Prognostic performance of soluble urokinase plasminogen activator receptor for heart failure or mortality in Western and Asian patients with acute breathlessness.

AIMS: The performance of circulating soluble urokinase plasminogen activator receptor (suPAR) for predicting the composite endpoint of subsequent heart failure (HF) hospitalisation and/or death at 1 year was assessed in (i) patients with undifferentiated breathlessness, and generalisability was compared in (ii) disparate Western versus Asian sub-cohorts, and in (iii) the sub-cohort adjudicated with HF. METHODS AND RESULTS: Patients with acute breathlessness were recruited from the emergency departments in New Zealand (NZ, n = 612) and Singapore (n = 483). suPAR measured in the presentation samples was higher in patients incurring the endpoint (n = 281) compared with survivors (5.2 ng/mL vs 3.1 ng/mL, P < 0.0001). The discriminative power of suPAR for endpoint prediction was c-statistic of 0.77 in the combined population, but was superior in Singapore than NZ (c-statistic: 0.83 vs 0.71, P < 0.0001). Although the highest suPAR tertile (>4.37 ng/mL) was associated with risks of >4-fold in NZ, >20-fold in Singapore, and ≥3-fold in HF for incurring the outcome, there was no interaction between country and suPAR levels after adjustment. Multivariable analysis indicated suPAR to be robust in predicting HF/death at 1-year [hazard ratio: 1.9 (95% CI:1.7 to 2.0) per SD increase] and improved risk discrimination for outcome prediction in HF (∆0.06) and for those with NT-proBNP >1000 pg/mL (∆0.02). CONCLUSION: suPAR is a strong independent predictor of HF and/or death at 1 year in acutely breathless patients, in both Asian and Western cohorts, and in HF. suPAR may improve stratification of acutely breathless patients, and in acute HF, for risk of later onset of heart failure or mortality.

Cardiac Troponin T and NT-proBNP for Prediction of 30-Day Readmission or Death in Patients with Acute Dyspnea: Data from the Akershus Cardiac Examination 2 Study.

INTRODUCTION: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) measurements are recommended in patients with acute dyspnea. We aimed to assess the prognostic merit of cTnT compared to NT-proBNP for 30-day readmission or death in patients hospitalized with acute dyspnea. METHODS: We measured cTnT and NT-proBNP within 24 h in 314 patients hospitalized with acute dyspnea and adjudicated the cause of the index admission. Time to first event of readmission or death ≤30 days after hospital discharge was recorded, and cTnT and NT-proBNP measurements were compared head-to-head. RESULTS: Patients who died (12/314) or were readmitted (71/314) within 30 days had higher cTnT concentrations (median: 32.6, Q1-Q3: 18.4-74.2 ng/L vs. median: 19.4, Q1-Q3: 8.4-36.1 ng/L; p for comparison <0.001) and NT-proBNP concentrations (median: 1,753.6, Q1-Q3: 464.2-6,862.0 ng/L vs. median 984, Q1-Q3 201-3,600 ng/L; for comparison p = 0.027) compared to patients who survived and were not readmitted. cTnT concentrations were associated with readmission or death within 30 days after discharge both in the total cohort (adjusted hazard ratio [aHR]: 1.64, 95% confidence interval [CI]: 1.30-2.05) and in patients with heart failure (HF) (aHR: 1.58, 95% CI: 1.14-2.18). In contrast, NT-proBNP concentrations were not associated with short-term events, neither in the total cohort (aHR: 1.10, 95% CI: 0.94-1.30) nor in patients with adjudicated HF (aHR: 1.06, 95% CI: 0.80-1.40). CONCLUSION: cTnT concentrations are associated with 30-day readmission or death in patients hospitalized with acute dyspnea, as well as in patients adjudicated HF.

Study of the Role of Plasma NT-proBNP in the Diagnosis of Heart Failure.

BACKGROUND: The diagnosis of heart failure (HF) remains essentially clinical-Based. However, the history, physical examination, and chest radiograph findings are often inadequate in the diagnosis because multiple other conditions that affect the cardiopulmonary system mimic the symptoms of HF. N-terminal pro-BNP (NT-proBNP) has long been used for diagnosing HF. N-terminal pro-BNP values vary with different patient parameters. There is a scarcity of Indian studies on this topic. Especially with the use of newer drugs like angiotensin receptor neprilysin inhibitor (ARNI), it is important to have data from our own population on the same. AIMS AND OBJECTIVES: (i) To assess the role of NT-proBNP in the diagnosis of HF. (ii) Achieve diagnostic clarity in cases having cardiorespiratory symptoms and signs like acute onset dyspnea, pedal edema, and basal crepitations. (iii) To study the effect of various factors like age, body mass index (BMI), and creatinine on NT-proBNP. (iv) Establish a relation between NT-proBNP levels and left ventricular ejection fraction (LVEF), disease severity, and etiology of HF. MATERIALS AND METHODS: An observational prospective study of 50 patients presenting with acute onset breathlessness was carried out, fulfilling inclusion and exclusion criteria over a period of 10 months. Detailed history and examination of the patients were obtained. Venous sample for the measurement of NT-proBNP was collected within 24 hours of onset of symptoms. Other relevant blood and radiographic investigations were obtained. The NT-proBNP "cut-offs" set forth by the American Heart Association (AHA)/American College of Cardiology (ACC) were used to "rule in" or "rule out" HF. Two-dimensional echocardiography (2D Echo) was used to confirm the diagnosis. The correlation between NT-proBNP and various parameters like age, BMI, creatinine, and LVEF was obtained. Sensitivity and specificity tests were applied as well. RESULTS: Out of the 50 patients presenting with acute onset dyspnea, the most common cause was ischemic heart disease (IHD) (44%) followed by dilated cardiomyopathy (DCM) (32%), chronic obstructive pulmonary disease (COPD) (10%), anemia (4%), followed by other causes. The median NT-proBNP value was the highest for IHD patients (9485 pg/mL), followed by DCM (8969 pg/mL), followed by COPD (2846 pg/mL), and followed by anemia (850 pg/mL). There is a significant positive correlation between NT-proBNP and age (coefficient of correlation r = 0.4007, significance level p = 0.0389, and class interval = 0.137-0.61). There is a significant negative correlation between creatinine clearance and NT-proBNP (coefficient of correlation r = -0.372, significance level p = 0.007, and class interval = -0.58 to -0.105). There was significant negative correlation between LVEF and NT-proBNP (coefficient of correlation r = -0.36, significance level p = 0.009, and class interval = -0.58 to -0.09). Higher LVEF is associated with lower NT-proBNP values. There is marked heterogeneity in the values though. CONCLUSION: It is seen that the values of NT-proBNP vary with factors like age, BMI, and creatinine clearance in addition to LVEF. This may lead to falsely positive or falsely negative diagnosis of HF. With the above observations in mind, it can be concluded that NT-proBNP can help diagnose HF but only in addition to clinical findings.

Immunoglobulin signature predicts risk of post-acute COVID-19 syndrome.

Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which - combined with age, history of asthma bronchiale, and five symptoms during primary infection - is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS.

Is carbonic anhydrase inhibition useful as a complementary therapy of Covid-19 infection?

The ongoing Covid-19 is a contagious disease, and it is characterised by different symptoms such as fever, cough, and shortness of breath. Rising concerns about Covid-19 have severely affected the healthcare system in all countries as the Covid-19 outbreak has developed at a rapid rate all around the globe. Intriguing, a clinically used drug, acetazolamide (a specific inhibitor of carbonic anhydrase, CA, EC 4.2.1.1), is used to treat high-altitude pulmonary oedema (HAPE), showing a high degree of clinical similarities with the pulmonary disease caused by Covid-19. In this context, this preliminary study aims to provide insights into some factors affecting the Covid-19 patients, such as hypoxaemia, hypoxia as well as the blood CA activity. We hypothesise that patients with Covid-19 problems could show a dysregulated acid-base status influenced by CA activity. These preliminary results suggest that the use of CA inhibitors as a pharmacological treatment for Covid-19 may be beneficial.

Pulmonary function and functional capacity in COVID-19 survivors with persistent dyspnoea.

The purpose of this study was to examine the physiological mechanisms of persistent dyspnoea in COVID-19 survivors. Non-critical patients (n = 186) with varying degrees of COVID-19 severity reported persistent symptoms using a standardized questionnaire and underwent pulmonary function and 6-minute walk testing between 30 and 90 days following the onset of acute COVID-19 symptoms. Patients were divided into those with (n = 70) and without (n = 116) persistent dyspnoea. Patients with persistent dyspnoea had significantly lower FVC (p = 0.03), FEV1 (p = 0.04), DLCO (p = 0.01), 6-minute walk distance (% predicted, p = 0.03), and end-exercise oxygen saturation (p < 0.001), and higher Borg 0-10 ratings of dyspnoea and fatigue (both p < 0.001) compared to patients without persistent dyspnoea. We have shown that dyspnoea is a common persistent symptom across varying degrees of initial COVID-19 severity. Patients with persistent dyspnoea had greater restriction on spirometry, lower DLCO, reduced functional capacity, and increased exertional desaturation and symptoms. This suggests that there is a true physiological mechanism that may explain persistent dyspnoea after COVID-19.

Economic Evaluation of an N-terminal Pro B-type Natriuretic Peptide-Supported Diagnostic Strategy Among Dyspneic Patients Suspected of Acute Heart Failure in the Emergency Department.

Our objective was to perform an economic evaluation of an N-terminal pro B-type natriuretic peptide (NT-proBNP)-supported diagnostic strategy in dyspneic patients suspected of acute heart failure in the emergency department (ED). A decision-tree model was developed to evaluate clinical outcomes and costs for NT-proBNP-supported assessment compared with clinical assessment alone over 6 months from the United States (US) Medicare perspective. The model considered rule-in/rule-out cutoffs identified in the ICON and ICON-RELOADED studies. Acute heart failure prevalence, diagnostic accuracies, and medical resource use conditional on disease status and test results were derived from ICON-RELOADED. Several assumptions based on previous studies of NT-proBNP acute dyspnea and verified with clinicians were applied to medical resource use and assessed in sensitivity analyses. Compared with clinical assessment alone, NT-proBNP-supported assessment improved overall probability of correct diagnosis by a relative 7% (18% for true-positive and 5% for true-negative). This led to relative reductions in medical resource use in ED and hospital, including fewer initial hospitalizations (-14%), required echocardiograms (-31%), cardiology admissions (-16%), intensive care unit admissions (-12%), ED readmissions (-3%), and hospital readmissions (-22%). NT-proBNP use decreased average inpatient management costs by a relative 10%, yielding cost savings of US$2,337 per patient ED visit. These findings were robust in sensitivity analyses. In conclusion, based on a contemporary trial of patients with acute dyspnea, this analysis reaffirmed that using NT-proBNP as a diagnostic tool may improve the management of patients with dyspnea presenting to EDs and is likely to be cost-saving from the US Medicare perspective.

High-sensitivity cardiac troponin T and N-terminal pro-B-type natriuretic peptide in acute heart failure: Data from the ACE 2 study.

BACKGROUND: To assess if cardiac troponins can improve diagnostics of acute heart failure (AHF) and provide prognostic information in patients with acute dyspnea. METHODS: We measured cardiac troponin T with a high-sensitivity assay (hs-cTnT) in 314 patients hospitalized with acute dyspnea. The index diagnosis was adjudicated and AHF patients were stratified into AHF with reduced or preserved ejection fraction (HFrEF/HFpEF). The prognostic and diagnostic merit of hs-cTnT was compared to the merit of N-terminal pro-B-type natriuretic peptide (NT-proBNP). RESULTS: In the total population, median age was 73 (quartile [Q] 1-3 63-81) years and 48% were women. One-hundred-forty-three patients were categorized as AHF (46%) and these patients had higher hs-cTnT concentrations than patients with non-AHF-related dyspnea: median 38 (Q1-3 22-75) vs. 13 (4-25) ng/L; p < 0.001. hs-cTnT concentrations were similar between patients with HFrEF and HFpEF (p = 0.80), in contrast to NT-proBNP, which was higher in HFrEF (p < 0.001). C-statistics for discriminating HFpEF from non-AHF-related dyspnea was 0.80 (95% CI 0.73-0.86) for hs-cTnT, 0.79 (0.73-0.86) for NT-proBNP, and 0.83 (0.76-0.89) for hs-cTnT and NT-proBNP in combination. Elevated hs-cTnT remained associated with HFpEF in logistic regression analysis after adjusting for demographics, comorbidities and renal function. During median 27 months of follow-up, 114 (36%) patients died in the total population. Higher hs-cTnT concentrations were associated with increased risk of all-cause mortality after adjustment for clinical variables and NT-proBNP: hazard ratio 1.30 (95% CI 1.07-1.58), p = 0.009. CONCLUSION: hs-cTnT measurements improve diagnostic accuracy for HFpEF and provide independent prognostic information in unselected patients with acute dyspnea.

A left shift in the oxyhaemoglobin dissociation curve in patients with severe coronavirus disease 2019 (COVID-19).

Critically ill patients with coronavirus disease 2019 (COVID-19) present with hypoxaemia and are mechanically ventilated to support gas exchange. We performed a retrospective, observational study of blood gas analyses (n = 3518) obtained from patients with COVID-19 to investigate changes in haemoglobin oxygen (Hb-O2 ) affinity. Calculated oxygen tension at half-saturation (p50 ) was on average (±SD) 3·3 (3·13) mmHg lower than the normal p50 value (23·4 vs. 26·7 mmHg; P < 0·0001). Compared to an unmatched historic control of patients with other causes of severe respiratory failure, patients with COVID-19 had a significantly higher Hb-O2 affinity (mean [SD] p50 23·4 [3·13] vs. 24·6 [5.4] mmHg; P < 0·0001). We hypothesise that, due to the long disease process, acclimatisation to hypoxaemia could play a role.

A proposed ABCD scoring system for better triage of patients with COVID-19: Use of clinical features and radiopathological findings.

BACKGROUND AND AIMS: Currently there are limited tools available for triage of patients with COVID -19. We propose a new ABCD scoring system for patients who have been tested positive for COVID-19. METHODS: The ABCD score is for patients who have been tested positive for COVID-19 and admitted in a hospital. This score includes age of the patient, blood tests included leukopenia, lymphocytopenia, CRP level, LDH level,D-Dimer, Chest radiograph and CT Scan, Comorbidities and Dyspnea. RESULTS: The triage score had letters from alphabets which included A, B, C, D. The score was developed using these variables which outputs a value from 0 to 1. We had used the code according to traffic signal system; green(mild), yellow moderate) and red(severe). The suggestions for mild (green)category: symptomatic treatment in ward, in moderate (yellow) category: active treatment, semi critical care and oxygen supplementation, in severe (red) category: critical care and intensive care. CONCLUSIONS: This study is, to our knowledge, is the first scoring tool that has been prepared by Indian health care processional's and used alphabets A, B,C,D as variables for evaluation of admitted patients with COVID-19. This triage tool will be helpful in better management of patients with COVID-19. This score component includes clinical and radiopathological findings.A multi-centre study is required to validate all available scoring systems.

Effect of a Triage-Based Screening Protocol on Diagnosis and Treatment of Acute Coronary Syndrome in a Tanzanian Emergency Department: A Prospective Pre-Post Study.

Background Evidence suggests that acute coronary syndrome (ACS) is underdiagnosed in sub-Saharan Africa. Triage-based interventions have improved ACS diagnosis and management in high-income settings but have not been evaluated in sub-Saharan African emergency departments (EDs). Our objective was to estimate the effect of a triage-based screening protocol on ACS diagnosis and care in a Tanzanian ED. Methods and Results All adults presenting to a Tanzanian ED with chest pain or shortness of breath were prospectively enrolled. Treatments and clinician-documented diagnoses were observed and recorded. In the preintervention phase (August 2018 through January 2019), ACS testing and treatment were dictated by physician discretion, as per usual care. A triage-based protocol was then introduced, and in the postintervention phase (January 2019 through October 2019), research assistants performed ECG and point-of-care troponin I testing on all patients with chest pain or shortness of breath upon ED arrival. Pre-post analyses compared ACS care between phases. Of 1020 total participants (339 preintervention phase, 681 postintervention phase), mean (SD) age was 58.9 (19.4) years. Six (1.8%) preintervention participants were diagnosed with ACS, versus 83 (12.2%) postintervention participants (odds ratio [OR], 7.51; 95% CI, 3.52-19.7; P<0.001). Among all participants, 3 (0.9%) preintervention participants received aspirin, compared with 50 (7.3%) postintervention participants (OR, 8.45; 95% CI, 3.07-36.13; P<0.001). Conclusions Introduction of a triage-based ACS screening protocol in a Tanzanian ED was associated with significant increases in ACS diagnoses and aspirin administration. Additional research is needed to determine the effect of ED-based interventions on ACS care and clinical end points in sub-Saharan Africa.

Red Blood Cell Distribution Width, Neutrophil-to-Lymphocyte Ratio, and In-Hospital Mortality in Dyspneic Patients Admitted to the Emergency Department.

Red blood cell distribution width (RDW) and neutrophil-to-lymphocyte ratio (NLR) have shown a prognostic value in various clinical settings. We aimed to investigate the association between RDW, NLR, and in-hospital mortality in patients with dyspnea. In this retrospective study with the Medical Information Mart for Intensive Care III database (version 1.4), adult patients who came to the emergency department with dyspnea were included. Patients' comorbidities, hematological parameters within the first 48 hours after admission to the emergency department, and in-hospital mortality were extracted. The relationships between RDW, NLR, and in-hospital mortality were analyzed with the receiver operating characteristic (ROC) curve analysis and multivariate logistic regression model. We found that hospital survivors had significantly lower NLR than those who died. However, RDW was not significantly increased in patients who died during the hospitalization. The area under the ROC curve of NLR for predicting in-hospital mortality was 0.62. On multivariate analysis, NLR was not independently associated with in-hospital mortality. On further analysis, lymphocyte percentage was independently associated with in-hospital mortality, with an odds ratio of 0.56. Therefore, we concluded that RDW and NLR are not reliable parameters to predict in-hospital mortality in critically ill patients admitted to the emergency department with dyspnea.

Chronic obstructive pulmonary disease (COPD) is associated with a higher level of serum uric acid. A systematic review and meta-analysis.

INTRODUCTION: Recent studies have suggested that patients with chronic obstructive pulmonary disease (COPD) may have a higher level of serum uric acid compared with individuals without COPD, although the data are still limited. The current systematic review and meta-analysis was conducted to summarize all available data. MATERIAL AND METHODS: A systematic review was performed using the MEDLINE and EMBASE databases from their inception to July 2019. Studies that were eligible for the meta-analysis must have consisted of two groups of participants, patients with COPD and individuals without COPD. The eligible studies must have reported either mean or median level of serum uric acid and its standard deviation (SD) or interquartile range of participants in both groups. Mean serum uric acid level and SD of participants in both groups were extracted from each study and the mean difference (MD) was calculated. Pooled MD was then computed by combining MDs of each study using random effects model. RESULTS: A total of eight studies with 1,612 participants met the eligibility criteria and were included in the data analysis. The serum uric acid level among patients with COPD was significantly higher than individuals without COPD with the pooled MD of 0.91 mg/dL (95% CI: 0.45-1.38; I2 = 89%). CONCLUSIONS: The current study found a significantly higher level of serum uric acid among patients with COPD than individuals without COPD.

Focused cardiac ultrasound and point-of-care NT-proBNP assay in the emergency room for differentiation of cardiac and noncardiac causes of respiratory distress in cats.

OBJECTIVE: To assess the accuracy of focused cardiac ultrasound (FOCUS) and point-of-care N-terminal proBNP assay in the emergency setting for differentiation of cardiac from noncardiac causes of respiratory distress in cats. DESIGN: Prospective diagnostic accuracy study between 2014 and 2016. SETTING: Emergency room at an urban university teaching hospital. ANIMALS: Forty-one client-owned cats presenting for evaluation of respiratory distress. INTERVENTIONS: Emergency clinicians made an initial diagnosis of noncardiac or cardiac cause of respiratory distress based on physical examination (PE) findings and history. The diagnoses were updated after performing FOCUS and point-of-care N-terminal B-type natriuretic peptide (POC-BNP). Reference standard diagnosis was determined by agreement of a board-certified cardiologist and critical care specialist with access to subsequent radiographs and echocardiograms. MEASUREMENTS AND MAIN RESULTS: Forty-one cats were enrolled. Three cats with incomplete data and 1 cat with an uncertain reference standard diagnosis were excluded. The remaining 37 cats were used for analysis: 21 cardiac and 16 noncardiac cases. The ratio of left atrial to aortic root diameter (LA:Ao) measured by FOCUS was significantly correlated with LA:Ao measured by echocardiography (R = 0.646, P < 0.0001). Emergency clinicians correctly diagnosed 27 of 37 (73.0%), yielding a PE positive percent agreement = 76.2% (95% CI, 52.8-91.8%) and negative percent agreement = 68.8% (95% CI, 41.3-89.0%). Five noncardiac and 5 cardiac cats were misdiagnosed. Post FOCUS, overall percent agreement improved to 34 of 37 (91.9%), with positive percent agreement = 95.2% (95% CI, 76.2-99.9%) and negative percent agreement = 87.5% (95% CI, 61.7-98.5%). The POC-BNP yielded an overall percent agreement = 32/34 (94.1%), positive percent agreement = 100% (95% CI, 82.4-100.0%), and negative percent agreement = 86.7% (95% CI, 59.5-98.3%) in differentiating cardiac versus noncardiac cases. CONCLUSIONS: FOCUS evaluation of basic cardiac structure and LA:Ao by trained emergency clinicians improved accuracy of diagnosis compared to PE in cats with respiratory distress. FOCUS and POC-BNP are useful diagnostics in the emergent setting.

Why COVID-19 Silent Hypoxemia Is Baffling to Physicians.

Patients with coronavirus disease (COVID-19) are described as exhibiting oxygen levels incompatible with life without dyspnea. The pairing-dubbed happy hypoxia but more precisely termed silent hypoxemia-is especially bewildering to physicians and is considered as defying basic biology. This combination has attracted extensive coverage in media but has not been discussed in medical journals. It is possible that coronavirus has an idiosyncratic action on receptors involved in chemosensitivity to oxygen, but well-established pathophysiological mechanisms can account for most, if not all, cases of silent hypoxemia. These mechanisms include the way dyspnea and the respiratory centers respond to low levels of oxygen, the way the prevailing carbon dioxide tension (PaCO2) blunts the brain's response to hypoxia, effects of disease and age on control of breathing, inaccuracy of pulse oximetry at low oxygen saturations, and temperature-induced shifts in the oxygen dissociation curve. Without knowledge of these mechanisms, physicians caring for patients with hypoxemia free of dyspnea are operating in the dark, placing vulnerable patients with COVID-19 at considerable risk. In conclusion, features of COVID-19 that physicians find baffling become less strange when viewed in light of long-established principles of respiratory physiology; an understanding of these mechanisms will enhance patient care if the much-anticipated second wave emerges.

Diagnostic and Prognostic Utilities of Insulin-Like Growth Factor Binding Protein-7 in Patients With Dyspnea.

OBJECTIVES: This study examined whether insulin-like growth factor binding protein-7 (IGFBP7) would aid in the diagnosis and prognosis of acute heart failure (HF) beyond N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration. BACKGROUND: IGFBP7 is associated with impaired ventricular relaxation and worse prognosis. METHODS: The ICON-RELOADED (International Collaborative of NT-proBNP-Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department) study was a prospective, multicenter clinical trial that enrolled subjects presenting with dyspnea. Six-month prognosis for death or repeat hospitalization was obtained. RESULTS: Among 1,449 patients, 274 (18.9%) were diagnosed with acute HF. Those with IGFBP7 concentrations in the highest quartile were older, male, had hypertension and HF, had lower estimated glomerular filtration rate (eGFR) and lowest ejection fraction (41 ± 20%; all p < 0.001). Independent predictors of IGFBP7 were age, male sex, history of diabetes, history of HF, and eGFR. Median concentrations of NT-proBNP (2,844 ng/ml vs. 99 ng/ml) and IGFBP7 (146.1 ng/ml vs. 86.1 ng/ml) were higher in those with acute HF (both; p < 0.001). Addition of IGFBP7 to NT-proBNP concentrations improved discrimination, therefore increasing the area under the receiver operating curve for diagnosis of acute HF (from 0.91 to 0.94; p < 0.001 for differences). Addition of IGFBP7 to a complete model of independent predictors of acute HF improved model calibration. IGFBP7 significantly reclassified acute HF diagnosis beyond NT-proBNP (net reclassification index: +0.25). Higher log2-IGFBP7 concentrations in patients with acute HF predicted death or rehospitalization at 6 months (hazard ratio: 1.84 per log2-SD; 95% confidence interval: 1.30 to 2.61; p = 0.001). In Kaplan-Meier analyses, supramedian concentrations of IGFBP7 were associated with shorter event-free survival (log-rank: p < 0.001). CONCLUSIONS: Among patients with acute dyspnea, concentrations of IGFBP7 add to NT-proBNP for diagnosis of acute HF and provide added prognostic utility for short-term risk.

TNFR1 is associated with short-term mortality in patients with diabetes and acute dyspnea seeking care at the emergency department.

BACKGROUND: Circulating levels of TNF alpha receptor 1 (TNFR1) and 2 (TNFR2) are associated with increased long-term mortality and impaired kidney function. AIM: To study association between circulating levels of TNFR1 and TNFR2 and short-term mortality in patients with diabetes and dyspnea. POPULATION AND METHODS: Patients aged ≥ 18 years seeking at emergency department (ED) during daytime on weekdays between December 2013 and July 2018, with diabetes and acute dyspnea, identified at the triage process, were included. Participants (n = 291) were triaged according to Medical Emergency Triage and Treatment System-Adult score, and blood samples were collected. Association between TNFR1 and TNFR2, respectively, and 90-day mortality were estimated by Cox regression models adjusted for age, sex, BMI, creatinine and CRP. RESULTS: Univariate models showed significant associations between TNFR1 and TNFR2, respectively, and CRP, age and creatinine. TNFR1 and TNFR2 tended to be elevated in patients with the highest triage level, compared to patients with lower triage levels (ns). In longitudinal analyses, TNFR1 but not TNFR2 was associated with increased short-term mortality, HR adjusted for age, BMI and creatinine 1.43 (95% CI 1.07-1.91), but not in the model also adjusted for CRP, HR 1.29 (95% CI 0.94-1.77). In secondary analysis for quartile 4 versus quartiles 1-3 of TNFR1, corresponding HRs were 2.46 (95% CI 1.27-5.15) and 2.21 (95% CI 1.07-2.56). CONCLUSIONS: We found a trend for the association between circulating TNFR1 levels and short-term mortality in patients with diabetes and acute dyspnea at the ED, possibly suggesting an inflammatory pathway for the association.

High-Flow Oxygen Therapy During Exercise Training in Patients With Chronic Obstructive Pulmonary Disease and Chronic Hypoxemia: A Multicenter Randomized Controlled Trial.

OBJECTIVE: The study aimed to evaluate whether high-flow oxygen therapy (HFOT) during training was more effective than oxygen in improving exercise capacity in hypoxemic chronic obstructive pulmonary disease (COPD). METHODS: A total of 171 patients with COPD and chronic hypoxemia were consecutively recruited in 8 rehabilitation hospitals in a randomized controlled trial. Cycle-ergometer exercise training was used in 20 supervised sessions at iso inspiratory oxygen fraction in both groups. Pre- and post-training endurance time (Tlim), 6-minute walking distance (6MWD), respiratory and limb muscle strength, arterial blood gases, Barthel Index, Barthel Dyspnea Index, COPD Assessment Test, Maugeri Respiratory Failure questionnaire, and patient satisfaction were evaluated. RESULTS: Due to 15.4% and 24.1% dropout rates, 71 and 66 patients were analyzed in HFOT and Venturi mask (V-mask) groups, respectively. Exercise capacity significantly improved after training in both groups with similar patient satisfaction. Between-group difference in post-training improvement in 6MWD (mean: 17.14 m; 95% CI = 0.87 to 33.43 m) but not in Tlim (mean: 141.85 seconds; 95% CI = -18.72 to 302.42 seconds) was significantly higher in HFOT. The minimal clinically important difference of Tlim was reached by 47% of patients in the V-mask group and 56% of patients in the HFOT group, whereas the minimal clinically important difference of 6MWD was reached by 51% of patients in the V-mask group and 69% of patients in the HFOT group, respectively. CONCLUSION: In patients with hypoxemic COPD, exercise training is effective in improving exercise capacity. IMPACT STATEMENT: The addition of HFOT during exercise training is not more effective than oxygen through V-mask in improving endurance time, the primary outcome, whereas it is more effective in improving walking distance.

COVID-19 patients' clinical characteristics, discharge rate, and fatality rate of meta-analysis.

The aim of this study was to analyze the clinical data, discharge rate, and fatality rate of COVID-19 patients for clinical help. The clinical data of COVID-19 patients from December 2019 to February 2020 were retrieved from four databases. We statistically analyzed the clinical symptoms and laboratory results of COVID-19 patients and explained the discharge rate and fatality rate with a single-arm meta-analysis. The available data of 1994 patients in 10 literatures were included in our study. The main clinical symptoms of COVID-19 patients were fever (88.5%), cough (68.6%), myalgia or fatigue (35.8%), expectoration (28.2%), and dyspnea (21.9%). Minor symptoms include headache or dizziness (12.1%), diarrhea (4.8%), nausea and vomiting (3.9%). The results of the laboratory showed that the lymphocytopenia (64.5%), increase of C-reactive protein (44.3%), increase of lactic dehydrogenase (28.3%), and leukocytopenia (29.4%) were more common. The results of single-arm meta-analysis showed that the male took a larger percentage in the gender distribution of COVID-19 patients 60% (95% CI [0.54, 0.65]), the discharge rate of COVID-19 patients was 52% (95% CI [0.34,0.70]), and the fatality rate was 5% (95% CI [0.01,0.11]).