The kidney requires a large number of mitochondria to remove waste from the blood and regulate fluid and electrolyte balance. Mitochondria provide the energy to drive these important functions and can adapt to different metabolic conditions through a number of signalling pathways (for example, mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) pathways) that activate the transcriptional co-activator peroxisome proliferator-activated receptor-γ co-activator 1α (PGC1α), and by balancing mitochondrial dynamics and energetics to maintain mitochondrial homeostasis. Mitochondrial dysfunction leads to a decrease in ATP production, alterations in cellular functions and structure, and the loss of renal function. Persistent mitochondrial dysfunction has a role in the early stages and progression of renal diseases, such as acute kidney injury (AKI) and diabetic nephropathy, as it disrupts mitochondrial homeostasis and thus normal kidney function. Improving mitochondrial homeostasis and function has the potential to restore renal function, and administering compounds that stimulate mitochondrial biogenesis can restore mitochondrial and renal function in mouse models of AKI and diabetes mellitus. Furthermore, inhibiting the fission protein dynamin 1-like protein (DRP1) might ameliorate ischaemic renal injury by blocking mitochondrial fission.

The United States is in an acceleration phase of the COVID-19 pandemic. Currently there is no known effective therapy or vaccine for treatment of SARS-CoV-2, highlighting urgency around identifying effective therapies. Objective: The purpose of this study was to evaluate the role of hydroxychloroquine therapy alone and in combination with azithromycin in hospitalized patients positive for COVID-19. Design: Multi-center retrospective observational study. Setting: The Henry Ford Health System (HFHS) in Southeast Michigan: large six hospital integrated health system; the largest of hospitals is an 802-bed quaternary academic teaching hospital in urban Detroit, Michigan. Participants: Consecutive patients hospitalized with a COVID-related admission in the health system from March 10, 2020 to May 2, 2020 were included. Only the first admission was included for patients with multiple admissions. All patients evaluated were 18 years of age and older and were treated as inpatients for at least 48 h unless expired within 24 h. Exposure: Receipt of hydroxychloroquine alone, hydroxychloroquine in combination with azithromycin, azithromycin alone, or neither. Main outcome: The primary outcome was in-hospital mortality. Results: Of 2,541 patients, with a median total hospitalization time of 6 days (IQR: 4-10 days), median age was 64 years (IQR:53-76 years), 51% male, 56% African American, with median time to follow-up of 28.5 days (IQR:3-53). Overall in-hospital mortality was 18.1% (95% CI:16.6%-19.7%); by treatment: hydroxychloroquine + azithromycin, 157/783 (20.1% [95% CI: 17.3%-23.0%]), hydroxychloroquine alone, 162/1202 (13.5% [95% CI: 11.6%-15.5%]), azithromycin alone, 33/147 (22.4% [95% CI: 16.0%-30.1%]), and neither drug, 108/409 (26.4% [95% CI: 22.2%-31.0%]). Primary cause of mortality was respiratory failure (88%); no patient had documented torsades de pointes. From Cox regression modeling, predictors of mortality were age>65 years (HR:2.6 [95% CI:1.9-3.3]), white race (HR:1.7 [95% CI:1.4-2.1]), CKD (HR:1.7 [95%CI:1.4-2.1]), reduced O2 saturation level on admission (HR:1.5 [95%CI:1.1-2.1]), and ventilator use during admission (HR: 2.2 [95%CI:1.4-3.3]). Hydroxychloroquine provided a 66% hazard ratio reduction, and hydroxychloroquine + azithromycin 71% compared to neither treatment (p < 0.001). Conclusions and relevance: In this multi-hospital assessment, when controlling for COVID-19 risk factors, treatment with hydroxychloroquine alone and in combination with azithromycin was associated with reduction in COVID-19 associated mortality. Prospective trials are needed to examine this impact.

1In this multi-center quasi-experimental study of 213 patients, we demonstrate early short course 2 of methylprednisolone in moderate to severe COVID-19 patients reduced the composite endpoint 3 of escalation of care from ward to ICU, new requirement for mechanical ventilation, and 4 mortality. 5Abstract 1

Background There is no proven antiviral or immunomodulatory therapy for COVID-19. The disease progression associated with the pro-inflammatory host response prompted us to examine the role of early corticosteroid therapy in patients with moderate to severe COVID-19. Methods We conducted a single pre-test, single post-test quasi-experiment in a multi-center health system in Michigan from March 12 to March 27, 2020. Adult patients with confirmed moderate to severe COVID were included. A protocol was implemented on March 20, 2020 using early, short-course, methylprednisolone 0.5 to 1 mg/kg/day divided in 2 intravenous doses for 3 days. Outcomes of standard of care (SOC) and early corticosteroid groups were evaluated, with a primary composite endpoint of escalation of care from ward to ICU, new requirement for mechanical ventilation, and mortality. All patients had at least 14 days of follow-up. Results We analyzed 213 eligible subjects, 81 (38%) and 132 (62%) in SOC and early corticosteroid groups, respectively.The composite endpoint occurred at a significantly lower rate in the early corticosteroid group (34.9% vs. 54.3%, p=0.005). This treatment effect was observed within each individual component of the composite endpoint. Significant reduction in median hospital length of stay was also observed in the early corticosteroid group (8 vs. 5 days, p &lt; 0.001). Multivariate regression analysis demonstrated an independent reduction in the composite endpoint at 14-days controlling for other factors (aOR: 0.41; 95% CI [0.22 – 0.77]). Conclusion An early short course of methylprednisolone in patients with moderate to severe COVID-19 reduced escalation of care and improved clinical outcomes.

To characterize CT-ndings of COVID-19 pneumonia and their value in diagnosis and outcome prediction. METHODS Chest CTs of 182 patients with a con rmed diagnosis of COVID-19 infection by RT-PCR were evaluated for the presence of CT-abnormalities and their frequency. Regarding the patient outcome each patient was categorized in 5 progressive stages and the duration of hospitalization was determined. Regression analysis was performed to nd which CT ndings are predictive for patient outcome and to assess prognostic factors for the hospitalization duration. RESULTS Multivariate statistical analysis con rmed a higher age (OR= 1.023, p= 0.025), a higher total visual severity score (OR= 1.038, p= 0.002) and the presence of crazy paving (OR= 2.160, p= 0.034) as predictive parameters for patient outcome. A higher total visual severity score (+ 0.134 days; p= 0.012) and the presence of pleural effusion (+ 13.985 days, p= 0.005) were predictive parameters for a longer hospitalization duration. CONCLUSIONS An increasing percentage of lung opacity as well as the presence of crazy paving and a higher age are associated with a worse patient outcome. The presence of a higher total visual severity score and pleural effusion are signi cant predictors for a longer hospitalization duration.

No abstract

A recurring source of contention between clinicians and radiologists continues to be examination appropriateness when imaging pregnant patients. With the multitude of references on potential radiation risks to the fetus, radiologists tend to be cautious and hesitant about exposing the fetus to radiation. This tendency is often interpreted by referring physicians as intrusion into and delay in the care of their patients. The risk burden of radiation exposure to the fetus has to be carefully weighed against the benefits of obtaining a critical diagnosis quickly and using a single tailored imaging study. In general, there is lower than expected awareness of radiation risks to the fetus from imaging pregnant patients. Modalities that do not use ionizing radiation, such as ultrasonography and magnetic resonance imaging, should be the preferred examinations for evaluating an acute condition in a pregnant patient. However, no examination should be withheld when an important clinical diagnosis is under consideration. Exposure to ionizing radiation may be unavoidable, but there is no evidence to suggest that the risk to the fetus after a single imaging study and an interventional procedure is significant. All efforts should be made to minimize the exposure, with consideration of the risk versus benefit for a given clinical scenario.

No abstract