Citations

Abstract Background Hidradenitis suppurativa (HS) is a chronic, relapsing, debilitating skin disease characterized by deep‐seated nodules, abscesses and tunnels. Objectives To investigate the efficacy of bimekizumab using International Hidradenitis Suppurativa Severity Score System (IHS4) outcomes in patients with moderate to severe HS in the pooled BE HEARD I and II Phase 3 studies. Methods Patients received (initial/maintenance) bimekizumab 320 mg every 2 weeks (Q2W)/Q2W, bimekizumab Q2W/every 4 weeks (Q4W), bimekizumab Q4W/Q4W or placebo/bimekizumab Q2W. Change from baseline (CfB) in IHS4, IHS4 severity stages and the dichotomous IHS4‐55/75/90/100 (an improvement of at least 55%/75%/90%/100% in IHS4 from baseline) are reported to Week 48. Lesion count data by lesion type are reported to Week48. Results In total, 1014 patients were enrolled across BE HEARD I and II. At baseline, mean (standard deviation [SD]) IHS4 for bimekizumab‐treated patients ranged from 33.4 (25.4) for bimekizumab Q2W/Q2W to 36.0 (34.0) for bimekizumab Q2W/Q4W versus 30.6 (21.8) for placebo. At Week16, patients receiving bimekizumab demonstrated greater reductions in mean (SD) IHS4 from baseline, ranging from −17.2 (24.8) for bimekizumab Q4W/Q4W to −17.8 (21.1) for bimekizumab Q2W/Q2W versus −6.1 (16.3) for placebo. Proportions of patients with severe HS at baseline ranged from 83.7% (bimekizumab Q2W/Q2W) to 88.4% (bimekizumab Q2W/Q4W) and decreased by ~50% to Week48 across all treatment arms, ranging from 28.6% (placebo/bimekizumab Q2W) to 34.3% (bimekizumab Q2W/Q2W). Proportions of patients with IHS4 = 0 at Week48 ranged from 23.7% (bimekizumab Q2W/Q4W) to 26.7% (placebo/bimekizumab Q2W). At Week16, IHS4‐55, IHS4‐75, IHS4‐90 and IHS4‐100 thresholds were achieved by greater proportions of patients treated with bimekizumab versus placebo, while comparable improvements were seen across treatment arms from Week16 to Week48. At Week16, lesion counts were lower for patients treated with bimekizumab versus placebo, decreasing to comparable numbers across all groups at Week48. Conclusions Bimekizumab‐treated patients showed improvements across IHS4 outcome measures.

ABSTRACT Background and Aims Cellular senescence is a hallmark of several liver diseases, including primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Senescent cholangiocytes exhibit a senescence‐associated secretory phenotype (SASP), characterized by profibroinflammatory mediator release. Current cost‐effective biomarkers predicting disease progression, particularly for PSC, are limited and often lack mechanistic relevance. We sought to define a plasma biomarker signature for PSC and PBC. Methods Plasma from early‐ and late‐stage PSC and PBC, alcoholic liver disease (ALD), inflammatory bowel disease (IBD) patients, and healthy controls was analyzed. Seventy‐one analytes were quantified using Luminex Multiplex Immunoassay or enzyme‐linked immunosorbent assay (ELISA). Principal component analysis (PCA) identified key patterns. Findings from the PSC cohort were then applied to additional cohorts. Results Second principal component (PC2) (17 analytes, 17.1% variability) best separated PSC from controls. ANOVA showed significant differences in PC2 between early PSC vs. controls ( p = 0.0001), late PSC vs. controls ( p < 0.0001), and early vs. late PSC ( p < 0.0001). PC2 analytes also distinguished early PBC vs. controls ( p < 0.0332), late PBC ( p < 0.0001), and ALD ( p < 0.0001), and early vs. late PBC ( p < 0.0001), but not IBD vs. controls ( p = 0.119). Logistic regression using PC2 demonstrated strong discrimination of early‐ and late‐stage PSC (AUC = 0.86) and control vs. early‐stage PSC (AUC = 0.83). Conclusion This is the first study to define a plasma SASP biomarker signature associated with cholestatic liver disease. These analytes track disease stage and represent both mechanistic indicators and potential clinical trial endpoints.

OBJECTIVE Spinal ultrasound is used to investigate occult dysraphism in neonates with sacrococcygeal dimples. Inappropriate imaging studies may be performed despite the Choosing Wisely Canada guidelines. The objective of this study was to assess the appropriateness of spinal ultrasounds performed in 2 Canadian provinces and to compare the diagnostic accuracy of spinal ultrasound and MRI in predicting the need for neurosurgical intervention. METHODS This multicenter retrospective cohort study identified spinal ultrasounds in neonates younger than 6 months of age from January 1, 2017, to December 30, 2018, in Alberta and British Columbia, Canada. The authors collected data on patient demographic characteristics, reasons for requested imaging, the presence of any imaging abnormalities, and the ultimate need for intraspinal surgery. Ultrasounds were deemed appropriate if the Choosing Wisely guidelines were followed for ordering. The authors compared high-risk findings on spinal ultrasound and MRI to the need for surgery using sensitivities, specificities, positive predictive values (PPV), and negative predictive values (NPV). RESULTS A total of 1043 ultrasounds were ordered in 1042 neonates, most commonly by pediatricians (49%), family doctors (27%), and neonatologists (16%). Three hundred eighty-three ultrasounds (37%) were deemed inappropriately ordered. Sixty-nine infants (7%) of the cohort received an MRI and 11 (1%) ultimately underwent neurosurgical intervention. None of the patients who had an inappropriately ordered ultrasound underwent surgery. Spinal ultrasound, compared to surgery, had a sensitivity of 36%, specificity of 98%, PPV of 17%, and NPV of 99%. Spinal MRI, compared to surgery, had a sensitivity of 73%, specificity of 76%, PPV of 38%, and NPV of 94%. CONCLUSIONS Although spinal ultrasound has an acceptable specificity in predicting surgery, it remains a poor screening test (36% sensitivity). Given that approximately 37% of spinal ultrasounds were inappropriately ordered in this study period, the authors estimate that if physicians followed the Choosing Wisely Guidelines more closely, it would result in an estimated potential cost savings of CAD$1,856,769 over a decade for Canada with minimal surgical impact and a very low risk of missing surgically relevant spinal dysraphism.

Purpose: To determine current dacryocystorhinostomy (DCR) practice patterns of American Society of Ophthalmic Plastic and Reconstructive Surgery members and identify surgeon and case-related factors impacting preference for endoscopic versus external DCR and the use of preoperative imaging. Methods: A cross-sectional web-based anonymous 16-question survey was distributed to 277 American Society of Ophthalmic Plastic and Reconstructive Surgery members enrolled in survey-based research. The survey assessed surgeons’ demographics, practice settings, surgical preferences, and imaging practices. Responses were summarized and compared using statistical tests for frequency distribution. Results: A total of 111 surgeons (40.0%) responded to the survey. Utilization of endoscopic DCR (endoDCR) was highly variable, with 57% of junior surgeons (<5 years in practice) using it for >66% of their cases, compared with only 18.3% of surgeons with >15 years postfellowship experience. High utilization of endoDCR (>66% of cases) was more common in academic surgeons compared with private practice (48.4% vs. 19.6%, p < 0.01). The most cited reasons for endoDCR were scar avoidance and revision surgery. For external DCR, anatomical barriers and concern for mass/need for biopsy were common indications. Most surgeons only order imaging for certain indications, such as prior sinonasal surgery, facial trauma, suspected tumor, or atypical presentation. Conclusion: Utilization of endoDCR was correlated with years in practice, with younger surgeons preferring the endoscopic technique. A large majority felt that the relevance of imaging is low in most patients. Future research is needed to standardize case-based indications for endoscopic versus external approaches and preoperative imaging.

Background In 2019, the “Facts on Hand” direct-to-consumer advertising (DTCA) campaign, featuring former NFL quarterback John Elway, was launched to raise awareness of Dupuytren's contracture (DC) and its nonsurgical treatment options. Although DTCA has been shown to influence health care behavior in other specialties, its impact on treatment patterns for hand conditions remains unclear. Methods Google Trends was used to examine the influence of direct-to-consumer advertising (DTCA) on Internet-based information-seeking behavior related to DC. Changes in the proportion of surgical and nonsurgical management of DC were evaluated using 2016–2021 Medicare provider billing claims. Results Search interest in DC peaked during the campaign period, with breakout-level increases (>5000%) for terms such as “John Elway,” “needle aponeurotomy,” and “hand surgeon near me.” Medicare data revealed regionally significant increases in CCH utilization, particularly in the Midwest (+10%) and Northeast (+5%), with corresponding declines in fasciectomy. Regional overlap between increased search activity and shifts in treatment patterns suggests a geographically reinforced campaign effect. Conclusion The “Facts on Hand” campaign was associated with increased public interest in DC and coincided with regionally specific shifts in treatment utilization. Although the campaign emphasized a nonsurgical option, breakout searches for terms such as “hand surgeon near me” and “Dupuytren's surgery” suggest that treatment-specific advertising may have encouraged broader engagement with treatment overall. These findings highlight the potential for DTCA to not only raise awareness of the condition itself but also prompt patients to seek specialist care.

A retrospective review of multidisciplinary velopharyngeal insufficiency (VPI) Clinic records from 2010 to 2024 was completed. Inclusion criteria for the review were diagnosis of childhood apraxia of speech (CAS) and documented evaluation for velopharyngeal dysfunction (VPD). Adequacy of velopharyngeal closure and perceptual judgment of resonance were identified as primary outcome measures. Surgical interventions and speech outcomes were also described. This review identified 74 children who were diagnosed with CAS and evaluated for VPD in the VPI Clinic. For the subset (n = 50) of children who had surgical intervention, speech therapy, and long-term follow-up, all had improved velopharyngeal closure and resonance.

Peroxisome-proliferator–activated receptor delta (PPARδ) regulates metabolic, mitochondrial, and inflammatory pathways implicated in neurodegeneration, making it an attractive therapeutic target for amyotrophic lateral sclerosis (ALS). In this study, we evaluated two PPARδ agonists, KD3010 and T3D-959, in two established ALS/FTD mouse models: an AAV-mediated C9orf72 G4C2-repeat expansion model (C9-149R) and the TDP-43Q331K transgenic model. Drug treatment was initiated prior to the emergence of key disease features and continued for 9–10 months. Comprehensive behavioral, neuropathological, and biomarker analyses revealed marked differences between the two models. C9-149R mice exhibited reduced body weight and subtle behavioral alterations without robust motor deficits, whereas TDP-43Q331K mice developed pronounced, progressive motor and cognitive impairments accompanied by a ~7-fold elevation in plasma neurofilament light chain (NfL). Despite effective target engagement—particularly for T3D-959—neither PPARδ agonist improved motor performance, cognitive behavior, neuroanatomical measures, plasma NfL levels, or disease-associated molecular phenotypes in either model. Prolonged KD3010 treatment resulted in loss of target engagement, consistent with drug tolerance, while T3D-959 sustained PPARδ activation without therapeutic benefit. Together, these findings demonstrate that PPARδ agonism is insufficient to modify disease progression in these ALS/FTD mouse models and underscore the importance of publishing well-powered negative preclinical studies to refine therapeutic strategies for ALS.

The glomerular filtration rate (GFR) is a key indicator of kidney function, yet no ideal method exists for its direct measurement. This two-part review examines the development of GFR measurement techniques, focusing on their physiologic basis, performance characteristics, and clinical applications. Part 1 reviews endogenous markers used to estimate GFR (eGFR), including creatinine- and cystatin C-based equations, with emphasis on their derivation, limitations, and clinical use. Part 2 addresses exogenous filtration markers and measured GFR (mGFR) methodologies, highlighting comparative performance and specific uses. Emphasis is placed on innovation in marker development, highlighting the need for continued development and standardization to enhance accuracy and clinical utility.