Renal Recovery in Critically Ill Adult Patients Treated with Veno-Venous Or Veno-Arterial Extra Corporeal Membrane Oxygenation: a Retrospective Cohort Analysis.

INTRODUCTION: Patients on extracorporeal membrane oxygenator (ECMO) therapy are critically ill and often develop acute kidney injury (AKI) during hospitalisation. Little is known about the association of exposure to and the effect of the type of ECMO and extent of renal recovery after AKI development. AIM OF THE STUDY: In patients who developed AKI, renal recovery was characterised as complete, partial or dialysis-dependent at the time of hospital discharge in both the Veno-Arterial (VA) and Veno-Venous (VV) ECMO treatment groups. MATERIAL AND METHODS: The study consisted of a single-centre retrospective cohort that includes all adult patients (n=125) who received ECMO treatment at a tertiary academic medical centre between 2015 to 2019. Data on demographics, type of ECMO circuit, comorbidities, exposure to nephrotoxic factors and receipt of renal replacement therapy (RRT) were collected as a part of the analysis. Acute Kidney Injury Network (AKIN) criteria were used for the diagnosis and classification of AKI. Group differences were assessed using Fisher's exact tests for categorical data and independent t-tests for continuous outcomes. RESULTS: Sixty-four patients received VA ECMO, and 58 received VV ECMO. AKI developed in 58(91%) in the VA ECMO group and 51 (88%) in the VV ECMO group (p=0.77). RRT was prescribed in significantly higher numbers in the VV group 38 (75%) compared to the VA group 27 (47%) (p=0.0035). At the time of discharge, AKI recovery rate in the VA group consisted of 15 (26%) complete recovery and 5 (9%) partial recovery; 1 (2%) remained dialysis-dependent. In the VV group, 22 (43%) had complete recovery (p=0.07), 3(6%) had partial recovery (p=0.72), and 1 (2%) was dialysis-dependent (p>0.99). In-hospital mortality was 64% in the VA group and 49% in the VV group (p=0.13). CONCLUSIONS: Renal outcomes in critically ill patients who develop AKI are not associated with the type of ECMO used. This serves as preliminary data for future studies in the area.

Renal replacement treatment initiation with twice-weekly versus thrice-weekly haemodialysis in patients with incident dialysis-dependent kidney disease: rationale and design of the TWOPLUS pilot clinical trial.

INTRODUCTION: The optimal haemodialysis (HD) prescription-frequency and dose-for patients with incident dialysis-dependent kidney disease (DDKD) and substantial residual kidney function (RKF)-that is, renal urea clearance ≥2 mL/min/1.73 m2 and urine volume ≥500 mL/day-is not known. The aim of the present study is to test the feasibility and safety of a simple, reliable prescription of incremental HD in patients with incident DDKD and RKF. METHODS AND ANALYSIS: This parallel-group, open-label randomised pilot trial will enrol 50 patients from 14 outpatient dialysis units. Participants will be randomised (1:1) to receive twice-weekly HD with adjuvant pharmacological therapy for 6 weeks followed by thrice-weekly HD (incremental HD group) or outright thrice-weekly HD (standard HD group). Age ≥18 years, chronic kidney disease progressing to DDKD and urine output ≥500 mL/day are key inclusion criteria; patients with left ventricular ejection fraction <30% and acute kidney injury requiring dialysis will be excluded. Adjuvant pharmacological therapy (ie, effective diuretic regimen, patiromer and sodium bicarbonate) will complement twice-weekly HD. The primary feasibility end points are recruitment rate, adherence to the assigned HD regimen, adherence to serial timed urine collections and treatment contamination. Incidence rate of clinically significant volume overload and metabolic imbalances in the first 3 months after randomisation will be used to assess intervention safety. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Institutional Review Board of Wake Forest School of Medicine in North Carolina, USA. Patient recruitment began on 14 June 2019, was paused between 13 March 2020 and 31 May 2020 due to COVID-19 pandemic, resumed on 01 June 2020 and will last until the required sample size has been attained. Participants will be followed in usual care fashion for a minimum of 6 months from last individual enrolled. All regulations and measures of ethics and confidentiality are handled in accordance with the Declaration of Helsinki. TRIAL REGISTRATION NUMBER: NCT03740048; Pre-results.

Frequency of Transition From Stage A to Stage B Heart Failure After Initiating Potentially Cardiotoxic Chemotherapy.

OBJECTIVES: This study sought to determine the prevalence of American Heart Association/American College of Cardiology Foundation (AHA/ACCF) heart failure (HF) stages after potentially cardiotoxic chemotherapy was initiated. BACKGROUND: For individuals receiving potentially cardiotoxic chemotherapy, the frequency of transitioning from Stage A to more advanced HF stages is not well described. METHODS: In 143 Stage A HF patients with breast cancer, lymphoma and leukemia, renal cell carcinoma, or sarcoma prior to and then at 3, 6, and 12 to 24 months after potentially cardiotoxic chemotherapy was initiated, we obtained blinded cardiac magnetic resonance measurements of left ventricular ejection fraction (LVEF). RESULTS: Three months after potentially cardiotoxic chemotherapy was initiated, 18.9% of patients transitioned from Stage A to Stage B HF. A total of 83% and 80% of patients with Stage A HF at 3 months, respectively, exhibited Stage A HF at 6 and 12 to 24 months; 68% and 56% of those with Stage B HF at 3 months, respectively, exhibited Stage B HF at 6 and 12 to 24 months (p < 0.0001 and p = 0.026, respectively). CONCLUSIONS: Transitioning from Stage A to Stage B or remaining in Stage A HF 3 months after potentially cardiotoxic chemotherapy was initiated relates to longer-term (6 to 24 months post-treatment) assessments of HF stage.

Pharmacologic Treatment of Hypertensive Urgency in the Outpatient Setting: A Systematic Review.

BACKGROUND: Hypertensive urgency (HU), defined as acute severe uncontrolled hypertension without end-organ damage, is a common condition. Despite its association with long-term morbidity and mortality, guidance regarding immediate management is sparse. Our objective was to summarize the evidence examining the effects of antihypertensive medications to treat. METHODS: We searched the PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Cochrane Database of Systematic Reviews, Web of Science, Google Scholar, and Embase through May 2016. STUDY SELECTION: We evaluated prospective controlled clinical trials, case-control studies, and cohort studies of HU in emergency room (ER) or clinic settings. We initially identified 11,223 published articles. We reviewed 10,748 titles and abstracts and identified 538 eligible articles. We assessed the full text for eligibility and included 31 articles written in English that were clinical trials or cohort studies and provided blood pressure data within 48 h of treatment. Studies were appraised for risk of bias using components recommended by the Cochrane Collaboration. The main outcome measured was blood pressure change with antihypertensive medications. Since studies were too diverse both clinically and methodologically to combine in a meta-analysis, tabular data and a narrative synthesis of studies are presented. RESULTS: We identified only 20 double-blind randomized controlled trials and 12 cohort studies, with 262 participants in prospective controlled trials. However, we could not pool the results of studies. In addition, comorbidities and their potential contribution to long-term treatment of these subjects were not adequately addressed in any of the reviewed studies. CONCLUSIONS: Longitudinal studies are still needed to determine how best to lower blood pressure in patients with HU. Longer-term management of individuals who have experienced HU continues to be an area requiring further study, especially as applicable to care from the generalist.

The effect of pharmaceuticals on the nanoscale structure of PEO-PPO-PEO micelles.

We present results on the effects of various hydrophobic drugs and additives on the micellar structure of Pluronic F127 solutions. Small-angle neutron scattering experiments on 5wt% F127 solutions were used to measure micelle core size (R(1)), micelle corona size (R(2)), intermicellar interaction distance (R(int)), polydispersity (sigma), and aggregation number (N(agg)); dynamic light scattering was used to measure critical micelle concentration (CMC); and ultraviolet spectroscopy was used to measure drug solubility and apparent micelle-water partition coefficient (K(mw)). The core and corona size were found to generally increase in the presence of the drugs, as did R(int). Both sigma and N(agg) were found to decrease in the presence of most of the drugs, and the CMC was found to vary considerably with no clear correlation. A design of experiments (DOE) approach was used to analyze the results and build empirical correlations. All of the parameters from the SANS experiments were found to depend strongly on drug solubility, with a weak dependence on K(mw) in most cases. The aggregation number, however, was found to depend strongly on both K(mw) and solubility. The correlations can be used to roughly predict the structural parameters of F127 micelles for other hydrophobic drugs.