Citations

Abstract INTRODUCTION Premenopausal bilateral oophorectomy (PBO) before the age of 46 years is associated with an increased risk of dementia. We investigated the long‐term effects of PBO performed before age 50 years on amyloid beta (Aβ), tau, and neurodegeneration imaging biomarkers of Alzheimer's disease (AD). METHODS Mayo Clinic Cohort Study of Oophorectomy and Aging‐2 participants were divided into early PBO (< 46 years; n = 61), and late PBO (46–49 years; n = 51) groups and were compared to referent women who did not undergo PBO ( n = 119). RESULTS Early PBO was associated with thinner entorhinal cortex ( p = 0.014), higher tau load at higher levels of Aβ load ( Pp = 0.005), higher Aβ load ( p = 0.026), and smaller temporal lobe cortical thickness ( p = 0.022), only at older ages compared to the referent group. DISCUSSION PBO before the age of 46 years is associated with entorhinal cortex thinning, elevated tau at higher Aβ levels, along with an AD‐like pattern of atrophy at older ages. CLINICAL TRIALS REGISTRATION NCT03821857 sex‐specific effects of endocrine disruption on aging and AD. Highlights Premenopausal bilateral oophorectomy (PBO) before the ages of 46 (early PBO) years and ages 46 to 49 (late PBO) years was studied. Early PBO was associated with reduced entorhinal cortex thickness later in life. Early PBO was associated with greater amyloid beta (Aβ) load at older ages. Early PBO was associated with greater Alzheimer's disease pattern of atrophy at older ages. Early PBO was associated with higher tau load at higher Aβ levels.

Context : A common component within rehabilitation recommendations for baseball pitchers is employment of an interval throwing program. However, there is a lack of a consistent set of advocated guidelines for program content and implementation for athletes at the professional and collegiate levels. Design : Cross-sectional study. Methods : A survey was developed to obtain clinician views regarding the composition and implementation of interval throwing programs for baseball pitchers. The survey was divided into demographic information and sections on criteria to begin throwing programs, frequency of throwing, soreness management, warm-up components, program components and regulation of a program, and criteria to achieve permitting live throwing. Clinicians including physicians, physical therapists, and certified athletic trainers who evaluate and treat musculoskeletal injuries among baseball pitchers at the professional-level and/or collegiate-level clinician received the survey. Responses were tabulated and compared between the professional-level clinician and collegiate-level clinician groups using chi-square analyses with statistical significance set at P ≤ .05. Results : The survey was completed by 166 clinicians (collegiate level = 81, professional-level clinician = 85). There were no statistical differences between groups for allowing warm-up throws, program regulation, maximum distance allowed, managing soreness, or criteria to achieve before permitting live throwing. Between-group differences included criteria to begin a program (≤.03), warm-up distance ( P ≤ .02), nonthrowing warm-up methods ( P ≤ .04), non-warm-up distance ( P ≤ .01), using ratings of perceived exertion ( P < .01), throwing frequency ( P < .01), and program components ( P ≤ .04). Conclusions : Responses appear to mirror interval throwing program designs previously reported in the literature but there are modifications and additions utilized by clinicians at different playing levels.

OBJECTIVE Endovascular intracranial aneurysm (IA) management has significantly evolved over the last 2 decades. Despite these advancements, the aneurysm recanalization rate after coil embolization remains a concern. Statins have been found to affect vascular repair and remodeling; therefore, the authors hypothesized that patients receiving statin therapy at the time of coil embolization would have lower aneurysm recurrence and retreatment rates compared with patients not receiving statin therapy. METHODS A post hoc analysis was conducted of the primary data from patients enrolled in the Hydrogel Endovascular Aneurysm Treatment Trial focusing on the impact of statin use on the recurrence rates of 3- to 14-mm IAs after endovascular coiling. The primary outcome measured included aneurysm recurrence over 18–24 months using the Raymond-Roy Occlusion Classification. Secondary outcomes included major and minor recurrence rates and retreatment rates. Propensity score matching based on patient and aneurysm characteristics was performed to mitigate selection bias. RESULTS A total of 577 patients with data on statin use were eligible for this analysis. Of these, 178 (30.8%) patients were using statins and 399 (69.2%) were not. After propensity score matching, 156 (39.2%) patients were included in the statin group and 242 (60.8%) in the nonstatin group. The recurrence rate was 3.8% (6/156) in the statin group and 10.7% (26/242) in the nonstatin group (p = 0.013). In a subgroup analysis, statin use significantly reduced recurrence in patients with unruptured aneurysms (1.6% vs 9.7%, p = 0.005), but not in those with ruptured aneurysms (12.5% vs 13.6%, p = 0.876). CONCLUSIONS Statin use was associated with a reduced rate of aneurysm recurrence in patients who underwent endovascular coiling for IAs with a decreased rate of retreatment during the follow-up period. Statins are a relatively low-risk treatment and may be an effective therapy to reduce recanalization of IAs, although further prospective studies are warranted to validate these findings.

Abstract Vasculitic neuropathy is caused by inflammatory destruction of nerve blood vessels resulting in nerve ischaemia. Nerve vasculitis can be divided into two categories based on vessel size: large-arteriole vasculitis (≥75 µm) and microvasculitis (&lt;75 µm). Herein, we characterize the clinical features of nerve large-arteriole vasculitis in comparison to nerve microvasculitis. This is a retrospective cohort study of patients evaluated and biopsied at Mayo sites between 2001 and 2020. We collected clinical and histopathological data from patients whose nerve biopsies were either diagnostic or highly suggestive of nerve vasculitis. Two hundred and seventy-eight cases were identified: 125 cases of large-arteriole vasculitis and 153 cases of microvasculitis. Nerve large-arteriole vasculitis presented with a more acute (50.4% versus 26.8%) versus chronic onset (33.6% versus 57.5%) than nerve microvasculitis (P = 0.0001). Nerve microvasculitis had longer mean time to diagnosis (10.5 versus 4.3 months; P &lt; 0.0001) and longer time to plateau (8.9 versus 3.5 months; P &lt; 0.0001). Nerve large-arteriole vasculitis typically presented as distal asymmetric polyneuropathy (48.0%), whereas nerve microvasculitis typically presented as radiculoplexus neuropathy/polyradiculoneuropathy (more proximal involvement of shoulder and thigh) (43.8%) (P &lt; 0.0001). Systemic autoimmune disease was more common in nerve large-arteriole vasculitis (70.4% versus 22.9%, odds ratio, 8.0; 95% confidence interval, 4.7–13.7; P &lt; 0.0001). Nerve microvasculitis was significantly related to non-systemic vasculitis (71% versus 23%, odds ratio, 7.9; 95% confidence interval, 4.6–13.6; P &lt; 0.0001). Nerve microvasculitis had more autonomic involvement (24.2% versus 7.2%, odds ratio, 4.1; 95% confidence interval, 1.9–8.9; P = 0.0002). Nerve large-arteriole vasculitis and nerve microvasculitis have different but overlapping clinical features. Nerve large-arteriole vasculitis usually presents with acute onset, distal asymmetric polyneuropathy, associated with other autoimmune diseases and systemic involvement. In contrast, nerve microvasculitis usually presents with a subacute/chronic onset, as radiculoplexus neuropathy/polyradiculopathy (distal and proximal pattern) with autonomic involvement, and is more often a form of non-systemic vasculitis.

Abstract The immune system is a key player in the onset and progression of neurodegenerative disorders. While brain resident immune cell‐mediated neuroinflammation and peripheral immune cell (eg, T cell) infiltration into the brain have been shown to significantly contribute to Alzheimer's disease (AD) pathology, the nature and extent of immune responses in the brain in the context of AD and related dementias (ADRD) remain unclear. Furthermore, the roles of the peripheral immune system in driving ADRD pathology remain incompletely elucidated. In March of 2023, the Alzheimer's Association convened the Alzheimer's Association International Conference (AAIC), Advancements: Immunity, to discuss the roles of the immune system in ADRD. A wide range of topics were discussed, such as animal models that replicate human pathology, immune‐related biomarkers and clinical trials, and lessons from other fields describing immune responses in neurodegeneration. This manuscript presents highlights from the conference and outlines avenues for future research on the roles of immunity in neurodegenerative disorders. Highlights The immune system plays a central role in the pathogenesis of Alzheimer's disease. The immune system exerts numerous effects throughout the brain on amyloid‐beta, tau, and other pathways. The 2023 AAIC, Advancements: Immunity, encouraged discussions and collaborations on understanding the role of the immune system.

Purpose: To identify areas of consensus among experts on the performance of endothelial keratoplasty by using a modified Delphi approach, to help create a framework for novice surgeons to adopt these procedures. Methods: Thirty-one international experts in endothelial keratoplasty participated. Two rounds of electronic survey were followed by a hybrid, virtual meeting. Consensus was set at 75%, and results with agreement between 70% and 75% were deemed as achieving near consensus. Results: A consensus was reached for 98 statements covering the preoperative, intraoperative, and postoperative aspects of Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping endothelial keratoplasty/Descemet stripping automated endothelial keratoplasty. Four statements achieved near consensus, and consensus could not be achieved for 11 statements. For DMEK, the panel supported a peel technique to prepare tissue for endothelium out DMEK, implanted via an injector and supported by a near full air/gas fill as a baseline procedure onto which more advanced techniques can be built. DMEK tissue should be marked to ensure correct orientation. An inferior peripheral iridotomy should be used to prevent pupil block when a near full air/gas fill in used in endothelial keratoplasty (EK). Descemet stripping automated endothelial keratoplasty was considered preferable to Descemet stripping endothelial keratoplasty where access to microkeratome preparation was available. Conclusions: The Delphi process allowed areas of consensus on the performance of EK to be established by a group of international experts. The statements generated are a helpful framework for novice surgeons learning EK. Further research is needed to help determine what specific tomographic features indicate EK, when guttae are considered visually significant and how to approach combined aphakia and endothelial dysfunction.

Background: The joint College of American Pathologists/American College of Medical Genetics and Genomics Cytogenetics Committee works to ensure the competency and proficiency of clinical cytogenetic testing laboratories through proficiency testing (PT) programs for various clinical tests offered by such laboratories, including the evaluation of cytogenetic abnormalities in solid tumors. Methods: Review and analyze 25 years (1999–2023) of solid tumor chromosome analysis PT results, utilizing G-banded karyograms. A retrospective review of results from 1999 to 2023 was performed, identifying the challenges addressing solid tumors. The chromosomal abnormalities and overall performance were evaluated. Results: A total of 21 solid tumor challenges were administered during the period 1999–2018. No solid tumor challenges were administered during the period 2019–2023. Challenges consisted of metaphase images and accompanying clinical history for the evaluation of numerical and/or structural abnormalities. All 21 cases reached 80% grading consensus for abnormality recognition. However, five cases (24%) failed to reach consensus for nomenclature reporting by participating laboratories. These cases illustrate errors in reporting chromosomal abnormalities, including whole-arm translocations and those involving sex chromosomes. In addition, they highlight the challenges with differentiation of terminal and interstitial deletions, difficulties in identifying correct breakpoints, and omission of brackets in neoplastic cases. Conclusions: This comprehensive 25-year review demonstrates the exceptional proficiency of cytogenetic laboratories in accurately identifying chromosome abnormalities in solid tumors, while also highlighting the challenges of reporting specific types of chromosomal abnormalities.

Background: Syncope is a common presenting complaint in the outpatient setting and requires a thoughtful and meticulous approach to history-taking skills. This is crucial in discerning cardiac versus non-cardiac etiologies, underscoring the pivotal role of healthcare professionals in the diagnostic process. Case Report: This is a case of a 76-year-old male who presented to the primary care clinic following an episode of syncope with abrupt loss of consciousness. Given the presentation, there was a high suspicion of cardiac etiology, and further testing was pursued. An electrocardiogram (ECG) demonstrated normal sinus rhythm with a pre-existing first-degree atrioventricular (AV) block. The Holter monitor was without sustained arrhythmias. A dobutamine stress echocardiogram was negative for myocardial ischemia, though a resting transthoracic echocardiogram demonstrated findings consistent with cardiac amyloidosis. Further evaluation with cardiology confirmed the diagnosis of transthyretin (ATTR) cardiac amyloidosis. He was initiated on appropriate treatment and underwent a dual chamber implantable cardioverter defibrillator (ICD) given his presentation. The patient ultimately succumbed to his disease 5 years after his diagnosis. Conclusion: If the cardiac etiology of syncope is suspected, further cardiac structural evaluation is necessary. Cardiac amyloidosis, although rare, is a cause of cardiogenic syncope that should not be overlooked. It should be considered in the differential diagnosis in the appropriate clinical setting, highlighting the need for a broad and comprehensive approach to diagnosis.