Factors associated with post-hospitalization dialysis dependence in ECMO patients who required continuous renal replacement therapy.

OBJECTIVE: This single center retrospective study aimed to describe the variables associated with outpatient dialysis dependence in extracorporeal membrane oxygenation (ECMO) patients who needed continuous renal replacement therapy (CRRT) for acute kidney injury (AKI) during their hospitalization. METHODS: Retrospective study of patients who required ECMO-CRRT. RESULTS: Between the years of 2016 and 2022, 202 patients required ECMO-CRRT. One hundred and six patients (52.5%) survived their hospitalization and were followed up for a median of 391 [133, 1005] days. Eighty-one patients (76.5%) recovered kidney function and were dialysis-free before hospital discharge. Twenty-five patients (23.5%) were hemodialysis-dependent after hospitalization. On multivariate regression analysis, hyperlipidemia (odds ratio, OR 6.08 [1.67-22]) and CRRT duration (OR 1.09 [1.03-1.15]) were associated with the need for dialysis post-hospitalization. In this group, 16 patients eventually became dialysis-free, after a median of 49 [34.7, 78.5] days. These patients had a higher median baseline glomerular filtration rate (GFR) compared to those who never recovered renal function (93 mL/min/1.73 m2 [82.4, 104.3] vs. 63.8 mL/min/1.73 m2 [37.9, 83], p = .009). Their follow-up GFR was lower compared to those who recovered renal function before hospital discharge; (87 mL/min/1.73 m2 [68.2, 98.9] vs. 99 mL/min/1.73 m2 [79, 118], p = .07). CONCLUSIONS: AKI requiring CRRT was associated with high mortality in patients receiving ECMO. Nonetheless, most ECMO survivors became dialysis-free before hospital discharge. Variables associated with the need for outpatient dialysis included hyperlipidemia and prolonged need for CRRT during hospitalization.

Outcomes of patients with COVID-19 requiring extracorporeal membrane oxygenation and continuous renal replacement therapy in the United States.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection is associated with significant morbidity and mortality. Some patients develop severe acute respiratory distress syndrome and kidney failure requiring the combination of extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). METHODS: Retrospective cohort study of 127 consecutive patients requiring combined ECMO and CRRT support in intensive care units at an ECMO center in Marietta, GA, United States. RESULTS: Sixty and 67 patients with and without COVID-19, respectively, required ECMO-CRRT support. After adjusting for confounding variables, patients with COVID-19 had increased mortality at 30 days (hazard ratio [HR], 5.19; 95% confidence interval [CI], 2.51-10.7; P<0.001) and 90 days (HR, 6.23; 95% CI, 2.60-14.9; P<0.001). CONCLUSIONS: In this retrospective study, patients with COVID-19 who required ECMO-CRRT had increased mortality when compared to patients without COVID-19.

Mechanically tuned 3 dimensional hydrogels support human mammary fibroblast growth and viability.

BACKGROUND: Carcinoma associated fibroblasts (CAFs or myofibroblasts) are activated fibroblasts which participate in breast tumor growth, angiogenesis, invasion, metastasis and therapy resistance. As such, recent efforts have been directed toward understanding the factors responsible for activation of the phenotype. In this study, we have investigated how changes in the mechanical stiffness of a 3D hydrogel alter the behavior and myofibroblast-like properties of human mammary fibroblasts (HMFs). RESULTS: Here, we utilized microbial transglutaminase (mTG) to mechanically tune the stiffness of gelatin hydrogels and used rheology to show that increasing concentrations mTG resulted in hydrogels with greater elastic moduli (G'). Upon encapsulation of HMFs in 200 (compliant), 300 (moderate) and 1100 Pa (stiff) mTG hydrogels, it was found that the HMFs remained viable and proliferated over the 7 day culture period. Specifically, rates of proliferation were greatest for HMFs in moderate hydrogels. Regarding morphology, HMFs in compliant and moderate hydrogels exhibited a spindle-like morphology while HMFs in stiff hydrogels exhibited a rounded morphology with several large cellular protrusions. Quantification of cell morphology revealed that HMFs cultured in all mTG hydrogels overall assumed a more elongated phenotype over time in culture; however, few significant differences in morphology were observed between HMFs in each of the hydrogel conditions. To determine whether matrix stiffness upregulated expression of ECM and myofibroblast markers, western blot was performed on HMFs in compliant, moderate and stiff hydrogels. It was found that ECM and myofibroblast proteins varied in expression during both the culture period and according to matrix stiffness with no clear correlation between matrix stiffness and a myofibroblast phenotype. Finally, TGF-ß levels were quantified in the conditioned media from HMFs in compliant, moderate and stiff hydrogels. TGF-ß was significantly greater for HMFs encapsulated in stiff hydrogels. CONCLUSIONS: Overall, these results show that while HMFs are viable and proliferate in mTG hydrogels, increasing matrix stiffness of mTG gelatin hydrogels doesn't support a robust myofibroblast phenotype from HMFs. These results have important implications for further understanding how modulating 3D matrix stiffness affects fibroblast morphology and activation into a myofibroblast phenotype.