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Objective: Acute trauma care has significantly reduced mortality over the last two decades. The last study to examine the epidemiology of traumatic amputees predates these gains. The majority of those who sustain traumatic amputation are male; therefore, limited data exist on female amputees. This study aimed to (1) provide a current epidemiological analysis of traumatic amputees and (2) compare male and female amputees. Design: All patients sustaining a major limb amputation in the National Trauma Data Bank from 2013 to 2017 were identified. First, descriptive analyses of patient demographics and injury characteristics were performed and compared with a previous 2000-2004 National Trauma Data Bank study. Second, female and male traumatic amputees were compared in this study. Results: From2013 to 2017, we identified 7016 patientswho underwent major limb amputation. Compared with previous years, the current amputees were older and more severely injured. Mortality was 6.3% in the current years compared with 13.4% in the previous years (odds ratio, 0.44, 95% CI = 0.37-0.51, P < 0.001). After multivariable analysis, mortality remained significantly decreased, with no difference in hospital length of stay. Conclusions: Contemporary National Trauma Data Bank analysis demonstrated that patients with traumatic amputations, regardless of sex, often survive until hospital discharge, despite more severe injuries. [ABSTRACT FROM AUTHOR]

Case: A 51-year-old woman, who had previously undergone C5-C7 anterior cervical discectomy and fusion, presented with symptomatic hardware failure and subsequently underwent instrumentation removal. Her postoperative course was complicated by an esophageal perforation. Despite initial repair using a rotational flap, the leak persisted, prompting esophageal reconstruction with a radial forearm free flap (RFFF). Conclusion: Persistent esophageal perforation is exceedingly rare and difficult to treat. This report discusses the surgical technique for RFFF, an excellent option for revising failed sternocleidomastoid rotational flaps. The decision between rotational repair and free flap reconstruction depends on factors such as defect size, vascularization, wound condition, and donor site morbidity. [ABSTRACT FROM AUTHOR]

Case: A 32-year-old woman with bilateral Madelung deformity presented with severe pain and arthritis of the radiocarpal and distal radioulnar joints. At final follow-up, 17 months for the left and 12 months for the right wrist, she had excellent functional results with no pain. Range of motion was 30° of flexion and 30° of extension with full pronosupination. Conclusion: There is paucity in the literature regarding salvage procedures in adults with this deformity. We demonstrate treatment with distal ulna excision and an radioscapholunate arthrodesis. This procedure may be indicated in Madelung deformity and proximal radiocarpal and distal radioulnar joint arthritis. [ABSTRACT FROM AUTHOR]

Case: A 12-year-old girl presented with significant right elbow pain following a fall during soccer which caused an osseous triceps avulsion injury and nondisplaced type II Salter-Harris radial neck fracture. The patient was treated with successful open repair utilizing suture anchor fixation, resulting in full return of function and return to previous activities. Conclusion: Timely and accurate diagnosis and treatment of displaced triceps sleeve avulsion injuries is critical and can result in excellent patient outcomes and return to previous functional level. This unique case contributes to the diagnosis and management of this rare condition in pediatric populations. [ABSTRACT FROM AUTHOR]

BACKGROUND: It is unclear whether sex-based differences in cardiovascular outcomes exist in late-onset hypertension. METHODS: This is a population-based cohort study in Ontario, Canada of 266 273 adults, aged ≥66 years with newly diagnosed hypertension. We determined the incidence of the primary composite cardiovascular outcome (myocardial infarction, stroke, and congestive heart failure), all-cause mortality, and cardiovascular death by sex using Cox proportional hazard models adjusted for demographic factors and comorbidities. RESULTS: The mean age of the total cohort was 74 years, and 135 531 (51%) were female. Over a median follow-up of 6.6 (4.7–9.0) years, females experienced a lower crude incidence rate (per 1000 person-years) than males for the primary composite cardiovascular outcome (287.3 versus 311.7), death (238.4 versus 251.4), and cardiovascular death (395.7 versus 439.6), P<0.001. The risk of primary composite cardiovascular outcome was lower among females (adjusted hazard ratio, 0.75 [95% CI, 0.73–0.76]; P<0.001) than in males. This was consistent after adjusting for the competing risk of allcause death with a subdistributional hazard ratio, 0.88 ([95% CI, 0.86–0.91]; P<0.001). CONCLUSIONS: Females had a lower risk of cardiovascular outcomes compared with males within a population characterized by advanced age and new hypertension. Our results highlight that the severity of outcomes is influenced by sex in relation to the age at which hypertension is diagnosed. Further studies are required to identify sex-specific variations in the diagnosis and management of late-onset hypertension due to its high incidence in this group. [ABSTRACT FROM AUTHOR]

Introduction: Studies have shown an inverse association between the risk of breast cancer in women and physical activity. However, information on the association between cardiorespiratory fitness (CRF) assessed objectively by a standardized test and the risk of developing breast cancer is limited. Purpose: To examine the CRF-breast cancer risk association in healthy females. Methods: This retrospective study was derived from the Exercise Testing and Health Outcomes Study cohort (n = 750,302). Female participants (n = 44,463; mean age ± SD; 55.1 ± 8.9 yr) who completed an exercise treadmill test evaluation (Bruce protocol) at the Veterans Affairs Medical Centers nationwide from 1999 to 2020 were studied. The cohort was stratified into four age-specific CRF categories (Least-fit, Low-fit, Moderate-fit, and Fit), based on the peak METs achieved during the exercise treadmill test. Results: During 438,613 person-years of observation, 994 women developed breast cancer. After controlling for covariates, the risk of breast cancer was inversely related to exercise capacity. For each 1-MET increase in CRF, the risk of cancer was 7% lower (HR, 0.93; 95% CI, 0.90-0.95; P < 0.001). When risk was assessed across CRF categories with the Least-fit group as the referent, the risk was 18% lower for Low-fit women (HR, 0.82; 95% CI, 0.70-0.96; P = 0.013), 31% for Moderate-fit (HR, 0.69; 95% CI, 0.58-0.82; P < 0.001), and 40% for Fit (HR, 0.60; 95% CI, 0.47-0.75; P < 0.001). Conclusions: We observed an inverse and graded association between CRF and breast cancer risk in women. Thus, encouraging women to improve CRF may help attenuate the risk of developing breast cancer. [ABSTRACT FROM AUTHOR]

Abnormal encoding of somatosensory modalities (ie, mechanical, cold, and heat) are a critical part of pathological pain states. Detailed phenotyping of patients' responses to these modalities have raised hopes that analgesic treatments could one day be tailored to a patient's phenotype. Such precise treatment would require a profound understanding of the underlying mechanisms of specific pain phenotypes at molecular, cellular, and circuitry levels. Although preclinical pain models have helped in that regard, the lack of a unified assay quantifying detailed mechanical, cold, and heat pain responses on the same scale precludes comparing how analgesic compounds act on different sensory phenotypes. The conflict avoidance assay is promising in that regard, but testing conditions require validation for its use with multiple modalities. In this study, we improve upon the conflict avoidance assay to provide a validated and detailed assessment of all 3 modalities within the same animal, in mice. We first optimized testing conditions to minimize the necessary amount of training and to reduce sex differences in performances. We then tested what range of stimuli produce dynamic stimulus-response relationships for different outcome measures in naive mice. We finally used this assay to show that nerve injury produces modality-specific sex differences in pain behavior. Our improved assay opens new avenues to study the basis of modality-specific abnormalities in pain behavior. [ABSTRACT FROM AUTHOR]

Women's rugby is a collision sport that relies heavily on body composition and physical characteristics of strength and power to achieve competitive success. Furthermore, the seasonal nature presents a variety of physical challenges that can cause fluctuations in a player's physical development. Therefore, the purpose of this study was to determine the differences in anthropometry, strength, and power characteristics between forwards and backs in women's rugby union athletes in England and to identify changes throughout a season. Forty-seven players were recruited from the English premiership women's rugby during the 2020-2021 season. Players were split into forwards and backs and underwent body composition testing by dual-energy X-ray absorptiometry and strength and power tests (countermovement jump, drop jump [DJ], and isometric midthigh pull) on 3 separate occasions (preseason, midseason, postseason). Overall, forwards had significantly (p < 0.01) higher body mass, fat mass, lean mass [LM], bone mineral content, and take off momentum, and backs had significantly higher (p < 0.01, d > 0.5) jump height, reactive strength, and shorter DJ contact time. When observing seasonal changes, there were statistically significant differences (p < 0.01) or moderate-to-large practical differences (d > 0.5) in LM, reactive strength index modified, time to take-off, and DJ flight time [FT] among forwards when comparing 3 testing time frames. For backs, statistically significant differences (p < 0.01) or moderate-to-large practical differences (d > 0.5) were reported in LM and DJ FT throughout the season. In conclusion, the strength and power testing and characteristics shown in this study could support coaches and junior women's rugby athletes to have a basic understanding of English premiership physical standards. [ABSTRACT FROM AUTHOR]

The menopausal transition accelerates neuromuscular ageing in females compared to males. Males and females experience different trajectories of neuromuscular function across the lifespan, with females demonstrating accelerated deconditioning in later life. We hypothesize that the menopause is a critical period in the female lifespan, during which the dramatic reduction in sex hormone concentrations negatively impacts synaptic input to the motoneuron pool, as well as motor unit discharge properties. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hypertensive disorders of pregnancy are associated with cardiovascular disease; however, patterns of blood pressure (BP) recovery are understudied. We compared pregnancy and postpartum BP trajectories among individuals with hypertensive disorders of pregnancy who developed persistent hypertension at 1-year postpartum compared with individuals with normalization of BP. METHODS: We used data from a randomized clinical trial of individuals with overweight, obesity, and hypertensive disorders of pregnancy conducted in the first year after delivery. Pregnancy BPs were obtained during prenatal visits; postpartum BPs were prospectively obtained through home monitoring. Demographic characteristics and trajectories were compared by hypertensive status (systolic BP ≥130 mm Hg, diastolic BP ≥80 mm Hg, or use of antihypertensive medications) at 1 year. We used repeated BP measures to fit separate mixed-effects linear regression models for pregnancy and postpartum using restricted cubic splines. RESULTS: We included 129 individuals; 75 (58%) individuals progressed to hypertension by 1-year postpartum. Individuals with hypertension were older, delivered at earlier gestational ages, and had higher body mass index at 1-year postpartum compared with those with normalization. Individuals with hypertension had similar BP trajectories during pregnancy to those with BP normalization but a significantly different BP trajectory (P<0.01 for systolic and diastolic BPs) in the first year postpartum. These differences persisted in multivariable models after adjustment for early pregnancy body mass index, age, and severity of hypertensive disorder of pregnancy (P<0.01 for systolic and diastolic BPs). CONCLUSIONS: BP trajectories in the first year postpartum, but not during pregnancy, may provide important information for risk stratification after a hypertensive disorder of pregnancy. [ABSTRACT FROM AUTHOR]

Case: We report a case in the United States of a 12-year-old girl with multidrug-resistant tuberculous (MDR-TB) osteomyelitis of the hand managed with surgical debridement and second-line anti-TB therapy. The disease course was complicated by dissemination and multifocal progression. Conclusion: Despite early intervention, multidrug resistance makes TB treatment challenging and facilitated progression to disseminated disease in this case. We review the difficulties in diagnosis and treatment of pediatric MDR-TB. [ABSTRACT FROM AUTHOR]

Case: A 61-year-old woman with recurrent left L5 radiculopathy underwent revision L4-5 decompression complicated by incidental durotomy requiring primary repair. Postoperative course was complicated by wound drainage and headache. Repeat magnetic resonance imaging demonstrated cerebrospinal fluid dissecting a plane deep to the dura mater but superficial to the arachnoid, with the collection compressing the cauda equina in an atypical horizontal and linear fashion. Nonoperative treatment was ineffective, and she required revision decompression and dural repair. Conclusion: Spine surgeons should recognize this finding on postoperative imaging as a potential sign of an incomplete dural repair necessitating return to the operating room. [ABSTRACT FROM AUTHOR]

Case: Glomus tumors of the hand are rare tumors that occur predominantly in the subungual region. Though multicentric glomus tumors have been reported in the subungual region involving the nailbed, monostotic multiple intraosseous glomus tumors have not been reported so far. We report a case of a 36 year-old woman who presented with a 5-year history of intermittent thumb pain, aggravated with exposure to cold or pressure. A glomus tumor of the thumb was excised, but symptoms returned 3 months later. She ultimately underwent curettage with bone grafting of a recurrent glomus tumor at the same site, and has been free of symptoms for 1.5 years. Conclusion: Intraosseous glomus tumors may present as multiple synchronous lesions. This, to the best of our knowledge, is the first case report of monostotic multiple intraosseous glomus tumors. [ABSTRACT FROM AUTHOR]

Case: A 61-year-old woman with lower back and radicular leg pain underwent minimally invasive spinal fusion at L5-S1. By postoperative day 6, she exhibited erythema, wound dehiscence, and necrotic changes. Although a necrotizing infection was initially suspected, multiple debridements and antibiotic therapy failed to improve her condition. The patient was eventually diagnosed with pyoderma gangrenosum (PG) and was managed with immunosuppressants and extended wound care. Conclusion: PG is a rare dermatosis that is often misdiagnosed, leading to inappropriate treatment, debridements, and additional complications. Prompt identification and multidisciplinary collaboration are key to preventing unnecessary interventions and achieving the best outcomes. [ABSTRACT FROM AUTHOR]

Case: A 22-year-old woman with Klippel-Feil syndrome who underwent cervical disc arthroplasty (CDA) presented 3 months postoperatively with worsening neck pain and radiculopathy. Work-up was negative for infection, but single-photon emission computed tomography revealed increased metabolic activity in the vertebral body below the implant. During revision, the implant was grossly loose and multiple cultures grew Cutibacterium acnes. She was treated with an antibiotic course and conversion to anterior fusion without recurrence. Conclusion: This report highlights the rare presentation of an early periprosthetic infection after CDA caused by C. acnes. [ABSTRACT FROM AUTHOR]

Iron deficiency (ID) in nonanemic athletes has become more prevalent, creating a need to investigate the relationship between iron supplementation and iron deficiency in female athletes who are not anemic. The objective of this systematic review was to determine the impact of iron supplementation on athletic performance in iron-deficient, nonanemic (IDNA) female athletes. The search strategy was conducted in February 2022 using PubMed and CINAHL databases. Nine records that focused only on IDNA female athletes were included in the review, with a total of 355 female participants. The inclusion criteria were adult female athletes found to be IDNA. Iron supplementation of any form, dose, or duration and athletic performance measures were used. The exclusion criteria included adolescents, being injured, consuming other supplements or medications, or not measuring athletic performance. Five studies in this review concluded that iron supplementation improved iron status and enhanced physiological adaption. However, the other studies found that iron supplementation did not affect training. Some limitations in the studies reviewed include small sample size, shorter training duration, broad training regimens, exercise protocol, and measurement timing. Further determination of the level at which iron supplementation should be considered for female athletes who are IDNA is warranted. [ABSTRACT FROM AUTHOR]

Case: A 76-year-old woman with multiple myeloma and osteoporosis presented with right hip pain and an impending atypical femoral fracture in the setting of chronic bisphosphonate use. After preoperative medical optimization, she was scheduled for prophylactic intramedullary nail fixation. Intraoperatively, the patient experienced episodes of severe bradycardia and asystole associated with intramedullary reaming, which ceased after distal venting of the femur. No additional intraoperative or postoperative complications were encountered, and the patient recovered uneventfully. Conclusion: Femoral canal venting may be an appropriate intervention for similar transient dysrhythmias caused by intramedullary reaming. [ABSTRACT FROM AUTHOR]

Benitez, B, Dinyer-McNeeley, TK, McCallum, L, Kwak, M, Succi, PJ, and Bergstrom, HC. Load-specific performance fatigability, coactivation, and neuromuscular responses to fatiguing forearm flexion muscle actions in women. J Strength Cond Res 37(4): 769–779, 2023—This study examined the effects of fatiguing, bilateral, dynamic constant external resistance (DCER) forearm flexion on performance fatigability, coactivation, and neuromuscular responses of the biceps brachii (BB) and triceps brachii (TB) at high (80% 1 repetition maximum [1RM]) and low (30% 1RM) relative loads in women. Ten women completed 1RM testing and repetitions to failure (RTF) at 30 and 80% 1RM. Maximal voluntary isometric force was measured before and after RTF. Electromyographic (EMG) and mechanomyographic (MMG) amplitude (AMP) and mean power frequency (MPF) signals were measured from the BB and TB. Performance fatigability was greater (p < 0.05) after RTF at 30% (%∆ = 41.56 ± 18.61%) than 80% (%∆ = 19.65 ± 8.47%) 1RM. There was an increase in the coactivation ratio (less coactivation) between the initial and final repetitions at 30%, which may reflect greater increases in agonist muscle excitation (EMG AMP) relative to the antagonist for RTF at 30% than 80% 1RM. The initial repetitions EMG AMP was greater for 80% than 30% 1RM, but there was no difference between loads for the final repetitions. For both loads, there were increases in EMG MPF and MMG AMP and decreases in MMG MPF that may suggest fatigue-dependent recruitment of higher-threshold motor units. Thus, RTF at 30 and 80% 1RM during DCER forearm flexion may not necessitate additional muscle excitation to the antagonist muscle despite greater fatigability after RTF at 30% 1RM. These specific acute performance and neuromuscular responses may provide insight into the unique mechanism underlying adaptations to training performed at varying relative loads. [ABSTRACT FROM AUTHOR]

Objective: Ringette and female ice hockey are high participation sports in Canada. Despite policies disallowing body checking, both sports have high injury and concussion rates. This study aimed to compare physical contact (PC), head contact (HC), and suspected injury and concussion incidence rates (IRs) in female varsity ringette and ice hockey. Design: Cross-sectional. Setting: Canadian ice arenas. Participants: Eighteen Canadian female university ringette and ice hockey tournament/playoff games in the 2018-2019/2019-2020 seasons. Assessment of Risk Factors: Game video-recordings were analyzed using Dartfish video-analysis software to compare both sports. Main Outcome Measures: Univariate Poisson regression analyses (adjusted for cluster by team, offset by game-minutes) were used to estimate PC, HC, and suspected injury IRs and incidence rate ratios (IRRs) to compare rates across sports. Proportions of body checks (level 4-5 trunk PC) and direct HC (HC1) penalized were reported. Results: Analyses of 36 team-games (n = 18 ringette, n = 18 hockey) revealed a 19% lower rate of PCs in ringette than ice hockey {IRR = 0.81 [95% confidence interval (CI), 0.73-0.90]}, but a 98% higher rate of body checking [IRR = 1.98 (95% CI, 1.27-3.09)] compared to ice hockey. Ringette had a 40% higher rate of all HC1s [IRR = 1.40 (95% CI, 1.00-1.96)] and a 3-fold higher rate of suspected injury [IRR = 3.11 (95% CI, 1.13-8.60)] than ice hockey. The proportion of penalized body checks and HC1s were low across sports. Conclusions: Body checking and HC1 rates were significantly higher in ringette compared to ice hockey, despite rules disallowing both, and very few were penalized. These findings will inform future injury prevention research in ringette and female ice hockey. [ABSTRACT FROM AUTHOR]

Sprinting speed plays a crucial role in many sports, and it is considered a fundamental motor skill. Various training methods can be used to improve sprinting speed. Researchers have shown strength and plyometric training (PT) to be effective in improving sprinting speed. However, most studies have reviewed the effects of strength and PT on sprinting performance in adults and young males. There is a paucity of research that has reviewed the effects of strength and PT on sprinting performance in young females across maturation (pre-peak height, mid-peak height, and post-peak height velocity: peak height velocity student athletes, age 10–16 years). Moreover, no previous review has provided practical strength and PT strategies for young female student-athletes that acknowledge important factors such as growth, forces, and enjoyment. Therefore, this review highlights the importance of progressive strength and PT on sprinting performance in young females and provides practical training programs that can be implemented within a school curriculum. More specifically, this review provides exercise progressions in strength and power training for an eight-week training block that can be easily implemented by strength and conditioning coaches within a school term. [ABSTRACT FROM AUTHOR]

Cases: Two elderly women each presented with a unilateral, erythematous rash 1 year after total knee arthroplasty (TKA) for osteoarthritis. Both cases were diagnosed as postsurgical nummular eczema (NE) and treated successfully with topical corticosteroids. Conclusion: We highlight a novel clinical presentation of postsurgical NE associated with TKA, previously reported only with breast reconstruction. Postsurgical NE may mimic periprosthetic infection or implant-related allergic contact dermatitis. Timely diagnosis and appropriate treatment in these cases prevented unnecessary testing and hospital admission for revision surgery. This case series highlights the varied presentation and wide differential diagnosis associated with postsurgical NE. [ABSTRACT FROM AUTHOR]

Introduction: A paucity of research exists examining the importance of muscle morphological and functional characteristics for elite female sprint performance. Purpose: This study aimed to compare lower body muscle volumes and vertical jumping power between elite and subelite female sprinters and assess the relationships of these characteristics with sprint race and acceleration performance. Methods: Five elite (100 m seasons best [SBE100], 11.16 ± 0.06 s) and 17 subelite (SBE100, 11.84 ± 0.42 s) female sprinters underwent: 3T magnetic resonance imaging to determine the volume of 23 individual leg muscles/compartments and five functional muscle groups; countermovement jump and 30 m acceleration tests. Results: Total absolute lower body muscle volume was higher in elite versus subelite sprinters (+15%). Elite females exhibited greater muscle volume of the hip flexors (absolute, +28%; relative [to body mass], +19%), hip extensors (absolute, +22%; relative, +14%), and knee extensors (absolute, +21%), demonstrating pronounced anatomically specific muscularity, with relative hip flexor volume alone explaining 48% of sprint performance variability. The relative volume of five individual muscles (sartorius, gluteus maximus, adductor magnus, vastus lateralis, illiopsoas) were both distinct between groups (elite > subelite) and related to SBE100 (r = 0.553–0.639), with the combination of the sartorius (41%) and the adductor magnus (17%) explaining 58% of the variance in SBE100. Elite female sprinters demonstrated greater absolute countermovement jump power versus subelite, and absolute and relative power were related to both SBE100 (r = −0.520 to −0.741) and acceleration performance (r = 0.569 to 0.808). Conclusions: This investigation illustrates the distinctive, anatomically specific muscle volume distribution that facilitates elite sprint running in females, and emphasizes the importance of hip flexor and extensor relative muscle volume. [ABSTRACT FROM AUTHOR]

Spinal and extrapelvic lesions causing sciatic symptoms are well recognized in clinical research and practice.1–5 We present a 35-yr-old woman with a history of axial back pain and fibromyalgia who presented with episodes of radicular type pain down her legs and associated bilateral tingling in her feet. Medicinal and therapeutic interventions for traditional sciatica etiologies failed to provide relief. Lumbar magnetic resonance imaging showed mild multilevel degenerative changes and partially visualized fibroids, but no other significant spinal pathology was appreciated. Subsequent pelvic magnetic resonance imaging revealed an enlarged retroverted uterus with multiple fibroid lesions. The patient elected for laparoscopic myomectomy, which improved her likelihood of fertility while drastically alleviating her axial spine and lower extremity symptomology. This case reinforces the importance of keeping a broad differential that includes intrapelvic etiologies when traditional workup and treatment for sciatic neuropathy fails. To our knowledge, this is the first reported case of sciatic neuropathy secondary to uterine fibroids treated with the intent of both fertility improvement and pain relief. [ABSTRACT FROM AUTHOR]

Case: A 56-year-old woman underwent a left total hip arthroplasty (THA) after developing avascular necrosis after chemotherapeutic treatment of breast cancer. She presented approximately 2 years after index THA with left groin pain and complaints of instability. Imaging revealed pseudodislocation of the ceramic femoral head with erosion through the acetabular component. Intraoperative evaluation revealed a dissociated polyethylene liner, damaged acetabular locking mechanism, metallosis, and well-fixed and aligned components. Treatment consisted of component retention, bone grafting, and dual-mobility liner cementation into the acetabular component. Conclusions: The two-year follow-up demonstrated a pain-free, well-functioning hip, bone graft incorporation, and no evidence of loosening. [ABSTRACT FROM AUTHOR]

Case: A 32-year-old patient was diagnosed with a vertical patella fracture nonunion after a bone–patellar tendon–bone (BTB) anterior cruciate ligament reconstruction. In addition, a 1 × 2 × 1 cm patellar bone defect was noticed at the graft harvesting site. The patient was treated surgically with open reduction and internal fixation and iliac crest bone autograft which resulted in fracture union. Conclusion: Many intraoperative and postoperative risk factors for iatrogenic patella fracture when harvesting BTB autograft were identified. Surgeons should be aware of technical skills needed to prevent this complication and should treat the fracture appropriately to avoid nonunion and optimize the outcome. [ABSTRACT FROM AUTHOR]

Case: Ten days after L3-L5 instrumented posterior lumbar spinal fusion, an 85-year-old woman developed Grade 4 spondylolisthesis at L5-S1 after a minor fall. She underwent posterior open reduction and internal fixation with extension of fusion from L2 to the pelvis. The preexisting hardware at L5 caused partial laceration of the right L5 nerve root. One year after surgery, computed tomography demonstrated maintenance of correction and fusion at L5-S1. Conclusion: High-grade lumbosacral spondylolisthesis can occur with minor trauma after short-segment lumbar fusion. Maintenance of correction and fusion is achievable with posterior open reduction and internal fixation to the pelvis alone. Preexisting hardware can damage nerve roots causing permanent neurological deficits. [ABSTRACT FROM AUTHOR]

Case: A 43-year-old woman with dermatomyositis presented with Mycobacterium avium complex (MAC) knee septic arthritis with superimposed polymicrobial infection. After poor infection control with antibiotic therapy, she underwent debridement and antibiotic cement spacer placement, followed by knee arthrodesis 6 months later. At 2-year follow-up, she had no pain and was ambulating without assistive devices. Conclusion: As far as we know, this is the first reported case of MAC native-knee septic arthritis successfully treated with antibiotic cement spacer followed by knee arthrodesis. This case sheds insight on treatment strategies for a rare native-knee infection. [ABSTRACT FROM AUTHOR]

Objectives: To describe injury and concussion rates and mechanisms in female high school rugby players. Design: Two-year prospective cohort study. Setting: High school rugby. Participants: Participants included 214 female High school rugby players (year 1) and 207 female High school players (year 2) from the Calgary Senior High School Athletics Association 2018 and 2019 rugby competition. Intervention: None. Main Outcome Measures: Match and training injury and concussion. Injury definition included any injury resulting in time loss, inability to complete a session, and/or requiring medical attention. Details of reported injuries were collected on injury report forms and validated by a certified athletic therapist on a validated online injury surveillance platform. Exposure hours for players were tracked using paper or virtual weekly exposure forms by team designates. Results: A match incidence rate (IR) = 93.7 injuries/1000 match hours (95% confidence intervals (CI): 78.6-11.7) and training IR = 5.3 injuries/1000 training hours (95% CI: 4.0-6.9) were estimated. The tackle accounted for 109 (70%) match and 37 (44%) training injuries. Tackling was the most frequent mechanism of injury (IR = 37.5 injuries/1000 match hours, 95% CI: 27.5-51.8 and 1.2 injuries/1000 training hours, 95% CI: 0.7-2.4). Sixty-two match concussions (IR = 37.5 concussions/1000 match hours, 95% CI: 26.8-52.3) and 16 training concussions (IR = 1.0 concussions/1000 training hours, 95% CI: 0.7-1.4) occurred. Of 78 reported concussions, 78% for match and 56% for training were physician diagnosed. Tackling was the most frequent mechanism of concussion in matches (IR = 18.1 concussions/1000 match hours, 95% CI:11.4-28.6). Conclusions: Injury and concussion rates in female high school rugby are high. The tackle accounted for the highest proportion of injuries. Prevention strategies (eg, tackle policy change, tackle-training programs, and neuromuscular training) should be explored to increase sport safety. [ABSTRACT FROM AUTHOR]

Background: Limited information on the normal range of urination frequencies in women is available to guide bladder health promotion efforts. Objectives: This study used data from the Boston Area Community Health (BACH) Survey to (a) estimate normative reference ranges in daytime and nighttime urination frequencies in healthy women based on two operational definitions of "healthy" and (b) compare urination frequencies by age, race/ethnicity, and fluid intake. Methods: A secondary analysis of cross-sectional interview data collected from female participants was performed using less restrictive ("healthy") and strict ("elite healthy") inclusion criteria. All analyses were weighted to account for the BACH sampling design. Normative reference values corresponding to the middle 95% of the distribution of daytime and nighttime urination frequencies were calculated overall and stratified by age, race/ethnicity, and fluid intake. Generalized linear regression with a log-link was used to estimate rate ratios of daytime and nighttime urination frequencies by age, race/ethnicity, and fluid intake. Results: Of the 2,534 women who completed the BACH follow-up interviews, 1,505 women met healthy eligibility criteria, and 300 met elite healthy criteria. Overall, reference ranges for urination frequencies were 2–10 times/day and 0–4 times/night in healthy women and 2–9 times/day and 0–2 times/night in elite healthy women. Women ages 45–64 years, but not 65+ years, reported a greater number of daytime urination than those aged 31–44 years, whereas women 65+ years reported a greater number of nighttime urination. Black women reported fewer daytime urination and more nighttime urinations than White women. Women who consumed less than 49 oz daily reported fewer daytime and nighttime urinations than those who drank 50–74 oz; drinking 75+ oz had only a small effect on urination frequencies. Discussion: Normative reference values for daytime and nighttime urination frequencies were similar in women using strict and relaxed definitions of health. These results indicate a wide range of "normal" urination frequencies, with some differences by age, race/ethnicity, and fluid intake. Future research is needed to examine urination frequencies in minority women and whether fluid intake amount and type influence the development of lower urinary tract symptoms. [ABSTRACT FROM AUTHOR]

Background: The National Health and Nutrition Examination Survey data indicate that the proportion of US adults with hypertension that had controlled blood pressure (BP) declined from 2013 to 2014 through 2017 to 2018. We analyzed data from National Health and Nutrition Examination Survey 2009 to 2012, 2013 to 2016, and 2017 to 2020 to confirm this finding.Methods: Hypertension was defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg or antihypertensive medication use. BP control among those with hypertension was defined as systolic BP <140 mm Hg and diastolic BP <90 mm Hg.Results: The age-adjusted prevalence of hypertension was 31.5% (95% CI, 30.3%-32.8%), 32.0% (95% CI, 30.6%-33.3%), and 32.9% (95% CI, 31.0%-34.7%) in 2009 to 2012, 2013 to 2016, and 2017 to 2020, respectively (P trend=0.218). The age-adjusted prevalence of hypertension increased among non-Hispanic Asian adults from 27.0% in 2011 to 2012 to 33.5% in 2017 to 2020 (P trend=0.003). Among Hispanic adults, the age-adjusted prevalence of hypertension increased from 29.4% in 2009 to 2012 to 33.2% in 2017 to 2020 (P trend=0.029). In 2009 to 2012, 2013 to 2016, and 2017 to 2020, 52.8% (95% CI, 50.0%-55.7%), 51.3% (95% CI, 47.9%-54.6%), and 48.2% (95% CI, 45.7%-50.8%) of US adults with hypertension had controlled BP (P trend=0.034). Among US adults taking antihypertensive medication, 69.9% (95% CI, 67.8%-72.0%), 69.3% (95% CI, 66.6%-71.9%), and 67.7% (95% CI, 65.2%-70.3%) had controlled BP in 2009 to 2012, 2013 to 2016, and 2017 to 2020, respectively (P trend=0.189). Among all US adults with hypertension and those taking antihypertensive medication, a decline in BP control between 2009 to 2012 and 2017 to 2020 occurred among those ≥75 years, women, and non-Hispanic black adults.Conclusions: These data confirm that the proportion of US adults with hypertension who have controlled BP has declined. [ABSTRACT FROM AUTHOR]

Background and Objectives: In recent years, researchers have sought to address the challenges of obtaining informed consent for participation in acute stroke trials. We studied outcomes related to the use of deferral of consent in the phase 3 Alteplase Compared to Tenecteplase (AcT) trial., Methods: As part of our protocol, we captured methods of consent, participant withdrawals, door-to-randomization times, and door-to-needle times. Participants at 3 sites were invited to complete a survey of attitudes regarding consent for AcT and for acute stroke trials generally., Results: The AcT trial enrolled 1,600 participants from 22 centers across Canada of whom 1,537 were enrolled through deferral of consent (96.0%) and 63 (4.0%) were enrolled by prospective verbal consent followed by written informed consent. Of those enrolled by deferral of consent, 95% (1,454/1,537) consented to ongoing participation. Door-to-randomization times were similar regardless of method of consent, with an overall median of 30 minutes (interquartile range [IQR] 22-42): 29 minutes (IQR 22-42) in the deferral of consent group vs 32 minutes (IQR 25-44) in the prospective consent group ( p = 0.1602). Survey respondents overwhelming agreed or strongly agreed with the use of deferral of consent in AcT (86%) and in any acute stroke trial (76%)., Discussion: Deferral of consent was broadly acceptable to participants in the AcT trial as demonstrated by low rates of withdrawal and by survey results. Door-to-randomization times using deferral of consent in AcT were short, although a system of prospective verbal consent used at 1 center took only slightly longer. These results support the importance of innovation around consent for acute stroke trials.

Background and Objectives: The 21-point Brain Care Score (BCS) is an index that ranks behaviors and clinical measurements with the aim of encouraging lifestyle adjustments to lower the incidence of age-related brain disease, including stroke, late-life depression (LLD), and dementia. A higher BCS at baseline is associated with a lower risk of these outcomes. We aimed to investigate whether the associations between BCS and stroke, LLD, and dementia risks are independent of genetic predisposition for these conditions and quantify the effect of healthy lifestyle across genetic risk distributions for these outcomes., Methods: Using the UK Biobank (UKB) prospective cohort study, we computed baseline BCSs and polygenic scores to estimate genetic predisposition for stroke and LLD and APOE ε allele status to stratify dementia risk. As for outcomes again in UKB, we measured incidence of stroke, LLD, and dementia. We used multivariate Cox proportional hazard models to assess associations between BCS, genetic predisposition, and these outcomes. We also conducted stratified and interaction analyses to estimate the incidence of these outcomes across quartiles of genetic risk and BCS., Results: We included 368,340 UKB participants (median age 58 years (interquartile range 51-63 years), 46.3% male). Independent of genetic risk, a 5-point increase in BCS corresponded to lowered hazards of stroke (hazard ratio [HR] 0.70, 95% CI 0.68-0.73), LLD (HR 0.65, 95% CI 0.63-0.67), and dementia (HR 0.82, 95% CI 0.78-0.85). Incidences of all 3 outcomes were higher among participants with high genetic risk of these outcomes. However, these increased risks were offset for individuals with a higher BCS (incidence rates per 1,000 person-years were 2.76 vs 1.19 for stroke, 7.34 vs 4.46 for LLD, and 3.64 vs 2.05 for dementia, when comparing low and high BCS)., Discussion: Across different genetic predispositions for stroke, LLD, and dementia, healthier lifestyle behaviors are protective for brain health, demonstrating the nondeterminism of genetic risk. Furthermore, differences in BCS behave as aggregate risk estimators of all 3 outcomes. Further work is needed to prospectively investigate the utility and performance of the BCS as a targeted intervention in populations at elevated genetic risk of age-related brain disease.

Background and Objectives: Epidemiologic studies suggest increasing incidence and prevalence of myasthenia gravis (MG) among the elderly population outside the United States. We aimed to provide an estimation of MG incidence and prevalence and their trend among the Medicare Fee-For-Service (FFS)-covered elderly US population., Methods: We performed a retrospective longitudinal study using Medicare claims data (2006-2019). Study-eligible beneficiaries were aged 65 years and older, had at least 1 month of FFS Part A/B coverage, and were without any health maintenance organization insurance coverage. Study-eligible beneficiaries were aggregated into 2-year periods from 2006-2007 through 2018-2019. MG cases were ascertained using a validated algorithm of 2 MG claims within each 2-year period, from 2 outpatient office visits or a combination of 1 inpatient admission and 1 outpatient office visit, separated by ≥ 28 days. Period prevalence was calculated from MG-ascertained cases divided by FFS Part A/B beneficiaries and reported as cases per 100,000 population. Incident cases were determined among MG prevalent cases if the initial MG claim occurred in that period after a full calendar year since coverage initiation. Incidence was calculated as case counts per 100,000 at-risk beneficiary person-years (PYs) in each period excluding 2006-2007. Trends of prevalence and incidence over time were examined with Poisson regression. All-cause mortality of each 2-year period was calculated., Results: The period prevalence of MG increased from 81 to 119 per 100,000 FFS A/B population from 2006-2007 to 2018-2019 ( p < 0.001). Increasing trends of prevalence were observed in all sex (male/female), age (65-69/70-74/75-79/80+), race/ethnic (African American/Asian/Hispanics of any race/non-Hispanic White/other), and census region (Northeast/Midwest/South/West) subgroups. MG incidence increased from 12.2 to 13.3 per 100,000 PYs from 2008-2009 to 2018-2019 ( p < 0.05). Increasing incidence trends were significant in the following subgroups: men and women; all age groups except 75-79 years; White non-Hispanic race; Northeast, Midwest, and South census regions. All-cause mortality among MG beneficiaries was stable from 6.26 deaths per 100 PYs in 2006-2007 to 5.67 in 2018-2019 ( p = 0.18)., Discussion: Increasing trends in MG prevalence and incidence in the elderly US population, with variation in rates of certain subgroups, are confirmed in this 14-year period.

Background and Objectives: Disentangling brain aging from disease-related neurodegeneration in patients with multiple sclerosis (PwMS) is increasingly topical. The brain-age paradigm offers a window into this problem but may miss disease-specific effects. In this study, we investigated whether a disease-specific model might complement the brain-age gap (BAG) by capturing aspects unique to MS., Methods: In this retrospective study, we collected 3D T1-weighted brain MRI scans of PwMS to build (1) a cross-sectional multicentric cohort for age and disease duration (DD) modeling and (2) a longitudinal single-center cohort of patients with early MS as a clinical use case. We trained and evaluated a 3D DenseNet architecture to predict DD from minimally preprocessed images while age predictions were obtained with the DeepBrainNet model. The brain-predicted DD gap (the difference between predicted and actual duration) was proposed as a DD-adjusted global measure of MS-specific brain damage. Model predictions were scrutinized to assess the influence of lesions and brain volumes while the DD gap was biologically and clinically validated within a linear model framework assessing its relationship with BAG and physical disability measured with the Expanded Disability Status Scale (EDSS)., Results: We gathered MRI scans of 4,392 PwMS (69.7% female, age: 42.8 ± 10.6 years, DD: 11.4 ± 9.3 years) from 15 centers while the early MS cohort included 749 sessions from 252 patients (64.7% female, age: 34.5 ± 8.3 years, DD: 0.7 ± 1.2 years). Our model predicted DD better than chance (mean absolute error = 5.63 years, R 2 = 0.34) and was nearly orthogonal to the brain-age model (correlation between DD and BAGs: r = 0.06 [0.00-0.13], p = 0.07). Predictions were influenced by distributed variations in brain volume and, unlike brain-predicted age, were sensitive to MS lesions (difference between unfilled and filled scans: 0.55 years [0.51-0.59], p < 0.001). DD gap significantly explained EDSS changes ( B = 0.060 [0.038-0.082], p < 0.001), adding to BAG (Δ R 2 = 0.012, p < 0.001). Longitudinally, increasing DD gap was associated with greater annualized EDSS change ( r = 0.50 [0.39-0.60], p < 0.001), with an incremental contribution in explaining disability worsening compared with changes in BAG alone (Δ R 2 = 0.064, p < 0.001)., Discussion: The brain-predicted DD gap is sensitive to MS-related lesions and brain atrophy, adds to the brain-age paradigm in explaining physical disability both cross-sectionally and longitudinally, and may be used as an MS-specific biomarker of disease severity and progression.

Objectives: The objective of this study was to estimate the incidence, timing, and type of new cancer diagnosis among patients with cryptogenic stroke., Methods: We used data from the ARCADIA trial, which enrolled patients with cryptogenic stroke and atrial cardiopathy. Participants were prospectively followed, and serious adverse events were assessed every 3 months or sooner if investigators were alerted between visits to an event. Kaplan-Meier statistics were used to estimate the cumulative incidence of a cancer diagnosis within the first year after randomization., Results: Among 878 participants without baseline history of cancer, 13 (1.5%) were diagnosed with incident cancer in the year after randomization, comprising 12 solid cancers (3 prostate, 2 breast, 2 gastrointestinal, and 5 other primary sites) and 1 hematologic cancer (non-Hodgkin lymphoma). The cumulative incidences of a cancer diagnosis were 0% at 3 months, 0.6% (95% CI 0.2%-1.5%) at 6 months, and 2.0% (95 CI 1.1%-3.4%) at 1 year. The median time from index stroke to cancer diagnosis was 261 days (interquartile range 183-358)., Discussion: In a multicenter cryptogenic stroke cohort with prospective follow-up, the 1-year cumulative incidence of a cancer diagnosis was 2%. This rate may be an underestimation because of the clinical trial population and exclusion of cancers diagnosed immediately after stroke., Trial Registration Information: ClinicalTrials.gov Identifier: NCT03192215. Registered June 20, 2017. First patient enrolled February 1, 2018.

Background and Objectives: Although most spontaneous intracerebral hemorrhages (ICHs) are due to cerebral small vessel diseases (SVDs), between 1 in 7 and 1 in 10 are due to a macrovascular cause. Rapid diagnosis has important therapeutic and prognostic implications but sometimes requires digital subtraction angiography (DSA), an invasive procedure which cannot be performed in all patients. MRI provides optimal sensitivity for markers of SVD but was not included in previous risk stratification scores. We aimed to create and validate a risk stratification score for macrovascular causes of ICH including MRI findings to guide diagnosis and further investigations., Methods: We pooled data from 2 large observational study cohorts (London/United Kingdom and Graz/Austria) of consecutive patients with ICH who had brain MRI and at least 1 angiographic modality within 90 days of symptom onset. The primary outcome was a macrovascular cause of ICH (arteriovenous malformation/dural arteriovenous fistula, aneurysm, cavernoma, or cerebral venous thrombosis), with the diagnosis based on neurovascular multidisciplinary meetings. Using lasso logistic regression, we built the MRI Assessment of the Causes of intRacerebral haemOrrhage (MACRO) score to assess the probability of a macrovascular cause. We performed internal validation using bootstrapping and external validation in an independent cohort (Bern/Switzerland)., Results: We included 1,043 patients with ICH (mean age 66 years, 42% female), 78 of whom had a macrovascular cause (7.5%). The final score includes age (0-39, 40-69, or ≥70), location of ICH (lobar, deep, or infratentorial), and SVD markers on MRI (≥1 microbleed, ≥1 lacune, presence of cortical superficial siderosis, or white matter hyperintensities using the Fazekas scale). The MACRO score showed an optimism-adjusted c -statistic of 0.90 (95% CI 0.88-0.93), superior to existing CT-based scores ( p < 0.001). In external validation, the c -statistic was 0.87 (95% CI 0.80-0.94). MACRO scores ≥6 (59.5% of patients) indicated a very low risk of a macrovascular cause (0.2%), while scores ≤2 (9% of patients) indicated a high risk (48.9%)., Discussion: The MRI-based MACRO score shows excellent performance in predicting the likelihood of macrovascular causes of spontaneous intracerebral hemorrhage, making it useful in guiding further investigations. Important limitations include the observational study design and the performance of DSA in a minority of patients.

Background and Objectives: Cerebral amyloid angiopathy (CAA) is common in older adults and is associated with dementia. Less is known whether this association is mediated by Alzheimer disease (AD) neuropathologic changes, the examination of which was the objective of this study., Methods: This was a retrospective cross-sectional examination of the Kaiser Permanente Washington database of the Adult Changes in Thought (ACT) autopsy cohort with information on CAA, dementia, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) (amyloid neuritic plaques), and Braak (tau neurofibrillary tangles). CAA was diagnosed by immunohistochemistry and dementia by ACT Consensus Diagnostic Conference. AD neuropathology was categorized by CERAD scores and Braak stages. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% CIs of the associations of CAA with dementia, adjusting for age at death and sex, and with additional adjustments separately for CERAD scores (moderate-severe vs mild-absent), Braak stages (V-VI vs 0-IV), APOE ε4, and stroke. Formal mediation analyses were conducted to estimate age-sex-adjusted OR (95% CI) for natural indirect effects (NIEs) of CERAD scores and Braak stages., Results: The 848 participants had a mean age of 86.7 ± 4.6 years at death, and 57.6% were female. CAA was present in 322 participants (38.0%), of whom 152, 145, and 25 had mild, moderate, and severe CAA, respectively. Dementia was present in 384 participants (45.3%), of whom 317 had AD. Dementia was more common in those with CAA than without (53.7% vs 40.1%; age-sex-adjusted OR 1.57, 95% CI 1.18-2.10). This association remained significant after separate adjustment for other covariates but lost significance when adjusted for CERAD scores (OR 1.27, 95% CI 0.93-1.71) and Braak stages (OR 0.96, 95% CI 0.69-1.33). Findings from our formal mediation analyses show that ORs (95% CIs) for NIE of CERAD scores and Braak stages were 1.25 (1.13-1.37) and 1.63 (1.38-1.88), respectively, and CERAD scores and Braak stages mediated 53% and 111% of the total association, respectively., Discussion: We observed a significant association between CAA and dementia that disappeared when adjusted for CERAD or Braak stages. Findings from our mediation analyses suggest that the CAA-dementia association may be potentially mediated by AD neuropathologic changes. This hypothesis needs to be tested in future mechanistic studies in AD accounting for unmeasured confounders.

Objectives: To describe a novel subtype of autoimmune myopathy, immune-mediated megaconial myopathy (IMMM), myopathologically characterized by giant mitochondria (megaconia)., Methods: In this case series, we reviewed the Mayo Clinic Muscle Pathology database, between 2018 and 2023, to identify patients with megaconial pathology, subacute progressive weakness, and hyperCKemia, clinically resembling myositis. We recruited 1 patient from another institute, who had similar clinicopathologic features., Results: Five patients were identified. Age at onset of weakness ranged from 19 to 45.5 years. All patients had proximal weakness, elevated creatine kinase levels (1,214 to 5,920 U/L), negative myositis antibodies, necrotizing myopathology, and nonnecrotic myofibers harboring giant mitochondria. Immunohistochemical studies conducted in 4 patients showed sarcolemmal MHC-1 and C5b9 immunoreactivities. Megaconial pathology was considered pathognomonic of congenital muscular dystrophy due to biallelic pathogenic variants in CHKB . Sequencing of CHKB in 4/5 patients was unrevealing. Immunomodulatory therapy improved weakness and hyperCKemia in 4 treated patients. Of interest, all patients had coexisting pancreatic diseases (3 cystic fibrosis-related exocrine pancreatic insufficiency, 1 pancreatic cancer, and 1 pancreatitis)., Discussion: In addition to incurable CHKB -congenital muscular dystrophy, giant mitochondria can also occur in this new subtype of treatable autoimmune myopathy, IMMM. The association between IMMM and pancreatic disorders remains to be elucidated.

Background and Objectives: All 4 previous nationwide surveys of multiple sclerosis (MS) in Japan were conducted before the discovery of anti-aquaporin-4 (AQP4) antibodies; thus, neuromyelitis optica spectrum disorder (NMOSD) was included in MS, as optic-spinal MS. We aimed to clarify the epidemiologic features and trends of MS and NMOSD in Japan separately using a fifth nationwide survey., Methods: The primary survey, in which a questionnaire was sent to 3,799 selected departments (including neurology/internal medicine, pediatrics, and ophthalmology), explored the estimated number and prevalence of patients with MS or NMOSD in 2017, and the secondary survey collected detailed characteristics of the patients using a second questionnaire., Results: The response rates for the primary and secondary surveys were 60.1% and 53.9%, respectively. The estimated total number of patients with MS or NMOSD was 24,800, 2.5-fold higher than that in the fourth survey in 2003. The crude prevalence was 19.6 per 100,000 patients (14.2 for MS and 5.4 for NMOSD), compared with 7.7 per 100,000 patients in the fourth survey. Patients with MS showed milder disability (median Expanded Disability Status Scale [EDSS] score: 2.0 [interquartile range 1.0-4.5] vs 2.5 [1.0-6.0]), decreased secondary progression (8.5% vs 15.2%), and increased usage of disease-modifying drugs (63.7% vs 37.2%) compared with those with conventional MS in the fourth survey. The proportions of oligoclonal bands and Barkhof criteria fulfillment on MRI, which are features of classical MS, increased with advancing year of birth. Patients with NMOSD also showed less disability and shorter disease duration than patients with optic-spinal MS in the fourth survey (EDSS score: 3.5 [2.0-5.5] vs 3.8 [2.0-6.0]; disease duration: 8.0 [3.9-14.8] vs 10.0 [5.0-16.0]). Among patients with NMOSD, disability was exacerbated by a history of longitudinally extensive spinal cord lesions and anti-AQP4 antibody positivity, which both decreased with advancing year of birth., Discussion: The prevalences of MS (particularly with classical features) and NMOSD have been increasing in Japan, suggesting the contribution of environmental factors. However, disabilities in patients with MS and NMOSD have been mitigated. Extensive usage of various disease-modifying drugs could be a factor contributing to this disability mitigation in MS.

Objectives: To observe medication cost trends for 5 common neurologic conditions., Methods: We quantified annual out-of-pocket (OOP) and total medication costs for patients seen by a neurologist with epilepsy, multiple sclerosis (MS), Parkinson disease (PD), peripheral neuropathy (PN), and dementia/Alzheimer's disease in a commercial claims database cross-sectionally from 2012 to 2021., Results: We identified 186,144 patients with epilepsy, 54,676 with MS, 45,909 with PD, 169,127 with PN, and 60,861 with dementia/Alzheimer. OOP costs for MS medications increased each year, by 217% on average. Branded epilepsy medications had higher OOP costs than generics. Decreases ranging from 48% to 80% in annual OOP costs of duloxetine, pregabalin, rasagiline, rivastigmine, and memantine were observed in the years after generic introduction., Discussion: Preferentially selecting generic medications reduces OOP costs, other than for MS where costs continue to increase. Policy solutions, such as cost caps, are needed.

Background and Objectives: Isolated REM sleep behavior disorder (iRBD) is strongly associated with synucleinopathies. Previous iRBD cohort studies have primarily focused on older (>50 years), male-predominant cohorts. Risk of phenoconversion in women and younger adults remains unclear. The study aimed to determine clinical features associated with conversion to a defined neurodegenerative disorder in women and men with iRBD., Methods: One hundred eighty-six women and 186 men with iRBD were matched by polysomnography month. Baseline clinical variables and subsequent neurodegenerative outcomes were abstracted by chart review. Kaplan-Meier curves assessed conversion rates. Cox proportional hazards modeling evaluated factors associated with phenoconversion risk., Results: Age at iRBD diagnosis was younger in women compared with men (54.9 vs 62.5 years, p < 0.01). Forty-eight patients (12.9%), including 18 women (9.7%) and 30 men (16.1%), phenoconverted during a median follow-up of 6.0 years. Conversion rates were lower in antidepressant users and patients with chronic pain or psychiatric comorbidity while rates were higher in those with vascular comorbidity. Only age at diagnosis (HR 1.09, 95% CI 1.06-1.13) was associated with phenoconversion after adjusting for RBD symptom duration; sex; antidepressant use; and psychiatric, chronic pain, and vascular comorbidities., Discussion: Age at diagnosis was independently associated with phenoconversion risk in women and men with iRBD.

Background and Objectives: The incidence of stroke among young adults was rising globally, but the death burden of stroke in young adults in China is lacking. We aimed to examine the temporal trends in mortality and years of life lost (YLLs) caused by stroke among young adults from 2005 to 2020 across China., Methods: Based on the data from the National Mortality Surveillance System in China, we estimated the number and age-standardized rate of mortality and YLLs due to stroke and its subtypes among young adults aged 15-49 years during 2005-2020, for both China and its 31 mainland provinces., Results: During 2005-2020, the age-standardized mortality rate of stroke among young adults aged 15-49 years in China decreased by 21.0%, from 5.9/100,000 to 4.7/100,000, and the YLL rate decreased from 286.9/100,000 to 229.5/100,000. The age-standardized mortality rate among young adults due to intracerebral hemorrhage (ICH) showed a significant downward trend with a decrease of 26.3% while that of ischemic stroke (IS) and subarachnoid hemorrhage (SAH) decreased by 4.5% and 0.6%, respectively. In 2020, the mortality rate of ICH was 3.5 times higher than that of IS (3.3/100,000 vs 0.9/100,000) among young adults in China. The male/female ratio of age-standardized mortality rate of stroke in young adults increased from 2.0 in 2005 to 3.1 in 2020. The age-standardized mortality rate of IS and SAH in young men increased by 11.0% and 2.5%, respectively. In 2020, Tibet (18.4/100,000), Jilin (10.4/100,000), and Qinghai (8.3/100,000) were the top 3 provinces holding the highest age-standardized mortality rate due to stroke among young adults. Tibet was found to have the highest mortality rate due to ICH and SAH while that of IS was higher in northeast China., Discussion: In China, the death burden caused by ICH among young adults was substantially higher than that of IS. The increasing death burden of IS and SAH among young men requires special attention. Evidence-based intervention strategies are needed to improve the outcomes of stroke and alleviate the death burden due to stroke among young adults in Chinese population.

Background and Objectives: Recent technological advances have enabled visualizing in vivo a subset of chronic active brain lesions in persons with multiple sclerosis (pwMS), referred to as "paramagnetic rim lesions" (PRLs), with iron-sensitive MRI. PRLs predict future clinical disease progression, making them a promising clinical and translational imaging marker. However, it is unknown how disease progression is modified by PRL evolution (PRL disappearance, new PRL appearance). This is key to understanding MS pathophysiology and may help inform selection of sensitive endpoints for clinical trials targeting chronic active inflammation. To this end, we assessed the longitudinal associations between PRL disappearance and new PRL appearance and clinical disability progression and brain atrophy., Methods: PwMS and healthy controls (HCs) were included from a larger prospective, longitudinal cohort study at the University at Buffalo if they had available 3T MRI and clinical visits at baseline and follow-up timepoints. PwMS with sufficient clinical data for confirmed disability progression (CDP) analysis were included in a Disability Progression Cohort, and pwMS and HCs with brain volumetry data at baseline and follow-up were included in MS and HC Brain Atrophy cohorts. PRLs were assessed at baseline and follow-up and assigned as disappearing, newly appearing, or persisting at follow-up. Linear models were fit to compare annualized PRL disappearance rates or new PRL appearance (yes/no) with annualized rates of CDP and progression independent of relapse activity (PIRA) or with annualized rates of brain atrophy, adjusting for covariates including baseline PRL number and follow-up time. Statistical analyses were corrected for false discovery rate (FDR; i.e., q -value)., Results: In total, 160 pwMS (73.8% female; mean baseline age 46.6 ± 11.4 years; mean baseline disease duration 13.8 ± 10.6 years; median follow-up time 5.6 [interquartile range 5.2-7.8] years; 26.9% progressive MS) and 27 HCs (74.1% female; mean baseline age 43.9 ± 13.6 years; median follow-up time 5.4 [5.2-5.6] years) were enrolled. Greater PRL disappearance rates were associated with reduced rates of CDP (β mean = -0.262, 95% CI -0.475 to -0.049, q = 0.028) and PIRA (β mean = -0.283, 95% CI -0.492 to -0.073, q = 0.036), and new PRL appearance was associated with increased rates of PIRA (β mean = 0.223, 95% CI 0.049-0.398, q = 0.036). By contrast, no associations between new PRL appearance or PRL disappearance and brain volume changes survived FDR correction ( q > 0.05)., Discussion: Our results show that resolution of existing PRLs and lack of new PRLs are associated with improved clinical outcomes. These findings further motivate the need for novel therapies targeting microglia-mediated brain inflammation and adoption of clinical strategies to prevent appearance of new PRL.

Background and Objectives: Intramuscular fat fraction (FF), assessed with quantitative MRI (qMRI), has emerged as one of the few responsive outcome measures in CMT1A patients. The main limitation for its use in future therapeutic trials is the time required for the manual segmentation of individual muscles. This study aimed to evaluate the accuracy and responsiveness of a fully automatic artificial intelligence (AI)-based segmentation pipeline to assess disease progression in a cohort of CMT1A patients over 1 year., Methods: Twenty CMT1A patients were included in this observational, prospective, longitudinal study. FF was measured twice a year apart using qMRI in the lower limbs. Individual muscle segmentation was performed fully automatically using a trained convolutional neural network with or without human quality check (QC). The corresponding results were compared with those obtained by fully manual (FM) segmentation using the Dice similarity coefficient (DSC). FF progression and its standardized response mean (SRM) were also computed in individual muscles over the single central slice and a 3D volume to define the most sensitive region of interest., Results: AI-based segmentation showed excellent DSC values (>0.90). Significant global FF progression was observed at thigh (+0.71% ± 1.28%; p = 0.016) and leg (+1.73% ± 2.88%, p = 0.007) levels, similarly to that calculated using the FM technique ( p = 0.363 and p = 0.634). FF progression of each individual muscle was comparable when computed from either the central slice or the 3D volume. The best SRM value (0.70) was obtained for the FF progression computed using the AI-based technique with human QC in the 3D volume at the leg level. The time required for fully automatic segmentation using AI with a QC was 10 hours for the entire data set compared with 90 hours for the FM., Discussion: qMRI combined with AI-based segmentation can be considered as a process ready for assessing longitudinal FF changes in CMT1A patients. Given the slow FF progression at a thigh level and the large heterogeneity between muscles and individuals, FF should be quantified from a 3D volume at the leg level for longitudinal analyses. A QC performed after the AI-based segmentation is still advised given the increased SRM value.

Background and Objectives: A quarter of ischemic strokes are of lacunar clinical subtype and have an underlying recent small subcortical infarct (RSSI), but their long-term outcomes remain poorly characterized. Hemosiderin deposits (HDs) have been noted in RSSIs at chronic stages and might mimic primary hemorrhage. We characterized HDs' morphology, frequency, and clinical relevance., Methods: Participants with RSSIs were identified from a prospective longitudinal study and evaluated on 3T MRI including susceptibility-weighted imaging (SWI) from stroke diagnosis to 12 months. We categorized HDs in RSSIs on SWI at all available time points into 4 types (spots, smudge, rim, cluster) and assessed their associations with demographic factors, stroke-related factors, and image markers with adjusted logistic regression., Results: HDs were observed in 43 (55.0%) of 108 participants within 3 months and 83 (76.9%) of 108 within 12 months after stroke onset. The mean time to first detection of HDs was 87 (interquartile range 53-164) days. A "rim" pattern (similar to late appearance of primary hemorrhage) occurred in at least 26.5% of RSSIs at all follow-up time points, mainly those located in the lentiform/internal capsule (50.0%) or thalamus (36.4%). Infarct volume (odds ratio [OR] 1.003, 95% CI 1.001-1.006; p = 0.004) and the total small vessel disease (SVD) score at baseline (OR 2.50, 95% CI 1.28-4.86, p = 0.007) independently predicted HDs at 12 months. HDs were positively associated with more lacunes (OR 1.60, 95% CI 1.13-2.26, p < 0.01), but not the Fazekas score, number of microbleeds, basal ganglia mineral deposit score, or clinical outcomes., Discussion: HDs occur commonly in RSSIs and may be associated with infarct volume and SVD score. Hemosiderin "rim" is common in RSSIs, urging caution to avoid mistaking ischemic RSSI for primary hemorrhage in subacute and chronic stages.