The unfavorable clinical outcome of COVID-19 in smokers is mediated by H3K4me3, H3K9me3 and H3K27me3 histone marks

Smoking could predispose individuals to a more severe COVID-19 by upregulating a particular gene known as mdig, which is mediated through a number of well-known histone modifications. Smoking might regulate the transcription-activating H3K4me3 mark, along with the transcription-repressing H3K9me3 and H3K27me3 marks, in a way to favor SARS-CoV-2 entry by enhancing the expression of ACE2, NRP1 and NRP2, AT1R, CTSD and CTSL, PGE2 receptors 2–4, SLC6A20 and IL-6, all of which interact either directly or indirectly with important receptors, facilitating viral entry in COVID-19.

Decreased CD8+ Lymphocytic Infiltration in Multifocal and Multicentric Glioblastomas

PurposeMultifocal and multicentric glioblastomas (mGBMs) are associated with a poorer prognosis compared to unifocal glioblastoma (uGBM). The presence of CD8+ tumor-infiltrating lymphocytes (TILs) is predictive of clinical outcomes in human malignancies. Here, we examined the CD8+ lymphocytic infiltration in mGBMs.MethodsThe clinical data of 57 consecutive IDH wildtype primary mGBM patients with histopathological diagnoses were retrospectively reviewed. CD8+ TILs were quantitatively evaluated by immunohistochemical staining. The survival function of CD8+ TILs was assessed by Kaplan–Meier analysis and Cox proportional hazard models.ResultsNo significant difference in the concentration of CD8+ TILs was observed among foci from the same patient (P>0.150). The presence of CD8+ TILs was similar between multifocal and multicentric GBMs (P=0.885). The concentration of CD8+ TILs was significantly lower in mGBMs than in uGBMs (P=0.002). In mGBM patients, the CD8+ TIL level was associated with preoperative KPS (P=0.018). The median overall survival (OS) of the 57 mGBMs was 9 months. A low CD8+ TIL level (multivariate HR 4.404, 95% CI 1.954-9.926, P=0.0004) was an independent predictor of poor OS, while postoperative temozolomide chemotherapy (multivariate HR 6.076, 95% CI 2.330-15.842, P=0.0002) was independently associated with prolonged OS in mGBMs.ConclusionsDecreased CD8+ TIL levels potentially correlate with unfavorable clinical outcome in mGBMs, suggesting an influence of the local immuno-microenvironment on the progression of mGBMs.

Microsurgical management of midbrain cavernous malformations: does lesion depth influence the outcome?

Background The purpose of this study was to clarify whether the intrinsic depth of midbrain cavernous malformations (MCMs) influenced the surgical outcome. Methods The authors conducted a retrospective study of 76 consecutive patients who underwent microsurgical resection of a MCM. The vascular lesions were categorized into 4 distinct groups based on how these lesions had altered the brainstem surface. Additionally, it was verified whether the actual aspect of the brainstem surface could be predicted only by evaluating the pertinent preoperative MRI slices. Clinical outcome was assessed by determining the modified Rankin Scale Score (mRS) before and after surgery. Results Twenty-three MCMs (30.3%) were located deeply within the midbrain. The overlying midbrain surface appeared to be normal (group nl). In 33 patients (43.4%), the midbrain surface showed only a yellowish discoloration (group yw). In another 14 individuals (18.4%), the midbrain surface was distorted by the underlying MCM and bulging out while the vascular lesion still remained covered by a thin parenchymal layer (group bg). In the smallest group comprising 6 patients (7.9%), the exophytic MCM had disrupted the midbrain surface and was clearly visible at microsurgical exposure (group ex). The mean mRS decreased in the group nl from 1.43 preoperatively to 0.61 at follow-up. Conclusion This study demonstrates in a large patient population that a deep intrinsic MCM location is not necessarily associated with an unfavorable clinical outcome after microsurgical lesionectomy. Predicting the aspect of the midbrain surface by evaluating preoperative MR images alone was not sufficiently reliable.

SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome.

Baseline Cerebral Ischemic Core Quantified by Different Automatic Software and Its Predictive Value for Clinical Outcome

PurposeThis study aims to investigate the agreement of three software packages in measuring baseline ischemic core volume (ICV) and penumbra volume (PV), and determine their predictive values for unfavorable clinical outcome in patients with endovascular thrombectomy (EVT).MethodsPatients with acute ischemic stroke who underwent computed tomographic perfusion (CTP) were recruited. Baseline CTP measurements including ICV and PV were calculated by three software packages of IntelliSpace Portal (ISP), Rapid Processing of Perfusion and Diffusion (RAPID), and fast-processing of ischemic stroke (F-STROKE). All patients received EVT, and the modified Rankin scale (mRS) at 90 days after EVT was assessed to determine the clinical outcomes (favorable: mRS = 0–2; unfavorable: mRS = 3–6). The agreement of CTP measurements among three software packages was determined using intraclass correlation coefficient (ICC). The associations between CTP measurements and unfavorable clinical outcome were analyzed using logistic regression. Receiver operating characteristic curves were conducted to calculate the area under the curve (AUC) of CTP measurements in predicting unfavorable clinical outcome.ResultsOf 223 recruited patients (68.2 ± 11.3 years old; 145 males), 17.0% had unfavorable clinical outcome after EVT. Excellent agreement between F-STROKE and RAPID was found in measuring ICV (ICC 0.965; 95% CI 0.956–0.973) and PV (ICC 0.966; 95% CI 0.956–0.973). ICVs measured by three software packages were significantly associated with unfavorable clinical outcome before (odds ratios 1.012–1.018, all P < 0.01) and after (odds ratios 1.003–1.014, all P < 0.05) adjusted for confounding factors (age, gender, TOAST classification, and NIHSS on admission). In predicting unfavorable clinical outcome, ICV measured by F-STROKE showed similar performance to that measured by RAPID (AUC 0.701 vs. 0.717) but higher performance than that measured by ISP (AUC 0.629).ConclusionsThe software of F-STROKE has excellent agreement with the widely used analysis tool of RAPID in measuring ICV and PV. The ischemic core volume measured by both F-STROKE and RAPID is a stronger predictor for unfavorable clinical outcome after EVT compared to ISP.

High Serum Complement Component C4 as An Unique Predictor of Unfavorable Outcomes in Diabetic Stroke

Objective: Previous studies demonstrated that diabetic stroke patient had a poor prognosis and excess activation of the complement system in the peripheral blood. In this study, the association of serum complement levels with prognosis of diabetic stroke was examined. Methods: Patients with acute ischemic stroke were recruited and were divided into two groups according to the history of diabetes. Baseline data on the admission including C3 and C4 were collected. Neurologic function at discharge was the primary outcome and was quantified by the National Institutes of Health Stroke Scale (NIHSS). Results: A total of 426 patients with acute ischemic stroke (116 diabetic stroke and 310 non-diabetic stroke) were recruited in this study. There were significant differences on hypertension, CHD, TG, HDL, FGB, C4, and mortality rate between two groups. Furthermore, the values of complement protein levels were divided into tertiles. In diabetic stroke group, serum C4 level at acute phase in the upper third was independently associated with NIHSS score at discharge and concurrent infection. This associations were not significant in non-diabetic stroke. Conclusion: High serum C4 level at admission, as an unique significant predictor, was associated with unfavorable clinical outcome in the diabetic stroke, independently of traditional risk factors.