Citations

ABSTRACTPortopulmonary hypertension (PoPH), a type of pulmonary arterial hypertension (PAH) in patients with liver disease, is associated with high morbidity and mortality. The relationship between cardiopulmonary hemodynamics, PAH therapy, and survival in PoPH remains unclear. We performed a retrospective cohort study of PoPH patients from the international pulmonary hypertension (PH) meta‐registry, PVRI GoDeep. PAH was defined by a mean pulmonary arterial pressure > 20 mmHg, pulmonary arterial wedge pressure ≤ 15 mmHg, and a pulmonary vascular resistance (PVR) > 2 Wood Units. PoPH diagnoses were assigned by each center's PH specialist based on international guidelines at the time of enrollment. 246 incident PoPH patients met eligibility criteria and were included in the analysis, equally split between males (51%) and females (49%), with a median age of 54 years. When compared to both patients with IPAH and those with other subtypes of PAH (not classified as PoPH or IPAH), those with PoPH had significantly lower 5‐year survival rates (46% vs. 68% vs. 65%, log‐rank p < 0.001). Amongst the PoPH patients, however, there was no significant difference in 5‐year survival when dichotomized by disease severity, either by a PVR of 5 Wood Units or a CI of 2.5 L/min/m2. Treatment of the PoPH patients with PAH‐targeted therapies was associated with significantly higher 5‐year survival rates compared to those not receiving such treatments, as shown by Kaplan–Meier analysis. This survival benefit was observed for PDE5i (50% vs. 34%, log‐rank p = 0.029), ERA (58% vs. 34%, log‐rank p < 0.001), and the combination of PDE5i and/or ERA (51% vs. 22%, log‐rank p < 0.001), as well as any PAH‐targeting treatment (50% vs. 26%, log‐rank p = 0.007). Corresponding survival advantage was noted when including only PoPH patients with MELD Score ≥ 13. PoPH is a disease with significantly worse long‐term survival than other PAH subtypes, but targeted PAH therapy is associated with a robust survival benefit. Survival did not differ across high‐risk PVR and cardiac index thresholds, suggesting the factors that influence prognosis and survival in PoPH may be unique as compared to other PAH subtypes, and warrant further investigation.

BACKGROUND There is a scarcity of artificial intelligence models trained on frozen pathology. One way to expand the clinical utility of models trained on permanent pathology is by applying them to frozen sections and fine-tune based on weaknesses. OBJECTIVE To qualitatively evaluate a deep learning model trained on permanent pathology to classify squamous cell carcinoma on Mohs surgery frozen sections to learn model shortcomings and inform retraining and fine-tuning. MATERIALS AND METHODS The authors trained a model for classification of tumor on 746 skin biopsy slides and tested it on 15 Mohs surgery frozen sections. The authors estimated performance metrics and compared the regions of interest generated by the model with the original H&E slides. RESULTS The model achieved an AUC-ROC of 0.985 and 0.796 for tumor classification in permanent pathology and in frozen sections, respectively. Regions of interest for frozen sections with scarce tumor areas were inaccurate, focusing on normal tissue for slides classified as false negative, or highlighting structures different from tumor (e.g., inflammation, muscle, and nerves) for slides classified as true positive. CONCLUSION Deep anatomical structures more commonly present in Mohs frozen pathology might represent data out-of-distribution for models trained on permanent pathology, potentially leading to inadequate model outputs.

ABSTRACTIntroductionPulsed‐field ablation (PFA) is a novel and effective modality for ablation in patients with atrial fibrillation (AF). Available case reports and small series showed promising results in patients with congenital heart disease. However, PFA ablation in Fontan patients has not been reported yet.Methods and ResultsWe present a 35‐year‐old patient with a history of Fontan palliation for hypoplastic left heart who underwent successful ablation for AF with PFA. We describe procedure characteristics and illustrate the potential benefits of PFA in this patient population.ConclusionWe present a case of PFA for AF in Fontan palliation. PFA was feasible and successful in our case. Long‐term outcomes are yet to be determined.

Background: Recurrent anterior shoulder instability may lead to capsuloligamentous and bony lesions of the glenoid and humerus. To date, there is no clear consensus on how to best measure anterior glenoid bone loss (GBL) in the setting of recurrent instability. The objective of this study, therefore, was to evaluate the accuracy and reliability of 7 different methods of measuring anterior GBL on three-dimensional models based on computed tomography. Methods: Eight levels of GBL in the anterior and anteroinferior directions were virtually generated in 14 three-dimensional healthy glenoid models. GBL was measured with 7 different methods: based on a height/width ratio (M1), based on surface area within a circle (M2 and M3), based on linear distance within a circle, (M4, M5, and M6), and based on a volume ratio (M7). For each method, the measurement accuracy was assessed by comparing the calculated value with the true amount of generated GBL. The measurement reliability was assessed by computing the score variance and intraclass correlation coefficient. Results: The most accurate (average measurement error of <2% and largest proportion with error <5%) and reliable (ICC >0.96) measurement methods for GBL were M2 (based on surface area) and M5 (based on the linear distance). The average measurement error for the other methods ranged between 3% and 11% for anterior GBL and between 2% and 9% for anteroinferior GBL. For anterior GBL, the measurement increased by an average of 0.5% for each 1% increase in circle radius, leading to an overestimation of GBL with a larger circle diameter Conclusion: The methods for calculating glenoid bone loss performed better for the more common direct anterior bone loss rather than the less common anteroinferior-directed bone loss. Both an area-based method (M2) and linear distance–based method (M5) resulted in accurate and reliable measurements of glenoid bone loss; however, the linear distance–based methods may be easier to perform clinically. The height-width ratio and volume methods were less accurate and reliable. Level of Evidence: Level IV ; case series; diagnostic studies. See Instructions for Authors for a complete description of levels of evidence.

Abstract Background The CCDC26 germline variant rs55705857 is causal for development of IDH mutant (IDHmut) adult glioma. However, ~60% of IDHmut patients do not carry the rs55705857 risk allele. We aimed to identify variants associated with developing IDHmut glioma among patients that do not have the rs55705857 risk allele and to further understand development of IDHwt glioma. Methods We used three datasets that included 1216 IDHmut and 1442 IDHwt glioma patients and a case–case design to perform genome-wide association (GWAS) analyses comparing IDHmut versus IDHwt glioma. Analyses were performed overall and stratified by rs55705857 genotype and sex. Multivariable logistic regression and regression trees were used to develop models to predict IDH status using germline variants, age, and contrast enhancement on MRI. Results Three regions were identified comparing IDHmut versus IDHwt: rs55705857 (meta P-value [P] = 1.35 × 10−43), PHLDB1 (rs7125115, P = 3.46 × 10−17), and D2HGDH (rs71430382, P = 2.43 × 10−12). When analyzing only patients that do not have the rs55705857 risk allele, PHLDB1 (rs7125115, P = 1.73 × 10−13) and D2HGDH (rs71430382, P = 8.86 × 10−10) were identified. Among patients who have the rs55705857 risk allele, four variants between ROBO1 and ROBO2 (rs4680975, P = 4.65 × 10−7) increased the likelihood of having an IDHwt tumor. Tumor expression of ROBO1 was associated with rs4680975 genotype in IDHwt patients that have the rs55705857 risk allele (P = 0.034). Multivariable logistic analysis demonstrated that rs55705857, rs71430382 (D2HGDH), and age predicted IDH mutation status. Conclusions To understand the development of adult glioma, we demonstrate that D2HGDH and PHLDB1 should be prioritized for functional studies in IDHmut tumors. The ROBO1 region warrants further investigation in IDHwt tumors.

Background/Objectives: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may report abnormalities in voice and speech; however, no formal research has been conducted in this area. Methods: An online mixed-methods survey was completed by 685 people with ME/CFS. A total of 302 respondents completed the qualitative component (44.09%). Questions assessed disease experience with ME/CFS and post-exertional malaise without prompting on specific symptoms. Within the qualitative results, a search of the terms “speech, voice,” “words,” and “speak” was conducted. Results: Excluding neurocognitive associations, colloquial phrases, and “speech therapy,” there were 38 mentions of the terms in the context of voice or speech changes across 28 unique qualitative survey responses (9.27%). Conclusions: A notable portion of respondents reported voice or speech changes when responding to open-ended qualitative questions about their disease experience. More research is needed regarding the implications of voice and speech anomalies in ME/CFS pathology and disease monitoring.

In 2023, the VAS international working group on Buerger’s Disease (BD) recommended two diagnostic criteria based on a prior Delphi study: “definitive” and “suspected”. The “definitive” criteria are history of smoking, typical angiography, and typical histopathological features. All three features are mandatory to confirm a “definitive” diagnosis of BD. The conundrum is—what features should be considered typical of BD angiography? According to this review, segmental occlusion of infrapopliteal arteries, corkscrew collaterals that appear to continue the occluded arterial segment (Martorell’s sign) or bypass the segmental occlusion, absence of atherosclerotic plaque or aneurysm could differentiate BD from ASO. Hence, for “typical” BD angiography, these manifestations should certainly be considered. However, data for differentiating angiography patterns of BD from the small- and medium-sized vasculitis including Behcet’s disease, scleroderma, hepatitis associated vasculitis, and anti-phospholipid syndrome are limited. Further studies for investigating the angiography pattern in BD patients in early and late presentation of BD, particularly in the patients with long-term follow up, are highly recommended.

Abstract Motivation Efforts to address health disparities are often limited by the lack of robust computational tools for inferring genetic ancestry by calculating an individual’s genetic similarity to continental groups. We have already shown that a preferred alternative to self-described race is using ancestry-informative markers (AIMs) that can be classified into ancestral components and used to estimate their similarity to those of known populations to identify continental groups. However, real-world genomic data can present challenges, including limited availability of germline DNA, a small number of AIMs for each sample, and the use of different variant calling software, limiting the application of existing solutions. Results Here, we describe a novel supervised machine-learning tool AncestryGeni, which infers genetic ancestry for samples with even a hundred markers and is applicable to any genomic data, including whole exome sequencing (WES) and RNA sequencing (RNA-Seq) data. Applying AncestryGeni to a real-world genomic dataset obtained from the Multiple Myeloma Research Foundation (MMRF) CoMMpass study, we show that it is more accurate than the commonly used FastNGSadmix when using nonstandard genomic material. We also demonstrate that when using AncestryGeni, the tumor-derived sequence obtained from WES and RNA-Seq can be a robust data source to accurately estimate an individual’s genetic similarity to a continental group. Availability and implementation AncestryGeni pipeline is available at https://github.com/eelhaik/AncestryGeni/tree/main.

Overtraining syndrome (OTS) is a significant medical condition observed predominantly in endurance athletes and characterised by a decline in performance and disruptions in multiple physiological functions. Given the increasing popularity of endurance training and the complex nature of OTS diagnosis, there is a compelling need for comprehensive case studies. The case series summarises one professional runner, one competitive runner and one recreational runner who were diagnosed with OTS. Key parameters observed include symptoms, diagnostic journey, recovery initiatives and return-to-sport outcomes. All three athletes showed typical OTS manifestations, including impaired performance and multisystem dysfunction (ie, endocrine, nervous, immune and gastrointestinal systems). Following a mandated cessation from training, active recovery strategies were instituted. Two of the three athletes successfully returned to competition. Specific recovery patterns and potential relapse indicators were also identified. The comprehensive examination of the cases underscores the complex nature of OTS diagnosis, its multifaceted symptoms and the critical importance of structured recovery. The case series elucidates the importance of heightened awareness and early intervention to diagnose and manage OTS. In addition, we propose an anecdotal Return to Running Protocol individualised to the athlete’s response.

Introduction The field of neuromodulation has experienced substantial growth, accompanied by an increase in clinical practice guidelines aimed at supporting evidence-based practice. However, adherence to reporting standards remains critical in the development of a comprehensive and transparent clinical practice guideline. This study evaluated the reporting quality of guidelines on neurostimulation for chronic pain by assessing compliance with the Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist and the Appraisal of Guidelines for Research and Evaluation (AGREE) checklist and explored predictors of reporting quality. Methods A search strategy was conducted from database inception to April 17, 2024 to identify guideline articles on neurostimulation treatment (spinal cord stimulation, dorsal root ganglion stimulation, peripheral nerve stimulation) for chronic pain. Primary outcomes included the percentage of completed RIGHT and AGREE checklist items. Secondary outcomes included the identification of under-reported checklist items, predictors of reporting quality, and agreement between the two checklists. Results A total of 24 guideline articles were included, with a mean percentage of completed items being 55.12%±12.68% for the RIGHT checklist and 52.16%±10.51% for the AGREE checklist. Items that were most frequently under-reported (<25% completion) included themes of population-specific considerations, cost/resource implications, guideline limitations, recommendation development process, magnitude of benefit versus magnitude of harm, and statement of competing interests and how they were managed. Secondary analysis revealed no significant associations between RIGHT/AGREE reporting quality and journal impact factor, year of publication, number of authors, or guideline themes. There was good inter-checklist agreement between the RIGHT and AGREE checklists (intraclass correlation coefficient 0.76, 95% CI 0.44 to 0.90), suggesting overlapping but distinct evaluation criteria. Conclusions Current guidelines of neurostimulation for chronic pain exhibit significant variability in reporting items, with notable deficiencies in the description of key methodological areas. While adherence to established checklists such as RIGHT and AGREE remains poor and inconsistent, these tools provide a critical framework for enhancing comprehensiveness, transparency, and methodological rigor in future guideline development.