EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19.

Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Two-way ANOVA when the distribution of the error terms is skew t

In this article, we assume that the distribution of the error terms is skew t in two-way analysis of variance (ANOVA). Skew t distribution is very flexible for modeling the symmetric and the skew datasets, since it reduces to the well-known normal, skew normal, and Student's t distributions. We obtain the estimators of the model parameters by using the maximum likelihood (ML) and the modified maximum likelihood (MML) methodologies. We also propose new test statistics based on these estimators for testing the equality of the treatment and the block means and also the interaction effect. The efficiencies of the ML and the MML estimators and the power values of the test statistics based on them are compared with the corresponding normal theory results via Monte Carlo simulation study. Simulation results show that the proposed methodologies are more preferable. We also show that the test statistics based on the ML estimators are more powerful than the test statistics based on the MML estimators as expected. However, power values of the test statistics based on the MML estimators are very close to the corresponding test statistics based on the ML estimators. At the end of the study, a real life example is given to show the implementation of the proposed methodologies. © 2017, © 2017 Taylor & Francis Group, LLC

Skull metastasis of follicular thyroid carcinoma

Metastasis of a follicular thyroid carcinoma (FTC) to the skull is very rare. We present a case of solitary lytic skull metastasis of a FTC in a 30-year-old woman. The patient presented with bulging on the left side of the head. Neuro-imaging techniques showed a lesion with an osteolytic component in the left frontal region. After a left frontal craniectomy the tumour was removed totally. The histopathological examination revealed a well-differentiated FTC metastasis and a complete total thyroidectomy was subsequently performed. The patient was given thyroid-stimulating hormone (TSH) suppression therapy followed by whole body iodine-131 (I-113) internal radiation

Estimation and testing in one-way anova when the errors are skew-normal [Estimación y pruebas de hipótesis en ANOVA a una vía cuando los errores se distribuyen como normal sesgados]

We consider one-way analysis of variance (ANOVA) model when the error terms have skew- normal distribution. We obtain the estimators of the model parameters by using the maximum likelihood (ML) and the modified maximum likelihood (MML) methodologies (see, Tiku 1967). In the ML method, iteratively reweighting algorithm (IRA) is used to solve the likelihood equations. The MML approach is a non-iterative method used to obtain the explicit estimators of model parameters. We also propose new test statistics based on these estimators for testing the equality of treatment effects. Simulation results show that the proposed estimators and the tests based on them are more efficient and robust than the corresponding normal theory solutions. Also, real data is analysed to show the performance of the proposed estimators and the tests. © 2015 Revista Colombiana de Estadística. All right received