Sympathetic response following unannounced loss of balance during walking in young adults - laboratory study.

BACKGROUND: An unannounced balance loss during walking, i.e., balance perturbation, is a stressful event that changes the activity of the Sympathetic Nervous System (SNS). We examined SNS response to unannounced balance perturbation during walking, simulating real-life conditions of balance loss. RESEARCH QUESTION: Do laboratory-induced unannounced balance losses during walking cause a sympathetic response, and if so - does it habituate after a series of perturbations? METHODS: 34 young adults underwent a series of six successive unannounced balance perturbations while walking on a treadmill. Sympathetic activity was monitored continuously using Electrodermal Activity and compared before and immediately after each unannounced perturbation. RESULTS: All perturbations elicited a significant increase in Electrodermal Activity (p<0.001), indicating a phasic increase in the sympathetic drive. The relative phasic increase of Electrodermal Activity caused by the first perturbation was significantly higher than the last perturbation (p<0.05). Three types of Electrodermal Activity behavior were observed: Steady level tonic SNS activity, increased SNS activity, and decreased SNS activity. SIGNIFICANCE: Balance loss during walking triggers phasic SNS response, this response habituates after a series of unannounced balance perturbations. In addition, three distinct patterns of tonic sympathetic activity may imply variations in the ability of the SNS response to habituate across individuals.

The use of time-dynamic patterns of temperature and flexible generalized models to clarify the relations between temperature and semen quality.

BACKGROUND: Sperm quality has decreased over the last decades worldwide. It is affected, among others, by season and heat. This study aimed to address the association between ambient temperature and sperm quality by assessing its shape using flexible multivariate models and identifying distinct time-dynamic patterns of temperature change based on unsupervised analysis. MATERIAL AND METHODS: A retrospective population-based study has been conducted, including all samples of males attending the Fertility and In-Vitro-Fertilization unit at a single medical center during 2016-2022. Flexible generalized models were fitted to characterize the relations between sperm quality and temperature while accounting for patients characteristics, and to identify temperature levels that correspond with the optimal sperm quality. This information was then used to estimate adjusted slope coefficients at specified time-windows. RESULTS: In total, 4555 sperm samples were provided by 3229 individuals. Sperm concentration, motility and progressive motility were higher by 8 %, 11 % and 16 %, respectively, during the spring versus the fall season. Furthermore, their quality during early spermatogenesis improved with temperature, until a certain optimum around 23 °C-24 °C. Increasing temperature at later developmental stages was associated with lower sperm concentration and higher motility. Sperm concentration and motility were highest following a period of moderate gradual warming. Motility was higher and sperm concentration was lower, following a period with heatwaves or summer. CONCLUSIONS: This study assessed temperature role in sperm production quality by considering both average and time-dynamic temperatures. It identified several temperature change patterns over time and stratified the analysis by them. The differences in the relations across stages of spermatogenesis were addressed. Several mechanisms may explain the associations found, including heat-induced apoptosis of the sperm cells, and destruction of sperm cells DNA integrity by over-production of reactive oxygen species. The gradual global warming necessitates exploration of individual response to outdoor temperature in relations to genetic predisposition, lifestyle, and other health characteristics.

Impact of PROphet Test in Changing Physicians' Therapeutic Decision-Making for Checkpoint Immunotherapy in Non-Small-Cell Lung Cancer.

PURPOSE: Immune Checkpoint Inhibitor (ICI) regimens are approved for first-line treatment of metastatic nononcogene-driven NSCLC. Guidelines do not differentiate which patients with PD-L1 ≥ 50% should receive ICI monotherapy. The clinically validated PROphet NSCLC plasma proteomic-based test is designed to inform this therapeutic decision. METHODS: One hundred oncologists were presented with 3 "virtual" metastatic NSCLC cases with PD-L1 scores and asked to recommend an approved first-line regimen. They then watched an online educational webinar on the PROphetNSCLC test. Postwebinar, the same cases were represented with the addition of a PROphet result, and oncologists again recommended a first-line regimen. Responses were compared to assess the impact on first-line treatment selection. RESULTS: Treatment recommendation changed in 39.6% of PROphet-tested cases, with 93% of physicians changing at least 1 case. In the PD-L1 ≥ 50% group, 89% of physicians changed their recommendation, followed by 77%, in PD-L1 < 1%, and 36% in PD-L1 1% to 49%. ​In the PD-L1 ≥ 50%, PROphet POSITIVE group, the recommendation for ICI monotherapy increased from 60% to 89%. ​For the PD-L1 ≥ 50%, PROphet NEGATIVE group, the recommendation for monotherapy dropped from 60% to 9%. In the PD-L1 < 1%, PROphet NEGATIVE group, 35% of patients were spared toxicity from ICI compared to 11% in PROphet untested cases. CONCLUSION: Adding PROphet to PD-L1 expression impacted therapeutic decision making in first-line NSCLC. PROphet identifies those predicted to have an overall survival benefit from ICI monotherapy versus combination versus chemotherapy, improving the probability of efficacy and reducing toxicity for some patients.

Utility of NICaS Non-Invasive Hemodynamic Monitoring in Critically Ill Patients with COVID-19.

(1) Background: COVID-19 presented many challenges to effective treatments, such as managing cardiovascular insufficiency while mitigating risks to healthcare providers. This study utilized NICaS, a non-invasive hemodynamic monitor that provides advanced data via whole-body impedance analysis. We investigated the associated trends in hemodynamic parameters obtained by the NICaS device and their correlation with in-hospital all-cause mortality during COVID-19 hospitalization in the intensive care unit. (2) Methods: Data from 29 patients with COVID-19 admitted to the intensive care unit and monitored with NICaS between April 2020 and February 2021 were analyzed retrospectively. (3) Results: Decreasing cardiac output and cardiac power were significantly associated with death. Total peripheral resistance was significantly increasing in non-survivors as was total body water percentage. Those admitted with a heart rate above 90 beats per minute had a significantly reduced survival. (4) Conclusions: Non-invasive hemodynamic monitoring via the NICaS device is simple and effective in evaluating critically ill patients with COVID-19 and may help guide clinical management via remote monitoring. Controlling tachycardia may help ensure adequate oxygen supply-demand ratio. A hint toward a beneficiary effect of a restrictive fluid balance may be observed.

Trends in decision-making by primary care physicians regarding common infectious complaints.

BACKGROUND: Primary care physicians played an important role in the global response during the COVID-19 pandemic, but with the absence of laboratory and diagnostics services, the move to telehealth and the focus on respiratory assessment, they faced increased uncertainty when making clinical decisions. OBJECTIVES: This paper aims to examine the impact of the pandemic on decisions made by primary care physicians, as measured by referrals to chest X-ray and laboratory tests and by prescriptions of antibiotics. METHODS: We conducted a retrospective study of all visits recorded with fever or cough, presenting to 209 community clinics in Southern Israel during the years 2018-2022. We describe changes in outcome rates across time and use multivariate generalised linear mixed effects model to compare the odds of referrals and prescriptions between periods, while accounting for gender, age, clinic sector, visit type, diagnosis, and season. RESULTS: In total, 609,823 visits to primary care physicians complied with the cohort definitions. Social restrictions were associated with a decline in all measured outcomes for primary care physician decisions, most prominently among ages 20-59, for throat culture referral during the first lockdown (OR = 0.46) and for cephalosporine prescription during the second lockdown (OR = 0.55). This trend persisted following the cancellation of the restrictions. CONCLUSIONS: Despite higher uncertainty during the COVID-19 social restrictions, the overall course of clinical decision-making processes was maintained, and was associated with a reduction in the use of auxiliary resources, which can improve the quality of patient care by lowering costs and supporting prevention of future antibiotics resistance.

Plasma Proteome-Based Test for First-Line Treatment Selection in Metastatic Non-Small Cell Lung Cancer.

PURPOSE: Current guidelines for the management of metastatic non-small cell lung cancer (NSCLC) without driver mutations recommend checkpoint immunotherapy with PD-1/PD-L1 inhibitors, either alone or in combination with chemotherapy. This approach fails to account for individual patient variability and host immune factors and often results in less-than-ideal outcomes. To address the limitations of the current guidelines, we developed and subsequently blindly validated a machine learning algorithm using pretreatment plasma proteomic profiles for personalized treatment decisions. PATIENTS AND METHODS: We conducted a multicenter observational trial (ClinicalTrials.gov identifier: NCT04056247) of patients undergoing PD-1/PD-L1 inhibitor-based therapy (n = 540) and an additional patient cohort receiving chemotherapy (n = 85) who consented to pretreatment plasma and clinical data collection. Plasma proteome profiling was performed using SomaScan Assay v4.1. RESULTS: Our test demonstrates a strong association between model output and clinical benefit (CB) from PD-1/PD-L1 inhibitor-based treatments, evidenced by high concordance between predicted and observed CB (R2 = 0.98, P < .001). The test categorizes patients as either PROphet-positive or PROphet-negative and further stratifies patient outcomes beyond PD-L1 expression levels. The test successfully differentiates between PROphet-negative patients exhibiting high tumor PD-L1 levels (≥50%) who have enhanced overall survival when treated with a combination of immunotherapy and chemotherapy compared with immunotherapy alone (hazard ratio [HR], 0.23 [95% CI, 0.1 to 0.51], P = .0003). By contrast, PROphet-positive patients show comparable outcomes when treated with immunotherapy alone or in combination with chemotherapy (HR, 0.78 [95% CI, 0.42 to 1.44], P = .424). CONCLUSION: Plasma proteome-based testing of individual patients, in combination with standard PD-L1 testing, distinguishes patient subsets with distinct differences in outcomes from PD-1/PD-L1 inhibitor-based therapies. These data suggest that this approach can improve the precision of first-line treatment for metastatic NSCLC.

Effect of angiotensin receptor neprilysin inhibitor on physical activity in patients with heart failure with reduced ejection fraction, monitored by implantable electronic device home monitoring.

AIMS: Angiotensin receptor neprilysin inhibitor (ARNI) therapy is a cornerstone in the treatment of heart failure with reduced ejection fraction (HFrEF), with significant improvement in mortality as well as morbidity and quality of life. However, maximal ARNI doses often result in hypotension. Recent studies with 'real world' experience suggest that lower doses of ARNI are as effective as higher doses.In order to evaluate the symptomatic effect of low-dose ARNI in HFrEF patients, we analyzed physical activity data obtained via home monitoring of patients with cardiac implantable electronic devices (CIEDs). METHODS: We retrospectively analyzed physical activity data obtained from HFrEF patients with CIED-active home monitoring during the years 2021-2022. Patients with ARNI therapy were further divided into subgroups according to the administered dose. Low-dose ARNI included doses of up to 24/26 mg sacubitril/valsartan daily. Intermediate dose and high dose included doses of 72/78-120/130 mg/day, and 144/156-194/206 mg/day, respectively. RESULTS: A total of 122 patients had home monitoring-compatible CIEDs and HFrEF during the study period. Sixty-four of these patients were treated with ARNI. Administration of low-dose ARNI resulted in a 20% increase in daily activity when compared with patients without ARNI treatment ( P  = 0.038). Change in physical activity of patients in the intermediate-dose and high-dose groups was not significant. Younger patients, patients with cardiac resynchronization therapy, and patients without diabetes mellitus were more physically active. CONCLUSION: Low-dose ARNI had a beneficial effect on physical activity in HFrEF patients. MH via CIED provided real-life objective data for patients' follow-up.

Transesophageal echocardiography and computerized tomography angiography mismatch in left atrial appendage thrombus evaluation.

BACKGROUND: Transesophageal echocardiography (TEE) is the gold standard test for the diagnosis of left atrial appendage (LAA) thrombus. Nonetheless, computerized tomography angiography (CTA) is readily used to exclude LAA thrombus before pulmonary vein isolation (PVI) and LAA closure procedures. We aimed to assess the comparability of LAA thrombus diagnosis using chest CTA scans in patients with atrial fibrillation who underwent TEE. METHODS: Retrospective collection of consecutive patients with atrial fibrillation who underwent TEE and chest CTA within 30 days and had evidence of spontaneous echo contrast (SEC) or LAA thrombus on TEE. Clinical, demographic, and echo data were collected. Prospective analysis of the CTA for evidence of LAA thrombus in the same group of patients was performed. We compared the findings of the two modalities. RESULTS: Out of 1550 patients with atrial fibrillation who underwent TEE examinations in the study period, 63 patients underwent TEE within 30 days of a chest CTA scan. Twenty-three patients had LAA thrombus and 40 had some degree of SEC according to TEE. On CTA, 11 were interpreted as positive with a high level of suspicion for the presence of an LAA thrombus. Six patients (26.1%) had LAA thrombus according to both CT and TEE. Therefore, low concordance was found between test results (chi-squared continuity correction = 5.5, df  = 1, and P -value = 0.01902). CONCLUSION: The discrepancy between CTA and TEE results suggests these examinations might be more suitable as complementary examinations to exclude LAA thrombus.

Correlation between baseline immature platelets fraction levels and peak troponin in patients with acute myocardial infarction.

INTRODUCTION: Elevated peak cardiac troponin levels have been linked with increased morbidity and mortality in patients with acute myocardial infarction (AMI). Immature Platelets are young and relatively large platelets that are hyper-reactive and pro-thrombotic compared to regular platelets. Increased immature platelet fraction (IPF) has been associated with an elevated risk of thrombotic events. We hypothesize that patients with higher IPF levels during AMI, will experience a more severe infarct, leading to elevated peak troponin levels. METHODS: Clinical data from patients admitted to the cardiology division between 2018 and 2022, who were diagnosed with AMI and underwent an IPF testing. Univariate and multivariate regression analyses were performed to identify predictors of elevated peak troponin. RESULTS: Among the 277 patients diagnosed with AMI who underwent IPF testing, 113 had (STEMI) and 164 had (NSTEMI). The median value of IPF of 4.2% was used as the threshold for defining elevated IPF. Notably, among STEMI patients, those with IPF ≥ 4.2% had significantly higher peak troponin levels ( P  = 0.021). Conversely, no significant difference in peak troponin levels was observed among NSTEMI patients ( P  = 0.348). Multivariate analysis identified patients with STEMI in the higher IPF group as one of the significant predictors for elevated peak troponin levels. CONCLUSION: This study revealed a correlation between higher baseline IPF levels and increased peak troponin levels specifically in STEMI patients, while no such association was found in NSTEMI patients. Incorporating IPF levels above the median into risk stratification scores for STEMI patients may provide valuable support for adopting a more proactive therapeutic approach.