure (defined as TAPSE / tricuspid annular plane systolic excursion <16mm), in relation to a group without a certain comorbidity. There was no difference found in relation to sex, T2DM and interestingly with the presence of AF. Conclusion Glomerular filtration rate, serum iron and hemoglobin concentration showed to be inversely correlated to NTproBNP levels. Comorbidities can be attributing factors for cardiac decompensation, however in CKD the mechanism of increased NTproBNP is probably related mostly by the elimination reduction, thus the high levels can be interpreted incorrectly.

Abstract Background Large language models (LLMs) offer promise for systematic review data extraction, but performance in complex multidisciplinary domains and utility for clinical statement generation remain insufficiently described. Objectives To evaluate Google NotebookLM for AI-assisted data extraction and RAND/UCLA consensus statement generation in a systematic review of IBD, obesity, and cardiometabolic comorbidities. Methods Studies were organized into domain-specific notebooks; structured prompts generated standardized evidence tables. Two independent reviewers validated outputs against full-text articles using a four-category error classification. Cell-level accuracy and critical accuracy (cells free of major factual errors) were the primary metrics; workflow time was compared against a published conventional extraction benchmark. Concordance between AI-generated and expert-finalized statements was assessed. Results Across 57 articles, 1,710 data cells were extracted; 151 (8.83%) were flagged, yielding 91.17% cell-level accuracy. Major factual errors occurred in only 4 cells (0.23%), for a critical accuracy of 99.77%. Most errors were minor omissions (59.6%) or incomplete extractions (30.5%); domain error rates ranged from 7.08% to 11.33%. The pipeline required 17.7 versus a projected 165.1 person-hours (89.3% reduction). PICO-structured prompting generated 70 candidate statements; 58 of 112 finalized panel statements (51.8%) were AI-derived, and 85.7% were retained in the finalized set. Conclusion Google NotebookLM demonstrates feasibility as a primary extraction and synthesis tool in a multidisciplinary systematic review, with extractive incompleteness as the principal limitation and substantial time savings over conventional approaches. Its novel application to RAND/UCLA consensus statement generation extends AI-assisted evidence synthesis to clinical consensus generation workflow.

Leucine-rich glioma-inactivated-1 (LGI1) IgG-associated autoimmune encephalitis typically presents with faciobrachial dystonic seizures, hyponatremia, and temporal lobe MRI abnormalities. However, the clinical spectrum of LGI1 IgG-associated AE extends beyond these classical features, with reports of diverse seizure semiologies and atypical presentations challenging traditional diagnostic paradigms. This study reports a male in his late 60s presenting with recurrent episodes of right foot cramping and electric shock-like pain, progressing to generalized tonic-clonic seizures. Initial workup suggested chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but LGI1 IgG antibodies were subsequently detected. Despite treatment with intravenous immunoglobulin (IVIG), the seizures persisted. This case highlights the heterogeneity in LGI1 encephalitis presentations. The patient’s proprioceptive-induced reflex seizures represent a rare manifestation of the disease. Treatment with rituximab, a B-cell depleting therapy, resulted in significant improvement, suggesting its potential effectiveness in LGI1 encephalitis with a resistant seizure course. The case also emphasizes the intricate interplay between the mesial temporal lobe, basal ganglia, and frontal regions in LGI1 encephalitis pathophysiology.

The adult chronic pancreatitis (CP) working group, formed at the inception of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC), has developed a robust framework and infrastructure to conduct clinical, translational, and mechanistic studies of CP. At its core is PRO spective Evaluation of C hronic Pancreatitis for E pid E miologic and Translational Stu D ies (PROCEED), the first longitudinal cohort study of CP in US adults, launched in 2017. PROCEED has developed a well-annotated clinical data set of over 2000 deeply-phenotyped participants, a biorepository and an imaging repository. Investigators have published promising data on blood-based and imaging-based biomarkers of CP diagnosis and pain, which are awaiting validation. Clinical observations include classification of patients into mechanism-based pain phenotypes using responses to PROMIS questionnaires, prevalence and predictors of opioid use, prevalence of psychological comorbidity, and osteopathy in CP patients. Pilot clinical trials have evaluated the effect of oral indomethacin on pancreatic fluid prostaglandin E2 levels and Internet-based cognitive behavioral therapy (CBT) for chronic pain. Results of pilot trials have led to an ongoing definitive randomized clinical trial for CBT. The rich environment and resources have facilitated mentorship and academic development of many early-stage investigators. Investigators outside of the consortium have opportunities for collaboration. In the next 5 years, the working group plans to further strengthen the research platform, complete primary and key secondary analyses of PROCEED and ancillary studies, continue efforts to develop biomarkers for diagnosis and prognosis of CP, and complete ongoing clinical trials to address unanswered questions in the field.