Clinical and organizational factors associated with mortality during the peak of first COVID-19 wave: the global UNITE-COVID study

Purpose: To accommodate the unprecedented number of critically ill patients with pneumonia caused by coronavirus disease 2019 (COVID-19) expansion of the capacity of intensive care unit (ICU) to clinical areas not previously used for critical care was necessary. We describe the global burden of COVID-19 admissions and the clinical and organizational characteristics associated with outcomes in critically ill COVID-19 patients. Methods: Multicenter, international, point prevalence study, including adult patients with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) and a diagnosis of COVID-19 admitted to ICU between February 15th and May 15th, 2020. Results: 4994 patients from 280 ICUs in 46 countries were included. Included ICUs increased their total capacity from 4931 to 7630 beds, deploying personnel from other areas. Overall, 1986 (39.8%) patients were admitted to surge capacity beds. Invasive ventilation at admission was present in 2325 (46.5%) patients and was required during ICU stay in 85.8% of patients. 60-day mortality was 33.9% (IQR across units: 20%–50%) and ICU mortality 32.7%. Older age, invasive mechanical ventilation, and acute kidney injury (AKI) were associated with increased mortality. These associations were also confirmed specifically in mechanically ventilated patients. Admission to surge capacity beds was not associated with mortality, even after controlling for other factors. Conclusions: ICUs responded to the increase in COVID-19 patients by increasing bed availability and staff, admitting up to 40% of patients in surge capacity beds. Although mortality in this population was high, admission to a surge capacity bed was not associated with increased mortality. Older age, invasive mechanical ventilation, and AKI were identified as the strongest predictors of mortality

Co-infection and ICU-acquired infection in COIVD-19 ICU patients: a secondary analysis of the UNITE-COVID data set

Background: The COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients.Methods: This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson's Chi-squared and continuous variables by Mann-Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the "full" matching method.Results: Data were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO.Conclusions: In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)

Adipocytes IGFBP-2 expression in prepubertal obese children.

Aims of the study were to measure insulin-like growth factor-binding protein-2 (IGFBP-2) expression by abdominal subcutaneous adipocytes and to assess the relationship between IGFBP-2 expression, circulating IGFBP-2, obesity, and insulin sensitivity in obese children. Thirty-eight obese children were recruited. Insulin sensitivity was assessed by intravenous glucose tolerance test and body composition by total-body dual-energy X-ray absorptiometry. Serum free and total IGF-I, IGFBP-2, adiponectin, and leptin were measured. Relative quantification of IGFBP-2 mRNA by subcutaneous adipose tissue biopsies was obtained using real-time PCR. Circulating IGFBP-2 was positively associated with insulin sensitivity, in agreement with previous studies. IGFBP-2 expression was associated with fat mass percentage (r = 0.656; P < 0.02), insulin sensitivity (r = -0.604; P < 0.05), free IGF-I (r = 0.646; P < 0.05), and leptin (r = 0.603; P < 0.05), but not with circulating IGFBP-2 (r = 0.003, P = ns). The association between IGFBP-2 expression and adiposity (r = 0.648; P < 0.05) was independent of insulin sensitivity (covariate). In conclusion, circulating IGFBP-2 was positively associated with insulin sensitivity. IGFBP-2 was expressed by subcutaneous abdominal adipocytes of obese children and increased with adiposity, independently from the level of insulin sensitivity. IGFBP-2 expression may potentially be one of the local mechanisms used by adipocytes to limit further fat gain

Keratin-14 Expression in Pneumocytes as a Marker of Lung Regeneration/Repair during Diffuse Alveolar Damage

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Echocardiographic Quantification of Superior Vena Cava (SVC) Flow in Neonates: Pilot Study of Modified Technique

Ultrasound Superior Vena Cava (SVC) flow assessment is a common measure of systemic and cerebral perfusion, although accuracy is limited. The aim of this study was to evaluate whether any improvements in accuracy could be achieved by measuring stroke distance from the instantaneous mean velocity, rather than from peak velocity, and by directly tracing area from images obtained with a high frequency linear probe. Paired phase contrast magnetic resonance imaging (PCMRI) and ultrasound assessments of SVC flow were performed in a pilot cohort of 7 infants. Median postnatal age, corrected gestation and weight at scan were 7 (2-74) days, 34.8 (31.7-37.2) weeks 1870 (970-2660) g. Median interval between PCMRI and ultrasound scans was 0.3 (0.2-0.5) h. The methodology trialed here showed a better agreement with PCMRI (mean bias -8 mL/kg/min, LOA -25-+8 mL/kg/min), compared to both the original method reported by Kluckow et al. (mean bias + 42 mL/kg/min, LOA -53-+137 mL/kg/min), and our own prior adaptation (mean bias + 23 mL/kg/min, LOA -25-+71 mL/kg/min). Ultrasound assessment of SVC flow volume using the modifications described led to enhanced accuracy and decreased variability compared to prior techniques in a small cohort of premature infants

In Vivo Confocal Microscopy 1 Year after Autologous Cultured Limbal Stem Cell Grafts

PURPOSE: To correlate clinical, impression cytologic, and in vivo confocal microscopy findings on the corneal surface after cultured limbal stem cell transplantation. DESIGN: Prospective, interventional, noncomparative, masked case series. PARTICIPANTS: Thirteen patients with limbal stem cell deficiency after unilateral (9 eyes) or bilateral (2 eyes) chemical burn, liquid nitrogen injury (1 eye), or herpes simplex virus infection (1 eye). METHODS: Limbal cells were harvested from healthy or less affected eyes, cultured on 3T3 cells and fibrin glue, and transplanted to the patient's injured eye. Patients underwent clinical examination and impression cytologic examination of the central cornea before and 1 year after intervention. In vivo confocal microscopy scans were obtained in all corneal quadrants after 1 year. The interexamination agreement was established by calculation of the Cohen's \u3ba coefficient. MAIN OUTCOME MEASURES: Results of surgery were assessed considering clinical signs (successful: restoration of transparent, avascular, and stable corneal epithelium without neovascularization in central corneal surface; partially successful: recurrence of superficial neovascularization; failed: recurrent epithelial defects, pannus, and inflammation), phenotype of cells covering the corneal surface (conjunctivalized corneal surface: cytokeratin 12 [cK12]-negative and mucin 1 [MUC1]-positive cells; mixed epithelium: cK12-positive and MUC1-positive cells; corneal epithelium: cK12-positive and MUC1-negative cells), and cell morphologic features (corneal epithelium: multilayered polygonal and flat cells with hyperreflective nuclei; conjunctival epithelium: stratified cuboidal or polygonal cells, hyperreflective cytoplasm, and barely defined borders; epithelial transition: transition of epithelial cells from the cornea to the conjunctiva over the corneal surface). RESULTS: We found a moderate to substantial degree of concordance between confocal microscopy and clinical evaluation (\u3ba = 0.768) and between confocal microscopy and impression cytologic analysis (\u3ba = 0.629). Confocal microscopy showed that 46.2% of patients exhibited corneal epithelium in the central and peripheral cornea, 30.8% showed an irregular mixed corneal and conjunctival epithelium, and 23.0% showed conjunctival epithelium. Palisades of Vogt were absent in all (100.0%) patients, and the cornea-conjunctiva epithelial transition localized approximately 1 mm internally on the cornea. CONCLUSIONS: Confocal microscopy provides objective measures of the corneal epithelium and may significantly improve the evaluation of outcomes after cultured limbal stem cell graft

Accelerated corneal crosslinking to treat Acanthamoeba and Fusarium coinfection of the cornea

A 44-year-old man presented with Acanthamoeba and Fusarium coinfection keratitis. Fifteen years before, he had hyperopic laser in situ keratomileusis, and the coinfection was under the flap. The keratitis was nonresponsive to topical and systemic therapy; therefore, accelerated corneal crosslinking (CXL) with photoactivated riboflavin (photoactivated chromophore for keratitis) was performed to prevent a corneal perforation. After the treatment, there was unexpected rapid corneal melting with subsequent perforation. A reconstructive penetrating keratoplasty was promptly performed and was effective in resolving the coinfection. The current protocol for the application of photoactivated riboflavin CXL should be improved, and clinical criteria for applying this technique are required. Photoactivated riboflavin CXL might be an effective alternative to conventional agents in some cases of fungal and/or amoeba keratitis. However, in cases of deep stromal infections on previous surgically treated anterior stroma, it should not be considered a viable option. \ua9 2018 ASCRS and ESCR