Impact of Pulmonary Hypertension Hemodynamic Phenotype on Incident Atrial Fibrillation.

INTRODUCTION: Atrial fibrillation/flutter (AF) is common among patients with pulmonary hypertension (PH) and is associated with poor clinical outcomes. AF has been shown to occur more commonly among patients with postcapillary PH, although AF also occurs among patients with precapillary PH. The goal of this study was to evaluate the independent impact of PH hemodynamic phenotype on incident AF among patients with PH. METHODS: We retrospectively identified 262 consecutive patients, without a prior diagnosis of atrial arrhythmias, seen at the PH clinic at Mayo Clinic, Florida, between 1997 and 2017, who had right heart catheterization and echocardiography performed, with follow-up for outcomes through 2021. Kaplan-Meier analysis and Cox-proportional hazards regression modeling were used to evaluate the independent effect of PH hemodynamic phenotype on incident AF. RESULTS: Our study population was classified into two broad PH hemodynamic groups: precapillary (64.9%) and postcapillary (35.1%). The median age was 59.5 years (Q1: 48.4, Q3: 68.4), and 72% were female. In crude models, postcapillary PH was significantly associated with incident AF (HR 2.17, 95% CI: 1.26-3.74, p = 0.005). This association was lost following multivariable adjustment, whereas left atrial volume index remained independently associated with incident AF (aHR 1.30, 95% CI: 1.09-1.54, p = 0.003). CONCLUSION: We found PH hemodynamic phenotype was not significantly associated with incident AF in our patient sample; however, echocardiographic evidence of left atrial remodeling appeared to have a greater impact on AF development. Larger studies are needed to validate these findings and identify potential modifiable risk factors for AF in this population.

Use of prophylactic ureteral stents in gynecologic surgery.

BACKGROUND: The aim of this study was to evaluate rate of complications with the use of prophylactic ureteral localization stents (PULSe) in gynecologic surgery. To compare the occurrence of complications according to the indication of surgery. METHODS: This retrospective study included 1248 women who underwent 1275 different gynecologic surgeries with PULSe between 2007 and 2020. Data was collected regarding patient characteristics (age, sex, race, ethnicity, parity, previous pelvic surgery, creatinine), operative characteristics (trainee, guidewire use, indication) and complications in the first 30 days (ureteral injury, urinary tract complication, re-stenting, hydronephrosis, urinary tract infection (UTI), pyelonephritis, emergency room visit, re-admission). RESULTS: Median age was 57 years (range: 18-96 years), most women were Caucasian (88.9%), and had previous pelvic surgery (77.7%). Indication of surgery was benign for 459 (36.0%), female pelvic medicine and reconstructive surgery (FPMRS) for 545 (42.7%), and gynecologic oncology (gyn-onc) for 271 (21.3%). Disabling complications occurred rarely with 8 patients (0.6%) having a ≥III Clavien Dindo Grade (CDG), and only 1 (0.08%) ≥IV CDG. Statistically significant differences between benign, FPMRS, and gyn-onc groups were noted for re-stenting (0.9% vs. 0.0% vs. 1.1%, P=0.020), hydronephrosis (0.9% vs. 0.2% vs. 2.2%, P=0.014), UTI (4.6% vs. 9.4% vs. 7.0%, P=0.016), and re-admission (2.4% vs. 1.1% vs. 4.4%, P=0.014). CONCLUSIONS: The incidence of 30-day CDG III and IV complications after PULSe placement is low. FPMRS patients had a higher rate of complicated UTI, however gyn- onc patients appear to be at overall higher risk of stent related complications when compared to surgeries for FPMRS or benign indications.

Clinical differences in symptomology, characteristics, and risk factors in patients with post-acute sequelae of COVID-19: an experience from a tertiary-care academic center.

Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus SARS-CoV-2 and has caused significant mortality and morbidity since it was first recognized in Wuhan, China in December 2019. Patients may suffer from a constellation of symptoms termed post-acute sequelae of COVID-19 (PASC) . Here we present findings of a retrospective cohort study describing the prevalence and predicting factors of patient-reported post-acute sequelae of COVID-19 (PASC). Categorical variables were summarized as frequency (percentage) and compared between vaccine status groups using Fisher's exact test. Continuous variables were reported as median (range) and compared between the groups using Kruskal-Wallis test. All tests were two-sided with p value <0.05 considered statistically significant. Survey data from 132 patients with a median age of 45 years, 68% female, 83% Caucasian/Non-Hispanic. The most frequently reported PASC symptoms include fatigue (84.8%), dyspnea (54.5%), cognitive dysfunction (53%), myalgias (37.1%), lightheadedness or vertigo (36.4%), chest pain (34.8%), palpitations (34.8%), headaches (34.1%), arthralgias (31.8%), and unrefreshing sleep (31.1%). There is mounting evidence that supports higher prevalence of PASC in women, White/Caucasian, and middle-aged individuals. This knowledge can provide guidance to clinical practices to anticipate and support healthcare and self-care needs for patients at higher risk to developing PASC.

Cancer and Vascular Comorbidity Effects on Dementia Risk and Neuropathology in the Oldest-Old.

BACKGROUND: Dementia, vascular disease, and cancer increase with age, enabling complex comorbid interactions. Understanding vascular and cancer contributions to dementia risk and neuropathology in oldest-old may improve risk modification and outcomes. OBJECTIVE: Investigate the contributions of vascular factors and cancer to dementia and neuropathology. METHODS: Longitudinal clinicopathologic study of prospectively followed Mayo Clinic participants dying≥95 years-old who underwent autopsy. Participants were stratified by dementia status and compared according to demographics, vascular risk factors, cancer, and neuropathology. RESULTS: Participants (n = 161; 83% female; 99% non-Hispanic whites)≥95 years (95-106 years-old) with/without dementia did not differ based on demographics. APOE ɛ2 frequency was higher in no dementia (20/72 [28%]) versus dementia (11/88 [12%]; p = 0.03), but APOE ɛ4 frequency did not differ. Coronary artery disease was more frequent in no dementia (31/72 [43%]) versus dementia (23/89 [26%]; p = 0.03) associated with 56% lower dementia odds (odds ratio [OR] = 0.44 [confidence interval (CI) = 0.19-0.98]; p = 0.04) and fewer neuritic/diffuse plaques. Diabetes had an 8-fold increase in dementia odds (OR = 8.42 [CI = 1.39-163]; p = 0.02). Diabetes associated with higher cerebrovascular disease (Dickson score; p = 0.05). Cancer associated with 63% lower dementia odds (OR = 0.37 [CI = 0.17-0.78]; p < 0.01) and lower Braak stage (p = 0.01). CONCLUSION: Cancer exposure in the oldest-old was associated with lower odds of dementia and tangle pathology, whereas history of coronary artery disease was associated with lower odds of dementia and amyloid-ß plaque pathology. History of diabetes mellitus was associated with increased odds of dementia and cerebrovascular disease pathology. Cancer-related mechanisms and vascular risk factor reduction strategies may alter dementia risk and neuropathology in oldest-old.

Sex differences in comorbidities associated with Sjögren's disease.

Background: Little is known about the association of comorbidities with sex and age at diagnosis in Sjögren's disease. We tested the hypothesis that sex differences occur in comorbidities in patients with Sjögren's disease. Methods: Patients with Sjögren's disease were identified from 11/1974 to 7/2018 in the Mayo Clinic electronic medical record and assessed for 22 comorbidities according to sex and age at diagnosis. Results: Of the 13,849 patients identified with Sjögren's disease, 11,969 (86%) were women and 1,880 (14%) men, primarily white (88%) with a sex ratio of 6.4:1 women to men. The mean age at diagnosis was 57 years for women and 59.7 years for men, and 5.6% had a diagnosis of fibromyalgia at Sjögren's diagnosis. Men with Sjögren's disease were more likely than women to be a current or past smoker. The average time to diagnosis of comorbidities after diagnosis of Sjögren's disease was 2.6 years. The top comorbidities in patients with Sjögren's disease were fibromyalgia (25%), depression (21.2%) and pain (16.4%). Comorbidities that occurred more often in women were hypermobile syndromes (31:1), CREST (29:1), migraine (23:1), Ehlers-Danlos syndrome (EDS) (22:1), Raynaud's syndrome (15:1), SLE (13:1), systemic sclerosis (SSc) (13:1), and fibromyalgia (12:1). Women with Sjögren's disease were at increased risk of developing hypermobile syndromes (RR 7.27, CI 1.00-52.71, p = 0.05), EDS (RR 4.43, CI 1.08-18.14, p = 0.039), CREST (RR 4.24, CI 1.56-11.50, p = 0.005), migraine (RR 3.67, CI 2.39-5.62, p < 0.001), fibromyalgia (RR 2.26, CI 1.92-2.66, p < 0.001), Raynaud's syndrome (RR 2.29, CI 1.77-2.96, p < 0.001), SLE (RR 2.13, CI 1.64-2.76, p < 0.001), and SSc (RR 2.05 CI 1.44-2.92; p < 0.001). In contrast, men with Sjögren's were at increased risk for developing myocardial infarction (RR 0.44, CI 0.35-0.55, p < 0.001), atherosclerosis/CAD (RR 0.44, CI 0.39-0.49, p < 0.001), cardiomyopathy (RR 0.63, CI 0.46-0.86, p = 0.003), stroke (RR 0.66 CI 0.51-0.85, p = 0.001), and congestive heart failure (RR 0.70, CI 0.57-0.85, p < 0.001). Conclusions: The top comorbidities in Sjögren's disease were fibromyalgia, depression, and pain. Women with Sjögren's disease had a higher relative risk of developing fibromyalgia, depression, pain, migraine, hypermobile syndrome, EDS and other rheumatic autoimmune diseases. Men with Sjögren's disease had higher risk of developing cardiovascular diseases.

Phosphorylated tau sites that are elevated in Alzheimer's disease fluid biomarkers are visualized in early neurofibrillary tangle maturity levels in the post mortem brain.

INTRODUCTION: Alzheimer's disease (AD) biomarkers are increasingly more reliable in predicting neuropathology. To facilitate interpretation of phosphorylated tau sites as an early fluid biomarker, we sought to characterize which neurofibrillary tangle maturity levels (pretangle, intermediary 1, mature tangle, intermediary 2, and ghost tangle) are recognized. METHODS: We queried the Florida Autopsied Multi-Ethnic (FLAME) cohort for cases ranging from Braak stages I through VI, excluding non-AD neuropathologies and tauopathies. Thioflavin-S staining was compared to immunohistochemical measures of phosphorylated threonine (pT) 181, pT205, pT217, and pT231 in two hippocampal subsectors across n = 24 cases. RESULTS: Each phosphorylated tau site immunohistochemically labeled early neurofibrillary tangle maturity levels compared to advanced levels recognized by thioflavin-S. Hippocampal burden generally increased with each Braak stage. DISCUSSION: These results provide neurobiologic evidence that these phosphorylated tau fluid biomarker sites are present during early neurofibrillary tangle maturity levels and may explain why these fluid biomarker measures are observed before symptom onset. HIGHLIGHTS: Immunohistochemical evaluation of four phosphorylated tau fluid biomarker sites. Earlier neurofibrillary tangle maturity levels recognized by phosphorylated tau in proline-rich region. Advanced tangle pathology is elevated in the subiculum compared to the cornu ammonis 1 of the hippocampus. Novel semi-quantitative frequency to calculate tangle maturity frequency.