A path to tackle liver-stage parasites: Malaria parasites are evolutionarily prepared to resist drug attack. Resistance is emerging to even the latest frontline combination therapies, which target the blood stages of the Plasmodium parasite. As an alternative strategy, Antonova-Koch et al. investigated the possibilities of drugs against liver-stage parasites (see the Perspective by Phillips and Goldberg). To do so, they devised a luciferase-reporter drug screen for the rodent parasite Plasmodium berghei. Three rounds of increasingly stringent screening were used. From this regime, several chemotypes that inhibit Plasmodium mitochondrial electron transport were identified. Excitingly, several new scaffolds, with as-yet-unknown modes of action but solely targeting the parasites' liver stages, emerged as promising drug leads for further development. Science , this issue p. eaat9446 ; see also p. 1112

Pancreatic carcinoma is one of the tumors associated with a higher risk for thromboembolic events, with incidence rates ranging from 5% to 41% in previous retrospective series. We conducted a retrospective study in eleven Spanish hospitals that included 666 patients diagnosed with pancreatic carcinoma (any stage) between 2008 and 2011 and treated with chemotherapy. The main objective was to evaluate the incidence of venous thromboembolic events (VTE) in this population, as well as potential risk factors for thrombosis. The impact of VTE on mortality was also assessed. With a median follow-up of 9.3 months, the incidence of VTE was 22.1%; 52% were diagnosed incidentally. Our study was unable to confirm the ability of the Khorana score to discriminate between patients in the intermediate or high risk category for thrombosis. The presence of VTE proved to be an independent prognostic factor associated with increased risk of death (HR 2.39, 95% CI 1.96-2.92). Symptomatic events correlated with higher mortality than asymptomatic events (HR 1.72; 95% CI, 1.21-2.45; p = 0.002), but incidental VTE, including visceral vein thrombosis (VVT), negatively affected survival compared to patients without VTE. Subjects who developed VTE within the first 3 months of diagnosis of pancreatic carcinoma had lower survival rates than those with VTE after 3 months (HR 1.92, 95% CI 1.30-2.84; p<0.001). Pancreatic carcinoma is associated with a high incidence of VTE, which, when present, correlates with worse survival, even when thrombosis is incidental. Early onset VTE has a particularly negative impact.

Benign paroxysmal positional vertigo (BPPV) and bilateral vestibulopathy (BVL) are two completely different forms of vestibular disorder that occasionally occur in the same patient. We conducted a retrospective review searching for that coincidence in our database of the patients seen over a 15-year period and found this disorder in 23 patients, that is 0.4%. More frequently they occurred sequentially (10/23) and BPPV was diagnosed first. Simultaneous presentation occurred in 9/23 patients. It was subsequently studied, but in a prospective manner, in patients with BPPV on all of whom a video head impulse test was performed to search for bilateral vestibular loss; we found it was slightly more frequent (6/405). Both disorders were treated accordingly, and it was found that the results follow the general trend in patients with only one of those disorders.

Background: COVID-19, caused by SARS-CoV-2, has posed significant challenge to global healthcare systems, necessitating reliable biomarkers to predict disease severity and mortality. This systematic review and meta-analysis evaluated the prognostic value of novel biomarkers in COVID-19 patients. The aim of this study was to identify and prioritize the most prognostically relevant novel biomarkers associated with COVID-19 outcomes. Methods: We conducted a systematic review and meta-analysis of the available evidence. A systematic search of PubMed and Web of Science was performed to identify studies on the COVID-19 biomarkers. Observational studies that compared poor (severe disease/mortality) and good outcomes were included. For continuous measures, standard mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve analyses for the biomarkers were used. The risk of bias was assessed using the Newcastle–Ottawa scale. Results: Of the 2907 screened studies, 38 were included (21 in the meta-analysis). MR-proADM showed higher levels of prediction for poor outcomes (SMD = 1.40, 95% CI: 1.11–1.69; AUC 0.74–0.96; sensitivity, 85%; specificity, 71%). The neutrophil-to-lymphocyte ratio (NLR) showed a high correlation with disease severity (SMD = 1.07, 95% CI: 0.79–1.35; AUC 0.73–0.98; sensitivity, 86%; specificity, 78%). Increased KL-6 levels were associated with lung injury (SMD = 1.22, 95% CI: 0.24–2.19; AUC 0.85–0.95). Other biomarkers (suPAR, miR-155, Galectin-3) showed promise but lacked sufficient data for pooled analysis. Heterogeneity was observed among the included studies in terms of diagnostic accuracy. These findings indicate that elevated levels of MR-proADM, NLR, and KL-6 are significantly associated with COVID-19 prognostic accuracy to guide patient management. Conclusions: MR-proADM, NLR, and KL-6 levels demonstrated strong prognostic value for COVID-19 severity and mortality. These biomarkers can enhance clinical decision-making.