Despite Tocilizumab is now recognized as a concrete therapeutic option in patients with severe SARS-CoV-2 related respiratory failure, literature lacks about factors influencing the response to it in ...this context. Therefore, the aim of our study was to provide evidence about predictors of poor outcome in Tocilizumab treated patients in the real-world practice.
We retrospectively analyzed clinical, laboratory and chest computer tomography (CCT) data of patients firstly admitted in non Intensive Care Units (ICU) and suffering from severe respiratory failure, who were treated with the IL-6 antagonist Tocilizumab. We compared patients who died and/or required admission to ICU with oro-tracheal intubation (OTI) with those who did not.
Two hundreds and eighty-seven patients (29.9% females) with mean age ± SD 64.1 ± 12.6 years were the study population. In-hospital mortality was 18.8%, while the composite endpoint in-hospital mortality and/or ICU admission with OTI occurred in 23.7%. At univariate analysis, patients who died and/or were admitted to ICU with OTI were significantly older and co-morbid, had significantly higher values of creatinine, C-reactive protein (CRP) and procalcitonin and lower lymphocytes count, PaO2/FiO2 ratio (P/F) and room air pulsossimetry oxygen saturation (RAO2S) at hospital admission. Computed tomography ground glass opacities (CT-GGO) involving the pulmonary surface ≥ 50% were found in 55.4% of patients who died and/or were admitted to ICU with OTI and in 21.5% of patients who did not (p=0.0001). At multivariate analysis, age ≥ 65 years (OR 17.3, 95% CI: 3.7-81.0), procalcitonin ≥ 0.14 (OR 9.9, 95%CI: 1.7-56.1), RAO2S ≤ 90% (OR 4.6, 95%CI: 1.2-17.0) and CCT-GGO involvement ≥ 50% (OR 5.1, 95%CI: 1.2-21.0) were independent risk factors associated with death and/or ICU admission with OTI.
Tocilizumab has shown to improve outcome in patients with severe respiratory failure associated to SARS-CoV-2 related pneumonia. In our multicentre study focusing on Tocilizumab treated severe COVID-19 patients, age ≥ 65 years, procalcitonin ≥ 0.14 ng/mL, RAO2S ≤ 90% and CCT-GGO involvement ≥ 50% were independent factors associated with poor outcome.
Few data exists on predictive factors of hemorrhagic transformation (HT) in real-world acute ischemic stroke patients. The aims of this study were: (i) to identify predictive variables of HT (ii) to ...develop a score for predicting HT.
We retrospectively analyzed the clinical, radiographic, and laboratory data of patients with acute ischemic stroke consecutively admitted to our Stroke Unit along two years. Patients with HT were compared with those without HT. A multivariate logistic regression analysis was performed to identify independent predictors of HT on CT scan at 24 hours to develop a practical score.
The study population consisted of 564 patients with mean age 77.5±11.8 years. Fifty-two patients (9.2%) showed HT on brain CT at 24 hours (4.9% symptomatic). NIHSS score ≥8 at Stroke Unit admission (3 points), cardioembolic etiology (2 points), acute revascularization by systemic thrombolysis and/or mechanical thrombectomy (1 point), history of previous TIA/stroke (1 point), and major vessel occlusion (1 point) were found independent risk factors of HT and were included in the score (Hemorrhagic Transformation Empoli score (HTE)). The predictive power of HTE score was good with an AUC of 0.785 (95% CI: 0.749-0.818). Compared with 5 HT predictive scores proposed in the literature (THRIVE, SPAN-100, MSS, GRASPS, SITS-SIC), the HTE score significantly better predicted HT.
NIHSS score ≥8 at Stroke Unit admission, cardioembolism, urgent revascularization, previous TIA/stroke, and major vessel occlusion were independent predictors of HT. The HTE score has a good predictive power for HT. Prospective studies are warranted.
Grapevine rupestris stem pitting-associated virus (GRSPaV) is a widespread virus infecting Vitis spp. Although it has established a compatible viral interaction in Vitis vinifera without the ...development of phenotypic alterations, it can occur as distinct variants that show different symptoms in diverse Vitis species. The changes induced by GRSPaV in V. vinifera cv 'Bosco', an Italian white grape variety, were investigated by combining agronomic, physiological, and molecular approaches, in order to provide comprehensive information about the global effects of GRSPaV. In two years, this virus caused a moderate decrease in physiological efficiency, yield performance, and sugar content in berries associated with several transcriptomic alterations. Transcript profiles were analysed by a microarray technique in petiole, leaf, and berry samples collected at véraison and by real-time RT-PCR in a time course carried out at five grapevine developmental stages. Global gene expression analyses showed that transcriptomic changes were highly variable among the different organs and the different phenological phases. GRSPaV triggers some unique responses in the grapevine at véraison, never reported before for other plant-virus interactions. These responses include an increase in transcripts involved in photosynthesis and CO(2) fixation, a moderate reduction in the photosynthesis rate and some defence mechanisms, and an overlap with responses to water and salinity stresses. It is hypothesized that the long co-existence of grapevine and GRSPaV has resulted in the evolution of a form of mutual adaptation between the virus and its host. This study contributes to elucidating alternative mechanisms used by infected plants to contend with viruses.
Cornelia de Lange syndrome (CdLS) is a clinically heterogeneous developmental disorder characterized by facial dysmorphia, upper limb malformations, growth and cognitive retardation. Mutations in the ...sister chromatid cohesion factor genes NIPBL, SMC1A and SMC3 are present in ∼65% of CdLS patients. In addition to their canonical roles in chromosome segregation, the cohesin proteins are involved in other biological processes such as regulation of gene expression, DNA repair and maintenance of genome stability. To gain insights into the molecular basis of CdLS, we analyzed the affinity of mutated SMC1A and SMC3 hinge domains for DNA. Mutated hinge dimers bind DNA with higher affinity than wild-type proteins. SMC1A- and SMC3-mutated CdLS cell lines display genomic instability and sensitivity to ionizing radiation and interstrand crosslinking agents. We propose that SMC1A and SMC3 CdLS mutations affect the dynamic association between SMC proteins and DNA, providing new clues to the underlying molecular cause of CdLS.
Grapevine rupestris stem pitting-associated virus(GRSPaV) is a widespread virus infectingVitisspp. Although it has established a compatible viral interaction inVitis viniferawithout the development ...of phenotypic alterations, it can occur as distinct variants that show different symptoms in diverseVitisspecies. The changes induced by GRSPaV inV. viniferacv ‘Bosco’, an Italian white grape variety, were investigated by combining agronomic, physiological, and molecular approaches, in order to provide comprehensive information about the global effects of GRSPaV. In two years, this virus caused a moderate decrease in physiological efficiency, yield performance, and sugar content in berries associated with several transcriptomic alterations. Transcript profiles were analysed by a microarray technique in petiole, leaf, and berry samples collected at véraison and by real-time RT-PCR in a time course carried out at five grapevine developmental stages. Global gene expression analyses showed that transcriptomic changes were highly variable among the different organs and the different phenological phases. GRSPaV triggers some unique responses in the grapevine at véraison, never reported before for other plant–virus interactions. These responses include an increase in transcripts involved in photosynthesis and CO₂ fixation, a moderate reduction in the photosynthesis rate and some defence mechanisms, and an overlap with responses to water and salinity stresses. It is hypothesized that the long co-existence of grapevine and GRSPaV has resulted in the evolution of a form of mutual adaptation between the virus and its host. This study contributes to elucidating alternative mechanisms used by infected plants to contend with viruses.
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