Citations

Abstract Background After high‐level spinal cord injury (SCI), motor recovery of wrist extensors has significant functional consequences as it can facilitate grasp through tenodesis. A small seminal study from 1993 established widely used prognostic rules for wrist extensor recovery, though these have not been replicated with larger, real‐world samples since inception. Objective To determine the prognostic value of initial C5 sharp‐dull discrimination, C5 motor strength, and C6 motor strength on predicting 1‐year ipsilateral wrist extensor motor recovery for patients with SCI with neurological level of C4 or C5. Design Retrospective cohort replication study. Setting SCI Model Systems. Participants 35,675 total individuals with acute traumatic SCI with 219 cases of initial wrist extensor weakness (0/5–2/5) meeting inclusion criteria. Intervention Not applicable. Main outcome measure Recovery of wrist extensor strength to ≥3/5 at 1 year. Results The positive predictive and negative predictive values were 57% (95% CI, 47.4%–66.1%) and 66% (56.0%–75.1%) if initial C5 sharp‐dull discrimination was present, 61% (52.7%–69.3%) and 82% (71.4%–89.7%) if initial C5 myotome strength was at least antigravity, and 74% (63.7%–82.5%) and 74% (65.5%–81.4%) if initial C6 myotome strength was at least a 1/5 or 2/5. Synthesizing these three rules, an updated branched nomogram for functional wrist extensor recovery prediction was created. Conclusions In isolation, none of the previously established wrist extensor motor recovery predictive rules had as high of a prognostic value when using a larger dataset. As such, singular reliance on these prediction rules to identify who will gain 1‐year antigravity wrist extension should be approached with decreased certainty. The best positive and negative predictors were trace C6 strength and absent C5 strength, respectively. An updated nomogram provides more nuanced prognostic information to guide clinical care following acute SCI.

Abstract Background Dystonia and Parkinson's disease (PD) exhibit clinical and genetic overlap, but the relevance of dystonia gene variants in PD remains unclear. Objective The aim was to assess the frequency of dystonia‐linked pathogenic variants in PD. Methods We screened sequencing data from 15,684 individuals (8272 PD, 3200 atypical parkinsonism, and 4212 unaffected) from the Global Parkinson's Genetics Program (GP2) and Accelerating Medicines Partnership‐Parkinson's Disease (AMP‐PD) for variants in genes linked to isolated dystonia, dystonia‐parkinsonism, and myoclonus‐dystonia. Results Pathogenic variants were identified only in PD patients. Forty‐five PD individuals (0.54%) carried 26 distinct (likely) pathogenic variants in nine dystonia‐linked genes, most frequently in GCH1 , followed by VPS16 . Conclusion Though rare, pathogenic variants in dystonia‐linked genes are present in clinically and pathologically diagnosed PD. Our results reinforce GCH1 as a PD‐relevant gene with clinical implications, whereas variants identified in other genes are rare and of uncertain relation to the PD phenotype. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Abstract Background Although periodontitis and oral microbiota are linked to cardiometabolic diseases (CMD), it is unclear if they similarly predict CMD mortality. We compared the predictive ability of salivary microbiota and periodontal disease measures for CMD mortality in the National Health and Nutrition Examination Survey (NHANES). Methods We included 5,037 adults aged ≥30 years (mean age [± standard deviation (SD)]: 48[± 14]; 50% male) from the 2009–2010 and 2011–2012 NHANES cycles. We used 16S rRNA sequencing data from saliva to operationalize microbial composition and diversity. We calculated the relative abundance log‐ratio of Treponema (linked with periodontal disease) to Corynebacterium (linked with periodontal health) to compute the Microbial Indicator of Periodontitis (MIP). Interproximal periodontal probing depth and clinical attachment loss were measured from periodontal examinations. Mortality was ascertained through 2019. Survey‐weighted Cox models regressed mortality rates on MIP, microbial diversity, and periodontal measures to estimate hazard ratios and 95% confidence intervals (HR [95% CI]). Results Over 8.8 median follow‐up years, there were 81 CMD and 267 all‐cause deaths. After multivariable adjustment, MIP was associated with increased CMD mortality risk (HR per 1‐SD: 2.10 [1.30–3.38]). Neither microbial diversity nor periodontitis measures were associated with CMD mortality. MIP was associated with periodontitis in multivariable modeling (risk ratio per 1‐SD: 1.29 [1.22–1.39]). Conclusions In a nationally representative cohort, greater baseline salivary Treponema to Corynebacterium ratio predicted increased CMD mortality risk, while microbial diversity metrics and periodontal parameters were not significantly associated with CMD mortality. Longitudinal studies that further contextualize the oral microbiota are warranted. Plain Language Summary Bacteria in the mouth that cause gum disease are linked to cardiometabolic diseases (e.g., diabetes, cardiovascular disease, kidney disease). However, it is not well understood if bacteria of the mouth can predict the risk of death due to cardiometabolic diseases. We used data from a nationwide survey of US adults to explore whether bacteria from saliva, collected from a single time point, are associated with the future risk of cardiometabolic disease death. We found that people with higher levels of gum disease bacteria were more likely to die from cardiometabolic diseases. Future studies are needed to better understand the role of gum disease bacteria in the development of cardiometabolic diseases and the risk of death.

Abstract Background Posaconazole immediate release (IR) suspension is the standard product for enteral feeding tube (EFT) administration but has erratic pharmacokinetic behaviour, often resulting in subtherapeutic concentrations. Limited evidence suggests that posaconazole oral delayed-release (DR) tablets may be crushed. Methods This was a retrospective cohort study of hospitalized adults who received EFT administration of posaconazole IR suspension or crushed DR tablets between 2018 and 2024. Patients were eligible if they had at least one serum drug concentration drawn ≥5 days after posaconazole initiation. The primary outcome was attainment of therapeutic drug concentrations. Secondary outcomes included time to therapeutic serum concentration, adverse drug events, and frequency of occluded EFT. Results Of the included patients, 48 received IR suspension and 100 received DR tablets. Baseline characteristics and severity of illnesses were well balanced. Among IR suspension and crushed DR tablet recipients, 39% and 80% achieved therapeutic concentrations, respectively (P = 0.002). After adjusting for age, sex, BMI, drug interactions, posaconazole indication and malabsorptive conditions, crushed DR tablets were significantly more likely than IR suspension to achieve therapeutic posaconazole concentrations within 30 days (HR 5.22, 95% CI 2.35–11.61). Occluded EFTs were more frequent among crushed DR tablet recipients (27% versus 10%, P = 0.022), while no differences were observed in the occurrence of hepatotoxicity or hypokalaemia. Conclusions With EFT administration, crushed posaconazole DR tablets were associated with a greater likelihood of achieving therapeutic concentrations compared with IR suspension. The optimal technique for administering crushed DR tablets to prevent EFT complications warrants investigation.

Lacking effective therapeutics, cholangiocarcinoma (CCA) remains a deadly malignancy of the biliary tract. The Hippo pathway effector protein Yes-associated protein (YAP) is implicated in CCA pathogenesis and chemotherapeutic resistance; however, the oncogenic mechanisms underlying YAP regulation remain incompletely understood. An enhanced understanding of YAP and its role in CCA may uncover novel therapeutic targets and better define resistance pathways. Human CCA cells and murine syngeneic CCA models were utilized to explore the molecular relationship of YAP and protein tyrosine phosphatase 1B (PTP1B). Previous work in CCA has demonstrated that YAP interacts with multiple protein tyrosine phosphatases, including SHP2 and PTP1B. We observed that PTP1B pharmacologic inhibition was associated with increased cell proliferation and YAP target gene expression, while genetically enforced overexpression of PTP1B was associated with a decrease in YAP activation. Treatment of CCA cells in vitro and syngeneic, orthotopically implanted CCA murine tumors in vivo with standard cytotoxic chemotherapy, gemcitabine/cisplatin, had enhanced efficacy in the setting of PTP1B overexpression. These findings demonstrate that pYAPY357 can be modulated through protein tyrosine 1B phosphatase activity, and reducing pYAPY357 through enhanced phosphatase levels can sensitize CCA to chemotherapy.

Abstract Background: Medical education commonly utilizes the “see one, do one” two-step approach for teaching psychomotor skills; however, recent evidence suggests that Peyton’s four-step method leads to superior learning. The effect of Peyton’s four-step method on long term skill retention is less apparent and has never been assessed for Point-of-Care Ultrasound (POCUS). The purpose of this research project was to evaluate the effectiveness of Peyton’s four-step method on teaching the POCUS psychomotor skills of image acquisition to novice learners. Additionally, this research project assessed the influence of Peyton’s four-step method at three different points in time during the skill acquisition phase, in the setting of ongoing deliberate skill practice. Methods: A single-blinded, repeated measures interventional study based on experimental design was completed. PA students from one large academic medical center were randomized into a control group (using the two-step method) and intervention group (using Peyton’s four-step method). Students were taught POCUS of the aorta, bladder, heart, lungs, and kidneys. Students' POCUS skills were assessed during the immediate, intermediate, and delayed learning phases. At each assessment, an organ-specific score and a total score were obtained. Scores were compared using a Wilcoxon rank sum test. An ordinal logistic regression analysis was performed using a generalized linear mixed model with a multinomial distribution and cumulative logit link function to assess overall effect of Peyton's four-step method. Results: Students who were taught using Peyton’s method were found to have an increased likelihood of higher total scores compared to those taught using usual instruction (OR = 4.2, p = 0.003). Peyton’s method was found to have increased likelihood of higher scores for cardiac (OR = 2.3, p = 0.032), lung (OR = 2.5, p = 0.034), and kidney (OR = 3.0, p = 0.015). Student performance statistically improved with Peyton’s four-step method during the immediate (p = 0.031) and delayed (p = 0.011) skill acquisition phases, but not in the intermediate phase. Conclusion: Peyton’s four-step method improves overall psychomotor skill acquisition for POCUS. Peyton’s four-step method specifically improved psychomotor skills in the immediate skill acquisition phase and the delayed skill acquisition phase. The benefit of Peyton’s four-step method was more prominent in higher complexity POCUS applications.

501 Background: Targeted treatment options have significantly improved outcomes for patients with chronic lymphocytic leukemia (CLL), but oncology healthcare professionals (HCPs) who provide care for fewer numbers of patients with CLL are challenged to remain current with continuously changing treatment paradigms. To assess ongoing educational needs, we analyzed the treatment choices made by HCPs in an online survey for select cases of poor-prognosis CLL and compared these with the choices of experts in CLL treatment for the same clinical scenarios. Methods: As part of a CME program, HCPs could access an online algorithm to enter specific characteristics of a CLL case scenario and receive treatment recommendations from 5 US-based CLL experts. Experts made recommendations in July 2024 for 146 possible case patients built into the algorithm. After entering their case characteristics, HCPs were asked to enter their planned treatment prior to viewing the expert recommendations. We compared expert and HCP treatment choices across various case scenarios that were entered into the algorithm, with a focus on previously untreated CLL with del(17p)/mutated TP53 or R/R CLL. Results: Between August 2024 and February 2025, 346 cases were entered into the algorithm by 174 HCPs. Among responding HCPs, 38% were based in the UK/EU, 24% in the US, and 10% in Asia; 62% treated ≤10 patients with CLL per month and 49% sought recommendations for a specific patient in their practice. Among 231 cases of previously untreated CLL entered, 91 (39%) sought recommendations for del(17p)/mutated TP53 disease. For cases with no major comorbidities and previously untreated CLL with del(17p)/mutated TP53 , all experts recommended acalabrutinib or zanubrutinib; in 19 cases submitted by HCPs practicing in locations where second-generation BTK inhibitors (BTKi) are approved for CLL (including the US, EU, and Japan), 58% planned 1 of these treatments for this case scenario, 17% planned ibrutinib-based therapy, and 11% planned venetoclax-based therapy. Among case scenarios requiring third-line therapy after progressing with 2 regimens including a covalent BTKi and venetoclax plus an anti-CD20 Ab (with progression <2 years after completing treatment), all experts would recommend a noncovalent BTKi (eg, pirtobrutinib), with 1 expert indicating they would also consider CAR T-cell therapy. For the same case scenario among 6 US-based HCPs, 1 planned pirtobrutinib and 3 planned CAR T-cell therapy. Overall, after reviewing expert recommendations, 61% of HCP respondents whose planned treatment differed from the experts indicated that they would change their approach, and 20% indicated barriers to implementing the recommendations. Conclusions: Our findings provide insight into potential educational needs among HCPs who manage patients with CLL, suggesting that targeted expert-led education could benefit these HCPs.

Background: Coronary artery disease (CAD) is common among liver transplantation (LT) candidates, yet whether pre-transplant percutaneous coronary intervention (PCI) improves post-LT outcomes remains uncertain. Methods: We conducted a single-center, Institutional Review Board-approved cohort study of adults undergoing LT from 2005 to 2025. Asymptomatic candidates with significant stenosis on invasive angiography were included; prior coronary artery bypass grafting was excluded. The primary endpoint was major adverse cardiovascular events (MACE: myocardial infarction [MI], stroke/transient ischemic attack, new systolic dysfunction, post-LT coronary revascularization, or all-cause death). Results: Among 111 patients (median age 65 years; 84% male), 66 (59%) underwent PCI and 45 (41%) were managed medically. Over a median 32 months of follow-up, 61 patients (55%) experienced MACE. Composite MACE did not differ between PCI and non-PCI groups (52% vs. 60%, p = 0.40; log-rank p = 0.59). Fine–Gray modeling showed no association of PCI with MACE; independent predictors were prior MI (HR 1.81, 95% CI 1.01–3.24) and pre-transplant dialysis (HR 2.13, 95% CI 1.07–4.24). Major bleeding occurred in 7%. Matched and era-stratified analyses were concordant. Conclusions: In asymptomatic LT candidates with angiographically severe CAD, pre-LT PCI was not associated with a lower incidence of post-LT MACE.

In this video, the authors present the microsurgical treatment of a superior petrosal dural arteriovenous fistula (dAVF) associated with a symptomatic hemorrhagic brainstem cavernous malformation in a 38-year-old male. The patient underwent a retrosigmoid craniotomy for cavernoma evacuation and fistula disconnection. Intraoperative indocyanine green angiography revealed cortical venous reflux not evident on catheter angiography, prompting reclassification to a higher-grade fistula. Postoperatively, the patient returned to neurological baseline, and follow-up imaging confirmed complete fistula obliteration, cavernoma resection, and new appearance of a developmental venous anomaly (DVA). This case highlights the dynamic nature of dAVF venous drainage and illustrates the rare co-occurrence of dAVF, DVA, and brainstem cavernoma. The video can be found here: https://stream.cadmore.media/r10.3171/2025.7.FOCVID2553