Citations

Abstract Objective: We investigated differences in cognition between variants of progressive supranuclear palsy (PSP) including PSP-Richardson (PSP-RS) and subcortical and cortical variants using updated diagnostic criteria and comprehensive neuropsychological assessment. Method: We recruited 140 participants with PSP (age = 71.3 ± 6.9 years; education = 15.0 ± 2.8 years; 49.3% female) who completed neurological and neuropsychological assessment. Participants received diagnoses of PSP clinical variants at their evaluation (or retrospectively if evaluated before 2017) according to the Movement Disorder Society PSP criteria. We grouped variants as PSP-RS (62 participants), PSP-Cortical (25 with PSP-speech/language and 9 with PSP-corticobasal syndrome), and PSP-Subcortical (27 with PSP-parkinsonism, 11 with PSP-progressive gait freezing, and 6 with PSP-postural instability). Analysis of covariance adjusted for age assessed for differences in neuropsychological performance between variants across cognitive domains. Results: PSP-Cortical participants performed worst on measures of visual attention/working memory (Spatial Span Forward/Backward/Total), executive function (Frontal Assessment Battery), and language (Letter Fluency). PSP-RS participants performed worst on verbal memory (Camden Words). There were no significant group differences for the MoCA or indices of visuospatial function. There were no sex or education differences between PSP groups; however, there were differences in age at visit and disease duration. Conclusions: In a large sample of participants with PSP, there were differences in cognition across PSP-RS, PSP-Subcortical, and PSP-Cortical variants, with PSP-Cortical and, to a lesser extent, PSP-RS, performing worse on tests of attention and executive function. These findings suggest cognitive distinctions among PSP clinical variants and highlight the value of neuropsychological assessment in differential diagnosis of PSP subtypes for more accurate and timely clinical classification.

Abstract Outcomes in classic Hodgkin lymphoma (cHL) have steadily improved; however, additional therapies are needed for patients who relapse or do not respond to novel agents. Here, we report the efficacy and safety of camidanlumab tesirine (Cami), an anti-CD25 antibody-drug conjugate, in patients with relapsed/refractory cHL after brentuximab vedotin/programmed cell death protein 1 inhibitor therapies from the phase 2 ADCT-301-201 study. Eligible patients were adults with cHL who had received ≥3 previous lines of systemic therapy (or ≥2 if ineligible for hematopoietic stem cell transplant). Patients received 45 μg/kg Cami (IV, once every 3 weeks) in cycles 1 to 2, followed by 30 μg/kg IV once every 3 weeks for ≤1 year. The primary end point was overall response rate (ORR) per 2014 Lugano classification. Secondary end points included complete response rate (CRR), progression-free survival (PFS), and overall survival (OS). In total, 117 patients were enrolled with a median age of 37.0 years (range, 19-87). The ORR was 70.1% (95% confidence interval [CI], 60.9-78.2), with a CRR of 33.3% (95% CI, 24.9-42.6). The median PFS was 9.13 months (95% CI, 5.3-15.0); median OS was not reached. Thirty-three (28.2%) patients discontinued treatment because of treatment-emergent adverse events; the most common reasons were skin and subcutaneous tissue disorders (n = 10 [8.5%] patients), infections and infestations (n = 5 [4.3%]), and nervous systems disorders (n = 5 [4.3%]). Guillain-Barré–type or polyradiculopathy-type events occurred in 8 (6.8%) patients. Cami was efficacious in this heavily pretreated population; however, the efficacy was overshadowed by substantial issues with the safety profile. This trial was registered at www.clinicaltrials.gov as #NCT04052997.

We describe the first use of phage therapy in Canada for the treatment of a life-threatening periprosthetic joint infection (PJI), with successful outcome. PJI is a devastating complication of joint replacement surgery, with high morbidity and mortality. Our patient presented with early sepsis from a chronic recalcitrant multidrug-resistant (MDR) Staphylococcus epidermidis hip PJI which had repeatedly failed standard therapy. She had previously undergone 10 operations of the right hip, and only three weeks after completing a prolonged course of daptomycin following her most recent hip revision, she developed a draining sinus tract. Given the high burden of disease, inability to achieve surgical source control, and lack of antibiotic treatment options for long-term suppressive therapy, bacteriophage (phage) therapy was pursued. The patient underwent irrigation and debridement with complex flap reconstruction: intraoperative tissue cultures again yielded MDR S. epidermidis. We developed a novel phage therapy protocol for this patient, with twice daily, intra-articular and intravenous (7 × 109 PFU/dose) phage delivery over a planned 14-day course. Complete healing of the wound with cessation of drainage occurred within one month after treatment. A marked improvement in right hip pain and mobility occurred within three months after treatment. Twelve months following phage treatment, there is normalization of serum inflammatory markers with diminished pain, increased mobility, and no recurrent surgery. Our patient continues to improve and is currently living independently at home, with sustained clinical control of infection.

Key Points Significant heterogeneity in patient characteristics, urine metabolic studies, and kidney outcomes exist among enteric hyperoxaluria patients from diverse etiologies. Structurally induced malabsorption and exocrine pancreatic insufficiency have the highest kidney stone event rates. Patients with structurally induced malabsorption have up to 18% ESKD incidence at 5 years. Background Enteric hyperoxaluria (EH) is a risk factor for calcium oxalate nephrolithiasis and kidney disease. The study compares patient characteristics and urine metabolic profiles at the time of EH diagnosis and kidney stones and ESKD events during follow-up in a cohort with diverse causes of EH. Methods Adult patients with newly documented elevated urinary oxalate excretion >40 mg/24 h between January 1, 2010, and October 10, 2023, and a known enteric diagnosis including inflammatory bowel disease, exocrine pancreatic insufficiency (EPI), celiac disease, structural intestinal malabsorption (SIM), or malabsorptive bariatric surgery (Bariatric) were identified. Event rates and cumulative incidence of kidney stones and ESKD were assessed. Results Among 814 identified patients, the most common enteric etiology was Bariatric ( n =524, 64%). Patients with ulcerative colitis had the highest prevalence of kidney stones at EH diagnosis (93.6%) compared with other enteric etiologies ( P = 0.002). Patients with SIM had the highest urinary oxalate, lower urinary citrate, and volume, compared with other enteric etiologies ( P < 0.05). Calcium oxalate supersaturation was similar among the enteric groups ( P = 0.67). Median stone event rate for the overall cohort was 0.70 stone events/year during a mean (SD) follow-up of 5.0 (3.9) years. The SIM and EPI groups experienced the highest stone events (median [IQR] 1.24 [0.28–2.40] and 1.20 [0.41–1.99] events/year, respectively) while the Bariatric group had the lowest event rates (median [IQR] 0.45 [0.00–1.66 events/year]; P < 0.001). The SIM group had the highest ESKD incidence (17.8% 5 years postdiagnosis; log-rank test P < 0.001). Conclusions We describe a large EH cohort from diverse enteric etiologies. Significant heterogeneity exists in patient characteristics, urine metabolic risk factors, and adverse kidney outcomes. Patients with SIM and EPI experienced the highest kidney stone events and patients with SIM had the highest ESKD incidence. This study highlights the urgent need for more granular information regarding the natural history and risk factors for kidney complications for patients with EH to support interventional trials to improve outcomes.

ABSTRACTObjectivesSaddle nose deformity (SND) can be associated with nasal septal perforation (NSP). Both SND and NSP are observed in granulomatosis with polyangiitis (GPA) patients. This study aimed to compare the prevalence and severity of SND in GPA vs. non‐GPA patients with NSP.MethodologyNSP patients who visited tertiary rhinology or facial plastic surgery clinics from January 2010 through December 2023 were grouped into GPA and non‐GPA cohorts. The area of NSP, SND incidence, and SND severity (Daniel and Brenner's classification) were compared between the cohorts.ResultsOf 168 patients identified with NSP, 18 had GPA and 150 had non‐GPA diagnoses. Twelve GPA patients and 10 non‐GPA patients had SND. The odds ratio for SND association in GPA patients with NSP vs. non‐GPA patients was 31.3 (95% CI: 9.5–102.9), and 19.4 (95% CI: 4.3–87.7) after controlling for the NSP area. GPA patients with SND had a larger NSP area (median 670 mm2, IQR: 315.5–1061.3) compared to non‐GPA patients with SND (175.3 mm2, 113.1–204.1; p < 0.001). The severity of SND was similar between GPA and the non‐GPA group (p = 0.09). The area of NSP did not predict the severity of SND (p = 0.17).ConclusionGPA diagnosis was associated with larger NSPs and a higher risk of SND compared to non‐GPA etiologies; however, the severity of saddling did not differ between GPA and non‐GPA etiologies. GPA is an independent risk factor associated with SND irrespective of the size of septal perforation. The NSP area did not predict the severity of SND.Level of Evidence: 4.

Objectives Cervical spine (c-spine) X-ray (XR) remains an important tool for pediatric trauma patients. XR is a low radiation alternative to multidetector CT (MDCT). Our primary aims were to analyze the sensitivity of a negative c-spine XR and to analyze what factors lead to additional imaging after a negative c-spine XR. Methods A retrospective cohort study was conducted at a level 1 pediatric trauma center from 2012 to 2021. We compared the group with negative c-spine XR and no additional imaging to the group with negative c-spine XR followed by additional c-spine MDCT and/or MRI. Results There were 2,081 negative XRs and 1,974 (95%) had their c-spines cleared without additional imaging. No patient required an operation for a clinically significant c-spine injury in this group, and we consider this no missed injuries. The remaining 108 patients had additional c-spine imaging after negative c-spine XR for c-spine clearance (24 MDCT, 76 MRI, 8 MDCT and MRI). Indications for additional c-spine imaging were pain (48.1%), Glasgow Coma Scale (GCS) score ≤14 (43.5%), and paresthesia (8.3%). Patients who received additional imaging were more likely to have a GCS score ≤12 (25.4% vs 4.1%), Injury Severity Score >15 (21.9% vs 8.1%), Level 1 Trauma activation (21% vs 5%), Abbreviated Injury Scale head score of 4 or 5 (29% vs 5%), be intubated (30% vs 2%), and have non-accidental trauma as their mechanism of injury (20% vs 1%) (p value<0.0001, for all). Five patients who received additional imaging were treated with a cervical collar, but no operative intervention. Conclusions In this cohort, screening XR had a sensitivity of 100% for clinically significant c-spine injuries. GCS was the most significant predictor of obtaining additional imaging. A negative XR combined with a normal physical examination in an evaluable pediatric patient is a safe way of clearing the c-spine. Level of evidence Study contains level III evidence.

Abstract Purpose To evaluate the effectiveness of subcutaneous glucagon in reducing motion artifact during prostate MRI through intraindividual comparison. Methods At our institution patients undergoing a clinical prostate MRI exam receive 1 mg of subcutaneous glucagon before scanning. From February 15, 2024 to February 11, 2025 33 such patients were recruited to undergo an additional, research exam without glucagon. All exams were acquired at 3T. An axial T2-weighted spin-echo series (T2-WI) was acquired within both exams. Evaluation of the T2-WI series was done by three experienced radiologists using the criteria of diagnostic quality (0–3 scale), PI-QUALv2 (0–3 sum), motion artifact (significant, visible, none), and reviewer preference (five-point relative scale). Due to differences in prescribed coverage, the scan times for the two T2-WI sequences were in general different for each subject. Results were stratified using the acquisition time ratio (Trel) between the glucagon vs. non-glucagon scans. Wilcoxon tests assessed score differences. Results Across all 33 subjects, no significant differences were found between glucagon and non-glucagon scans. However, the observed negative correlation between glucagon preference and Trel (p = 0.026) led to stratification into low-Trel (n = 16) and high-Trel (n = 17) groups. In the low-Trel group the glucagon scans provided significantly improved diagnostic quality (p = 0.048), PI-QUALv2 sum (p = 0.049), motion scores (p = 0.047), and reader preference (p = 0.042). Conclusion Subcutaneous glucagon provides improved image quality in prostate T2-WI MRI when scan duration remains within 1.25× of that of a non-glucagon T2-WI series. The benefit appears to decrease with longer scan times.

Abstract Rationale Pulmonary hypertension (PH) is associated with significant morbidity and mortality. Ground-glass opacities (GGOs) are common in Group 1 PH, but their clinical significance is unclear. Objectives We sought to characterize the clinical features and outcomes of patients with Group 1 PH with and without GGOs in the PVDOMICS study, a prospective multicenter cohort study aimed at deep phenotyping PH. Methods Patients with incident and prevalent PH were enrolled across seven U.S. centers. We included patients with Group 1 PH and excluded those with parenchymal lung disease or without chest imaging, resulting in a cohort of 242 patients. Results GGOs were common among patients with Group 1 PH (43% prevalence), associated with female sex, younger age, prostanoid use, and longer disease duration. GGOs were more common among patients with familial pulmonary arterial hypertension and pulmonary veno-occlusive disease. GGOs were associated with established markers of disease severity, including echocardiographic (right ventricular systolic pressure and tricuspid annular plane systolic excursion), biomarkers (N-terminal pro B-type natriuretic peptide), and worse hemodynamics (higher mean pulmonary artery pressure, pulmonary vascular resistance, and pulmonary artery wedge pressure). GGOs were associated with worse transplant-free survival (hazard ratio, 2.49; 95% confidence interval = 1.43–4.32; P = 0.001) and had independent prognostic value for predicting transplant-free survival after adjusting for European Society of Cardiology and European Respiratory Society risk stratification (hazard ratio, 2.19; 95% confidence interval = 1.20–3.99; P = 0.01). Conclusions Overall, GGOs were associated with specific clinical characteristics and disease phenotypes, as well as worse hemodynamics, longer disease duration, prostanoid use, and worse survival. Future studies evaluating the pathophysiology and “omic” correlates of GGOs are warranted. Clinical trial registered with www.clinicaltrials.gov (NCT02980887).

Abstract Background: Understanding of the diagnosis and treatment of adults with community-acquired pneumonia (CAP) has evolved thanks to new evidence, experience, and emerging technologies. This document updates evidence-based clinical practice guidelines on four key questions for the diagnosis and management of adult patients with CAP. Methods: A multidisciplinary panel integrated systematic reviews of comparative evidence with other relevant research and clinical experience, then applied Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology to produce recommendations using the Evidence to Decision Framework. Results: The panel formulated clinical recommendations that address questions related to CAP, including lung ultrasound for diagnosis, empiric antibacterial therapy if a test for a respiratory virus is positive, antibiotic duration, and the use of systemic corticosteroids. Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with CAP.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate predictors of hypertrophic olivary degeneration (HOD) in patients with brainstem cerebral cavernous malformations (CCMs) and to examine its association with functional outcomes. METHODS: A cohort of 120 patients with brainstem CCM was analyzed using prospectively collected registry data and retrospective chart reviews. Demographic, clinical, radiological, and surgical data were evaluated. Predictors of HOD and poor functional outcomes were identified through univariate and multivariate analyses. RESULTS: The cohort included 54 females (45.0%), with a mean age at diagnosis of 43.8 years (SD = 16.5). Symptomatic hemorrhage was present in 70.8% of patients at diagnosis, and 28.3% underwent surgical intervention. Radiographic HOD was observed in 20% of patients (n = 24), with 87% of cases involving lesions within the Guillain–Mollaret triangle (GMT). Larger lesion size (odds ratio [OR] = 1.09, 95% CI: 1.01-1.19, P = .027), pontine location (OR = 19.81, P = .006), and GMT involvement (OR = 25.24, P < .001) were significantly associated with HOD. Repeated symptomatic hemorrhage and surgery, including the extent of resection, did not predict the development of HOD. Patients with HOD had worse functional outcomes at last follow-up ( P = .012), with GMT involvement remaining the sole independent predictor of mRS ≥3 (OR = 3.44, P = .040). CONCLUSION: HOD reflects trans-synaptic degeneration within the GMT and is strongly associated with lesion location and size. It serves as a radiological marker of cumulative damage to the brainstem. Preoperative imaging and risk stratification focusing on GMT involvement are critical for guiding management and counseling patients with brainstem CCM.