I ncidence of coronavirus disease (COVID-19)associated pulmonary aspergillosis (CAPA) in hospital intensive care units (ICUs) is 3.8%-33.3% (1-9). Variations might be explained by differences in patient populations and CAPA defi nitions used, complicating direct comparisons between studies.Diagnosing CAPA is complex because cases frequently lack typical radiologic features and European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) host factors ( 10) and because mycologic evidence is diffi cult to obtain. Serum galactomannan (GM) detection has low sensitivity in CAPA (7,10).The European Confederation of Medical Mycology and International Society for Human and Animal Mycology (ECMM/ISHAM) published consensus criteria for a CAPA defi nition (11). We used these criteria to perform an observational cohort study to assess CAPA incidence in patients with COVID-19 admitted to ICUs during the fi rst wave of the COVID-19 pandemic. The StudyWe collected partially prospective and partially retrospective data for 823 patients in 2 cohorts. The discovery cohort comprised patients with PCR-confi rmed or clinically presumed COVID-19 admitted to 4 ICUs in the Netherlands and 4 ICUs in Belgium during February 28-May 27, 2020. The validation cohort comprised patients with PCR-confi rmed COVID-19 admitted because of respiratory insuffi ciency to 3 participating ICUs in France during April 7-May 31, 2020 (Appendix Methods, Table 1, https://wwwnc.cdc.gov/EID/ article/27/11/21-1174-App1.pdf).

Background The literature regarding COVID-19 associated pulmonary aspergillosis (CAPA) has shown conflicting observations, including survival of CAPA patients not receiving antifungal therapy and discrepancy between CAPA diagnosis and autopsy findings. To gain insight into the pathophysiology of CAPA we performed a case-control study, in which we compared Aspergillus test profiles in CAPA patients and controls in relation to ICU-mortality. Methods A multinational case-control study, in which Aspergillus test results, use of antifungal therapy and mortality were collected from critically-ill COVID-19 patients. Patients were classified using the 2020 ECMM/ISHAM consensus case definitions. Results 219 critically-ill COVID-19 cases were analyzed, including one proven, 38 probable, 19 possible CAPA cases, 21 Aspergillus colonized patients, seven patients only positive for serum (1, 3)-ß-D-glucan (BDG), and 133 cases with no evidence of CAPA. Mortality was 53.8% in CAPA patients compared to 24.1% in patients without CAPA (p=0.001). Positive serum galactomannan (GM) and BDG were associated with increased mortality compared to serum biomarker negative CAPA patients (87.5% versus 41.7%, p=0.046; 90.0% versus 42.1%, p=0.029, respectively). For each point increase in GM or ten-point BDG serum concentration, the odds of death increased (GM, OR 10.208, 95%CI 1.621-64.291, p=0.013; BDG, OR 1.247, 95%CI 1.029-1.511, p=0.024). Conclusions CAPA is a complex disease, probably involving a continuum of respiratory colonization, tissue-invasion and angioinvasion. Serum biomarkers are useful for staging CAPA disease progression and, if positive, indicate angioinvasion and a high probability of mortality. There is need for a biomarker that distinguishes between respiratory tract colonization and tissue invasive CAPA disease.

Despite the large amount of human and experimental studies no effective (prophylactic) treatment exists for chemotherapy induced peripheral neuropathy (CIPN), a disabling side effect of many cancer treatments. One of the underlying reasons for this could be that often the preclinical animal models used are not the best representation of the clinical situation. We therefore present a systematic summary and comparison of all animal models currently described in literature for CIPN focusing on stimulus evoked pain-like behaviour and neurophysiological alterations in nerve function (650 included papers, and a comparison of 183 models), that resulted in a clear overview of the most effective and robust CIPN models using an administration route used in clinical practice. Using our three-step approach (step 1: efficacy; step; 2 robustness and step 3: mimicking the clinical situation) we show that all mice CIPN models treated with either paclitaxel or cisplatin using an administration route used in clinical practice seem suitable models. Three specific models using paclitaxel or cisplatin that stand out are 1) C57BL/6 female mice receiving paclitaxel and 2) CD1 male mice receiving paclitaxel and 3) C57BL/6 male mice receiving cisplatin. This overview may help scientists selecting suitable CIPN models for their research. We hypothesize that by using effective and robust animal models that mimic the clinical situation as much as possible, the translational value of preclinical study results with respect to the potential of identifying promising treatments for CIPN in the future, will prove. The methodology described in this paper, aimed at comparing animal models, is novel and can be used by scientist in other research fields as well.

ObjectiveTo compare the effectiveness of different technique modifications in laparoscopic donor nephrectomy.DesignSystematic review and meta-analyses.Data SourcesSearches of PubMed, EMBASE, Web of Science and Central from January 1st 1997 until April 1st 2014.Study DesignAll cohort studies and randomized clinical trials comparing fully laparoscopic donor nephrectomy with modifications of the standard technique including hand-assisted, retroperitoneoscopic and single port techniques, were included.Data-Extraction and AnalysisThe primary outcome measure was the number of complications. Secondary outcome measures included: conversion to open surgery, first warm ischemia time, estimated blood loss, graft function, operation time and length of hospital stay. Each technique modification was compared with standard laparoscopic donor nephrectomy. Data was pooled with a random effects meta-analysis using odds ratios, weighted mean differences and their corresponding 95% confidence intervals. To assess heterogeneity, the I2 statistic was used. First, randomized clinical trials and cohort studies were analyzed separately, when data was comparable, pooled analysis were performed.Results31 studies comparing laparoscopic donor nephrectomy with other technique modifications were identified, including 5 randomized clinical trials and 26 cohort studies. Since data of randomized clinical trials and cohort studies were comparable, these data were pooled. There were significantly less complications in the retroperitoneoscopic group as compared to transperitoneal group (OR 0.52, 95%CI 0.33–0.83, I2 = 0%). Hand-assisted techniques showed shorter first warm ischemia and operation times.ConclusionsHand-assistance reduces the operation and first warm ischemia times and may improve safety for surgeons with less experience in laparoscopic donor nephrectomy. The retroperitoneoscopic approach was significantly associated with less complications. However, given the, in general, poor to intermediate quality and considerable heterogeneity in the included studies, further high-quality studies are required.Trial RegistrationThe review protocol was registered in the PROSPERO database before the start of the review process (CRD number 42013006565).