Citations

Background Left ventricular assist devices (LVADs) are used as definitive therapy or as a bridge to heart transplant in patients with advanced heart failure. Thromboembolic complications such as acute ischemic stroke (AIS) are common among patients with LVAD support. This study aims to evaluate the current evidence on the efficacy and safety of mechanical thrombectomy (MT) in patients with AIS due to large vessel occlusions (LVO) and LVAD-support. Methods A comprehensive systematic review was conducted in PubMed, Embase, and Scopus to find observational studies with reports of ≥5 MTs in adult patients with LVAD support (PROSPERO registration code CRD42024597541). Rates of successful and complete reperfusion, favorable functional outcomes at 90 days (modified Rankin Scale (mRS) 0–2 or equal to pre-stroke mRS), mortality at 90 days, any intracerebral hemorrhage (ICH) and symptomatic ICH (sICH) were pooled using generalized linear mixed models. Results Eight studies were included with data from 51 patients and 62 MTs. The rate of successful reperfusion was 87.4% (95% CI 62.5% to 96.6%) and complete reperfusion rate was 57.3% (95% CI 35.1% to 76.9%). Rate of favorable functional recovery was 62.5% (95% CI 42.2% to 79.2%). Rate of sICH was 6.4% (95% CI 0.9% to 34.0%). Mortality rate was 16.7% (95% CI 7.1% to 34.7%). Between 25–40% of patients who were waiting for a heart transplant before their stroke received a heart transplant after MT. Conclusions MT for the emergent treatment of AIS in the setting of LVAD is relatively safe and efficacious for achieving successful reperfusion and good functional recovery.

Abstract Background Specialty societies, including the Infectious Diseases Society of America, strive to address gender and racial inequities in professional advancement. Microaggressions remain a persistent and pervasive barrier to these goals. Nonprofessional speaker introductions are a manifestation of race- and gender-based microaggressions, which have not been previously assessed at IDWeek. We assessed disparities in speaker introductions at IDWeek over a 7-year period that included formal gender equity initiatives introduced in 2016. Methods We conducted a retrospective observational study of video-recorded IDWeek speaker introductions from 2013 to 2019. Trained coders reviewed presentation video archives to assess a primary outcome of nonprofessional introductions: when a speaker's professional title was not used as the first introduction. We used descriptive statistics, Fisher exact tests, Cochrane-Armitage trend tests, and multivariable logistic regression to characterize relationships between speaker introductions and presentation year, speaker demographics, and speaker-moderator demographic concordance. Results Of 1940 videos reviewed, 48.9% of IDWeek speakers received nonprofessional introductions during and before 2016 vs 41.5% of speakers after 2016 (P = .0013). There was an increasing linear trend in the frequency of professional introductions by speaker age group from 47.1% for age <40 years to 65.3% for age >60 years (P < .0001). White moderators more frequently used nonprofessional introductions than moderators from backgrounds underrepresented in medicine (47.7% vs 29.1%, P = .0014). Women-men speaker-moderator pairs had more nonprofessional introductions (54.6%, P < .001). Conclusions In the largest assessment of microaggressions in speaker introductions at a national medical specialty conference, we highlighted some progress over time and ample opportunity to further standardize equitable speaker introductions, especially for women and junior speakers

Purpose of review This review provides a contemporary, evidence-based update on the pathophysiological mechanisms and rapidly evolving therapeutic options for recurrent pericarditis. Recent findings Recent studies have elucidated the pathogenesis of recurrent pericarditis, identifying autoinflammation as a key mechanism and interleukin-1 (IL-1) as a central modulator of the inflammatory cascade. Multiple clinical trials have investigated novel therapeutic approaches, particularly focusing on IL-1 inhibition. The recent FDA approval of IL-1 pathway blockade for recurrent pericarditis has revolutionized treatment, offering patients significantly improved quality of life and symptom management. Summary The enhanced understanding of the autoinflammatory nature of recurrent pericarditis, coupled with groundbreaking advances in targeted therapies, has transformed the treatment landscape for affected patients. The emergence of IL-1 inhibitors as an effective therapeutic option promises substantial improvements in clinical outcomes and patient well being. Clinicians must familiarize themselves with these new treatments, their efficacy, and potential limitations to optimize patient care and guide therapeutic decision-making in this challenging condition.

Abstract The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related blood factors that demonstrate ‘pro-aging’ or ‘pro-youthful’ effects on the mouse brain. The clinical relevance and combined effects of these factors for humans is unclear. We examined five previously identified brain rejuvenation factors in cerebrospinal fluid of adults with autosomal dominant forms of frontotemporal dementia and sporadic Alzheimer’s disease. Our frontotemporal dementia cohort included 100 observationally followed adults carrying autosomal dominant frontotemporal dementia mutations (Mage = 49.6; 50% female; 43% C9orf72, 24% GRN, 33% MAPT) and 62 non-carriers (Mage = 52.6; 45% female) with cerebrospinal fluid analysed on Somascan, and longitudinal (Mvisits = 3 years, range 1–7 years) neuropsychological and functional assessments and plasma neurofilament light chain. Our Alzheimer’s disease cohort included 35 adults with sporadic Alzheimer’s disease (Mage = 69.4; 60% female) and 56 controls (Mage = 68.8, 50% female) who completed the same cerebrospinal fluid and clinical outcome measures cross-sectionally. Levels of C-C motif chemokine ligand 11, C-C motif chemokine ligand 2, beta-2-micorglobulin, bone gamma-carboxyglutamate protein (aka Osteocalcin) and colony stimulating factor 2 in cerebrospinal fluid were linearly combined into a composite score, with higher values reflecting ‘pro-youthful’ levels. In genetic frontotemporal dementia, higher baseline cerebrospinal fluid rejuvenation proteins predicted slower decline across cognitive, functional, and neurofilament light chain trajectories; estimates were similar across genotypes. In transdiagnostic analyses, higher cerebrospinal fluid rejuvenation proteins associated with better functional, cognitive, and neurofilament light chain outcomes in adults with sporadic Alzheimer’s disease. Proteins with pre-clinical evidence for brain rejuvenation show translational clinical relevance in adults with Alzheimer’s disease and related dementias and warrant further investigation.

Abstract There are ~100 genes or copy number variants (CNVs) used in genetic testing for Autism Spectrum Disorder (ASD, or autism). These genes are protein-coding, and the associated phenotypes often extend beyond socio-behavioral traits seen in autism including cognitive/medical complexities, epilepsy, and ADHD. Here, we characterize 27 males with ASD through whole genome sequencing (WGS), delineating X-chromosome microdeletions that implicate the long non-coding RNA (lncRNA) PTCHD1-AS as an ASD-susceptibility gene (OR=2.56, p=0.01). Two Ptchd1-as knockout (KO) murine models, created by removing the evolutionarily conserved exon-3, show ASD-like features in males, increasing repetitive behaviors and impairing typical social behavior and communication without overt cognitive comorbidities or ADHD-like behaviors. Hippocampus-dependent synaptic function, complex learning, and locomotor activity are unaffected in KO mice. Native nuclear-enriched mouse Ptchd1-as showed sustained expression from post-natal day-7 onward in the dorsal striatum, a predominantly GABAergic brain region implicated in ASD. Multi-omics revealed transcriptomic alterations in striatal oligodendrocyte, astrocyte and neurons impacting myelination and plasticity pathways. Disrupting Ptchd1-as led to reductions in conventional Protein Kinase-C, altered Src and GSK3α/β phosphorylation, and an enhancement of synaptic plasticity (long-term potentiation and long-term depression). Together, these findings implicate striatal molecular and circuit level dysregulation via Ptchd1-as in ASD etiology.

AbstractBackgroundThe rapid development of blood‐based biomarkers (BBMs) has improved Alzheimer’s disease (AD) diagnostics with some tests now potentially suitable for clinical use. This aligns with the clinical availability of anti‐Aβ immunotherapies for early symptomatic AD, where BBMs can help address the increasing need for more rapid and early diagnosis. Clinical practice guidelines (CPG) can help guide healthcare professionals in incorporating BBMs into their clinical practice. The Alzheimer’s Association is collaborating with methodologists and a panel of 11 clinical and subject‐matter experts to develop a CPG for specialists, informed by a systematic review, on the use of BBMs for AD.MethodThe panel drafted several clinical questions prioritizing two questions on the use of BBMs in cognitively impaired or cognitively unimpaired individuals as the populations of immediate interest. Plasma p‐tau and Aβ biomarkers tests are index tests, and amyloid PET imaging, neuropathology, and CSF are reference standards. Experts in the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach are conducting a systematic review of the diagnostic accuracy of BBMs index tests by searching three databases (Pubmed, Embase, Cochrane Library) and will include assessments of the quality of collected evidence to inform the panel’s decision‐making process. Patients/caregivers and key external organizations will be engaged throughout.ResultThis session will cover preliminary evidence for answering the two clinical questions. At the time of abstract submission, the search strategy resulted in 880 titles/abstracts for the study selection process. Data abstraction, analysis, and evidence development are pending. Recommendations for answering clinical questions will be developed after July 2024, and all recommendations will be finalized and published by early 2025.ConclusionThe integration of BBMs into clinical care offers the potential to improve earlier and more accurate AD diagnosis for a broader patient population and expand access to new AD therapies. The development of evidence‐based CPGs is a critical step forward in optimizing and standardizing the clinical use of BBMs. As the field of AD diagnostics and treatment continues to evolve, this CPG on the use of BBMs for AD will expand and be regularly updated to include new target audiences/settings, patient populations, and associated evidence.

AbstractBackgroundTraumatic encephalopathy syndrome (TES) is the proposed clinical syndrome of the neurodegenerative disease chronic traumatic encephalopathy (CTE). As part of the 2021 TES NINDS consensus diagnostic criteria, certainty levels of underlying CTE neuropathology can be determined (i.e., suggestive, possible, probable) partially based on the presence/absence of supportive psychiatric features including but not limited to depression, anxiety, and apathy. These are ‘supportive’ because of their non‐specificity and unclear biological correlates in this setting. We examined the association between CSF biomarkers of amyloid, tau, neurodegeneration, microglial activation and neuroinflammation and supportive psychiatric features of TES in former American football players.MethodThe sample included 180 male former football players (120 professional, 60 college) from the DIAGNOSE CTE Research Project. Participants completed a lumbar puncture, and CSF assays were conducted for biomarkers of amyloid (Aβ40, Aβ42), p‐tau (p‐tau181, p‐tau231, p‐tau217), neurodegeneration (total tau), axonal degeneration (NfL), microglial activation (strem2) and neuroinflammation (GFAP, IL‐6). Biomarkers were log‐transformed. The Apathy Evaluation Scale (AES), Beck Depression Inventory‐II (BDI‐II) and the Beck Anxiety Inventory (BAI) self‐report questionnaires were completed by participants. Multivariable regression models tested the association between each CSF biomarker and each scale, controlling for age, race, body mass index, revised Framingham stroke risk profile and Alcohol Use Disorders Identification Test. P‐values were adjusted for multiple comparisons using false discovery rate methods.Result140 participants had successful LPs and available CSF for assays. 33(22%) reported moderate/severe anxiety, 34(22%) reported moderate/severe depression, and 51(33%) had an elevated AES score. Higher CSF concentrations of IL‐6 were associated with higher scores on the BAI (unstandardized‐β=0.016, 95%CI [0.017, 0.026], padj=0.004), BDI‐II (unstandardized‐β=0.013, 95%CI [0.004, 0.021], padj=0.008) and AES (unstandardized‐β=0.014, 95%CI [0.006,0.022], padj=0.002). There were no significant relationships between other biomarkers with the BDI‐II, BAI or AES.ConclusionIn this sample of former American football players, there were significant associations between IL‐6 (a proinflammatory cytokine) and reported symptoms of depression, anxiety, and apathy. CSF biomarkers of amyloid, tau and neurodegeneration had no associations, highlighting the role of neuroinflammatory processes in the manifestation of psychiatric symptoms of TES. Continued research on the biological correlates of TES features will inform future iterations of the criteria.