A pilot study for treatment of severe COVID-19 pneumonia by aerosolized formulation of convalescent human immune plasma exosomes (ChipEXO™)

This is a single-center prospective, open-label, single arm interventional study to test the safety and efficacy of recently described ChipEXO™ for severe COVID-19 pneumonia. The ChipEXO™ is a natural product derived from convalescent human immune plasma of patients recovered from moderate COVID-19 infection. In September 2021, 13 patients with pending respiratory failure were treated with ChipEXO™ adapted for aerosolized formulation delivered via jet nebulizer. Patients received 1-5x1010 nano vesicle/5 mL in distilled water twice daily for five days as an add-on to ongoing conventional COVID-19 treatment. The primary endpoint was patient safety and survival over a 28-day follow-up. The secondary endpoint was longitudinal assessment of clinical parameters following ChipEXO™ to evaluate treatment response and gain insights into the pharmacodynamics. ChipEXO™ was tolerated well without any allergic reaction or acute toxicity. The survival rate was 84.6% and 11 out of 13 recovered without any sequel to lungs or other organs. ChipEXO™ treatment was effective immediately as shown in arterial blood gas analyses before and two hours after exosome inhalation. During the 5 days of treatment, there was a sustainable and gradual improvement on oxygenation parameters: i.e. respiratory rate (RR) [20.8% (P < 0.05)], oxygen saturation (SpO2) [6,7% (P < 0.05)] and partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2) [127.9% (P < 0.05)] that correlated with steep decrease in the disease activity scores and inflammatory markers, i.e. the sequential organ failure assessment (SOFA) score (75%, p < 0.05), C-reactive protein (46% p < 0.05), ferritin (58% p = 0.53), D-dimer (28% p=0.46). In conclusion, aerosolized ChipEXO™ showed promising safety and efficacy for life-threatening COVID-19 pneumonia. Further studies on larger patient populations are required to confirm our findings and understand the pathophysiology of improvement toward a new therapeutic agent for the treatment of severe COVID-19 pneumonia

Association of Energy Adequacy with 28-Day Mortality in Mechanically Ventilated Critically Ill

Objective: This study investigates the relationship of nutritional risk status with 28-day mortality in critically ill. Materials and Methods: This retrospective study included critically ill adult patients receiving >48 hours receiving mechanical ventilation. Data on baseline characteristics and the modified Nutritional Risk in Critically ill (mNUTRIC) score were collected on day 1. Energy intake was recorded daily until death, discharge or until twelfth evaluable days. Patients were divided into 2 groups: a) received = 75% of prescribed energy. Results: One hundred and fifty patients were included in the study. Patients with <75% of prescribed energy intake had longer length of ICU stay, duration of mechanical ventilation (p<0.001) and higher 28-day mortality (p<0.001). In the multi-logistic regression analysis, BMI (OR 0.87, CI 0.85-0.95, p<0.001) and mNUTRIC score (OR 2.3, CI 1.4-2.93, p<0.001) were associated with 28-day mortality. In subgroup analysis, the decrease in daily energy intake was associated with an increase in 28-day mortality in patients with a high mNUTRIC score (high mNUTRIC score OR 1.65, CI 1.20-1.70, p<0.001), but this relationship was not observed in the low mNUTRIC score group. Conclusion: The mNUTRIC score is associated with 28-day mortality in mechanically ventilated critically ill. In patients with a high mNUTRIC score, receiving 05% of the prescribed energy may positively affect patient outcomes

The initial resuscitation of septic shock

Septic shock is the most severe form of sepsis, characterized by (a) persistent hypotension despite fluid resuscitation and (b) the presence of tissue hypoperfusion. Delays in the diagnosis and initiation of treatment of septic shock is associated with increasing risk for mortality. Early and effective fluid resuscitation and vasopressor administration play a crucial role in maintaining tissue perfusion in septic shock patients. A low diastolic arterial pressure (DAP) correlates with severity of arteriolar vasodilation, compromises left ventricle oxygen supply and can be used for identifying septic shock patients thatwould potentially benefit fromearlier vasopressor therapy. Controversy currently exists as to the balance of fluids and vasopressors to maintain target mean arterial pressure. The aim of this article is to review the rationale for fluid resuscitation and vasopressor therapy and the importance of both mean and diastolic blood pressure during the initial resuscitation of the septic shock. We relate our personal prescription of balancing fluids and vasopressors in the resuscitation of septic shock. (c) 2020 Elsevier Inc. All rights reserved

The value of internal jugular vein collapsibility index in sepsis

BACKGROUND: Rapid, accurate, and reproducible assessment of intravascular volume status is crucial in order to predict the efficacy of volume expansion in septic patients. The aim of this study was to verify the feasibility and usefulness of the internal jugular vein collapsibility index (IJV-CI) as an adjunct to the inferior vena cava collapsibility index (IVC-CI) to predict fluid responsiveness in spontaneously-breathing patients with sepsis. METHODS: Three stages of sonographic scanning were performed. Hemodynamic data were collected using the Ultrasonic Cardiac Output Monitor IA system (Uscom, Ltd., Sydney, NSW, Australia) coupled with paired assessments of IVC-CI and IJV-CI at baseline, after passive leg raise (PLR), and again in semi-recumbent position. Fluid responsiveness was assessed according to changes in the cardiac index (CI) induced by PLR. Patients were retrospectively divided into 2 groups: fluid responder if an increase in CI (Delta CI) >= I5% was obtained after PLR maneuver, and non-responder if Delta CI was <15%. RESULTS: Total of 132 paired scans of IJV and IVC were completed in 44 patients who presented with sepsis and who were not receiving mechanical ventilation (mean age: 54.6 +/- 16.1 years). Of these, 23 (52.2%) were considered to be responders. Responders had higher UV-CI and IVC-CI before PLR maneuver than non-responders (p<0.001). IN-CI of more than 36% before PLR maneuver had 78% sensitivity and 85% specificity to predict responder. Furthermore, less time was needed to measure venous diameters for IN-CI (30 seconds) compared with IVC-CI (77.5 seconds; p<0.001). CONCLUSION: UV-CI is a precise, easily acquired, non-invasive parameter of fluid responsiveness in patients with sepsis who are not mechanically ventilated, and it appears to be a reasonable adjunct to IVC-Cl

Vitamin D level is associated with mortality predictors in ventilator-associated pneumonia caused by Acinetobacter baumannii

Introduction: Vitamin D plays a role in host defense and is known to be associated with mortality in patients in the intensive care unit (ICU). We aimed to evaluate the relationships between vitamin D levels and predictors of mortality in patients with ventilator-associated pneumonia (VAP) caused by extensively drug-resistant Acinetobacter baumanii (XDR A. baumanii). Methodology: A retrospective single-center study was conducted in an 18-bed adult ICU of a teaching hospital, including all patients with VAP due to XDR A. baumanii. Levels of 25(OH) D, procalcitonin (PCT), C-reactive protein (CRP), n-terminal pro-BNP (NT-proBNP), as well as clinical scores (Sequential Organ Failure Assessment [SOFA], Acute Physiology And Chronic Health Evaluation [APACHE II], Clinical Pulmonary Infection Score [CPIS) were recorded. Results: Forty-for patients were studied over six months. All patients had vitamin D deficiency. The 28-day mortality in patients with 25(OH) D levels 10ng/mL (p = 0.001). The fourth-and seventh-day SOFA scores (p=0.04 and p=0.001) and first-and fourth-day procalcitonin levels (p = 0.03 and p = 0.004) were higher in patients with 25(OH) D levels <= 10 ng/mL. The clinical scores (SOFA, CPIS, and CEPPIS) and biomarkers (NT-proBNP, PCT) were negatively correlated with 25(OH) D levels in all study groups. Conclusions: Severe vitamin D deficiency was associated with adverse outcome in VAP due to XDR A. baumanii. Vitamin D levels may be a prognostic predictor of VAP. It is also important to evaluate the effect of rapid vitamin D replacement on mortality

Renal Resistive Index Measurement by Transesophageal Echocardiography: Comparison With Trans lumbar Ultrasonography and Relation to Acute Kidney Injury

Objectives: The aim of this study was to evaluate the relationship between transesophageal ultrasonography-derived renal resistive index values (RRITEE) and a standard translumbar renal ultrasound-derived RRI (RRITLUSG). The effectiveness of each method to predict acute kidney injury (AKI) after cardiac surgery also was compared. Design: A prospective observational study. Setting: A teaching university hospital. Participants: Sixty patients undergoing cardiac surgery. Interventions: First, RRI was measured with both methods after anesthesia induction. Second, another measurement was performed with TEE after cardiopulmonary bypass and immediately following the surgery with translumbar ultrasound. To test the correlation between the 2 methods and to plot a Bland-Altman graph, preoperative RRI values measured by both techniques were used. Receiver operating characteristic curves also were plotted to compare the diagnostic values of RRI measured intraoperatively by TEE after cardiopulmonary bypass and by RRITLUSG after surgery. Measurements and Main Results: There was a statistically significant correlation between the 2 RRI measurement approaches (r = 0.86, p < 0.0001). The Bland-Altman plot indicated good agreement between the methods. The area under the curve (AUC) of RRITEE in predicting AKI was 0.82 (95% confidence interval (Cl] = 0.64-0.9, p = 0.001), and the AUC of RRITLUSG after surgery was 0.85 (95% Cl = 0.7-0.98, p < 0.0001). In predicting AKI, an uncertainty zone for RRITEE values between 0.68 and 0.71 was computed by the gray-zone approach. Conclusions: RRITEE showed clinically acceptable agreement with RRITLUSG. Indeed, RRI measured intraoperatively with TEE was comparable to RRITLUSG in terms of detecting postoperative AKI. (C) 2015 Elsevier Inc. All rights reserved

Sarcopenic dysphagia following COVID-19 infection: A new danger

Oropharyngeal dysphagia is one of the complications of endotracheal intubation. As expected, cases of dysphagia following coronavirus disease 2019 (COVID-19) reported to date have all been intubated. We here report a case of sarcopenic dysphagia following severe COVID-19 pneumonia in a nonintubated older adult. The patient was an 85-year-old male who was readmitted to the hospital with dysphagia and subsequent aspiration pneumonia in the first week after his discharge from the COVID-19 unit. On physical examination, the patient was sarcopenic and malnourished. Flexible endoscopic evaluation of swallowing (FEES) revealed aspiration into the airway. Enteral feeding was initiated and the infusion rate gradually increased to achieve the desired protein-energy targets. Control FEES 2 months after discharge showed recovery of swallowing function, with no apparent penetration or aspiration. Clinicians caring for patients with COVID-19 should be aware that dysphagia, which is associated with increased mortality in older adults, may occur even in the absence of intubation. We recommend that the evaluation of dysphagia be part of the clinical assessment in older COVID-19 patients with malnutrition or sarcopenia

Peripartum cardiomyopathy mimicking acute aortic dissection: successful salvage with extracorporeal membrane oxygenation support

In this article, we report a case admitted with severe chest pain associated with ST segment elevation, pericardial effusion and aortic flap appearance in echocardiography at the 31 weeks of gestation, mimicking aortic dissection, but diagnosed with peripartum cardiomyopathy and successfully treated with extracorporeal membrane oxygenation after developing acute cardiogenic shock

Renal Resistive Index is Unsusceptible to Systemic Hemodynamics in Fluid Responsive Critically III Patients

Objective: The primary goal of fluid resuscitation in critically ill patients is to improve oxygen delivery to ensure adequate organ perfusion. Little evidence is known about renal response to fluids in the acute phase, so renal monitoring after the fluid challenge is fundamental during critical care stay. This study aimed to evaluate changes in the renal resistive index (RRI) and to compare these changes with hemodynamic parameters after fluid challenge in fluid responsive critically ill patients. Materials and Methods: Thirty patients older than 18 years who underwent sedation and received mechanical ventilation were prospectively studied. Twenty patients were fluid responsive and were included in the study. An increase of cardiac output (CO) by 10% or more after PLR measured by ultrasonic CO monitor suspected fluid responsiveness. 500 mL of isotonic solution was administered intravenously for 30 minutes. CO measurements were performed at 0, 1 and 30 minutes. RRI and mean arterial pressure (MAP) were measured by Doppler ultrasonography at 0 and 30 minutes. Repeated measures ANOVA method was used for statistical analysis and p<0.05 was considered significant. Results: CO increased significantly after fluid challenge when compared to baseline (from 3.48 +/- 1.14 to 4.34 +/- 1.43 L/min, p<0.001). MAP increased significantly after fluid administration when compared to baseline (80 +/- 19 to 86 +/- 17, p=0.002). RRI did not significantly differ from baseline after fluid challenge (62 +/- 9 to 60 +/- 10, p=0.11). There was a negative correlation between RRI and MAP at baseline and after fluid challenge. Conclusion: The effect of hemodynamic changes on renal perfusion after fluid challenge is controversial. In our study, 500 mL of crystalloid treatment for 30 minutes increased MAP and CO, but did not contribute to the improvement of RRI in patients who were fluid responsive. We found that fluid challenge did not improve RRI in the early phase of the fluid resuscitation in fluid responsive critically ill patients and RRI is unsusceptible to systemic hemodynamic changes during this period