Hypoalbuminemia in COVID-19: assessing the hypothesis for underlying pulmonary capillary leakage.

BACKGROUND: Since the first observations of patients with COVID-19, significant hypoalbuminaemia was detected. Its causes have not been investigated yet. OBJECTIVE: We hypothesized that pulmonary capillary leakage affects the severity of respiratory failure, causing a shift of fluids and proteins through the epithelial-endothelial barrier. METHODS: One hundred seventy-four COVID-19 patients with respiratory symptoms, 92 admitted to the intermediate medicine ward (IMW) and 82 to the intensive care unit (ICU) at Luigi Sacco Hospital in Milan, were studied. RESULTS: Baseline characteristics at admission were considered. Proteins, interleukin 8 (IL-8) and interleukin 10 (IL-10) in bronchoalveolar lavage fluid (BALF) were analysed in 26 ICU patients. In addition, ten autopsy ultrastructural lung studies were performed in patients with COVID-19 and compared with postmortem findings in a control group (bacterial pneumonia-ARDS and H1N1-ARDS). ICU patients had lower serum albumin than IMW patients [20 (18-23) vs 28 (24-33) g L-1 , P < 0.001]. Serum albumin was lower in more compromised groups (lower PaO2 -to-FiO2 ratio and worst chest X-ray findings) and was associated with 30 days of probability of survival. Protein concentration was correlated with IL-8 and IL-10 levels in BALF. Electron microscopy examinations of eight out of ten COVID-19 lung tissues showed loosening of junctional complexes, quantitatively more pronounced than in controls, and direct viral infection of type 2 pneumocytes and endothelial cells. CONCLUSION: Hypoalbuminaemia may serve as severity marker of epithelial-endothelial damage in patients with COVID-19. There are clues that pulmonary capillary leak syndrome plays a key role in the pathogenesis of COVID-19 and might be a potential therapeutic target.

Phenotyping congestion in patients with acutely decompensated heart failure with preserved and reduced ejection fraction: The Decongestion duRing therapY for acute decOmpensated heart failure in HFpEF vs HFrEF- DRY-OFF study.

AIMS: To evaluate pulmonary and intravascular congestion at admission and repeatedly during hospitalization for acute decompensated heart failure (ADHF) in HFrEF and HFpEF patients using lung (LUS) and inferior vena cava (IVC) ultrasound. METHODS AND RESULTS: Three-hundred-fourteen patients (82±9 years; HFpEF =172; HFrEF=142) admitted to Internal Medicine wards for ADHF were enrolled in a multi-center prospective study. At admission HFrEF presented higher indexes of pulmonary and intravascular congestion (LUS-score: 0.9 ±â€¯0.4 vs 0.7 ±â€¯0.4; p<0.01; IVC end-expiratory diameter: 21.6 ±â€¯5.1 mm vs 20±5.5 mm, p<0.01; IVC collapsibility index 24.4 ±â€¯17.4% vs 30.9 ±â€¯21.1% p<0.01) and higher Nt-proBNP values (8010 vs 3900 ng/l; p<0.001). At discharge, HFrEF still presented higher B-scores (0.4 ±â€¯4 vs 0.3 ±â€¯0.4; p = 0.023), while intravascular congestion improved to a greater extent, thus IVC measurements were similar in the two groups. No differences in diuretic doses, urine output, hemoconcentration, worsening renal function were found. At 90-days follow up HF readmission/death did not differ in HFpEF and HFrEF (28% vs 31%, p = 0,48). Residual congestion was associated with HF readmission/death considering the whole population; while intravascular congestion predicted readmission/death in the HFrEF, no association between sonographic indexes and the outcome was found in HFpEF. CONCLUSIONS: Serial assessment of pulmonary and intravascular congestion revealed a higher burden of fluid overload in HFrEF and, conversely, a greater reduction in intravascular venous congestion with diuretic treatment. Although other factors beyond EF could play a role in congestion/decongestion patterns, our data may be relevant for further phenotyping HF patients, considering the importance of decongestion optimization in the clinical approach.

Residual congestion and long-term prognosis in acutely decompensated heart failure patients.

AIMS: Recent studies have established the role of residual congestion evaluated by lung ultrasound in estimating short-term risk of readmission or death in patients admitted for heart failure (HF) decompensation. However, if lung ultrasounds maintain a prognostic role of in long-term survival is still unknown. Aim of our study was to evaluate if residual congestion could predict all-cause mortality during 4 year follow up in a cohort of unselected patients admitted for acute decompensated HF. METHODS: One-hundred fifty patients were enrolled. The anterolateral chest was scanned to evaluate the presence of B-lines. A sonographic score was calculated attributing 1 to each positive sector (≥ 3 B-lines). Clinical, biochemical and echocardiographic data were recorded. A Cox proportional hazard regression analysis was performed to evaluate the association between variables and 4-year survival. RESULTS: During the follow-up, 86 patients (58%) died. Univariate analysis showed a significant correlation between the sonographic score at discharge and events occurrence at long term follow up (HR 1.21; CI 1.11-1.31; p < 0.001) suggesting that, on average, the increase of 1 point in the sonographic score was associated with an increase of approximately 20% in the risk of death. CONCLUSIONS: Our results suggest the role of LUS in the identification of more congested HF patients, that will be at risk for worse long term outcome.

Point-of-care ultrasound in internal medicine: A position paper by the ultrasound working group of the European federation of internal medicine.

Point-of-care ultrasound (POCUS) is increasingly used to assess medical patients. It has many uses in daily clinical practice, including improved diagnostic timeliness and accuracy, and providing information about a patient's prognosis and follow-up. It has been integrated into numerous specialities, but remains relatively undefined in internal medicine training programs. Ultrasonography is a useful tool in the standard clinical practice of internists in numerous clinical scenarios (Emergency Department, hospital ward, general and specific consultations, and home care). Although POCUS has been recently included in the European curriculum of internal medicine, there are differences between European internists in its use, ranging from not at all to well structured educational programs. The use of POCUS needs to be widespread in internal medicine departments, and to accomplish this we must encourage structured training. This document details the consensus-based recommendations by the European Federation of Internal Medicine (EFIM) Ultrasound working group. We establish POCUS core competencies and clinical settings for internists in a symptom-based approach. We also propose training requirements, providing a framework for training programs at a national level.

Lung ultrasonography in pulmonary tuberculosis: A pilot study on diagnostic accuracy in a high-risk population.

OBJECTIVES: The validity of lung ultrasound (LUS) in the diagnosis of interstitial or focal lung pathologies is well documented, we assessed its accuracy in the diagnosis of pulmonary tuberculosis (PTB). METHODS: Sonographic signs suggestive of PTB and their diagnostic accuracy were evaluated in patients admitted with clinical suspicion of PTB. Consolidations, subpleural nodules, pleural thickenings or irregularities and pleural effusion were assessed. LUS signs significantly associated with PTB in the univariate analysis (p < .05) were entered in a multivariate logistic regression model. RESULTS: PTB was confirmed in 51 out of 102 patients. Multiple consolidations (OR 3.54, 95%CI 1.43-8.78), apical consolidations (OR 9.65, 95%CI 3.02-30.78), superior quadrant consolidations (OR 4.01, 95%CI 1.76-9.14), and subpleural nodules (OR 5.29, 95%CI 2.27-12.33) were significantly associated with PTB diagnosis. Apical consolidation (OR 9.67, 95%CI 2.81-33.25, p 0.003) and subpleural nodules (OR 5.30, 95%CI 2.08-13.52, p 0.005) retained a significant association in a multivariate model, with an overall accuracy of 0.799. CONCLUSIONS: Our data suggest a possible role of LUS in the diagnosis of PTB, a high burden pathological condition for which the delay in diagnosis still represents a critical point in the control of the disease.

Chagas disease knocks on our door: a cross-sectional study among Latin American immigrants in Milan, Italy.

OBJECTIVES: We aimed to assess the prevalence and risk factors for Chagas disease (CD) in Latin American immigrants and to evaluate the accuracy of diagnostic tests. Moreover, we offered to all positive subjects a complete free-of-charge clinical/instrumental evaluation as well as benznidazole treatment in order to stage the disease and verify drug tolerability. METHODS: A cross-sectional survey of CD among Latin Americans living in Milan and its metropolitan area was conducted between July 2013 and July 2014. Blood samples were tested for serologic evidence of CD together with a questionnaire covering demographic and clinical-epidemiological information. RESULTS: Forty-eight (9.6%) of the 501 tested subjects were conclusively diagnosed as having CD. The highest prevalence of CD was among those from Bolivia (43/169, 25.4%) and El Salvador (4/68, 5.9%). Older age (adjusted odds ratio (aOR)] 1.05, p =0.004), a Bolivian origin (aOR 8.80; p =0.003), being born in the department of Santa Cruz (aOR 3.72, p =0.047), having lived in mud houses (aOR 2.68; p =0.019), and having an affected relative (aOR 12.77, p =0.001) were independently associated with CD. The ARCHITECT Chagas test showed the highest sensitivity (100%) and specificity (99.8%). Twenty-nine of the subjects with CD (60.4%) underwent disease staging, 10 of whom (35.7%) showed cardiac and/or digestive involvement. Benznidazole treatment was associated with high frequency of adverse reactions (19/27, 70.4%) and permanent discontinuation (8/27, 29.6%). CONCLUSIONS: CD is highly prevalent among Bolivians and Salvadorans living in Milan. Regions with a large Latin American immigrant population should implement programmes of active detection and treatment.

Non-linear dynamics and chaotic indices in heart rate variability of normal subjects and heart-transplanted patients.

OBJECTIVES: Heart rate variability (HRV) is characterised by a variety of linear, non-linear, periodical and non-periodical oscillations. The aim of the present study was mainly to investigate the role played by neural mechanisms in determining non-linear and non-periodical components. METHODS: Analysis was performed in 7 recently heart transplanted patients and in 7 controls of similar age whose HRV signal was collected during 24 h. Parameters that quantify non-linear dynamic behaviour, in a time series, were calculated. We first assessed the specific non-linear nature of the time series by a test on surrogate data after Fourier phase randomization. Furthermore, the D2 correlation dimension, K2 Kolmogorov entropy, and H self-similarity exponent of the signal were estimated. From this last parameter, the dimension D = 1/H can be obtained. In order to assess whether the dynamics of the system are compatible with chaotic characteristics, the entire spectrum of Lyapunov exponents was calculated. We used return maps to graphically represent the non-linear and non-periodical behaviours in patients and controls. RESULTS: Surrogate data suggest that the HRV time courses have unique non-linear characteristics. D2, K2 and 1/H parameters were significantly lower in transplanted subjects than in controls. Positivity of the first Lyapunov exponent indicates divergence of trajectories in state-space. Furthermore, the display of return maps on projections obtained after Singular Value Decomposition, especially in low-complexity data (as in transplanted patients), shows a structure which is suggestive of a strange attractor. These findings support the hypothesis that chaotic dynamics underlie HRV. CONCLUSION: These results indicate that non-linear dynamics are likely to be present in HRV control mechanisms, giving rise to complex and qualitatively different behaviours. System complexity decreases in transplanted patients and this may be related to loss of the neural modulation of heart rate.

Comparison of low-dose dobutamine ventriculography with low-dose dobutamine echocardiography for predicting regional improvement in left ventricular function after coronary artery bypass grafting.

The demonstration of a contractile reserve during low-dose dobutamine echocardiography (LDDE) identifies viable myocardium and predicts recovery of left ventricular (LV) function after myocardial revascularization in patients with chronic coronary artery disease. However, a technically difficult transthoracic visualization may limit the use of LDDE, thus requiring an alternative diagnostic procedure. The present study compares LDDE with low-dose dobutamine ventriculography (LDDV) in predicting an improvement in regional LV function after surgical revascularization. We studied 18 patients with coronary artery disease and LV dysfunction who were to undergo coronary artery bypass grafting. Preoperatively, all patients were evaluated for the presence of viable myocardium using LDDE and LDDV. Follow-up echocardiography at rest and left ventriculography were performed 4 months after successful revascularization to assess recovery of LV function. The sensitivity and specificity of LDDE to identify dysfunctional segments capable of recovering function were 63% and 71%, respectively, with a diagnostic accuracy of 68%. The sensitivity, specificity, and diagnostic accuracy of LDDE improved to 81%, 72%, and 76% when patients with optimal transthoracic evaluation were selected, whereas they were 30%, 77%, and 57%, respectively, in those who underwent suboptimal evaluation. The sensitivity, specificity, and diagnostic accuracy of LDDV were 66%, 75%, and 71%, respectively, with no difference in subgroups of patients. This study demonstrates that LDDV can be considered a useful technique for identifying the presence of myocardial viability and may provide an advantage over LDDE in patients with suboptimal echocardiographic visualization.