Traditional Cardiovascular Risk Factors and Coronary Microvascular Dysfunction in Women and Men: A Single-Center Study.

INTRODUCTION: Coronary microvascular dysfunction (CMD) is common in patients with and without obstructive epicardial coronary artery disease (CAD). Risk factors for the development of CMD have not been fully elucidated, and data regarding sex-associated differences in traditional cardiovascular risk factors for obstructive CAD in patients with CMD are lacking. METHODS: In this single-center, prospective registry, we enrolled patients with nonobstructive CAD undergoing clinically indicated invasive assessment of coronary microvascular function between November 2019 and March 2023. Associations between coronary microvascular dysfunction, traditional cardiovascular risk factors, and sex were assessed using univariate and multivariate regression models. RESULTS: Overall, 245 patients with nonobstructive CAD were included in the analysis (62.9% female; median age 68 (interquartile range: 59, 75). Microvascular dysfunction was diagnosed in 141 patients (57.5%). The prevalence of microvascular dysfunction was similar in women and men (59.0% vs. 57.0%; p = 0.77). No association was found between traditional risk factors for coronary atherosclerosis and CMD regardless of whether CMD was structural or functional. In women, but not in men, older age and the presence of previous ischemic heart disease were associated with lower coronary flow reserve (ß = -0.29; p < 0.01 and ß = -0.15; p = 0.05, respectively) and lower resistive reserve ratio (ß = -0.28; p < 0.01 and ß = -0.17; p = 0.04, respectively). CONCLUSION: For the entire population, no association was found between coronary microvascular dysfunction and traditional risk factors for coronary atherosclerosis. In women only, older age and previous ischemic heart disease were associated with coronary microvascular dysfunction. Larger studies are needed to elucidate risk factors for CMD.

Asymptomatic Dysphagia and Aspiration in Patients with Idiopathic Bronchiectasis.

PURPOSE: Although considered contributors to idiopathic bronchiectasis (IB), neither dysphagia nor silent aspiration have been systematically evaluated in IB patients. We aimed to explore the prevalence of asymptomatic dysphagia and silent aspiration in IB patients and to identify parameters predictive of their presence. METHODS: This prospective cohort study included IB patients from our Pulmonary Institute without prior history of dysphagia and without prior dysphagia workup. Swallowing function was assessed by the Eating Assessment Tool (EAT-10) questionnaire and by the Fiberoptic Endoscopic Evaluation of Swallowing (FEES) test. RESULTS: Forty-seven patients (31 females, mean age 67 ± 16 years) were recruited. An EAT-10 score ≥ 3 (risk for swallowing problems) was present in 21 patients (44.6%). Forty-two patients (89.3%) had at least one abnormal swallowing parameter in the FEES test. Six patients (12.7%) had a penetration aspiration score (PAS) in the FEES of at least 6, indicating aspiration. An EAT-10 score of 3 was found to be the ideal cutoff to predict aspiration in the FEES, with a good level of accuracy (area under the curve = 0.78, 95% CI 0.629-0.932, p = 0.03) and sensitivity of 83%. This cutoff also showed a trend towards a more severe disease using the FACED (forced expiratory volume, age, colonization with pseudomonas, extension of lung involvement, dyspnea) score (p = 0.05). CONCLUSION: Dysphagia is prevalent in IB and may be undiagnosed if not specifically sought. We recommend screening all patients with IB for dysphagia by the EAT-10 questionnaire and referring all those with a score of ≥ 3 to formal swallowing assessment.

Transition of care interventions to manage severe COVID-19 in the ambulatory setting: a systematic review.

BACKGROUND: Severe COVID-19, with the need in supplemental oxygen and hospitalization, leads to major burden on patients and healthcare systems. As a result, safe and effective ambulatory treatment strategies for severe COVID-19 are of urgent need. In this systematic review, we aimed to evaluate interventions to transition care to the ambulatory setting for patients with active severe COVID-19 that required supplemental oxygen. METHODS: We searched Medline, Scopus, Web of Science, and DOAJ databases to identify articles with original data published until the 1st of April 2023. Characteristics and outcomes of interventions to transition care to home management were reviewed. Given the heterogeneous settings and outcomes studied, a meta-analysis was not performed. RESULTS: Of the 235 studies identified, 11 observational studies, with 2645 patients, were included. The interventions were initiated from the emergency department, observation units or inpatient units, and included continuous home telemonitoring (n = 8), mobile applications (n = 2), and patient-initiated medical contact (n = 3). Included patients had an overall short length of hospital stay, high readmission rates, and positive patients' feedback. There was a lack of prospective controlled data and cost-effectiveness analyses. CONCLUSION: Our findings highlight the potential in treating severe COVID-19 at the ambulatory setting and the lack of high-quality data in this field. Dedicated medical teams, adjusted monitoring methods, improving clinical trajectory, and correct inclusion settings are needed for safe and effective transition of care.

Attitudes of Patients with Advanced Chronic Illnesses Toward Palliative Extubation in a Country Where It Is Illegal.

Background: Palliative extubation (PE) is the cessation of mechanical ventilation (MV) during terminal illness. Although PE is widely practiced in many countries, it remains illegal in others. Attitudes toward PE of patients at the highest risk for MV were scarcely explored before. Objective: To assess the attitudes of patients with advanced chronic illnesses (ACI) toward PE and other end-of-life decisions in a country where PE is illegal. Design: A prospective observational study using questionnaire-based interviews. Setting/Subjects: Patients with ACI hospitalized between 2021 and 2022 in a large tertiary center. Attitudes toward PE and mechanical ventilation were evaluated. Predictors for favoring/opposing PE were analyzed using multivariate logistical regression models. Results: A total of 152 (40% female, 75 ± 11 years) patients were included. The most common ACIs were advanced heart failure (32%), metastatic malignancy (32%), and chronic obstructive pulmonary disease (22%). Around 132 patients (87%) supported the legalization of PE, and their main reason was to avoid pain and suffering (87%). Legalization of PE would change the decision to avoid mechanical intubation in 34% of the cases. Most patients thought that the decision to perform PE should be made by the patient's physician and primary caregiver collaboratively (64%). Religious observance was an independent predictor for opposing PE (adjusted odds ratio 0.18; 95% confidence interval 0.06-0.59; p < 0.01), whereas the type of ACI was not. Conclusion: Most admitted patients with ACIs support the legalization of PE. Such policy change could have major impact on patients' end-of-life preferences. At-risk patients should be the focus of future studies in this area.

Management of acute exacerbations of COPD in the emergency department and its associations with clinical variables.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common cause for emergency department (ED) visits. Still, large scale studies that assess the management of AECOPD in the ED are limited. Our aim was to evaluate treatment characteristics of AE-COPD in the ED on a national scale. A prospective study as part of the COPD Israeli survey, conducted between 2017 and 2019, in 13 medical centers. Patients hospitalized with AECOPD were included and interviewed. Clinical data related to their ED and hospital stay were collected. 344 patients were included, 38% females, mean age of 70 ± 11 years. Median (IQR) time to first ED treatment was 59 (23-125) minutes and to admission 293 (173-490) minutes. Delayed ED treatment (> 1 h) was associated with older age (p = 0.01) and lack of a coded diagnosis of COPD in hospital records (p = 0.01). Long ED length-of-stay (> 5 h) was linked with longer hospitalizations (p = 0.01). Routine ED care included inhalations of short-acting bronchodilators (246 patients, 72%) and systemic steroids (188 patients, 55%). Receiving routine ED care was associated with its continuation during hospitalization (p < 0.001). In multivariate analysis, predictors for patients not receiving routine care were obesity (adjusted odds ratio 0.5, 95% CI 0.3-0.8, p = 0.01) and fever (AOR 0.3, 95% CI 0.1-0.6, p < 0.01), while oxygen saturation < 91% was an independent predictor for ED routine treatment (AOR 3.6, 95% CI 2.1-6.3, p < 0.01). Our findings highlight gaps in the treatment of AECOPD in the ED on a national scale, with specific predictors for their occurrence.

Early neutrophil gelatinase-associated lipocalin (NGAL) measurement could rule out future acute kidney injury in patients with acute coronary syndrome-Prospective observational study.

Background and Aims: The diagnosis of acute kidney injury (AKI) is of importance among patients with ST segment elevation (STEMI) undergoing primary coronary intervention (PCI). It is often delayed given the need in serial measurements of creatinine or other serum markers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proven marker for AKI, although its role as an early predictor in this setting was scarcely addressed before and was the aim of our study. Methods: Prospective observational study including 133 patients with STEMI treated with PCI. Plasma NGAL was drawn immediately before PCI (NGAL-0) and 24 h after (NGAL-24). Similar analysis of C-reactive protein (CRP) was performed for additional comparison. Results: Mean age was 62 ± 13 years, 78% were men, and 20 (15%) developed AKI after admission. Patients with AKI after admission demonstrated higher levels of NGAL-0 (164 vs. 95 ng/mL; p < 0.001) and NGAL-24 (142 vs. 93 ng/mL; p < 0.001). Levels of NGAL-0 and NGAL-24 were similar within the AKI and non-AKI groups. Using ROC curve analysis, NGAL-0 had best predictive ability for AKI development (AUC 0.841, 95% CI 0.80-0.96), compared with NGAL-24 (0.783, 95% CI 0.74-0.85), CRP-0 (0.701, 95% CI 0.58-0.83), and CRP-24 (0.781, 95% CI 0.66-0.90). The optimal NGAL-0 cutoff for AKI prediction was 125 ng/mL, with 70% sensitivity, 84% specificity, and 94% negative predictive value. Conclusions: Among STEMI patients, NGAL measurement upon admission are associated with AKI and may serve as a reliable marker for early AKI detection. Future studies may direct risk stratification using this single test can direct personalized evaluations during the admission, and focused interventions to prevent AKI.

Effect of Added Inhaled Corticosteroids to Systemic Steroids on COPD Exacerbation Outcomes.

BACKGROUND: COPD exacerbations are a major cause of morbidity and mortality. Although inhaled corticosteroids (ICS) have a role as long-term treatment, their efficacy in exacerbations, particularly as an adjunct to systemic steroids, remains unclear. METHODS: In this retrospective observational study, we analyzed data from 870 subjects admitted with COPD exacerbations to a tertiary medical center in Israel from January 2018-January 2023. We investigated the impact of adding ICS to standard systemic steroid treatment on hospital length of stay, intubation rates, and 30-d mortality using propensity score matching to account for confounders. RESULTS: The cohort, after matching, included 354 subjects treated with systemic steroids and ICS and 121 treated with systemic steroids alone. All characteristics were similar between the groups. Our analysis showed no differences in 30-d mortality (7.1% vs 5.8%, P = .63) or secondary outcomes (intubation, hospital length of stay, and readmission rates) between the groups. Subgroup analyses based on different eosinophil levels did not alter these findings. In multivariate analysis among the general cohort, eosinophil count < 150 cells/µL (adjusted odds ratio 0.45 [95% CI 0.21-0.87], P = .02) and high Charlson score (adjusted odds ratio 1.19 [95% CI 1.02-1.37], P = .02) were independent predictors for 30-d mortality. CONCLUSIONS: Despite the known benefits of ICS in managing chronic COPD, we did not find an added value of ICS to systemic steroids in exacerbations. These results underscore the necessity for individualized treatment strategies and further research into the role of ICS in COPD exacerbations.

Predicting the Outcomes of Inpatient Cardiac Evaluation for Syncope Using Validated Risk Scores.

BACKGROUND: Validated syncope risk scores were aimed to predict a cardiac etiology and are mainly used in the decision of hospital admission. Whether these scores could also predict the outcomes of inpatient cardiac evaluation is unknown and was the subject of our study. METHODS: This was an observational study including consecutive patients admitted for syncope evaluation. All patients completed prolonged electrocardiogram monitoring and an echocardiography before discharge. The area under the receiver-operating characteristic curve (AUC) was used to evaluate the ability of validated risk scores to predict positive inpatient findings. Subsequently, a multivariate regression was performed to identify independent predictors for positive cardiac evaluation, which were then incorporated into the best predictive risk scores. RESULTS: Three hundred ninety-seven patients were included, 56 (14%) with a positive inpatient cardiac evaluation. The Osservatorio Epidemiologico sulla Sincope Lazio and Canadian Syncope Risk Score achieved the largest AUC (0.701, 95% confidence interval [CI] 0.63-0.77 and 0.694, 95% CI 0.62-0.77, respectively). Yet, all scores provided relatively high sensitivity with low specificity. Multivariate regression revealed age ≥75 (adjusted odds ratio 3.50, 95% CI 1.5-7.9) and abnormal cardiac auscultation (adjusted odds ratio 4.79, 95% CI 2.5-9.1) to be independent predictors. Incorporating these factors led to a significantly higher prediction ability of the Osservatorio Epidemiologico sulla Sincope Lazio (AUC of 0.787, P < .01) and Canadian Syncope Risk Score (AUC 0.778, P < .01) modified scores. CONCLUSIONS: Current syncope risk scores provide limited prediction ability for the outcomes of inpatient cardiac syncope work-up. One should specifically consider age > 75 years and either cardiac murmur or irregular heart rate on examination very significant in implying a cardiac etiology for syncope. Although these factors may be obvious, current risk scores can be interpreted in such a fashion that ignores the importance of findings extracted from a good history and physical examination.

Impulse Oscillometry as an Alternative Lung Function Test for Hospitalized Adults.

BACKGROUND: Impulse oscillometry (IOS) is a noninvasive technique that measures lung physiology independently of patient effort. In the present study, we aimed to investigate the utility of IOS parameters in comparison with pulmonary function testing (PFT) among hospitalized subjects, with emphasis on obstructive and small airway diseases. METHODS: Sixty-one subjects hospitalized either with unexplained dyspnea or for pre-surgery evaluation were included in the study. All subjects underwent PFTs and IOS test. The correlation between IOS results and PFTs was examined in different subgroups. The ability of IOS parameters to predict abnormal PFTs was evaluated using the area under the receiver operating characteristic (ROC) curve, and optimal cutoff values were calculated. RESULTS: IOS results were found to correlate with PFT values. Subgroup analysis revealed that these correlations were higher in younger (age < 70) and non-obese (body mass index < 25kg/m2) subjects. The resonant frequency was an independent predictor and had the best predictive ability for abnormal FEV1/FVC (area under the ROC curve 0.732 [95% CI 0.57-0.90], optimal cutoff 17 Hz, 87% sensitivity, 62% specificity) and abnormal forced expiratory flow during the middle half of the FVC maneuver (area under the ROC curve 0.667 [95% CI 0.53-0.81], optimal cutoff 15 Hz, 77% sensitivity, 54% specificity). Area of reactance and the difference in respiratory resistance at 5 Hz and 20 Hz also showed a good predictive ability for abnormal FEV1/FVC (area under the ROC curve 0.716 and 0.730, respectively). CONCLUSIONS: We found that the IOS performed well in diagnosing small airway and obstructive diseases among hospitalized subjects. IOS might serve as an alternative to standard PFTs in non-cooperative or dyspneic hospitalized patients.

Cytokine fingerprint differences following infection and vaccination - what can we learn from COVID-19?

COVID-19 vaccination and acute infection result in cellular and humoral immune responses with various degrees of protection. While most studies have addressed the difference in humoral response between vaccination and acute infection, studies on the cellular response are scarce. We aimed to evaluate differences in immune response among vaccinated patients versus those who had recovered from COVID-19. This was a prospective study in a tertiary medical centre. The vaccinated group included health care workers, who had received a second dose of the BNT162b2 vaccine 30 days ago. The recovered group included adults who had recovered from severe COVID-19 infection (<94% saturation in room air) after 3-6 weeks. Serum anti-spike IgG and cytokine levels were taken at entry to the study. Multivariate linear regression models were applied to assess differences in cytokines, controlling for age, sex, BMI, and smoking status. In total, 39 participants were included in each group. The mean age was 53 ±14 years, and 53% of participants were males. Baseline characteristics were similar between the groups. Based on multivariate analysis, serum levels of IL-6 (ß=-0.4, p<0.01), TNFα (ß=-0.3, p=0.03), IL-8 (ß=-0.3, p=0.01), VCAM-1 (ß=-0.2, p<0.144), and MMP-7 (ß=-0.6, p<0.01) were lower in the vaccinated group compared to the recovered group. Conversely, serum anti-spike IgG levels were lower among the recovered group (124 vs. 208 pg/mL, p<0.001). No correlation was identified between antibody level and any of the cytokines mentioned above. Recovered COVID-19 patients had higher cytokine levels but lower antibody levels compared to vaccinated participants. Given the differences, these cytokines might be of value for future research in this field.

Routine in-hospital interventions during acute exacerbation of COPD are associated with improved 30-day care.

BACKGROUND: Implementing standard of care therapy for chronic obstructive pulmonary disease (COPD) has barriers. Hospitalization with an acute exacerbation of COPD (AECOPD) is a major adverse event that could also be an opportunity to improve patients' long-term care. OBJECTIVES: To evaluate which in-hospital interventions during AECOPD are associated with improved 30-day care. METHODS: This was a prospective study that included patients from 10 medical centers across Israel, hospitalized with AECOPD between 2017 and 2019. Patients were approached during hospitalization in internal medicine departments. A semi-structured follow-up call was performed 30 days after discharge, and six COPD areas of care were assessed. Multivariate analyses were used to analyze predictors for each area of care. RESULTS: 234 patients were included (mean age 69 years and 34% females). A lower 30-day readmission rate was independently associated with smoking cessation and prescription of renin-angiotensin blockers. Initiating or continuing long acting bronchodilators (LABD) during admission was an independent predictor for their 30-day use. Among patients with prior LABD treatment, only 38% continued at 30-days if it was not prescribed during admission (OR 4, 95% CI 1.98-8.08, p<0.01). In-hospital daily respiratory physiotherapy was an independent predictor for smoking cessation (AOR 5.1, 95% CI 1.1-23, p=0.04), while smoking cessation recommendation was not (p=0.28). Initiating a smoking cessation program (5%) or pulmonary rehabilitation (1%) after discharge was performed only by patients with a written referral. CONCLUSION: Routine procedures during hospitalization for AECOPD could impact patients' long-term care in areas with proven effects on disease outcomes.

Smoking and Respiratory Diseases in Patients with Coronary Microvascular Dysfunction.

BACKGROUND: Coronary microvascular disease (CMD) is common in patients with and without obstructive coronary artery disease, and is associated with adverse clinical outcomes. Respiratory-related variables are associated with pulmonary and systemic microvascular dysfunction, while evidence about their relationship with CMD is limited. We aim to evaluate respiratory-related variables as risk factors of CMD. METHODS: This is an observational, single-center study enrolling consecutive patients undergoing invasive evaluation of coronary microvascular function in the catheterization laboratory. Patients with evidence of obstructive coronary artery disease or with missing data were excluded. Associations between respiratory-related variables and indices of CMD were assessed using univariate and multivariate regression models. RESULTS: Overall, 266 patients (mean age 67 ± 11 years, 59% females) were included in the current analysis. Of those, 155 (58%) had evidence of CMD. Among the respiratory variables, independent predictors of CMD were current smoking (adjusted odds ratio [AOR] 2.5; 95% confidence interval [CI], 1.2-5; P = .01) and obstructive sleep apnea (AOR 5.7; 95% CI, 1.2-26; P = .03), while chronic obstructive pulmonary disease was not. Among ever-smokers, higher smoking pack-years was an independent risk factor for CMD (median 35 vs 25 pack-years, AOR 1.09; 95% CI, 1.04-1.13; P < .01), and was associated with higher rates of pathologic index of microcirculatory resistance and resistive reserve ratio. CONCLUSION: In patients undergoing invasive coronary microvascular evaluation, current smoking and obstructive sleep apnea are independently associated with CMD. Among smokers, higher pack-years is a strong predictor for CMD. Our findings should raise awareness for prevention and possible treatment options.

Coronary microvascular dysfunction in patients with Takotsubo syndrome.

BACKGROUND: The pathophysiology of Takotsubo syndrome (TTS) remains incompletely understood. While coronary microvascular dysfunction (CMD) is a potential pathophysiologic mechanism, evidence is limited. OBJECTIVES: We sought to evaluate CMD in patients with TTS. METHODS: Consecutive patients diagnosed with TTS were included and underwent coronary angiography with invasive microvascular function evaluation, including fractional flow reserve, Coronary Flow Reserve (CFR), Index of Microcirculatory Resistance (IMR), and Resistive Reserve Ratio (RRR). Patients had an echocardiography evaluation during their index admission and at approximately 6 weeks. RESULTS: Thirty patients were included (mean age 74 ±9, 90 % female). Twenty-five patients (83 %) had at least one abnormal coronary microvascular function parameter. Abnormal parameters included CFR<2.5 in 20 patients (67 %), IMR>25 in 18 patients (60 %), and RRR<3.5 in 25 (83 %). Longer time from symptoms to angiography correlated with a higher CFR (r = 0.51, P<0.01), and had an area under the receiver operating characteristic curve of 0.793 (95 % CI 0.60-0.98) for pathologic CFR. Patients with emotional trigger had a lower rate of pathologic IMR compared with non-emotional trigger (36 % vs 81 %, p = 0.01). Follow up echocardiography performed at a median of 1.5 months (IQR 1.15-6) showed an improvement in left ventricular ejection fraction for all patients (from mean of 40 % to 57 %). CONCLUSION: CMD was present in most patients with TTS. The role of microvascular function in TTS may vary according to the clinical presentation and RRR may be more sensitive for the diagnosis of CMD in TTS.

The Added Value of Bronchoalveolar Lavage for Pulmonary Tuberculosis Diagnosis in High-Risk Hospitalized Patients with Negative Sputum Samples.

Hospitalized patients with a high suspicion of pulmonary tuberculosis (HS-PTB) are isolated until a definite diagnosis can be determined. If doubt remains after negative sputum samples, bronchoscopy with bronchoalveolar lavage (BAL) is often sought. Still, evidence of the added value of BAL in this patient population is scarce. To address this issue, we included consecutive HS-PTB patients with negative sputum samples who underwent BAL between 2017 and 2018. Chest X-rays (CXR) and CT scans were evaluated by a chest radiologist blind to the final diagnosis. Independent predictors for PTB were assessed by multivariate regression, using all positive PTB patients between 2017 and 2019 (by sputum or BAL) as a control group (n = 41). Overall, 42 HS-PTB patients were included (mean age 51 ± 9, 36% female). BAL was a viable diagnostic for PTB in three (7%) cases and for other clinically relevant pathogens in six (14%). Independent predictors for PTB were ≥2 sub-acute symptoms (adjusted OR 3.18, 95% CI 1.04-9.8), CXR upper-lobe consolidation (AOR 8.70, 95% CI 2.5-29), and centrilobular nodules in chest CT (AOR 3.96, 95% CI 1.20-13.0, p = 0.02). In conclusion, bronchoscopy with BAL in hospitalized patients with HS-PTB had a 7% added diagnostic value after negative sputum samples. Our findings highlight specific predictors for PTB diagnosis that could be used in future controlled studies to personalize the diagnostic evaluation.