Purpose The outcomes of patients requiring invasive mechanical ventilation for COVID-19 remain poorly defined. We sought to determine clinical characteristics and outcomes of patients with COVID-19 managed with invasive mechanical ventilation in an appropriately resourced US health care system. Methods Outcomes of COVID-19 infected patients requiring mechanical ventilation treated within the Inova Health System between March 5, 2020 and April 26, 2020 were evaluated through an electronic medical record review. Results 1023 COVID-19 positive patients were admitted to the Inova Health System during the study period. Of these, 164 (16.0%) were managed with invasive mechanical ventilation. All patients were followed to definitive disposition. 70/164 patients (42.7%) had died and 94/164 (57.3%) were still alive. Deceased patients were older (median age of 66 vs. 55, p <0.0001) and had a higher initial d-dimer (2.22 vs. 1.31, p = 0.005) and peak ferritin levels (2998 vs. 2077, p = 0.016) compared to survivors. 84.3% of patients over 70 years old died in the hospital. Conversely, 67.4% of patients age 70 or younger survived to hospital discharge. Younger age, non-Caucasian race and treatment at a tertiary care center were all associated with survivor status. Conclusion Mortality of patients with COVID-19 requiring invasive mechanical ventilation is high, with particularly daunting mortality seen in patients of advanced age, even in a well-resourced health care system. A substantial proportion of patients requiring invasive mechanical ventilation were not of advanced age, and this group had a reasonable chance for recovery.

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Postnatal development of the mammary gland requires interactions between the epithelial and stromal compartments, which regulate actions of hormones and growth factors. IGF-I is expressed in both epithelial and stromal compartments during postnatal development of the mammary gland. However, little is known about how local expression of IGF-I in epithelium or stroma regulates mammary growth and differentiation during puberty and pregnancy-induced alveolar development. The goal of this study was to investigate the mechanisms of IGF-I actions in the postnatal mammary gland and test the hypothesis that IGF-I expressed in stromal and epithelial compartments has distinct functions. We established mouse lines with inactivation of the igf1 gene in mammary epithelium by crossing igf1/loxP mice with mouse lines expressing Cre recombinase under the control of either the mouse mammary tumor virus long-terminal repeat or the whey acidic protein gene promoter. Epithelial-specific loss of IGF-I during pubertal growth resulted in deficits in ductal branching. In contrast, heterozygous reduction of IGF-I throughout the gland decreased expression of cyclins A2 and B1 during pubertal growth and resulted in alterations in proliferation of the alveolar epithelium and milk protein levels during pregnancy-induced differentiation. Reduction in epithelial IGF-I at either of these stages had no effect on these indices. Taken together, our results support distinct roles for IGF-I expressed in epithelial and stromal compartments in mediating growth of the postnatal mammary gland.

Purpose: The outcomes of patients requiring invasive mechanical ventilation for COVID-19 remain poorly defined. We sought to determine clinical characteristics and outcomes of patients with COVID-19 managed with invasive mechanical ventilation in an appropriately resourced US health care system. Methods: Outcomes of COVID-19 infected patients requiring mechanical ventilation treated within the Inova Health System between March 5, 2020 and April 26, 2020 were evaluated through an electronic medical record review. Results: 1023 COVID-19 positive patients were admitted to the Inova Health System during the study period. Of these, 165 (16.1%) were managed with invasive mechanical ventilation. At the time of data censoring, 63/165 patients (38.1%) had died and 102/165 (61.8%) were still alive. Of the surviving 102 patients, 17 (10.3%) remained on mechanical ventilation, 51 (30.9%) were extubated but remained hospitalized, and 34 (20.6%) had been discharged. Deceased patients were older (median age of 66 vs. 55, p <0.0001). 75.7% of patients over 70 years old had died at the time of data analysis. Conversely, 71.2% of patients age 70 or younger were still alive at the time of data analysis. Younger age, non-Caucasian race and treatment at a tertiary care center were all associated with survivor status. Conclusion: Mortality of patients with COVID-19 requiring invasive mechanical ventilation is high, with particularly daunting mortality seen in patients of advanced age, even in a well-resourced health care system. A substantial proportion of patients requiring invasive mechanical ventilation were not of advanced age, and this group had a reasonable chance for recovery.

Background The nutrition needs of patients requiring extracorporeal membrane oxygenation (ECMO) have not been established in the literature. The purpose of this study is to investigate if current protein recommendations are adequate to achieve nitrogen equilibrium in patients on venovenous ECMO (VV ECMO). Methods Patients aged ≥18 years on VV ECMO admitted November 2016 through January 2018 with a documented nitrogen balance (NB) study were included. Patients were stratified by body mass index (BMI) into obese (BMI ≥ 30 kg/m2) and nonobese (BMI < 30 kg/m2) categories for analysis. Results After exclusions, 55 NB studies in 29 patients were analyzed. Twelve nonobese patients received a median of 2.1 g protein/kg actual body weight (ABW) (interquartile range [IQR]: 1.7–2.5), and median NB was −2.2 g/d (IQR: −7.4 to 2.8). In 17 obese patients, median protein delivery of 2 g protein/kg ideal body weight (IBW) (IQR: 1.7–2.5) achieved a median NB of −7.3 g/d (IQR: −12.6 to −2.8). Obese patients exhibited greater urinary urea nitrogen excretion than nonobese patients did (24.6 vs 17.6 g/d, P < 0.0001). Conclusions Obese and nonobese patients undergoing VV ECMO may require more protein than is currently recommended for critical illness. Monitoring nutrition delivery and serial NB to assess prescription adequacy should be incorporated into routine patient care. Further research is needed to confirm these findings and create specific guidelines for patients on VV ECMO.

Qamar ahmad ,* adam Green , † abhimanyu Chandel , ‡ James lantry, § mehul desai, § Jikerkhoun simou, § erik osborn , § ramesh sinGh , ¶ nitin Puri, † PatriCk moran , ¶ǁ heidi dalton , § alan sPeir , ¶ and ChristoPher kinG §The impact of the duration of noninvasive respiratory support (RS) including high-flow nasal cannula and noninvasive ventilation before the initiation of extracorporeal membrane oxygenation (ECMO) is unknown. We reviewed data of patients with coronavirus disease 2019 (COVID-19) treated with V-V ECMO at two high-volume tertiary care centers. Survival analysis was used to compare the effect of duration of RS on liberation from ECMO. A total of 78 patients required ECMO and the median duration of RS and invasive mechanical ventilation (IMV) before ECMO was 2 days (interquartile range [IQR]: 0, 6) and 2.5 days (IQR: 1, 5), respectively. The median duration of ECMO support was 24 days (IQR: 11, 73) and 59.0% (N = 46) remained alive at the time of censure. Patients that received RS for ≥3 days were significantly less likely to be liberated from ECMO (HR: 0.46; 95% CI: 0.26-0.83), IMV (HR: 0.42; 95% CI: 0.20-0.89) or be discharged from the hospital (HR: 0.52; 95% CI: 0.27-0.99) compared to patients that received RS for <3 days. There was no difference in hospital mortality between the groups (HR: 1.12; 95% CI: 0.56-2.26). These relationships persisted after adjustment for age, gender, and duration of IMV. Prolonged duration of RS before ECMO may result in lung injury and worse subsequent outcomes.

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