COVID-19-associated acute kidney injury patients treated with renal replacement therapy in the intensive care unit: A multicenter study in São Paulo, Brazil

Introduction Multicenter studies involving patients with acute kidney injury (AKI) associated with the disease caused by the new coronavirus (COVID-19) and treated with renal replacement therapy (RRT) in developing countries are scarce. The objectives of this study were to evaluate the demographic profile, clinical picture, risk factors for mortality, and outcomes of critically ill patients with AKI requiring dialysis (AKI-RRT) and with COVID-19 in the megalopolis of São Paulo, Brazil. Methods This multicenter, retrospective, observational study was conducted in the intensive care units of 13 public and private hospitals in the metropolitan region of the municipality of São Paulo. Patients hospitalized in an intensive care unit, aged ≥ 18 years, and treated with RRT due to COVID-19-associated AKI were included. Results The study group consisted of 375 patients (age 64.1 years, 68.8% male). Most (62.1%) had two or more comorbidities: 68.8%, arterial hypertension; 45.3%, diabetes; 36.3%, anemia; 30.9%, obesity; 18.7%, chronic kidney disease; 15.7%, coronary artery disease; 10.4%, heart failure; and 8.5%, chronic obstructive pulmonary disease. Death occurred in 72.5% of the study population (272 patients). Among the 103 survivors, 22.3% (23 patients) were discharged on RRT. In a multiple regression analysis, the independent factors associated with death were the number of organ dysfunctions at admission and RRT efficiency. Conclusion AKI-RRT associated with COVID-19 occurred in patients with an elevated burden of comorbidities and was associated with high mortality (72.5%). The number of organ dysfunctions during hospitalization and RRT efficiency were independent factors associated with mortality. A meaningful portion of survivors was discharged while dependent on RRT (22.3%).

Non-linear and Interaction Analyses of Biomarkers for Organ Dysfunctions as Predictive Markers for Sepsis: A Nationwide Retrospective Study

The Sequential Organ Failure Assessment (SOFA) score is predominantly used to assess the severity of organ dysfunction in sepsis. However, differences in prognostic value between SOFA subscores have not been sufficiently evaluated. This retrospective observational study used a large-scale database containing about 30 million patients. Among them, we included 38,869 adult patients with sepsis from 2006 to 2019. The cardiovascular and neurological subscores were calculated by a modified method. Associations between the biomarkers of the SOFA components and mortality were examined using restricted cubic spline analyses, which showed that an increase in the total modified SOFA score was linearly associated with increased mortality. However, the prognostic association of subscores varied widely: platelet count showed a J-shaped association, creatinine showed an inverted J-shaped association, and bilirubin showed only a weak association. We also evaluated interaction effects on mortality between an increase of one subscore and another. The joint odds ratios on mortality of two modified SOFA subscores were synergistically increased compared to the sum of the single odds ratios, especially in cardiovascular-neurological, coagulation-hepatic, and renal-hepatic combinations. In conclusion, total modified SOFA score was associated with increased mortality despite the varied prognostic associations of the subscores, possibly because interactions between subscores synergistically enhanced prognostic accuracy.

Preeclampsia: From Etiopathology to Organ Dysfunction

Preeclampsia is a hypertensive disorder of pregnancy affecting 6–12% of the population. There are various risk factors for the development of preeclampsia, ranging from advanced maternal age to genetics. The proposed etiologies for preeclampsia are abnormal placentation, immunological intolerance, endothelial damage, and genetic inheritance. The pathogenesis includes endothelial activation and dysfunction leading to vasospasm. Preeclampsia is divided into two stages: asymptomatic and symptomatic stages. Preeclampsia causes multiple organ involvement, namely central nervous system, respiratory, cardiovascular, hematological dysfunction, HELLP (hemolysis elevated liver enzymes, low platelets) syndrome, endocrine, renal, hepatic, and uteroplacental dysfunction. These organ dysfunctions increase morbidity and mortality in preeclamptic pregnant patients.

Alcohol withdrawal syndrome in ICU patients: Clinical features, management, and outcome predictors

Background Alcohol withdrawal syndrome (AWS) is a common condition in hospitalized patients, yet its epidemiology in the ICU remains poorly characterized. Methods Retrospective cohort of patients admitted to the Nantes University Hospital ICU between January 1, 2017, and December 31, 2019, and coded for AWS using ICD-10 criteria. The objective of the study was to identify factors associated with complicated hospital stay defined as ICU length of stay ≥7 days or hospital mortality. Results Among 5,641 patients admitted to the ICU during the study period, 246 (4.4%) were coded as having AWS. Among them, 42 had exclusion criteria and 204 were included in the study. The three main reasons for ICU admission were sepsis (29.9%), altered consciousness (29.4%), and seizures (24%). At ICU admission, median Cushman’s score was 6 [4–9] and median SOFA score was 3 [2–6]. Delirium tremens occurred in half the patients, seizures in one fifth and pneumonia in one third. Overall, 48% of patients developed complicated hospital stay, of whom 92.8% stayed in the ICU for ≥7 days, 36.7% received MV for ≥7 days, and 16.3% died during hospital stay. By multivariable analysis, two factors were associated with complicated hospital stay: a higher number of organ dysfunctions at ICU admission was associated with a higher risk of complicated hospital stay (OR, 1.18; 95CI, 1.05–1.32, P = 0.005), whereas ICU admission for seizures was associated with a lower risk of complicated hospital stay (OR, 0.14; 95%CI, 0.026–0.80; P = 0.026). Conclusions AWS in ICU patients chiefly affects young adults and is often associated with additional factors such as sepsis, trauma, or surgery. Half the patients experienced an extended ICU stay or death during the hospital stay. The likelihood of developing complicated hospital stay relied on the reason for ICU admission and the number of organ dysfunctions at ICU admission.

Sepsis-Induced Myocardial Dysfunction in Pediatric Septic Shock: Prevalence, Predictors, and Outcome—A Prospective Observational Study

There is a paucity of literature on the prevalence, predictors, prognostic markers, and outcomes of sepsis-induced myocardial dysfunction (SMD) in pediatric septic shock. The objectives of our study were to estimate the prevalence of SMD in pediatric septic shock by point-of-care functional echocardiography (POCFE) and to study the association of SMD with severity of illness, organ dysfunctions, and outcomes. This prospective, observational study was conducted over a period of 1 year (from July 2018 to July 2019) in a 12-bed, tertiary pediatric intensive care unit (PICU) of an academic and referral hospital in South India. Children presenting with septic shock were enrolled in the study. POCFE was done within 6 hours of PICU admission and patients were categorized as having SMD based on POCFE findings. The prevalence of SMD (left ventricle ± right ventricle) was 32% (32/100). More than half of the children (54.5%) died in SMD group, whereas only 7.5% died in non-SMD group (p < 0.001). SMD was associated with higher organ dysfunctions, worse patient outcomes, and was found to be an independent predictor of mortality. The median lactate levels were higher in SMD group (3.15 [2.7, 5] vs. 2 [1.3, 2.7], p < 0.001) as compared with non-SMD group. We observed significantly lower median lactate clearance at 6 hours in SMD than non-SMD (30.0% [−14.44, 44.22] vs. 59.8% [45.83, 71.43], p < 0.001). Lactate levels at 6 hours with a threshold of 2.4 mmol/L was a good predictor of SMD with sensitivity and specificity of 73 and 80%, respectively. SMD is not an uncommon entity in children with septic shock. SMD was associated with worse patient outcomes, organ dysfunction, and mortality. Serum lactate trends may predict SMD and can be used as prognosticate markers as well.

Effects of Lipoic Acid on Ischemia-Reperfusion Injury

Ischemia-reperfusion (I/R) injury often occurred in some pathologies and surgeries. I/R injury not only harmed to physiological functions of corresponding organ and tissue but also induced multiple tissue or organ dysfunctions (even these in distant locations). Although the reperfusion of blood attenuated I/R injury to a certain degree, the risk of secondary damages was difficult to be controlled and it even caused failures of these tissues and organs. Lipoic acid (LA), as an endogenous active substance and a functional agent in food, owns better safety and effects in our body (e.g., enhancing antioxidant activity, improving cognition and dementia, controlling weight, and preventing multiple sclerosis, diabetes complication, and cancer). The literature searching was conducted in PubMed, Embase, Cochrane Library, Web of Science, and SCOPUS from inception to 20 May 2021. It had showed that endogenous LA was exhausted in the process of I/R, which further aggravated I/R injury. Thus, supplements with LA timely (especially pretreatments) may be the prospective way to prevent I/R injury. Recently, studies had demonstrated that LA supplements significantly attenuated I/R injuries of many organs, though clinic investigations were short at present. Hence, it was urgent to summarize these progresses about the effects of LA on different I/R organs as well as the potential mechanisms, which would enlighten further investigations and prepare for clinic applications in the future.

Deciphering the role of the Pancreatic Secretome in Covid-19 associated Multi-Organ Dysfunctions

Emerging evidence indicates an intricate relationship between the SARS-CoV-2 infection and Multi-Organ Dysfunctions (MODs). Here, we have investigated the role of the Secretome of the SARS-CoV-2 infected pancreas and mechanistically linked it with the multi-organ dysfunction using the scRNA-seq analysis. We found that acinar-specific PRSS2, REG3A, REG1A, SPINK1, and ductal-specific SPP1, MMP7 genes are upregulated in alpha, beta, delta, and mesenchyme cells. Using extensive documented experimental evidence, we validated the association of upregulated pancreatic Secretome with coagulation cascade, complement activation, renin angiotensinogen system dysregulation, endothelial cell injury and thrombosis, immune system dysregulation, and fibrosis. Our finding suggests the influence of upregulated Secretome on multi-organ systems such as Nervous, Cardiovascular, Immune, Digestive, and Urogenital systems. In addition, we report that the secretory proteins IL1B, AGT, ALB, SPP1, CRP, SERPINA1, C3, TFRC, TNFSF10, and MIF are associated with diverse diseases. Thus, suggest the role of the pancreatic Secretome in SARS-CoV-2 associated MODs.

Hearing loss, tinnitus and vertigo among pediatric patients with COVID-19 infections: a review

Coronavirus disease 2019(COVID-19) is a rapidly spreading contagious respiratory disease caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) which manifests a plethora of health concerns. It may manifest with a wide range of clinical symptoms from no symptoms to respiratory failure and even multi-organ dysfunctions. The COVID-19 infection may present with otological manifestations such as hearing loss, tinnitus, vertigo, and otalgia. The otological manifestations may be due to the involvement of the eustachian tube and cochlea by COVID-19 infections. The damaging effect of the COVID-19 infection on the inner ear is a new finding which is yet to be explored. Pure tone audiometry and impedance audiometry are two important investigations for auditory assessment among pediatric patients with COVID-19 infection. Although hearing loss, tinnitus and vertigo are not common as fever and cough in COVID-19 patients, however, auditory-vestibular symptoms significantly affect the quality of life. Additionally, the anxiety associated with COVID-19 infections may attribute to aggravation of otoneurological symptoms like tinnitus. However, these otoneurological manifestations like hearing loss will affect the speech of the pediatric patients and result in morbid life in the current COVID-19 pandemic. Clinicians or pediatricians should be aware of the otoneurological manifestation in pediatric COVID-19 patients for early identification and management. This review article discusses the details of this epidemiology, etiopathology, assessment, and management of hearing loss, tinnitus, and vertigo among COVID-19 pediatric patients.