Evaluation of Lung Ultrasound in Assessment of Critically Ill patients in Respiratory Intensive Care Unit

Reaching a proper diagnosis for critically ill patients is like collecting pieces of puzzle and bed side lung ultrasound (LUS) becomes a crucial piece complementary to clinical and laboratory pieces. It is a bed side, real time tool for diagnosis of patients in ICU who are critical to be transferred to radiology unit especially in Covid-19 pandemic with risk of infection transmission. The aim was to evaluate the accuracy of lung ultrasound in assessment of critically ill patients admitted to Respiratory Intensive Care Unit (RICU), moreover to assess its diagnostic performance in different pulmonary diseases as compared to the gold standard approach accordingly. This observational prospective (cross sectional) study with a total 183 patients who met the inclusion criteria,were selected from patients admitted at the RICU;Chest Department, Zagazig University Hospitals, during the period from September 2019 to September 2021. LUS examination was performed to diagnose the different pulmonary diseases causing RF. All cases were examined by LUS on admission. From a total 183 patients, 111 patients 60.7% were males and 72 patients 39.3% were females, with a mean age of 56+/-12.77 years, 130 patients were breathing spontaneously received conservative management with O2 therapy, 32 patients needed NIV while 21 patients needed IMV with ETT. Exacerbated COPD was the most common disease finally diagnosed followed by bacterial pneumonia, exacerbated ILD, post Covid-19 fibrosis and pulmonary embolism in32, 29,27, 19 and 11 patients respectively with corresponding diagnostic accuracy of LUS 97.3%, AUC=0.943, 93.9% (AUC=0.922), 96.7%(AUC=0.920), 97.8%, AUC=0.895, and 97.8% respectively, while Covid-19 pneumonia was the final diagnosis in 8 patients with LUS diagnostic accuracy of 97.8% (AUC=0.869) with no statistical significant difference p-value=0.818 with bacterial pneumonia in distribution of US profiles. A profile was the commonest detected US profile among the studied patients followed by B profile, C profile, A/B profile and A' profile in 37.2%, 24.6%, 15.8% 4.9%, and 3.8% of cases respectively. Bed side LUS has a reliable, valuable diagnostic performance when integrated with clinical and laboratory data for the diagnosis of most pulmonary diseases in RICU.Copyright © 2023, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.

Targeting TLR-4 Signaling to Treat COVID-19-induced Acute Kidney Injury

The newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has turned into a potentially fatal pandemic illness. Numerous acute kidney injury (AKI) cases have been reported, although diffuse alveolar destruction and acute respiratory failure are the major symptoms of SARS-CoV-2 infection. The AKI, often known as a sudden loss of kidney function, carries a greater risk of mortality and morbidity. AKI was the second most frequent cause of death after acute respiratory distress syndrome (ARDS) in critically ill patients with coronavirus disease 2019 (COVID-19). While most patients with COVID-19 have moderate symptoms, some have severe symptoms, such as septic shock and ARDS. Also, it has been proven that some patients have severe symptoms, such as the failure of several organs. The kidneys are often affected either directly or indirectly. The major signs of kidney involvement are proteinuria and AKI. It is hypothesized that multiple mechanisms contribute to kidney injury in COVID-19. Direct infection of podocytes and proximal tubular cells in the kidneys may lead to acute tubular necrosis and collapsing glomerulopathy. SARS-CoV2 may also trigger a cascade of immunological responses that lead to AKI, including cytokine storm (CS), macrophage activation syndrome, and Toll-like receptor type-4 activation (TLR-4). Other proposed processes of AKI include interactions between organs, endothelial failure, hypercoagulability, rhabdomyolysis, and sepsis.Furthermore, ischemic damage to the kidney might result from the decreased oxygen supply. This article focuses on kidney injury's epidemiology, etiology, and pathophysiological processes. Specifically, it focuses on the CS and the role of TLR-4 in this process. To effectively manage and treat acute kidney damage and AKI in COVID-19, it is crucial to understand the underlying molecular pathways and pathophysiology.

Psychological Relationship of Mechanical Ventilation Power on Mortality of Covid-19 Critically Ill Patients

Introduction: ARDS is a type of lung injury that causes inflammation and makes it harder for oxygen to get into the bloodstream. Some treatments have been suggested, such as using less air with each breath, increasing pressure when breathing out, and using special positions or machines to help the lungs. But it's not clear how much these treatments can improve outcomes for patients with ARDS. So far, no studies have looked specifically at whether using more or less mechanical power to help patients breathe affects their chances of survival or other important measures of health. Objectives: This research aimed to investigate how the use of mechanical ventilation affects the likelihood of death in patients who are severely ill with COVID-19. Methods: This study adopts a cross-sectional design and retrospective analysis, observing critically ill patients who are being treated in the Special Isolation Ward of Dr. Soetomo Hospital's intensive care unit. The population for this study consists of critically ill patients who meet the inclusion and exclusion criteria. The research sample is obtained through randomized sampling, where all eligible individuals meeting the criteria are included in the sample size. Results: The study findings reveal a correlation between mechanical ventilation power and mortality among COVID-19 patients with ARDS. The mechanical power of ventilation is identified as a significant variable in this study, with a cut-off point of 17.4. Patients above this cut-off point are at 3.65 times higher risk of death compared to those below it. Moreover, there is evidence of a relationship between the mechanical power of ventilation variable and the P/F Ratio, as a higher mechanical power is associated with a decrease in the P/F Ratio. Conclusions: The study has identified a correlation between the P/F Ratio variable and mortality in COVID-19 patients with ARDS. On the other hand, there is no evidence of a relationship between the compliance variable and mortality in COVID-19 patients with ARDS. © 2023, Journal for ReAttach Therapy and Developmental Diversities. All Rights Reserved.

Medication Update

The article offers medical briefs. Topics include the authorization of a new drug called Gohibic for critically ill patients with COVID-19;the approval of an over-the-counter naloxone nasal spray for opioid overdose treatment;and the Food and Drug Administration approval of a long-acting antifungal called Rezzayo for the treatment of candidemia and invasive candidiasis for hypertension medications.

Recommendations of Nutritional Treatment for Patients with COVID-19 Infection (2023).

The standardized nutrition support therapy can improve the nutritional status, immunity, quality of life, and clinical outcomes of patients with novel coronavirus disease (COVID-19) infection. The latest Chinese government policy also clearly states that nutrition support therapy should be included in the whole process of treatment and recovery of patients with COVID-19. Therefore, the Beijing Quality Control and Improvement Center for Clinical Nutrition Therapy has organized relevant experts to formulate the Recommendations of Nutritional Treatment for Patients with COVID-19 Infection (2023), following the latest clinical nutrition guidelines, research evidence and clinical practice of nutrition support of COVID-19. The recommendations suggest that individualized nutrition management be implemented by fol-lowing the standardized pathway of nutrition management, which includes nutrition-risk screening, malnu-trition diagnosis, nutrition treatment and nutrition monitoring, and by taking into account the clinical char-acteristics of patients with COVID-19.Copyright © 2023, Peking Union Medical College Hospital. All rights reserved.

Derangement of Cardiovascular Regulatory Mechanisms in COVID-19 Patients in Intensive Care Unit and its Association with Mortality

The uncontrolled hyper-inflammation in critically ill patients with COVID-19 might be associated with a dysfunction of the cardiovascular regulatory mechanisms. In order to estimate the involvement of cardiovascular control in limiting the risk of mortality in COVID-19 patients we assessed the degree of asynchrony between heart period (HP) and systolic arterial pressure (SAP) variability at rest in supine condition (REST) and during an orthostatic challenge, namely the modified head-up tilt (MHUT), in 18 COVID-19 patients (age: 62± 10 yrs, 15 men) admitted in intensive care unit (ICU) for pneumonia. The patients were distinguished in two groups, i.e. survivors (SURVs) or non survivors (noSURVs) according to the outcome. Asynchrony between HP and SAP was assessed via a model-free nonlinear marker in the information domain, i.e. cross-sample entropy (CSampEn). Neither demographic indexes nor time domain markers could separate the two groups and this result held regardless of the experimental condition. Conversely, CSampEn could and, more precisely, noSURVs subjects had a significantly larger HP-SAP asynchrony when compared to SURVs in response to MHUT. We conclude that measures of the derangement of the cardiovascular control might be helpful to stratify the risk of mortality in COVID-19 critically ill patients. © 2022 Creative Commons.

Hepatobiliary long-term consequences of COVID-19: dramatically increased rate of secondary sclerosing cholangitis in critically ill COVID-19 patients.

BACKGROUND: Increasing evidence suggests that secondary sclerosing cholangitis (SSC), which can lead to cirrhosis or liver failure, may be a hepatobiliary long-term complication of COVID-19. The aim of this study was to estimate the frequency and outcome of this COVID-19 sequela and to identify possible risk factors. METHODS: This observational study, conducted at University Hospital Charité Berlin and Unfallkrankenhaus Berlin, Germany, involved hospitalized patients with COVID-19 pneumonia, including 1082 ventilated COVID-19 patients. We compared COVID-19 patients who developed SSC with a COVID-19 control group by univariate and multivariate analyses. RESULTS: SSC occurrence after COVID-19 was observed exclusively in critically ill patients with invasive ventilation, albeit with extreme clustering among them. One in every 43 invasively ventilated COVID-19 patients developed this complication. Risk factors preceding the development of secondary sclerosing cholangitis in critically ill COVID-19 patients (SSC-CIP) were signs of systemic reduced blood oxygen supply (e.g., low PaO2/FiO2, ischemic organ infarctions), multi-organ failure (high SOFA score) at admission, high fibrinogen levels and intravenous ketamine use. Multivariate analysis confirmed fibrinogen and increased plasma lactate dehydrogenase as independent risk factors associated with cholangiopathy onset. The 1-year transplant-free survival rate of COVID-19-associated SSC-CIP was 40%. CONCLUSIONS: COVID-19 causes SSC-CIP in a substantial proportion of critically ill patients. SSC-CIP most likely develops due to severe tissue hypoxia and fibrinogen-associated circulatory disturbances. A significant increase of patients with SSC-CIP is to be expected in the post-COVID era.

Nutritional status of patients with COVID-19 1-y post-ICU stay: A prospective observational study.

OBJECTIVES: Patients discharged from the intensive care unit (ICU) often experience physical complaints and poor nutritional intake, which negatively affect their nutritional status (NS). The aim of this study was to describe the NS of patients with COVID-19 1-y post-ICU stay. METHODS: This was an observational study of adult patients with COVID-19 1-y post-ICU stay. NS assessment (nutrient balance, body composition, and physical status) was performed. We examined nutritional intake and nutrition-related complaints. Nutritional requirements were determined with indirect calorimetry and body composition with bioelectrical impedance. Fat-free mass index (FFMI) and fat mass index (FMI) were calculated. Physical status was determined using handgrip strength, the 6-min walk test, and the 1-min sit-to-stand test. Descriptive statistics and paired sample t tests were used for analysis. RESULTS: We included 48 patients (73% men; median age 60 y [IQR 52;65]). Median weight loss during the ICU stay was 13%. One-y post-ICU stay, 12% of weight was regained. Median body mass index was 26 kg/m2 and 23% of the patients were obese (body mass index >30 kg/m2 and high FMI). Of the patients, 50% had high FMI and 19% had low FFMI. Median reported nutritional intake was 90% of measured resting energy expenditure. Nutrition-related complaints were seen in 16%. Percentages of normal values reached in physical tests were 92% of handgrip strength, 95% of 6-min walking distance, and 79% of 1-min sit-to-stand test. CONCLUSIONS: Despite almost fully regained weight and good physical recovery in adult patients 1-y post-ICU stay, NS remained impaired because of elevated FMI, even though reported nutritional intake was below the estimated requirements.

28-day prognostic value of coronary artery calcification burden in critically ill patients with COVID-19.

BACKGROUND: From pathophysiological mechanisms to risk stratification, much debate and discussion persist regarding the coronary artery disease as a risk factor for adverse outcomes in patients with COVID-19. Therefore, the aim of this study was to investigate the role of coronary artery calcification (CAC) burden by non-gated chest computed tomography (CT) for the prediction of 28-day mortality in critically ill patients with COVID-19 admitted to intensive care unit (ICU). METHODS: Consecutive critically ill adult patients with acute respiratory failure due to COVID-19 admitted to ICU who underwent non-contrast non-gated chest CT performed for pneumonia assessment between March and June 2020 (n â€‹= â€‹768) were identified. Patients were stratified in four groups: (a) CAC â€‹= â€‹0, (b) CAC 1-100, (c) CAC 101-300, and (d) CAC >300. RESULTS: CAC was detected in 376 patients (49%), of whom 218 (58%) showed CAC >300. CAC >300 was independently associated with ICU mortality at 28 days after admission (adjusted hazard ratio [aHR] 1.79, 95% confidence interval [CI] 1.36-2.36, p â€‹< â€‹0.001), and incrementally improved prediction of death over a model with clinical features and biomarkers assessed within the first 24h in ICU (likelihood ratio test â€‹= â€‹140 vs. 123, respectively, p â€‹< â€‹0.001). In the final cohort, 286 (37%) patients died within 28 days of ICU admission. CONCLUSION: In critically ill patients with COVID-19, a high CAC burden quantified with a non-gated chest CT performed for COVID-19 pneumonia assessment is an independent predictor of 28-day mortality, with an incremental prognostic value over a comprehensive clinical assessment during the first 24h in ICU.

Glycemic Control in Critically Ill COVID-19 Patients: Systematic Review and Meta-Analysis.

Background: Given the mortality risk in COVID-19 patients, it is necessary to estimate the impact of glycemic control on mortality rates among inpatients by designing and implementing evidence-based blood glucose (BG) control methods. There is evidence to suggest that COVID-19 patients with hyperglycemia are at risk of mortality, and glycemic control may improve outcomes. However, the optimal target range of blood glucose levels in critically ill COVID-19 patients remains unclear, and further research is needed to establish the most effective glycemic control strategies in this population. Methods: The investigation was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Data sources were drawn from Google Scholar, ResearchGate, PubMed (MEDLINE), Cochrane Library, and Embase databases. Randomized controlled trials, non-randomized controlled trials, retrospective cohort studies, and observational studies with comparison groups specific to tight glycemic control in COVID-19 patients with and without diabetes. Results: Eleven observational studies (26,953 patients hospitalized for COVID-19) were included. The incidence of death was significantly higher among COVID-19 patients diagnosed with diabetes than those without diabetes (OR = 2.70 [2.11, 3.45] at a 95% confidence interval). Incidences of death (OR of 3.76 (3.00, 4.72) at a 95% confidence interval) and complications (OR of 0.88 [0.76, 1.02] at a 95% confidence interval) were also significantly higher for COVID-19 patients with poor glycemic control. Conclusion: These findings suggest that poor glycemic control in critically ill patients leads to an increased mortality rate, infection rate, mechanical ventilation, and prolonged hospitalization.

Portable Chest Radiograph: A Boon for Critically Ill Patients With COVID-19 Pneumonia.

OBJECTIVE: In the present study, we evaluated the role of portable chest radiographs in critically ill patients with COVID-19 pneumonia in whom computed tomography (CT) of the chest was not feasible. METHODS: A retrospective chest X-ray study of patients under investigation for COVID-19 was performed in our dedicated COVID hospital (DCH) during the exponential growth phase of the COVID-19 outbreak (August-October, 2020). A total of 562 on-bed chest radiographs were examined comprising 289 patients (critically ill who couldn't be mobilized for CT) along with positive reverse transcription-polymerase chain reaction (RT-PCR) tests. We categorized each chest radiograph as progressive, with changes, or improvement in appearance for COVID-19, utilizing well-documented COVID-19 imaging patterns. RESULTS:  In our study, portable radiographs provided optimum image quality for diagnosing pneumonia, in critically ill patients. Although less informative than CT, nevertheless radiographs detected serious complications like pneumothorax or lung cavitation and estimated the evolution of pneumonia. CONCLUSION: A portable chest X-ray is a simple but reliable alternative for critically ill SARS-CoV-2 patients who could not undergo chest CT. With the help of portable chest radiographs, we could monitor the severity of the disease as well as different complications with minimal radiation exposure which would help in identifying the prognosis of the patient and thus help in medical management.

Modified SCOPE (mSCOPE) Score as a Tool to Predict Mortality in COVID-19 Critically Ill Patients.

INTRODUCTION: Efficient clinical scores predicting the outcome of severe COVID-19 pneumonia may play a pivotal role in patients' management. The aim of this study was to assess the modified Severe COvid Prediction Estimate score (mSCOPE) index as a predictor of mortality in patients admitted to the ICU due to severe COVID-19 pneumonia. MATERIALS AND METHODS: In this retrospective observational study, 268 critically ill COVID-19 patients were included. Demographic and laboratory characteristics, comorbidities, disease severity, and outcome were retrieved from the electronical medical files. The mSCOPE was also calculated. RESULTS: An amount of 70 (26.1%) of patients died in the ICU. These patients had higher mSCOPE score compared to patients who survived (p < 0.001). mSCOPE correlated to disease severity (p < 0.001) and to the number and severity of comorbidities (p < 0.001). Furthermore, mSCOPE significantly correlated with days on mechanical ventilation (p < 0.001) and days of ICU stay (p = 0.003). mSCOPE was found to be an independent predictor of mortality (HR:1.219, 95% CI: 1.010-1.471, p = 0.039), with a value ≥ 6 predicting poor outcome with a sensitivity (95%CI) 88.6%, specificity 29.7%, a positive predictive value of 31.5%, and a negative predictive value of 87.7%. CONCLUSION: mSCOPE score could be proved useful in patients' risk stratification, guiding clinical interventions in patients with severe COVID-19.

Impact of time to intubation on mortality and pulmonary sequelae in critically ill patients with COVID-19: a prospective cohort study.

QUESTION: We evaluated whether the time between first respiratory support and intubation of patients receiving invasive mechanical ventilation (IMV) due to COVID-19 was associated with mortality or pulmonary sequelae. MATERIALS AND METHODS: Prospective cohort of critical COVID-19 patients on IMV. Patients were classified as early intubation if they were intubated within the first 48 h from the first respiratory support or delayed intubation if they were intubated later. Surviving patients were evaluated after hospital discharge. RESULTS: We included 205 patients (140 with early IMV and 65 with delayed IMV). The median [p25;p75] age was 63 [56.0; 70.0] years, and 74.1% were male. The survival analysis showed a significant increase in the risk of mortality in the delayed group with an adjusted hazard ratio (HR) of 2.45 (95% CI 1.29-4.65). The continuous predictor time to IMV showed a nonlinear association with the risk of in-hospital mortality. A multivariate mortality model showed that delay of IMV was a factor associated with mortality (HR of 2.40; 95% CI 1.42-4.1). During follow-up, patients in the delayed group showed a worse DLCO (mean difference of - 10.77 (95% CI - 18.40 to - 3.15), with a greater number of affected lobes (+ 1.51 [95% CI 0.89-2.13]) and a greater TSS (+ 4.35 [95% CI 2.41-6.27]) in the chest CT scan. CONCLUSIONS: Among critically ill patients with COVID-19 who required IMV, the delay in intubation from the first respiratory support was associated with an increase in hospital mortality and worse pulmonary sequelae during follow-up.

Associations of body mass index with severe outcomes of COVID-19 among critically ill elderly patients: A prospective study.

Background and Aim: Few studies assessed the associations of overweight and obesity with severe outcomes of coronavirus disease 2019 (COVID-19) among elderly patients. This study was conducted to assess overweight and obesity in relation to risk of mortality, delirium, invasive mechanical ventilation (IMV) requirement during treatment, re-hospitalization, prolonged hospitalization, and ICU admission among elderly patients with COVID-19. Methods: This was a single-center prospective study that was done on 310 elderly patients with COVID-19 hospitalized in the intensive care unit (ICU). We collected data on demographic characteristics, laboratory parameters, nutritional status, blood pressure, comorbidities, medications, and types of mechanical ventilation at baseline. Patients were followed up during ICU admission and until 45 days after the first visit, and data on delirium incidence, mortality, need for a form of mechanical ventilation, discharge day from ICU and hospital, and re-hospitalization were recorded for each patient. Results: During the follow-up period, we recorded 190 deaths, 217 cases of delirium, and 35 patients who required IMV during treatment. After controlling for potential confounders, a significant association was found between obesity and delirium such that obese patients with COVID-19 had a 62% higher risk of delirium compared with normal-weight patients (HR: 1.62, 95% CI: 1.02-2.57). This association was not observed for overweight. In terms of other outcomes including ICU/45-day mortality, IMV therapy during treatment, re-hospitalization, prolonged hospitalization, and ICU admission, we found no significant association with overweight and obesity either before or after controlling for potential confounders. Conclusion: We found that obesity may be a risk factor for delirium among critically ill elderly patients with COVID-19.

Parallel Dysregulated Immune Response in Severe Forms of COVID-19 and Bacterial Sepsis via Single-Cell Transcriptome Sequencing.

Critically ill COVID-19 patients start developing single respiratory organ failure that often evolves into multiorgan failure. Understanding the immune mechanisms in severe forms of an infectious disease (either critical COVID-19 or bacterial septic shock) would help to achieve a better understanding of the patient's clinical trajectories and the success of potential therapies. We hypothesized that a dysregulated immune response manifested by the abnormal activation of innate and adaptive immunity might be present depending on the severity of the clinical presentation in both COVID-19 and bacterial sepsis. We found that critically ill COVID-19 patients demonstrated a different clinical endotype that resulted in an inflammatory dysregulation in mild forms of the disease. Mild cases (COVID-19 and bacterial non severe sepsis) showed significant differences in the expression levels of CD8 naïve T cells, CD4 naïve T cells, and CD4 memory T cells. On the other hand, in the severe forms of infection (critical COVID-19 and bacterial septic shock), patients shared immune patterns with upregulated single-cell transcriptome sequencing at the following levels: B cells, monocyte classical, CD4 and CD8 naïve T cells, and natural killers. In conclusion, we identified significant gene expression differences according to the etiology of the infection (COVID-19 or bacterial sepsis) in the mild forms; however, in the severe forms (critical COVID-19 and bacterial septic shock), patients tended to share some of the same immune profiles related to adaptive and innate immune response. Severe forms of the infections were similar independent of the etiology. Our findings might promote the implementation of co-adjuvant therapies and interventions to avoid the development of severe forms of disease that are associated with high mortality rates worldwide.

Efficacy and Safety of Garadacimab in Combination with Standard of Care Treatment in Patients with Severe COVID-19.

BACKGROUND: Garadacimab, a fully human IgG4 monoclonal antibody, inhibits the kallikrein-kinin pathway at a key initiator, activated coagulation factor XII (FXIIa), and may play a protective role in preventing the progression of COVID-19. This phase 2 study evaluated the efficacy and safety of garadacimab plus standard of care (SOC) versus placebo plus SOC in patients with severe COVID-19. METHODS: Patients hospitalised with COVID-19 were randomised (1:1) to a single intravenous dose of garadacimab (700 mg) plus SOC or placebo plus SOC. Co-primary endpoint was incidence of endotracheal intubation or death between randomisation and Day 28. All-cause mortality, safety and pharmacokinetic/pharmacodynamic parameters were assessed. RESULTS: No difference in incidence of tracheal intubation or death (p = 0.274) or all-cause mortality was observed (p = 0.382). Garadacimab was associated with a lower incidence of treatment-emergent adverse events (60.3% vs 67.8%) and fewer serious adverse events (34 vs 45 events) versus placebo. No garadacimab-related deaths or bleeding events were reported, including in the 45.9% (n = 28/61) of patients who received concomitant heparin. Prolonged activated partial thromboplastin time (aPTT), and increased coagulation factor XII (FXII) levels were observed with garadacimab versus placebo to Day 14, whilst FXIIa-mediated kallikrein activity (FXIIa-mKA) was suppressed to Day 28. CONCLUSION: In patients with severe COVID-19, garadacimab did not confer a clinical benefit over placebo. Transient aPTT prolongation and suppressed FXIIa-mKA showed target engagement of garadacimab that was not associated with bleeding events even with concomitant anticoagulant use. The safety profile of garadacimab was consistent with previous studies in patients with hereditary angioedema. GOV IDENTIFIER: NCT04409509. Date of registration: 28 May, 2020.