External Validation of the DCD-N Score and a Linear Prediction Model to Identify Potential Candidates for Organ Donation After Circulatory Death:A Nationwide Multicenter Cohort Study

Donation after circulatory death (DCD) is a procedure in which after planned withdrawal of life-sustaining treatment (WLST), the dying process is monitored. A DCD procedure can only be continued if the potential organ donor dies shortly after WLST. This study performed an external validation of 2 existing prediction models to identify potentially DCD candidates, using one of the largest cohorts. METHODS. This multicenter retrospective study analyzed all patients eligible for DCD donation from 2010 to 2015. The first model (DCD-N score) assigned points for absence of neurological reflexes and oxygenation index. The second model, a linear prediction model (LPDCD), yielded the probability of death within 60 min. This study determined discrimination (c-statistic) and calibration (Hosmer and Lemeshow test) for both models. RESULTS. This study included 394 patients, 283 (72%) died within 60 min after WLST. The DCD-N score had a c-statistic of 0.77 (95% confidence intervals, 0.71-0.83) and the LPDCD model 0.75 (95% confidence intervals, 0.68-0.81). Calibration of the LPDCD 60-min model proved to be poor (Hosmer and Lemeshow test, P < 0.001). CONCLUSIONS. The DCD-N score and the LPDCD model showed good discrimination but poor calibration for predicting the probability of death within 60 min. Construction of a new prediction model on a large data set is needed to obtain better calibration

Acute and chronic histopathological findings in renal biopsies in COVID-19

The dominant ICU admission diagnosis of COVID-19 patients is respiratory insufficiency, but 32–57% of hospitalized COVID-19 patients develop acute kidney injury (COVID-AKI). The renal histopathological changes accompanying COVID-AKI are not yet fully described. To obtain a detailed insight into renal histopathological features of COVID-19, we conducted a review including all studies reporting histopathological findings of diagnostic and postmortem kidney biopsies from patients with COVID-19 published between January 1, 2020, and January 31, 2021. A total of 89 diagnostic and 194 postmortem renal biopsies from individual patients in 39 published studies were investigated and were included in the analysis. In the diagnostic biopsy group, mean age was 56 years and AKI incidence was 96%. In the postmortem biopsy group, mean age was 69 years and AKI incidence was 80%. In the diagnostic biopsy group, the prevalence of acute glomerular diseases was 74%. The most common glomerular lesions were collapsing focal segmental glomerulosclerosis (c-FSGS) in 54% and thrombotic microangiopathy (TMA) in 9% of patients. TMA was also found in 10% of patients in the postmortem biopsy group. The most common acute tubular lesions was acute tubular necrosis (ATN) which was present in 87% of patients in the diagnostic and in 77% of patients in the postmortem biopsy group. Additionally, we observed a high prevalence of preexisting chronic lesions in both groups such as atherosclerosis and glomerulosclerosis. Histopathological changes in renal biopsies of COVID-19 patients show a heterogeneous picture with acute glomerular lesions, predominantly c-FSGS and TMA, and acute tubular lesions, predominantly ATN. In many patients, these lesions were present on a background of chronic renal injury. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10238-022-00941-x

A Method to Improve Continuous Renal Replacement Therapy Circuit Survival Time in Critically Ill Coronavirus Disease 2019 Patients With Acute Kidney Injury

Objectives: Optimizing continuous renal replacement therapy circuit survival in coronavirus disease 2019 patients admitted to the ICU. Design: Single-center prospective observational cohort study. Setting: Tertiary academic teaching ICU. Patients: Between March 19, 2020, and May 18, 2020, 11 out of 101 coronavirus disease 2019 patients were treated with continuous renal replacement therapy comprising 127 continuous renal replacement therapy days. Interventions: A nonrandomized observational comparison of circuit anticoagulation modalities using standard regional citrate anticoagulation, continuous IV heparin anticoagulation, or the combination of regional citrate anticoagulation with either continuous IV heparin or therapeutic dose nadroparin. Measurements and Main Results: Circuit patency was shorter than 24 hours using standard regional citrate anticoagulation or continuous IV heparin anticoagulation. Median circuit survival increased with at least 165% when the combination of regional citrate anticoagulation with either continuous IV heparin or therapeutic dose nadroparin was applied. Conclusions: Continuous renal replacement therapy circuit patency is diminished in coronavirus disease 2019 ICU patients. Combining regional citrate anticoagulation with either continuous IV heparin or therapeutic dose nadroparin increases filter survival as compared with regional citrate anticoagulation alone in this nonrandomized observational study

Comparison of renal histopathology and gene expression profiles between severe COVID-19 and bacterial sepsis in critically ill patients

BACKGROUND: The mechanisms driving acute kidney injury (AKI) in critically ill COVID-19 patients are unclear. We collected kidney biopsies from COVID-19 AKI patients within 30 min after death in order to examine the histopathology and perform mRNA expression analysis of genes associated with renal injury. METHODS: This study involved histopathology and mRNA analyses of postmortem kidney biopsies collected from patients with COVID-19 (n = 6) and bacterial sepsis (n = 27). Normal control renal tissue was obtained from patients undergoing total nephrectomy (n = 12). The mean length of ICU admission-to-biopsy was 30 days for COVID-19 and 3–4 days for bacterial sepsis patients. RESULTS: We did not detect SARS-CoV-2 RNA in kidney biopsies from COVID-19-AKI patients yet lung tissue from the same patients was PCR positive. Extensive acute tubular necrosis (ATN) and peritubular thrombi were distinct histopathology features of COVID-19-AKI compared to bacterial sepsis-AKI. ACE2 mRNA levels in both COVID-19 (fold change 0.42, p = 0.0002) and bacterial sepsis patients (fold change 0.24, p < 0.0001) were low compared to control. The mRNA levels of injury markers NGAL and KIM-1 were unaltered compared to control tissue but increased in sepsis-AKI patients. Markers for inflammation and endothelial activation were unaltered in COVID-19 suggesting a lack of renal inflammation. Renal mRNA levels of endothelial integrity markers CD31, PV-1 and VE-Cadherin did not differ from control individuals yet were increased in bacterial sepsis patients (CD31 fold change 2.3, p = 0.0006, PV-1 fold change 1.5, p = 0.008). Angiopoietin-1 mRNA levels were downregulated in renal tissue from both COVID-19 (fold change 0.27, p < 0.0001) and bacterial sepsis patients (fold change 0.67, p < 0.0001) compared to controls. Moreover, low Tie2 mRNA expression (fold change 0.33, p = 0.037) and a disturbed VEGFR2/VEGFR3 ratio (fold change 0.09, p < 0.0001) suggest decreased microvascular flow in COVID-19. CONCLUSIONS: In a small cohort of postmortem kidney biopsies from COVID-19 patients, we observed distinct histopathological and gene expression profiles between COVID-19-AKI and bacterial sepsis-AKI. COVID-19 was associated with more severe ATN and microvascular thrombosis coupled with decreased microvascular flow, yet minimal inflammation. Further studies are required to determine whether these observations are a result of true pathophysiological differences or related to the timing of biopsy after disease onset. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-021-03631-4

Rate control efficacy in permanent atrial fibrillation:a comparison between lenient versus strict rate control in patients with and without heart failure. Background, aims, and design of RACE II

BACKGROUND: Recent studies demonstrated that rate control is an acceptable alternative for rhythm control in patients with persistent atrial fibrillation (AF). However, optimal heart rate during AF is still unknown. OBJECTIVE: To show that in patients with permanent AF, lenient rate control is not inferior to strict rate control in terms of cardiovascular mortality, morbidity, neurohormonal activation, New York Heart Association class for heart failure, left ventricular function, left atrial size, quality of life, and costs. METHODS: The RACE II study is a prospective multicenter trial in The Netherlands that will randomize 500 patients with permanent AF (< or = 12 months) to strict or lenient rate control. Strict rate control is defined as a mean resting heart rate < 80 beats per minute (bpm) and heart rate during minor exercise < 110 bpm. After reaching the target, a 24-hour Holter monitoring will be performed. If necessary, drug dose reduction and/or pacemaker implantation will be performed. Lenient rate control is defined as a resting heart rate < 110 bpm. Patients will be seen after 1, 2, and 3 months (for titration of rate control drugs) and yearly thereafter. We anticipate a 25% 2.5-year cardiovascular morbidity and mortality in both groups. RESULTS: Enrollment started in January 2005 in 29 centers in The Netherlands and is expected to be concluded in June 2006. Follow-up will be at least 2 years with a maximum of 3 years. CONCLUSION: This study should provide data how to treat patients with permanent AF

A new tool to assess Clinical Diversity In Meta‐analyses (CDIM) of interventions

OBJECTIVE: To develop and validate Clinical Diversity In Meta-analyses (CDIM), a new tool for assessing clinical diversity between trials in meta-analyses of interventions.STUDY DESIGN AND SETTING: The development of CDIM was based on consensus work informed by empirical literature and expertise. We drafted the CDIM tool, refined it, and validated CDIM for interrater scale reliability and agreement in three groups.RESULTS: CDIM measures clinical diversity on a scale that includes four domains with 11 items overall: setting (time of conduct/country development status/units type); population (age, sex, patient inclusion criteria/baseline disease severity, comorbidities); interventions (intervention intensity/strength/duration of intervention, timing, control intervention, cointerventions); and outcome (definition of outcome, timing of outcome assessment). The CDIM is completed in two steps: first two authors independently assess clinical diversity in the four domains. Second, after agreeing upon scores of individual items a consensus score is achieved. Interrater scale reliability and agreement ranged from moderate to almost perfect depending on the type of raters.CONCLUSION: CDIM is the first tool developed for assessing clinical diversity in meta-analyses of interventions. We found CDIM to be a reliable tool for assessing clinical diversity among trials in meta-analysis.</p

The Role of Platelets in Extracorporeal Circuit Thrombogenesis

Objetivo: Identificar el riesgo de cáncer de piel en pobladores de los distritos de Olmos y Pimentel durante el periodo agosto-septiembre del 2016. Material y Método: Se realizó un estudio cuantitativo, descriptivo, transversal y no experimental, con la participación de 240 pobladores para el distrito de Pimentel y 200 pobladores para el distrito de Olmos; mediante un muestreo por conglomerados bietápico. A los pobladores se les captó en los distritos correspondientes durante su disponibilidad en los dos meses de ejecución; previo consentimiento, se les aplicó el cuestionario validado, donde una puntación ≥ 5 identifica riesgo alto de cáncer de piel. Para el análisis estadístico descriptivo se utilizaron las medidas de frecuencia, porcentaje y la media. Resultados: En el distrito de Olmos se obtuvo riesgo alto de cáncer de piel de 52%, con una diferencia de 28,2% respecto al distrito de Pimentel. La población de alto riesgo se encuentra entre los 50-65 años (17 y 7,9%) y de sexo masculino (29,5 y 12,1%) para los distritos de Olmos y Pimentel respectivamente. El factor de riesgo con mayor frecuencia en ambos distritos fue, haber vivido o vivir en zona geográfica de sol intenso, con un 89,0% en Olmos y 92,5% en Pimentel. Conclusiones: El riesgo de cáncer de piel en los pobladores del distrito de Olmos durante el periodo agosto-septiembre del 2016, fue de frecuencia alta, mientras que en el distrito de Pimentel, 2016, fue baja