Renal AAV2-Mediated Overexpression of Long Non-Coding RNA H19 Attenuates Ischemic Acute Kidney Injury Through Sponging of microRNA-30a-5p

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Pain,Function, and Satisfaction After Total Knee Arthroplasty,with or Without Bariatric Surgery

Background

The impact of obesity on patient-reported outcome (PRO) after total knee arthroplasty (TKA) surgery has demonstrated varying results. We evaluated knee pain, Activity in Daily Life function (ADL), and satisfaction after TKA surgery in patients with and without prior bariatric surgery (BS).

Methods

Scandinavian Obesity Surgery Registry (SOReg) and the Swedish Knee Arthroplasty Register (SKAR) were used to identify patients operated on with primary TKA for osteoarthritis (OA) between 2009 and 2019 that had a BS within 2 years before the TKA (BS group). These patients were compared to patients with TKA without prior BS (no BS group). The patients filled in the Knee injury and Osteoarthritis Outcome Score (KOOS) preoperatively and one year postoperatively as well as satisfaction with the surgery one year postoperatively. Multiple linear regression analysis was used to evaluate 1-year postoperative KOOS pain and ADL function between the 2 groups. Adjustments were made for sex, age, and preoperative KOOS pain and ADL function respectively.

Results

Forty-four patients were included in the BS group and 3,525 patients in the no BS group. We found no statistically or clinically significant difference in one-year postoperative KOOS pain and ADL function between the BS group and the no BS group. The majority of the patients in both groups were classified as satisfied or very satisfied one year postoperatively to the TKA.

Conclusions

Our results indicate that patients without BS prior to the TKA gain similar 1-year outcome in pain, ADL function and satisfaction as patients with prior BS.

Graphical abstract

     

Changes in DNA Damage Repair Gene Expression and Cell Cycle Gene Expression Do Not Explain Radioresistance in Tamoxifen-Resistant Breast Cancer

Tamoxifen-induced radioresistance, reported in vitro, might pose a problem for patients who receive neoadjuvant tamoxifen treatment and subsequently receive radiotherapy after surgery. Previous studies suggested that DNA damage repair or cell cycle genes are involved, and could therefore be targeted to preclude the occurrence of cross-resistance. We aimed to characterize the observed cross-resistance by investigating gene expression of DNA damage repair genes and cell cycle genes in estrogen receptor-positive MCF-7 breast cancer cells that were cultured to tamoxifen resistance. RNA sequencing was performed, and expression of genes characteristic for several DNA damage repair pathways was investigated, as well as expression of genes involved in different phases of the cell cycle. The association of differentially expressed genes with outcome after radiotherapy was assessed in silico in a large breast cancer cohort. None of the DNA damage repair pathways showed differential gene expression in tamoxifen-resistant cells compared to wild-type cells. Two DNA damage repair genes were more than two times upregulated (NEIL1 and EME2), and three DNA damage repair genes were more than two times downregulated (PCNA, BRIP1, and BARD1). However, these were not associated with outcome after radiotherapy in the TCGA breast cancer cohort. Genes involved in G₁, G₁/S, G₂, and G₂/M phases were lower expressed in tamoxifen-resistant cells compared to wild-type cells. Individual genes that were more than two times upregulated (MAPK13) or downregulated (E2F2, CKS2, GINS2, PCNA, MCM5, and EIF5A2) were not associated with response to radiotherapy in the patient cohort investigated. We assessed the expression of DNA damage repair genes and cell cycle genes in tamoxifen-resistant breast cancer cells. Though several genes in both pathways were differentially expressed, these could not explain the cross-resistance for irradiation in these cells, since no association to response to radiotherapy in the TCGA breast cancer cohort was found.     

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.