Citations

Background: Thrombo-inflammation is a hallmark of acute Covid-19, with higher thrombo-inflammatory markers during infection associated with adverse outcomes. We hypothesized that higher pre-pandemic biomarkers, reflecting a higher thrombo-inflammatory setpoint, might identify people at greater risk of severe manifestations of Covid-19. Hypothesis: Pre-pandemic inflammation markers are associated with risk of hospitalized or fatal (hereafter, “severe”) Covid-19 in a multi-ethnic US sample. Methods: From 2020-2023, C4R harmonized pre-pandemic measures and ascertained Covid-19 across 14 longstanding cohort studies. In 12 cohorts, we assessed biomarker data and covariates from the study visit closest to the pandemic for 6 analytes shown in the Table. HRs of severe Covid-19 by pre-pandemic biomarkers were estimated using cause-specific Cox regression, treating non-severe Covid-19 as a competing risk, and adjusting for pre-pandemic sociodemographic and clinical characteristics. Results: Biomarkers were measured a mean of 20 years before the pandemic with different sample sizes for each (Table footnote). Mean age at the start of the pandemic was in the 60s or 70s depending on the biomarker. The most represented race or ethnic groups were White and Black. The largest sample was for C-reactive protein, and there were 1,001 severe Covid-19 cases among 38,784 participants. In the adjusted models, considered individually, higher CRP, leukocyte count, factor VIII and fibrinogen, but not other markers, were associated with greater risk of severe Covid-19 (Table).Associations were robust across subgroups and time since biomarker measurement (example for C-reactive protein in Figure). Conclusions: In this prospective multi-study analysis of a multi-ethnic population, higher basal levels of thrombo-inflammation markers were associated with greater risk of severe Covid-19. Since we considered non-severe Covid-19 as a competing risk, associations may reflect factors related to progression to more serious Covid-19 illness.

Objective Studying the effect of deep brain stimulation (DBS) in the lateral hypothalamic area (LHA) in young and aging rats regarding memory changes, hippocampal neuronal dystrophy, and neurofilament expression. Methods Thirty-six male Sprague–Dawley rats were divided into two main groups: adult young (n = 18, 8 weeks old) and aged (n = 18, 24 months old). Each main group was further subdivided into three equal subgroups (n = 6) including control, sham, and DBS. DBS of LHA was conducted using high-frequency electric currents (130 Hz) for 1.5 h with 5-min breaks every 30 min for five consecutive days. Assessment of working memory was done using passive avoidance test (PAT). Then, the brain was dissected and hippocampal neuronal dystrophic damage was assessed as well as immunohistochemical examination of neurofilaments (NF68, NF200) expression. Results Aging rats had progressive hippocampal neuronal degeneration and downregulation of heavy and light chain neurofilaments, that was associated with progressive decline in working memory. Nevertheless, activation of DBS in the LHA enhanced memory function as it increased latency to entry in PAT (P < 0.001) compared to old normal and sham groups. Dystrophic damage score significantly decreased with DBS (P < 0.001) in the hippocampal CA1, CA3, and dentate gyrus regions. Moreover, DBS upregulated hippocampal NF68, NF200 expression (P < 0.001) in both young and old rats. We also found a significant positive correlation between working memory and NFs expression and a negative correlation between dystrophic damage score and NFs expression. Conclusions DBS in the LHA may have a neuroprotective effect in aging rats as it enhanced the working memory and decreased hippocampal neuronal dystrophy. This protective effect may be caused by the upregulation of neurofilaments.

ABSTRACTIntroductionArtificial Urinary Sphincter (AUS) placement is the preferred treatment for moderate to severe incontinence following prostate cancer treatment. While device related outcomes related to device survival are well reported, literature on quality‐of‐life outcomes, including the use of validated measures is limited.MethodsWe queried a prospectively maintained database of male patients undergoing primary AUS implantation from 2015 to 2023 at our institution. All patients completed a preoperative Michigan Incontinence Symptom Index (M‐ISI) and Patient Global Impression of Improvement (PGI‐I). Postoperative quality of life data was obtained by mailed correspondence. Surveys obtained following AUS reoperation/revision were excluded. Pairwise comparisons were performed between preoperative functional status and the Postoperative responses. Logistic regression analysis was performed to identify preoperative variables associated with a favorable PGI‐I score defined as “very much better or much better,” or a decrease in pad usage from > 1 pad per day to ≤ 1 pad per day.ResultsDuring the study timeframe, 383 patients underwent primary AUS placement, of which 163 patients (42%) completed a postoperative survey and were included in the study. Median age was 69.0 (IQR: 64–74) and 54.6% of patients had a history of pelvic radiation. The median time from surgery to the postoperative survey was 2.2 years (IQR: 0.9, 4.3). Compared to baseline, following AUS placement there was a significant improvement in the total M‐ISI score (10 [6, 16) vs 26 [22, 30]; p < 0.0001) (Minimally Important Difference = 4). This included improvements in the SUI subscore [4 (IQR 2, 6) vs 10 (IQR: 9, 12); p < 0.0001] and bother score [1 (IQR: 0, 3) vs 6 (IQR: 5, 7); p < 0.001)]. Pad usage significantly decreased following device placement (p < 0.0001). The vast majority of patients (90.7%) would “definitely or probably recommend to a friend/family member.” On univariable analysis, active smoking (ref. never) was associated with adverse pad use outcomes (OR: 0.1, 95% CI: 0–0.8; p = 0.03) and older age was associated with adverse PGI‐I outcome (OR: 0.93, 95% CI: 0.87–0.99; p = 0.02).ConclusionsFollowing AUS implantation, most patients have significant improvement in validated quality of life outcomes and low pad usage. These findings persist despite multiple preoperative comorbidities and should be considered when counseling patients before AUS placement.

Background: There is a spectrum of facial paralysis patient presentations from complete flaccid facial paralysis (CFFP) to facial aberrant reinnervation syndrome (FARS). Objective: To objectively compare how laypersons direct attention to faces with different facial paralysis subtypes using eye-tracking technology. Methods: Lay observers freely gazed at standardized videos of 24 individuals’ faces as follows: 8 with CFFP, 8 with FARS, and 8 nonparalyzed Controls performing common facial expressions. Eye-tracking measured observers’ gaze and extracted data as time in milliseconds looking at facial subsites. Mixed effects regression was used for comparative analyses. Results: A total of 85 observers completed the study. For faces at rest, measurable differences in gaze patterns were noted for CFFP faces (more attention spent on nonparalyzed hemiface), whereas FARS and Control faces showed similar symmetric gaze patterns. With dynamic movement (smiling and brow-elevation), gaze patterns for both CFFP and FARS faces became altered and asymmetrical compared with Control faces. Conclusions: Faces with CFFP and FARS are viewed differently by casual observers, which has implications for patient care and future research. While CFFP showed gaze alterations (compared with Control) in both rest and facial expression states, FARS caused gaze alterations only with facial movement.

The intrinsic reparative capacity of the adult mammalian kidney is restricted to the ability of scattered tubular-like cells (STCs) to repair damaged kidney cells. Our study provides evidence that chronic renal ischemia alters the mRNA/miRNA profile of angiogenic/vascular development genes of swine STCs, limiting their potential to repair injured tubular cells. Our observations may assist in developing new therapies to improve renal repair in individuals with chronic renal ischemia.

Background Strategies to estimate risk of cancer therapy‐related cardiac dysfunction (CTRCD) before initiating cardiotoxic cancer treatment are needed. We hypothesized that baseline ECG markers could identify patients at risk for CTRCD. Methods and Results In this retrospective cohort study, 1278 female patients with stage I–III HER2 (human epidermal growth factor receptor 2)‐positive breast cancer meeting the following inclusion criteria were included: baseline ECG with QRS <120 milliseconds, baseline echocardiogram, and ≥1 follow‐up echocardiogram. Quantitative measurements of ECG waveform parameters were performed using MUSE (GE Healthcare). The primary outcome of interest was CTRCD at 1 year, defined by left ventricular ejection fraction decline (≥10% to <53% or ≥16% from baseline), or clinical heart failure (New York Heart Association class III/IV). Mean age was 51.7±11.1 years, 990 (77%) received anthracyclines, and all received HER2‐targeted therapy. CTRCD occurred in 160 (13%) patients. In a multivariable Cox proportional hazards model adjusting for our previously published CTRCD risk score (composed of patient and treatment‐specific factors), 4 ECG markers remained independently associated with CTRCD risk: QRS axis, R‐wave duration (lead II), ST segment deviation (lead II), and Sokolow–Lyon voltage (all P <0.05). Compared with a model using only clinical CTRCD risk variables, addition of ECG parameters provided incremental value for predicting CTRCD risk ( P <0.001, likelihood ratio test) with continuous net reclassification improvement of 34.9% and integrated discrimination improvement of 3.4%. Conclusions Baseline ECG variables are predictive of subsequent CTRCD and provide incremental value to established clinical risk factors for CTRCD risk classification.

ABSTRACT Reduced functional capacity and poor sleep quality are common in pulmonary arterial hypertension (PAH). Wearable devices are an emerging, user‐friendly tool to capture activity and sleep information. We aimed to determine whether Fitbit‐derived activity and sleep trends provide clinically meaningful information in patients with PAH. Our prospective observational study recruited patients with PAH from across the United States using remote enrollment strategies and in‐person efforts. Participants wore a Fitbit device for 12 weeks at baseline and a subgroup with 1‐year follow‐up. A matched control cohort was generated from the All of Us Research Program and we evaluated changes in patients with PAH compared to matched controls. Among 110 patients with baseline monitoring, average daily steps correlated with 6MWD ( r = 0.61, p < 0.001) and percent rapid eye movement (REM) sleep ( r = 0.28, p = 0.008). In 44 PAH participants who completed baseline and 1‐year monitoring, there was a group‐time interaction for percent light sleep ( p = 0.024) and percent REM sleep ( p = 0.034), which demonstrated that sleep quality worsened in patients with PAH over 1 year compared to matched controls. Average daily steps decreased in patients with PAH from 5200 [IQR 3212–7458] at baseline to 4651 [IQR 2912–6827] at 1 year ( p = 0.008). In conclusion, our study demonstrated the potential clinical value of wearable devices by showing that activity and sleep quality are reduced in PAH compared to matched controls and these measures decline over time. Future studies should investigate if monitoring these health behaviors detects early functional decline and whether targeted interventions may improve outcomes.

ABSTRACT Background Although Percutaneous Coronary Intervention (PCI) is the cornerstone treatment acute myocardial infarction (AMI), its use in the elderly, specifically nonagenarians patients, is not well studied. This study sought to compare the outcomes and complications of nonagenarian patients who experienced AMI between those who underwent PCI and those who underwent medical treatment only. Methods We evaluated 301,440 nonagenarian (ages 90−99) patients who presented to the hospital with AMI who were listed in the National Inpatient Sample from 2016 to 2021. AMI was defined according to the ICD‐10 Diagnostic Codes. Multivariable logistic regression analysis was used to examine the association of PCI with primary outcomes of mortality and secondary outcomes. The temporal trend of both the incidence of PCI in nonagenarian patients as well as the mortality rate between 2016 and 2021 were expressed as percentages over time. Results Of the total ( n = 301,440) nonagenarian patients with AMI, 33,035 patients underwent PCI while 268,406 did not undergo PCI and rather, just utilized optimized medical therapy (OMT). Of these, 3290 (9.96%) died in the PCI group, and 43580 (16.24%) died in the OMT group. All of the secondary outcomes were significantly different between the PCI and OMT groups. Comparing the two groups, the PCI group was associated with decreased mortality (OR 0.63 [95% CI, 0.58−0.69]; p < 0.001), acute heart failure (OR 0.88 [95% CI, 0.82−0.95] p < 0.001), and AKI (OR 0.75 [95% CI, 0.70−0.79]; p < 0.001), and increased cardiogenic shock (OR 3.06 [95% CI, 2.77−3.38]. The temporal of PCI in nonagenarian patients showed an increase in frequency from about 8.3 in 2016 to about 13.7% in 2021. Furthermore, comparing the mortality between the PCI and OMT groups showed a significant difference with a decreased mortality in the PCI group. Conclusions Nonagenarian patients experiencing AMI who underwent PCI is associated with a significant mortality decrease compared to those who underwent OMT only. The PCI group was also associated with a significant decrease in multiple secondary complications including acute heart failure, AKI, acute stroke, and an increase in cardiogenic shock. Temporally, we have seen an increase in PCI being used in nonagenarian patients over the interval.