Citations

AbstractINTRODUCTIONThe Rey Auditory Verbal Learning Test (RAVLT) is a useful neuropsychological test for describing episodic memory impairment in dementia. However, there is limited research on its utility in early‐onset Alzheimer's disease (EOAD). We assess the influence of amyloid and diagnostic syndrome on several memory scores in EOAD.METHODSWe transcribed RAVLT recordings from 303 subjects in the Longitudinal Early‐Onset Alzheimer's Disease Study. Subjects were grouped by amyloid status and syndrome. Primacy, recency, J‐curve, duration, stopping time, and speed score were calculated and entered into linear mixed effects models as dependent variables.RESULTSCompared with amyloid negative subjects, positive subjects exhibited effects on raw score, primacy, recency, and stopping time. Inter‐syndromic differences were noted with raw score, primacy, recency, J‐curve, and stopping time.DISCUSSIONRAVLT measures are sensitive to the effects of amyloid and syndrome in EOAD. Future work is needed to quantify the predictive value of these scores.Highlights RAVLT patterns characterize various presentations of EOAD and EOnonAD Amyloid impacts raw score, primacy, recency, and stopping time Timing‐based scores add value over traditional count‐based scores

ObjectiveApproximately one third of individuals worldwide have not received a COVID‐19 vaccine. Although studies have investigated risk factors linked to severe COVID‐19 among unvaccinated people with rheumatic diseases (RDs), we know less about whether these factors changed as the pandemic progressed. We aimed to identify risk factors associated with severe COVID‐19 in unvaccinated individuals in different pandemic epochs corresponding to major variants of concern.MethodsPatients with RDs and COVID‐19 were entered into the COVID‐19 Global Rheumatology Alliance Registry between March 2020 and June 2022. An ordinal logistic regression model (not hospitalized, hospitalized, and death) was used with date of COVID‐19 diagnosis, age, sex, race and/or ethnicity, comorbidities, RD activity, medications, and the human development index (HDI) as covariates. The main analysis included all unvaccinated patients across COVID‐19 pandemic epochs; subanalyses stratified patients according to RD types.ResultsAmong 19,256 unvaccinated people with RDs and COVID‐19, those who were older, male, had more comorbidities, used glucocorticoids, had higher disease activity, or lived in lower HDI regions had worse outcomes across epochs. For those with rheumatoid arthritis, sulfasalazine and B‐cell–depleting therapy were associated with worse outcomes, and tumor necrosis factor inhibitors were associated with improved outcomes. In those with connective tissue disease or vasculitis, B‐cell–depleting therapy was associated with worse outcomes.ConclusionRisk factors for severe COVID‐19 outcomes were similar throughout pandemic epochs in unvaccinated people with RDs. Ongoing efforts, including vaccination, are needed to reduce COVID‐19 severity in this population, particularly in those with medical and social vulnerabilities identified in this study.

AbstractINTRODUCTIONDown syndrome (DS) is a genetic cause of early‐onset Alzheimer's disease (AD). The National Institute on Aging–Alzheimer's Association AT(N) Research Framework is a staging model for AD biomarkers but has not been assessed in DS.METHODData are from the Alzheimer's Biomarker Consortium–Down Syndrome. Positron emission tomography (PET) amyloid beta (Aβ; 15 mCi of [11C]Pittsburgh compound B) and tau (10 mCi of [18F]AV‐1451) were used to classify amyloid (A) –/+ and tau (T) +/–. Hippocampal volume classified neurodegeneration (N) –/+. The modified Cued Recall Test assessed episodic memory.RESULTSAnalyses included 162 adults with DS (aged M = 38.84 years, standard deviation = 8.41). Overall, 69.8% of participants were classified as A–/T–/(N)–, 11.1% were A+/T–/(N)–, 5.6% were A+/T+/(N)–, and 9.3% were A+/T+/(N)+. Participants deemed cognitively stable were most likely to be A–T–(N)– and A+T–(N)–. Tau PET (T+) most closely aligning with memory impairment and AD clinical status.DISCUSSIONFindings add to understanding of AT(N) biomarker profiles in DS.Highlights Overall, 69.8% of adults with Down syndrome (DS) aged 25 to 61 years were classified as amyloid (A)–/tau (T)–/neurodegeneration (N)–, 11.1% were A+/T–/(N)–, 5.6% were A+/T+/(N)–, and 9.3% were A+/T+/(N)+. The AT(N) profiles were associated with clinical Alzheimer's disease (AD) status and with memory performance, with the presence of T+ aligned with AD clinical symptomology. Findings inform models for predicting the transition to the prodromal stage of AD in DS.

AbstractPatients with viral myocarditis are at risk of sudden death and may progress to dilated cardiomyopathy (DCM). Currently, no disease‐specific therapies exist to treat viral myocarditis. Here it is examined whether reconstituted, lyophilized extracellular vesicles (EVs) from platelets from healthy men and women reduce acute or chronic myocarditis in male mice. Human‐platelet‐derived EVs (PEV) do not cause toxicity, damage, or inflammation in naïve mice. PEV administered during the innate immune response significantly reduces myocarditis with fewer epidermal growth factor (EGF)‐like module‐containing mucin‐like hormone receptor‐like 1 (F4/80) macrophages, T cells (cluster of differentiation molecules 4 and 8, CD4 and CD8), and mast cells, and improved cardiac function. Innate immune mediators known to increase myocarditis are decreased by innate PEV treatment including Toll‐like receptor (TLR)4 and complement. PEV also significantly reduces perivascular fibrosis and remodeling including interleukin 1 beta (IL‐1β), transforming growth factor‐beta 1, matrix metalloproteinase, collagen genes, and mast cell degranulation. PEV given at days 7–9 after infection reduces myocarditis and improves cardiac function. MicroRNA (miR) sequencing reveals that PEV contains miRs that decrease viral replication, TLR4 signaling, and T‐cell activation. These data show that EVs from the platelets of healthy individuals can significantly reduce myocarditis and improve cardiac function.

The incidence of both cataract and glaucoma is increasing globally. With increasing patient expectation and improved technology, premium intraocular lenses (IOLs), including presbyopia-correcting and toric IOLs, are being increasingly implanted today. However, concerns remain regarding the use of premium IOLs, particularly presbyopia-correcting IOLs, in eyes with glaucoma. This systematic review evaluates the use of premium IOLs in glaucoma. A comprehensive search of the MEDLINE database was performed from inception until 1 June 2023. Initial search yielded 1404 records, of which 12 were included in the final review of post-operative outcomes. Studies demonstrated high spectacle independence for distance and good patient satisfaction in glaucomatous eyes, with positive outcomes also in post-operative visual acuity, residual astigmatism, and contrast sensitivity. Considerations in patient selection include anatomical and functional factors, such as the type and severity of glaucomatous visual field defects, glaucoma subtype, presence of ocular surface disease, ocular changes after glaucoma surgery, and the reliability of disease monitoring, all of which may be affected by, or influence, the outcomes of premium IOL implantation in glaucoma patients. Regular reviews on this topic are needed in order to keep up with the rapid advancements in IOL technology and glaucoma surgical treatments.

ObjectiveThe aim was to study laryngological complaints in patients with hypermobile Ehlers‐Danlos syndrome (hEDS) or hypermobility spectrum disorders (HSD).MethodsA total of 363 patients met inclusion for the study by completing questions related to voice, upper airway, and swallowing between July 7, 2020 and July 13, 2022. Demographic data, voice‐related questions, and hypermobility diagnosis were analyzed retrospectively. From those, 289 patients were diagnosed with hEDS or HSD with 74 that did not meet the diagnostic criteria for either diagnosis serving as controls.ResultsThere were no statistically significant differences between patients with hEDS and HSD regarding Voice Handicap Index (VHI‐10) scores, voice, upper airway, or swallow complaints. However, more hEDS/HSD patients answered positively to the laryngeal dysfunction question versus controls (p = 0.031). 22.5% of hEDS/HSD patients (n = 65) reported hoarseness, of which 52.3% reported hoarseness >2 days/month. 33.9% (n = 98) with hEDS/HSD reported symptoms of dysphagia, and 27.0% (n = 78) reported laryngeal dysfunction symptoms. Controls demonstrated 20.3% prevalence of hoarseness, of which 46.7% reported hoarseness >2 days/month. 24.3% of controls had dysphagia and 14.9% laryngeal dysfunction symptoms. Of the 363 patients, VHI‐10 scores >11 were more likely in patients reporting >2 days of hoarseness/month (p = 0.001) versus those with <2 days of hoarseness/month. There was an increased prevalence of voice, upper airway, and dysphagia symptoms in hEDS/HSD patients compared with previously reported prevalence data in the general population.ConclusionA significant proportion of patients diagnosed with hypermobility due to hEDS or HSD were found to have voice, upper airway, and dysphagia symptoms. These rates are higher than those previously reported in the general population.Level of Evidence3 Laryngoscope, 134:773–778, 2024

ImportanceSystematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.ObjectiveTo assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022.ExposureTreatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19.Main Outcomes and MeasuresMain outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up.ResultsOf 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13).Conclusions and RelevanceIn this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19–related thromboembolism in patients with cancer.

Intravenous (IV) ketamine and FDA-approved intranasal (IN) esketamine are increasingly used for treatment-resistant depression (TRD). Preliminary studies have suggested a synergistic effect of ketamine and lamotrigine, although the data are inconclusive. Herein, we report the response to serial ketamine/esketamine treatment among patients with TRD with or without lamotrigine therapy. In this historical cohort study, we included adult patients with TRD who received serial IV racemic ketamine (0.5 mg/kg over 40−100 min) or IN esketamine (56/84 mg) treatments. A change in depressive symptoms was assessed using the 16-item Quick Inventory of Depressive Symptomatology self-report (QIDS-SR) scale. There were no significant differences in response or remission rates among the patients on or not on lamotrigine during the ketamine/esketamine treatments. For a percent change in the QIDS-SR from baseline, no interaction was found between the lamotrigine groups and treatment number (p = 0.70), nor the overall effect of the group (p = 0.38). There was a trend towards lower dissociation (based on the CADSS score) among current lamotrigine users, especially in patients who received IV ketamine. A major limitation is the limited number of patients taking lamotrigine (n = 13). This preliminary study provides insufficient evidence that continuing lamotrigine therapy attenuates the antidepressant effect of repeated ketamine/esketamine; however, there seems to be a signal toward attenuating dissociation with lamotrigine in patients receiving serial ketamine treatments. Further observational studies or randomized controlled trials are needed to replicate these findings.

BACKGROUND: Alcohol septal ablation (ASA) is a minimally invasive treatment for drug-refractory obstructive hypertrophic cardiomyopathy. Detailed assessment of pressure changes and predictors of mortality and procedure success are not well defined. METHODS: This is a single-center study evaluating pressure changes and predictors of mortality and procedure success in transseptal ASA. Survival analysis and predictors of mortality were assessed using the Kaplan-Meier analysis and Cox regression, respectively. RESULTS: A total of 156 patients were included (mean age, 67.3 years; 46.8% women). Left atrial (LA) pressure and left ventricular outflow tract (LVOT) gradient decreased, whereas aortic pulse pressure (PP) increased post-ASA. Patients with lower baseline mean LA pressure (<median, 19 mm Hg), LVOT gradient reduction >82% (gradient change median), and PP increase >19% (PP change median) had superior survival. On Cox univariable regression, baseline mean LA pressure >median (19 mm Hg; hazard ratio [HR], 2.09 [95% CI, 1.05–4.18]; P =0.036), residual LVOT gradient (HR, 1.02 [95% CI, 1.01–1.03]; P =0.003), and LVOT gradient percent reduction <median (82%; HR, 2.92 [95% CI, 1.46–5.83]; P =0.002) were predictors of mortality. When adjusting for age and sex, baseline LA v wave >median (28 mm Hg; HR, 2.36 [95% CI, 1.17–4.76]; P =0.016), baseline mean LA pressure >median (19 mm Hg; HR, 2.70 [95% CI, 1.33–5.50]; P =0.006), percentage reduction in gradient <median (82%; HR, 2.74 [CI, 1.37–5.50]; P =0.005), and percentage increase in PP <median (19.3%; HR, 2.09 [CI, 1.05–4.16]; P =0.035) predicted survival free of all-cause mortality. CONCLUSIONS: ASA is associated with an acute decrease in the LVOT gradient and LA pressures and increase in aortic PP. Mean LA pressure, percentage decrease in LVOT gradient, and increase in PP are strong predictors of survival free of all-cause mortality following ASA and are important variables for procedural guidance.