Impact of the COVID-19 Pandemic on Corneal Transplantation: A Report From the Italian Association of Eye Banks

Purpose: To analyze the impact of COVID-19 on Italian corneal transplantation from March-2020 to February 2021 compared to the same timeframe of the 2 previous years, in order to identify potential consequences of a global pandemic on corneal procurement and transplantation services during this time. Methods: This national, multicentric, retrospective cohort study evaluated data collected from 12 (100%) Italian eye banks from March 2020 to February 2021 (Group A). The number of tissues collected, distributed and discarded were compared with the same time-frame of the 2 previous years: 2019 and 2018 (group B and C, respectively). The different type of transplants performed were reported. Data were analyzed using a non-parametric Friedman test. Results: Corneal procurement and the percentage of distributed tissues reduced in 2020 by more than 30 and 15%, respectively, compared to the 2 previous years. During the pandemic corneal transplant surgery showed only a modest drop: the number of the penetrating keratoplasties (PKs) and the anterior lamellar keratoplasties (ALKs) decreased by about 30 and 20% in comparison with groups B and C, respectively; between the Endothelial Keratoplasties (EKs), the Descemet membrane endothelial keratoplasty (DMEK) increased slightly from March 2020 to February 2021. Conclusions: Italy was one of the first countries most affected by the outbreak of COVID-19, and the Italian government adopted severe measures to limit viral transmission. The pandemic generated several implications in corneal transplant activity during the first lockdown. Then an efficacious reaction with constant, vigorous work led to a resumption of transplant surgery to a near-normal standard. The increase of EKs, despite the pandemic, is a sign that the advance in corneal transplantation has gone ahead and it continues to evolve

Serelaxin as a potential treatment for renal dysfunction in cirrhosis: Preclinical evaluation and results of a randomized phase 2 trial

<div><p>Background</p><p>Chronic liver scarring from any cause leads to cirrhosis, portal hypertension, and a progressive decline in renal blood flow and renal function. Extreme renal vasoconstriction characterizes hepatorenal syndrome, a functional and potentially reversible form of acute kidney injury in patients with advanced cirrhosis, but current therapy with systemic vasoconstrictors is ineffective in a substantial proportion of patients and is limited by ischemic adverse events. Serelaxin (recombinant human relaxin-2) is a peptide molecule with anti-fibrotic and vasoprotective properties that binds to relaxin family peptide receptor-1 (RXFP1) and has been shown to increase renal perfusion in healthy human volunteers. We hypothesized that serelaxin could ameliorate renal vasoconstriction and renal dysfunction in patients with cirrhosis and portal hypertension.</p><p>Methods and findings</p><p>To establish preclinical proof of concept, we developed two independent rat models of cirrhosis that were characterized by progressive reduction in renal blood flow and glomerular filtration rate and showed evidence of renal endothelial dysfunction. We then set out to further explore and validate our hypothesis in a phase 2 randomized open-label parallel-group study in male and female patients with alcohol-related cirrhosis and portal hypertension. Forty patients were randomized 1:1 to treatment with serelaxin intravenous (i.v.) infusion (for 60 min at 80 μg/kg/d and then 60 min at 30 μg/kg/d) or terlipressin (single 2-mg i.v. bolus), and the regional hemodynamic effects were quantified by phase contrast magnetic resonance angiography at baseline and after 120 min. The primary endpoint was the change from baseline in total renal artery blood flow.</p><p>Therapeutic targeting of renal vasoconstriction with serelaxin in the rat models increased kidney perfusion, oxygenation, and function through reduction in renal vascular resistance, reversal of endothelial dysfunction, and increased activation of the AKT/eNOS/NO signaling pathway in the kidney. In the randomized clinical study, infusion of serelaxin for 120 min increased total renal arterial blood flow by 65% (95% CI 40%, 95%; <i>p <</i> 0.001) from baseline. Administration of serelaxin was safe and well tolerated, with no detrimental effect on systemic blood pressure or hepatic perfusion. The clinical study’s main limitations were the relatively small sample size and stable, well-compensated population.</p><p>Conclusions</p><p>Our mechanistic findings in rat models and exploratory study in human cirrhosis suggest the therapeutic potential of selective renal vasodilation using serelaxin as a new treatment for renal dysfunction in cirrhosis, although further validation in patients with more advanced cirrhosis and renal dysfunction is required.</p><p>Trial registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01640964" target="_blank">NCT01640964</a></p></div

Is pregnancy-related acute renal failure a disappearing clinical entity?

The actual disappearance of pregnancy-related acute renal failure (PR-ARF) is a common \u201cfeeling\u201d for nephrologists. The aim of this study was to exactly quantify this event by evaluating epidemiology and the extent of renal damage in PR-ARF. From 1958 to 1994, 84 cases of PR-ARF were observed (5.8% of total number of ARF needing dialysis). In four successive periods (1956-67, 1968-77, 1978-87, 1988-94), the incidence of PR-ARF fell from 43% to 0.5% with respect to the total number of ARF, and from 1/3000 to 1/18,000 with respect to the total number of pregnancies. Maternal mortality in the past was high (31%), but no cases of death in the last period were seen. Irreversible renal damage was recorded in 11.1% of PR-ARF, and, in particular, in 18.7% of cases of preeclampsia-eclampsia (PE-E). The worst maternal and renal prognosis occurred in PE-E that was complicated by abruptio placentae (AP). Neither disseminated intravascular coagulation (DIC), microangiopathic hemolytic anemia, nor prostacyclin imbalance were significantly related to the severity of renal damage. Heparin therapy did not modify DIC evolution and renal outcome and was aggravated by severe hemorragic complications. Support therapy with plasma infusion, antithrombin III, and antiplatelet agents seems to be helpful. In conclusion, PR-ARF has become a rare occurrence and, in our experience, no cases of death or irreversible renal damage were observed in the last 7 years. The most important reasons for this favorable evolution seem to be an improved medical care and more effective measures of careful prevention, mainly regarding tempestive delivery