Predictors of clinical evolution of SARS-CoV-2 infection in hematological patients: A systematic review and meta-analysis.

Main aim of this systematic review is to quantify the risk and identify predictors of clinical evolution of SARS-CoV-2 in hematological patients compared to different control populations. Two independent reviewers screened the literature assessing clinical outcomes of SARS-CoV-2 infection in adult patients with active hematological malignancies published up to June 2021. Primary outcome was COVID-19 related mortality, secondary outcomes were hospital and intensive-care admission, mechanical ventilation (MV), and thromboembolic events. Variables related to study setting, baseline patients' demographic, comorbidities, underlying hematological disease, ongoing chemotherapy, COVID-19 presentation, and treatments were extracted. A total of 67 studies including 10,061 hematological patients and 111,143 controls were included. Most of the studies were retrospective cohorts (51 studies, 76%) and only 19 (13%) provided data for a control group. A significant increased risk of clinical progression in the hematological population compared to the controls was found in terms of COVID-19 related mortality (OR, 2.12; 95% CI, 1.77-2.54), hospitalization (OR, 1.98; 95% CI, 1.15-3.43), intensive-care admission (OR, 1.77; 95% CI, 1.38-2.26), and MV (OR, 2.17; 95% CI, 1.71-2.75). The risk remained significantly higher in the subgroup analysis comparing hematological patients versus solid cancer. Meta-regression analysis of uncontrolled studies showed that older age, male sex, and hypertension were significantly related to worse clinical outcomes of COVID-19 in hematological population. Older age and hypertension were found to be associated also to thromboembolic events. In conclusion, hematological patients have a higher risk of COVID-19 clinical progression compared to both the general population and to patients with solid cancer.

Septin filament compaction into rings requires the anillin Mid2 and contractile ring constriction.

Septin filaments assemble into high-order molecular structures that associate with membranes, acting as diffusion barriers and scaffold proteins crucial for many cellular processes. How septin filaments organize in such structures is still not understood. Here, we used fission yeast to explore septin filament organization during cell division and its cell cycle regulation. Live-imaging and polarization microscopy analysis uncovered that septin filaments are initially recruited as a diffuse meshwork surrounding the acto-myosin contractile ring (CR) in anaphase, which undergoes compaction into two rings when CR constriction is initiated. We found that the anillin-like protein Mid2 is necessary to promote this compaction step, possibly acting as a bundler for septin filaments. Moreover, Mid2-driven septin compaction requires inputs from the septation initiation network as well as CR constriction and the ß(1,3)-glucan synthase Bgs1. This work highlights that anillin-mediated septin ring assembly is under strict cell cycle control.

Breakthrough invasive fungal infections in liver transplant recipients exposed to prophylaxis with echinocandins vs other antifungal agents: A systematic review and meta-analysis.

INTRODUCTION: Although echinocandins are recommended as first-line prophylaxis for high-risk orthotopic liver transplant (OLT) recipients, occurrence of breakthrough-invasive fungal infections (IFIs) remains a serious concern. We aim to assess the risk of breakthrough IFIs among OLT recipients exposed to prophylaxis with echinocandins compared to other antifungals. MATERIALS AND METHODS: Two authors independently searched PubMed-MEDLINE, Embase, study registries and reference lists from inception to March 2021, to retrieve randomised controlled trials (RCTs) or observational studies comparing efficacy and safety of echinocandins vs other antifungals for prophylaxis in OLT recipients. Data were independently extracted from two authors, and the quality of included studies was independently assessed according to ROB 2.0 tool for RCTs and ROBINS-I tool for observational studies. The primary outcome was occurrence of breakthrough IFI at the end of prophylaxis (EOP). RESULTS: 698 articles were screened, and ten studies (3 RCTs and 7 observational) were included. No difference between echinocandins and other antifungals in terms of breakthrough IFIs at the EOP emerged both from RCTs (odds ratio [OR] 0.85, 95% CI 0.24-2.99) and observational studies (OR 1.43, 95% CI 0.28-7.40). No difference emerged also for secondary outcomes. In the subgroup comparison between echinocandins and polyenes, a trend for higher risk of breakthrough IFI at the EOP (OR 4.82, 95% CI 0.97-24.03) was noted. CONCLUSIONS: Echinocandins do not seem to be associated with increased risk of breakthrough IFIs in OLT recipients. However, the large diversity in the comparator group hinders a definitive interpretation. Further studies exploring the relationship between echinocandin use and breakthrough IFIs according to specific comparators are warranted.

Increasing ergosterol levels delays formin-dependent assembly of F-actin cables and disrupts division plane positioning in fission yeast.

In most eukaryotes, cytokinesis is mediated by the constriction of a contractile acto-myosin ring (CR), which promotes the ingression of the cleavage furrow. Many components of the CR interact with plasma membrane lipids suggesting that lipids may regulate CR assembly and function. Although there is clear evidence that phosphoinositides play an important role in cytokinesis, much less is known about the role of sterols in this process. Here, we studied how sterols influence division plane positioning and CR assembly in fission yeast. We show that increasing ergosterol levels in the plasma membrane blocks the assembly of F-actin cables from cytokinetic precursor nodes, preventing their compaction into a ring. Abnormal F-actin cables form after a delay, leading to randomly placed septa. Since the formin Cdc12 was detected on cytokinetic precursors and the phenotype can be partially rescued by inhibiting the Arp2/3 complex, which competes with formins for F-actin nucleation, we propose that ergosterol may inhibit formin dependent assembly of F-actin cables from cytokinetic precursors.