Citations

Background: Neck lacerations sustained while playing ice hockey are rare but potentially fatal. Neck laceration protectors (NLPs) have been around for decades but only lately are becoming required by leagues given recent fatalities. Purpose: To outline the relevant neck anatomy at risk, describe rink-side evaluation and management techniques, review historical and contemporary NLP mandates, and conclude with evidence-based recommendations. Study Design: Narrative review; Level of evidence, 5. Methods: A review of the literature regarding neck lacerations in ice hockey was utilized for content collection. Google Scholar and PubMed were queried for peer-reviewed articles relevant to the topic. Keywords including “ice hockey,” “neck lacerations,” “neck laceration protector,” and combinations thereof were used to identify relevant literature. Results: Neck lacerations are rare but can be fatal given that they often damage zone II neurovascular structures. While numerous international leagues require mandates for NLPs, notable holdouts include the National Hockey League and the National Collegiate Athletic Association. Numerous materials and builds for NLPs are capable of withstanding penetration from a skate slash, although they possess differences in comfort and neck range of motion. Conclusion: NLPs have the capacity to prevent significant and potentially fatal laceration injuries in ice hockey. Based on the available data, implementing NLP mandates appears to be in the interest of player safety.

Background This study aimed to evaluate outcomes of different antibiotic durations in patients with severe diverticulitis. Methods Initial electronic medical record review identified 2437 adult patients who underwent sigmoid colectomy. Manual chart review identified 133 patients who underwent sigmoid resection and proximal diversion for Hinchey stage 3 or 4 diverticulitis. Patients who received a short antibiotic course (SAC, ≤5 days) were compared with those who received a long antibiotic course (LAC, >5 days). The primary composite outcome included superficial, incisional, organ-space infections or death within 30 days post procedure. Results A total of 53 SAC patients and 55 LAC patients were identified. The composite outcome occurred more frequently in LAC patients than in SAC patients (40% vs 15%; P = .005). Organ-space infection occurred more frequently in LAC patients than in SAC patients (31% vs 13%; P = .04). Conclusions Extended duration of antibiotics after adequate source control does not improve outcomes even in the setting of extensive intra-abdominal contamination.

ABSTRACT Introduction Positron emission tomography (PET) myocardial flow reserve (MFR) is a robust indicator of coronary vascular health and a strong predictor of cardiovascular risk. Clinical guidelines typically use fixed MFR thresholds (e.g., <2.0) to stratify risk, yet this approach overlooks individual variation, particularly by age and sex. We aimed to establish age- and sex-adjusted MFR percentiles and to evaluate their prognostic and predictive performance for cardiovascular risk assessment, in comparison with conventional fixed-threshold MFR approach. Methods Using data from the REFINE PET registry (24,820 patients from 12 sites), we measured PET MFR and derived age- and sex-adjusted MFR reference percentiles using quantile regression in patients without known coronary artery disease. All patients were categorized into percentile-based quartile groups. The primary outcome for prognostic and prediction analyses was major adverse cardiovascular events (MACE), defined as all-cause mortality, myocardial infarction, or heart-failure hospitalization. Time-to-event associations were evaluated using covariate-adjusted survival models, with cumulative incidence and hazard ratios (HR) estimated at 1 and 5 years in the derivation dataset, an independent but similar validation dataset A, and a high-risk validation dataset B. Predictive performance for MACE was assessed using discrimination, calibration, and reclassification metrics, comparing percentile-based models with models using a fixed MFR threshold (<2.0). Results Among participants (mean age 66.5 years; median follow-up 3.6 years), age- and sex-adjusted MFR quartile groups were strong independent predictors of MACE, with adjusted HR increasing stepwise across quartile groups at both early and later follow-up. At 1 year, HR (95% CI) comparing the lowest to the highest quartile group were 4.06 (3.41–4.82) in the derivation cohort, 3.31 (2.32–4.71) in validation cohort A, and 2.35 (2.05–2.70) in validation cohort B. At 5 years, the corresponding HR were 2.18 (1.86–2.56), 1.77 (1.31–2.40), and 1.59 (1.36–1.86). Percentile-based models demonstrated consistently higher discrimination, better calibration, and greater net reclassification for MACE at both time points compared with fixed-threshold MFR models. Although 67.2% of patients had preserved MFR (>2.0), cardiovascular risk increased steadily across MFR percentiles even within this range. Conclusion Age- and sex-adjusted MFR percentiles provide a reliable, clinically actionable measure of vascular health, improving cardiovascular risk stratification by better capturing age- and sex-related heterogeneity in vascular risk. Compared with traditional fixed-threshold approaches, MFR percentiles demonstrate improved predictive performance for cardiovascular risk assessment across diverse patient populations. CLINICAL PERSPECTIVE What is new? In a large, multinational real-world registry of more than 24,000 patients undergoing PET MPI, we derived age- and sex-adjusted myocardial flow reserve (MFR) percentiles, establishing a lifespan-based reference framework with age-specific reference values. Age- and sex-adjusted MFR percentiles showed a strong, graded association with 1- and 5-year cardiovascular risk and demonstrated improved prognostic and predictive performance compared with fixed MFR thresholds and models without MFR across independent derivation and validation datasets, including a higher-risk cohort. Lower adjusted MFR percentiles were consistently associated with higher risk of major adverse cardiovascular events, including all-cause mortality, myocardial infarction, and heart-failure hospitalization. What are the clinical implications? Age- and sex-adjusted MFR percentiles provide a personalized, dynamic measure of coronary vascular health that improves cardiovascular risk stratification by accounting for age- and sex-related heterogeneity. A percentile-based approach may help clinicians better identify patients at elevated cardiovascular risk who may warrant closer monitoring or intensified preventive strategies, while avoiding unnecessary intervention in lower-risk individuals. By integrating macrovascular and microvascular dysfunction, age- and sex-adjusted MFR percentiles offer a clinically interpretable marker of vascular aging that may inform future research on aging biomarkers, novel therapeutics and cardiovascular risk assessment across the spectrum of atherosclerotic and microvascular disease.

BACKGROUND AND OBJECTIVES: Anterior lumbar interbody fusion (ALIF) is a powerful procedure for sagittal correction and indirect decompression in the lumbar spine, though aggressive correction can cause stretch neuropraxia and implant subsidence. The aim of this study was to identify radiographic and clinical predictors of segmental correction, as well as to evaluate the degree to which segmental correction on supine intraoperative radiographs translates to postoperative upright alignment changes. METHODS: We identified patients treated with 1- or 2-level ALIF at a tertiary care center and extracted data on demographics, spinopelvic parameters, and surgical details. Patients treated with isolated ALIF and ALIF with supplementary posterior instrumentation were compared on pre- and postoperative intradiscal lordosis (IDL) and change in IDL. Multivariable linear regression was performed to identify independent predictors of postoperative IDL. RESULTS: We included 204 patients (median age 57 years, 55.4% male) treated at 258 levels, of whom 114 (55.9%) underwent supplementary posterior fixation and 150 (73.5%) underwent single-level implantation. Across all patients, postoperative IDL was significantly greater than preoperative segmental lordosis (25.4° vs 15.3°; P < .001). Standalone ALIF achieved less ΔIDL than circumferential fusion for L5/S1 procedures (7.4° vs 11.6°; P < .001), though ΔIDL for L3/4 and L4/5 was similar between the standalone and circumferential groups. Multivariable analysis showed postoperative IDL to be predicted by greater preoperative IDL (β = 0.26° per degree; [0.15, 0.36]; P < .001), L5/S1 [vs L4/5] implantation (β = 3.97°; [2.72, 5.21]; P < .001), use of supplementary posterior fixation (β = 1.80°; [0.70, 2.89]; P < .001), and greater implant lordosis (β = 0.62° per degree; [0.44, 0.79]; P < .001). CONCLUSION: Postoperative IDL after 1- or 2-level ALIF is best predicted by placement of larger interbody sizes, L5/S1 implantation, greater baseline IDL, and use of adjunct posterior fixation. Patients with higher preoperative lordosis experienced smaller postoperative increases in IDL, though this was likely influenced by a treatment bias.

Abstract Background Clinicians’ views on clinical readiness of Alzheimer's disease (AD) blood biomarkers (BBM) are not well understood. Method The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment Biofluid‐Based Biomarkers Professional Interest Area conducted a survey to elicit clinician opinions on AD BBM implementation, including contexts of use, assay selection, reporting and result interpretation. Result Clinician respondents ( n = 212) practiced in Europe (56%), North America (24%), Caribbean and Central or South America (11%) and other continents (9%). Most respondents were medical doctors (80%) practicing in secondary or tertiary care (88%) (Table 1). For 56% of respondents, CSF AD biomarkers or amyloid PET were accessible, but 48% agreed and 52% disagreed with implementation of AD BBM in any clinical context (Table 2). Respondents emphasized the need for data from diverse populations and educational resources to support test interpretation. Conclusion Surveyed clinicians generally agreed with published appropriate use recommendations but were divided on AD BBM readiness for clinical use.

Abstract Background Individuals with coexisting Alzheimer's disease (AD) and disorders of CSF dynamics such as normal‐pressure hydrocephalus (NPH) have lower CSF Aβ42 levels, which can confound interpretation of AD CSF‐biomarkers. However, little is known about how CSF dynamics influences plasma AD biomarkers. The objective of this study was to determine whether mass spectrometry‐based blood tests for AD are associated with disproportionately enlarged subarachnoid space hydrocephalus (DESH) on MRI. Method 509 Individuals from the Mayo Clinic Study of Aging, with MRI, 11C‐Pittsburgh compound B (Aβ) PET scans, and plasma phosphorylated‐tau protein 217, Aβ40 and Aβ42 were included. We performed an age‐adjusted logistic regression to determine whether abnormal values of p ‐Tau 217 (Abnormal if >1.55 pg/mL), %p‐tau217 defined as the ratio of phosphorylated Tau217 to non‐phosphorylated tau x 100% (Abnormal if >1.55%), Aβ42 (Abnormal if <41.5 pg/mL), and Aβ42/40 ratio (Abnormal if <0.094) were associated with the presence of DESH, as classified by a previously validated automated algorithm. Result Thirty‐two participants were classified as DESH‐positive. The median [IQR] age was 76.8 yrs [70.6, 82.9] for participants with DESH and 72.4 [59.3, 85.5] without DESH (Table 1). An abnormal plasma Aβ42 was associated with DESH (OR, 2.56 [1.19, 5.74], p = 0.018), but having an abnormal Aβ42/40 ratio (OR 2.01 [0.94, 4.56], p = 0.079) was not. There was no association between being DESH‐positive and an abnormal plasma p ‐tau217 (OR 1.30 [0.51, 3.09], p = 0.560) or with abnormal %plasma p ‐tau217 (OR 1.82 [0.74, 4.20], p = 0.17) (Figure 1). Subgroup analysis showed that only those participants who had an abnormal Aβ42 and positive amyloid PET (≥25 Centiloids) showed an association with DESH compared to biomarker‐ and PET‐negative participants (OR 3.10 [1.15, 8.43], p = 0.024 ) . Conclusion Understanding how CSF dynamics affect plasma biomarkers is critical for implementation. The relationship between lower Aβ42 and DESH is expected based on prior CSF studies, which can be addressed by using an amyloid ratio. p ‐tau217 shows robustness against DESH, making it a suitable biomarker in cases of abnormal cerebrospinal fluid dynamics although validation in a more severe CSF dynamics group is warranted.

Background: Ibrutinib is the only Bruton tyrosine kinase inhibitor (BTKi) with once-daily oral capsule, tablet, and oral suspension formulations approved in the United States across indications of chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström macroglobulinemia, and previously treated chronic graft-versus-host disease, and for mantle cell lymphoma in Europe. Patients with difficulty swallowing capsules or tablets may require alternative formulations or administration options to optimize treatment. Objectives: To evaluate the relative bioavailability of ibrutinib oral suspension relative to capsule or tablet formulations and to examine compatibility for optimal administration methods. Methods: Relative bioavailability of ibrutinib oral suspension was evaluated in healthy volunteers or patients in comparison to capsule or tablet formulations. Dose recovery and delivery, presence of impurities, particle size, and hold time were evaluated after in vitro mock oral suspension administration via syringe and nasogastric and percutaneous endoscopic gastrostomy (PEG) tubes. Results: Clinical bioavailability was comparable for ibrutinib oral suspension and capsules (420 mg/day) under the fasted state in healthy volunteers. Dose-normalized pharmacokinetic values were similar across ibrutinib formulations in patient studies. All evaluated enteral tubes achieved 90%–110% ibrutinib dose recovery regardless of tube type or syringe after 2 × 3 mL water rinses. Oral suspension preservative may be adsorbed into enteral tubes after a 60-minute hold time. Conclusion: Ibrutinib oral suspension bioavailability was comparable with ibrutinib tablet and capsule formulations. When dosed via standard enteral tube administration methods, ibrutinib oral suspension is stable and compatible with polyurethane, silicone, or polyvinyl nasogastric or PEG tubes. To ensure full dose recovery and prevent drug preservative adsorption into tubes, ibrutinib oral suspension should be administered immediately and followed by two rinses of 3 mL of water each. Ibrutinib oral suspension is a viable BTKi treatment option for patients requiring or preferring alternatives to oral capsules and tablets.

Abstract Background The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) randomized trial ( n = 977;ClinicalTrials.gov:NCT03243422) demonstrated that hearing intervention slowed 3‐year cognitive decline by 48% among a subgroup of participants. To further investigate differences by treatment with respect to cognitive benefit, we tested the hypothesis that hearing intervention is associated with improved neurodegeneration blood biomarkers 3‐years post‐randomization and assessed whether combining biomarkers and cognitive results improved power in the trial design. Method The ACHIEVE study is a multicenter, parallel‐arm, randomized trial (hearing intervention vs health education control) on 3‐year cognitive decline among adults 70–84years with untreated hearing loss and without substantial cognitive impairment. Participants were recruited from two populations: (1) a long‐standing cardiovascular health observational study (Atherosclerosis Risk in Communities [ARIC]), and (2) de novo community volunteers. Plasma was collected in year 3 in a subsample ( n = 540) while ARIC participants ( n = 164) also had baseline plasma. Glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) neurodegenerative biomarkers were derived using the Alamar CNS protein panel. Regression models estimated the association of treatment with 3‐year biomarkers and global cognitive differences in the combined sample and by recruitment source and annualized change from baseline in the ARIC sample. We included a simple composite score of the standardized outcomes (Table 2). Result Among the subsample, baseline characteristics were balanced by treatment. There were no significant differences on 3‐year neurodegeneration biomarker levels by treatment in the combined (Table 1) or de novo groups (Table 2). Among ARIC participants, intervention resulted in lower 3‐year GFAP (mean:‐0.415;95%CI:‐0.712,‐0.118) and NfL (mean:‐0.349;95%CI:‐0.652,‐0.046) (Table 2). Annualized change from baseline analyses among ARIC participants (Table 3) revealed intervention was associated with a slower rate of cognitive decline (difference‐in‐means:0.059;95%CI:0.018,0.100) and a slower rate of increase in GFAP (difference‐in‐means: ‐0.060;95%CI:‐0.112,‐0.009). Differences in estimates suggest combined score, relative to cognition alone, may increase power in clinical trials that show a positive effect (ARIC subgroup: p = 0.02vs. 0.08[Table 2] and p = 0.0009vs.0.048[Table 3]). Conclusion Hearing intervention was associated with positive 3‐year effects on neurodegeneration blood biomarkers in ARIC participants which parallels cognitive decline results. Results provides objective evidence of brain changes following hearing intervention and potential signal of a more powerful combined outcome approach for future brain health clinical trials.

Background This review evaluates the current evidence for the role of venoactive drugs (VADs) for venous origin chronic pelvic pain (VO-CPP) and provide insights to inform the design of an ideal randomized controlled trial (RCT) for future research. Methods A search was performed in the following databases: Ovid MEDLINE, Ovid EMBASE, Cochrane Library, and Scopus. Studies retrieved were screened for eligibility using Covidence software following PRISMA reviews’ methodology. The quality of RCTs and cross-over RCTs was assessed using the Cochrane review tools. Studies were reviewed by 3 physicians, with discrepancies resolved by consensus. A narrative review of the studies was conducted to identify and synthesize clinical outcomes and safety profile of VADs. Results Eleven studies (n = 748) were identified: 3 RCTs and 8 open-label prospective studies. Most participants were reproductive-age women with confirmed VO-CPP, diagnosed via imaging or laparoscopy. Micronized Purified Flavonoid Fraction (MPFF) was the most studied VAD. Pain assessment with VAS scores was the primary endpoint in all studies, with significant benefit in patients consistently demonstrated. Other endpoints included Pelvic Venous Clinical Severity Score (PVCSS) and Pelvic Varicose Vein Questionnaire (PVVQ), with improved symptoms and quality of life. Quantitative outcomes were also reported (reduced pelvic vein diameter; better venous hemodynamics). MPFF was safe, with few adverse events reported. Three RCTs had methodological limitations, with two judged high-risk for bias. Conclusions While many identified studies appear to be of low quality, the consistent beneficial effect on VO-CPP scores and the safety profile observed across all reviewed studies suggest that flavonoids have a positive role in the conservative management of pelvic venous disease (PeVD). Future well-designed RCTs are needed to confirm these findings. In the meantime, flavonoids should be considered a therapeutic option for symptomatic patients with PeVD who are not qualified for, not wishing, or are awaiting intervention.

Background: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, disabling, genetic disorder characterized by progressive heterotopic ossification (HO). FOP care pathways are complex, and there are many underrepresented patients globally. Objectives: This scoping review aimed to identify global FOP case reports and investigate real-world management practices. Evidence sources, eligibility criteria, and charting methods: International/local databases and congress proceedings were searched. Publications reporting patient-level data for ⩾1 patient with an FOP primary diagnosis, published January 2000–January 2024, were eligible. Publication details, patient demographics, disease presentation, and care pathway were extracted. Data were charted through categorization of themes and frequency analyses. Results: Of 6064 publications screened, 369 were eligible, reporting on 541 patients with FOP. Most publications (82.4% (304/369)) reported an individual case; the remaining reported 2–25 cases. Cases were from 57 countries, most commonly in the Asia/Pacific region (47.0% (254/541)). Most patients had reportedly seen a single specialist (64.8% (59/91)), and care from multidisciplinary teams was reported for only 5.5% (5/91). HO (84.7% (458/541)) and great toe malformations (66.7% (361/541)) were the most commonly reported signs, though mobility limitations (46.2% (96/208)) and growths/lesions (38.5% (80/208)) were most common before diagnosis. The predominant drug classes reported for FOP treatment were corticosteroids (52.6% (102/194)) and nonsteroidal anti-inflammatory drugs (39.7% (77/194)). Surgeries were reported in 35.1% (190/541) of patients. Where specified, the most common surgery types were malformation correction/bone resection (43.6% (78/179)) and biopsies (34.1% (61/179)). Conclusion: This scoping review synthesized valuable real-world insights from case reports of FOP, potentially supporting outreach initiatives in underserved regions and facilitating shared learnings on diagnosis and treatment. Although the inherent selection bias of case studies toward atypical cases limits definitive conclusions, some global trends in the clinical management practices were revealed.