Citations

Background: While tobacco use is a well-known risk factor for adverse outcomes after carpal tunnel release (CTR), the impact of non-tobacco nicotine products remains unclear. This study evaluated complications in CTR patients with non-tobacco nicotine dependence (NTND) compared with tobacco users and controls. Methods: Patients who underwent CTR with ≥2-year follow-up were identified using a large national database. After 1:1 propensity score matching, patients with NTND (n = 6319) were matched to controls, tobacco users (n = 86 430) were matched to controls, and patients with NTND (n = 6325) were matched to tobacco users. Matching was based on age, gender, Charlson comorbidity index, and comorbidities. Outcomes including 90-day medical complications, infection, emergency department (ED) visits, readmissions, and 2-year revision rates were compared using multivariable logistic regression. Results: Compared with controls, patients with NTND demonstrated higher 90-day medical complication rates (2.4% vs 1.7%; odds ratio [OR], 1.35; 95% CI, 1.04-1.77) and ED visits (10.3% vs 8.1%; OR, 1.16; 95% CI, 1.02-1.32). Compared with tobacco users, patients with NTND had decreased ED visits (10.4% vs 14.2%; OR, 0.74; 95% CI, 0.66-0.83) and revision surgery (1.9% vs 2.5%; OR, 0.78; 95% CI, 0.62-0.99), with no significant differences in medical complications, infection, or readmissions. Conclusions: Non-tobacco nicotine dependence was associated with increased medical complications and ED visits compared with controls, but decreased ED visits and revision surgery compared with tobacco users. There were no significant differences in medical complications, infections, or readmissions between tobacco users and patients with NTND. These findings underscore the importance of screening for non-tobacco nicotine use during preoperative evaluations for CTR.

ABSTRACT Right ventricular (RV) failure after left ventricular assist device (LVAD) implantation is a serious complication which may necessitate temporary mechanical support in refractory cases. Here we describe a 63‐year‐old man with end‐stage ischemic cardiomyopathy and severe combined pre‐ and post‐capillary pulmonary hypertension who developed persistent RV failure post‐LVAD. He was intolerant to speed optimization secondary to preload mismatch, and invasive hemodynamics confirmed LV underfilling. An Impella RP Flex was placed for RV support, and biventricular (BiV) pressure‐volume (PV) loops were utilized to ascertain hemodynamic response. With increasing Impella RP Flex support, left ventricular end‐diastolic volume increased with subsequent improvement in left ventricular performance. This case represents the first reported use of BiV PV loop analysis to characterize the physiological effects of Impella RP Flex in a patient with LVAD support, underscoring its utility in understanding device‐ventricular interactions.

Biological effectiveness in ion therapy varies with radiation quality and biological context, yet cancer cell response data acquired under well-characterized physical conditions remain limited. We investigated clonogenic survival and relative biological effectiveness (RBE) in PANC-1 and BxPC-3 pancreatic ductal adenocarcinoma (PDAC) cells irradiated at four positions along pristine 180.1 MeV proton and 352.4 MeV/u carbon ion Bragg curves, with 4 cm spread-out Bragg peak (SOBP) irradiation included as a clinically relevant comparison. Cell plane positioning and dose were verified in a water-tank system using an Advanced Markus ionization chamber, and Monte Carlo simulations using TOPAS provided dose-averaged linear energy transfer (LET D ) and microdosimetric quantities. RBE was calculated relative to 200 kVp X-rays using the linear-quadratic survival model. Across the sampled pristine beam positions, spanning LETD values of approximately 1-9 keV/μm for protons and 12-163 keV/μm for carbon ions, RBE increased with LET D . Proton RBE 10 exceeded the conventional clinical value of 1.1 at distal positions, whereas carbon ion RBE 10 increased from 2.3 to 5.2 in PANC-1 and from 1.3 to 3.7 in BxPC-3, with larger differences between cell lines observed near the Bragg peak. SOBP measurements showed different biological responses across field conditions despite comparable LET D . These physically characterized survival data provide PDAC-relevant benchmarks for evaluating whether RBE models reproduce biological responses across pristine and SOBP irradiation conditions, supporting the future integration of radiation-quality-dependent effects into ion planning.

Background Loss of finger motion after zone II flexor tendon repair remains common and is largely caused by adhesion formation. Although intrinsic vascular and cellular contributions to tendon healing have been examined in canine, avian, and primate models, prior studies have emphasized biochemical or perfusion-based endpoints without comprehensive assessment of functional and mechanical outcomes after clinically relevant repair. Consequently, the influence of intrinsic healing elements on early postoperative function remains unclear. In this study, we employed a novel avian model of intrasynovial (zone II) tendon injury, which enables clinically relevant operative repair, postoperative rehabilitation, and quantitative assessment of tendon function and biomechanics, to investigate the contribution of intrinsic healing elements to tendon repair. Questions/purposes (1) Does operative ablation of intrinsic healing elements worsen early ROM after zone II flexor tendon repair? (2) Does disruption of intrinsic pathways increase adhesion formation, as measured by normalized work of flexion and gross adhesion scores? (3) Does intrinsic tendon component ablation compromise mechanical properties, including ultimate load to failure and stiffness? (4) Does removal of intrinsic elements alter the expression of fibrotic and matrix-related genes during early healing? Methods Using a clinically relevant, large-animal avian ( Meleagris gallopavo ) model of zone II flexor tendon repair, flexor digitorum longus (FDL) tendons underwent sharp transection and primary repair and were assigned to one of four groups: (1) control repair with intact intrinsic elements (3 weeks postinjury, n = 11; 6 weeks postinjury, n = 18), (2) vincular ligation and transection (3 weeks postinjury, n = 12; 6 weeks postinjury, n = 16), (3) tenocyte cryoablation via intraoperative freeze-thaw devitalization (3 weeks postinjury, n = 13; 6 weeks postinjury, n = 13), or (4) complete tendon devitalization (3 weeks postinjury, n = 13; 6 weeks postinjury, n = 16). A total of 112 male and female birds were used for this study. Harvested tendons were evaluated at 3 and 6 weeks postoperatively. Outcomes included interphalangeal ROM, normalized work of flexion, semiquantitative gross adhesion scoring, ultimate load to failure, stiffness, qualitative histologic assessment, qualitative immunofluorescence, and quantitative PCR for fibrotic and matrix-related genes. Results Operative ablation of the intrinsic healing elements did not worsen total ROM and/or increase normalized work of flexion. All experimental groups demonstrated reduced total ROM of the operative digit at 3 weeks postoperatively compared with the contralateral nonoperative digit: mean ± SD control repair with intact intrinsic healing elements (50° ± 10° versus 14° ± 6°, mean difference 36.41° [95% confidence interval (CI) 26.87° to 45.94°]; p < 0.001), vincular disruption group (50° ± 10° versus 14° ± 7°, mean difference 35.97° [95% CI 21.44° to 45.51°]; p < 0.001), tenocyte cryoablation group (50° ± 10° versus 15° ± 8°, mean difference 35.27° [95% CI 25.99° to 44.55°]; p < 0.001), and complete tendon devitalization group (50° ± 10° versus 11° ± 4°, mean difference 38.97° [95% CI 29.44° to 48.50°]; p < 0.001). However, no differences between the groups were detected. Similarly, the total ROM was impaired at 6 weeks postinjury compared with the nonoperative digit in all groups. We did not detect any differences between the groups, and results did not demonstrate time-dependent differences between the two time points. Furthermore, normalized work of flexion, a proxy for peritendinous adhesion severity, was increased in all experimental groups at 3 weeks postinjury: mean ± SD control repair with intact intrinsic healing elements (0 ± 0 N mm/° versus 4 ± 3 N mm/°, mean difference -3.33 [95% CI -5.73 to -0.93]; p = 0.003), vincular disruption group (0 ± 0 N mm/° versus 4 ± 2 N mm/°, mean difference -3.09 [95% CI -5.49 to -0.69]; p = 0.006), tenocyte cryoablation group (0 ± 0 N mm/° versus 3 ± 2 N mm/°, mean difference -2.99 [95% CI -5.33 to -0.66]; p = 0.006), and complete tendon devitalization group (0 ± 0 N mm/° versus 4 ± 2 N mm/°, mean difference -3.31 [95% CI -5.70 to -0.91]; p = 0.003). However, no group differences were detected. At the 6-week follow-up, the normalized work of flexion was also elevated in all groups without any differences between the treatments. Furthermore, the integrity of the tendon intrinsic components has been presumed to be a major determinant of flexor tendon healing strength after zone II tendon repair. However, our results do not support this assumption. At both time points, there were no differences in ultimate load and stiffness between the experimental groups, and there were no group × time interaction effects. Additionally, structural removal of the intrinsic healing elements did not result in meaningful qualitative histologic differences in extrinsic fibrosis, neovascularization, or collagen fiber organization. The profibrotic gene, transforming growth factor beta induced (TGFBI), was upregulated in all experimental groups compared with the normal FDL tendon. Matrix remodeling, measured by matrix metalloproteinase 7 (MMP7) activity, was also activated in all groups relative to the normal FDL tendon. However, no differences were detected between the groups. Conclusion Operative ablation of intrinsic healing elements, including the flexor vincular system and resident tenocytes, did not worsen early ROM, adhesion formation, or mechanical properties after zone II flexor tendon repair in a clinically relevant large-animal model. Early healing was characterized by a robust fibrovascular response across all groups, indicating that extrinsic mechanisms predominate during the early reparative phase. Paradigms that modulate the extrinsic tendon healing mechanisms could represent a more viable approach to flexor tendon healing outcomes than focusing on bolstering the intrinsic components. Clinical Relevance Our findings suggest that early functional recovery in this model may depend more on modulation of the extrinsic fibrotic response than on preservation of intrinsic vascular or cellular elements, supporting the development of antiadhesion therapies. Additional preclinical studies are needed to identify the cellular niches that drive extrinsic fibrosis and adhesion formation, determine whether they can be selectively modulated without impairing tendon healing, and establish the translational relevance of these mechanisms across species before clinical application.

Hypertrophic cardiomyopathy is a common heritable heart disease. The disease is genetically, anatomically, and clinically heterogeneous. Hypertrophic cardiomyopathy is inherited in an autosomal dominant pattern but has allelic heterogeneity, incomplete penetrance, and variable expressivity. Beyond family screening, clinical evaluation for hypertrophic cardiomyopathy is often prompted by identification of symptoms or detection of a heart murmur, additionally, abnormal electrocardiogram or imaging results performed for another reason can provide evidence. Evaluation should include obtaining a patient’s history, a physical examination, cardiac imaging, and, often, genetic testing. Prognosis is variable; major causes of morbidity and mortality are caused by sudden cardiac death, heart failure, and atrial fibrillation with associated stroke risk. An understanding of the pathogenesis at the genetic, cellular, and individual levels helps clinicians to implement appropriate screening, recognise clinical manifestations, and improve the treatment of patients with hypertrophic cardiomyopathy. The understanding of this condition is evolving, with recent advances and insights into its pathogenesis, refinement of risk stratification, and use of artificial intelligence in screening, diagnosis, and prognostication.

Abstract Cellular senescence is a central hallmark of aging, yet its measurement in humans remains invasive, low-throughput and tissue-specific, precluding population-scale study. We developed Methylation-associated Gene Expression (MaGE) predictors: whole-blood DNA methylation proxies of p14 ARF , p16 INK4A and p21 CIP1 expression, plus a composite score, providing the first scalable measure of senescence-marker expression. Deployed across Generation Scotland (n=18,859), MaGE yielded 45 Bonferroni-significant associations spanning 18 incident diseases and all-cause mortality. The two strongest associations recapitulated the established tissue specificity of p21 CIP1 and p16 INK4A activation, with MaGE-p21 associating with incident alcoholic liver disease and MaGE-p16 with pulmonary fibrosis. In a separate study, MaGE tracked disease severity and treatment response in Crohn’s disease. MaGE is a scalable, interpretable biomarker of senescence that enables its study at population scale and offers a route to patient stratification in senolytic trials.

Background Aortic stenosis (AS) severity assessment relies on Doppler-derived mean gradient (MG), which is flow dependent. Atrial fibrillation (AF) causes stroke volume variability, which may lower measured gradients despite unchanged anatomic valvular severity. Guidelines recommend averaging MG over 5 cardiac cycles in AF, but this may underestimate true severity compared with sinus rhythm (SR). We evaluated the impact of transition from SR to AF on MG in AS. Methods We retrospectively studied adults with AS undergoing transthoracic echocardiography. Patients had paired SR and AF studies within 3 months, left ventricular ejection fraction ≥50%, and no more than mild valvular regurgitation. MG was measured by averaging over 3 cycles in SR and 5 cycles in AF, and the highest single-beat MG meeting quality criteria. Paired comparisons were performed with statistical testing. Agreement was assessed using intraclass correlation coefficient (ICC) and Bland-Altman analysis. Results Thirty patients were included (mean age 77 ± 10 years; 33% female). Left ventricular ejection fraction remained preserved in both rhythms. Averaged MG was lower in AF than SR (23.4 ± 12 vs 28.3 ± 12 mm Hg, P < .001). In contrast, the highest single-beat MG in AF was similar to SR (27.3 ± 11 vs 28.4 ± 12 mm Hg, P = .29). Agreement with SR was moderate for averaged MG (ICC 0.792, 95% CI 0.612-0.895) and higher for single-beat MG (ICC 0.897, 95% CI 0.797-0.949). Conclusions Averaging MG over 5 AF cycles underestimates AS severity. The highest single-beat MG better reflects SR measurements and may more accurately represent true severity.

ABSTRACT Introduction Epstein–Barr virus positive plasma cell neoplasms in immunocompetent hosts typically behave like aggressive lymphomas, often classified as plasmablastic lymphoma. We evaluated six sinonasal neoplasms in elderly males with unusually indolent courses at Mayo Clinic. Methods A single‐center, retrospective review of plasmablastic lymphoma cases identified six cases with unusually favorable outcomes. We analyzed clinical presentations, pathologic features, and treatment outcomes. Results All patients were male with age range 61‐80 years. Five patients had Ann Arbor stage IE disease and one had Stage IV; all lacked B symptoms, and LDH was normal in five. Histologic evaluation revealed mixed mature plasma cell and plasmablastic features in three cases and pure plasmablastic morphology in three. All cases demonstrated EBER and CD138 positivity with monotypic light chain restriction (3 κ , 3 λ ). Four patients recieved systemic chemotherapy, one had local radiation alone, and one was observed. No patients died of this disease within the follow‐up period. Conclusions These neoplasms show less aggressive behavior than typical plasmablastic lymphoma, suggesting this sinonasal disease represents a distinct indolent subset of EBV positive PCNs. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.