Unraveling the peripheral and local role of inflammatory cytokines in glioblastoma survival.

Glioblastoma (GBM) is a life-threatening disease that presents high morbidity and mortality. The standardized treatment protocol results in a global survival of less than three years in the majority of cases. Immunotherapies have gained wide recognition in cancer treatment; however, GBM has an immunosuppressive microenvironment diminishing the possible effectiveness of this therapy. In this sense, investigating the inflammatory settings and the tumoral nature of GBM patients are an important goal to create an individual plan of treatment to improve overall survival rate and quality of life of these patients. Thirty-two patients who underwent surgical resection of GBM were included in this study. Tumor samples and 10 mL of peripheral blood were collected and immediately frozen. TNF-a, IL-1a and IL-4 were evaluated in the tumor and TNF-a, IL-1a and TGF-b in the plasma by Luminex assay. Immunohistochemistry analysis to determine immune celular profile was done, including immunohistochemistry for CD20, CD68 and CD3. Three cases were excluded. Tumor topography, tumor nature, and tumor volume reconstructions were accurately analyzed by T1-weighted, T2-weighted, and FLAIR magnetic resonance imaging. We found that GBM patients with below median peripheral levels of TNF-a and IL-1a had a decreased survival rate when compared to above median patients. On the other hand, patients with below median peripheral levels of TGF-b increased overall survival rate. Intratumoral IL-1a above median was associated with higher number of macrophages and fewer with B cells. Furthermore, plasmatic TNF-a levels were correlated with intratumoral TNF-a levels, suggesting that peripheral cytokines are related to the tumoral microenvironment. Even though tumor size has no difference regarding survival rate, we found a negative correlation between intratumoral IL-4 and tumor size, where larger tumors have less IL-4 expression. Nevertheless, the tumoral nature had a significant effect in overall survival rate, considering that infiltrative tumors showed decreased survival rate and intratumoral TNF-a. Moreover, expansive tumors revealed fewer macrophages and higher T cells. In multiple variation analyzes, we demonstrated that infiltrative tumors and below median peripheral IL-1a expression represent 3 times and 5 times hazard ratio, respectively, demonstrating a poor prognosis. Here we found that peripheral cytokines had a critical role as prognostic tools in a small cohort of GBM patients.

Variation in postoperative outcomes of patients with intracranial tumors: insights from a prospective international cohort study during the COVID-19 pandemic.

BACKGROUND: This study assessed the international variation in surgical neuro-oncology practice and 30-day outcomes of patients who had surgery for an intracranial tumor during the COVID-19 pandemic. METHODS: We prospectively included adults aged ≥18 years who underwent surgery for a malignant or benign intracranial tumor across 55 international hospitals from 26 countries. Each participating hospital recorded cases for 3 consecutive months from the start of the pandemic. We categorized patients' location by World Bank income groups (high [HIC], upper-middle [UMIC], and low- and lower-middle [LLMIC]). Main outcomes were a change from routine management, SARS-CoV-2 infection, and 30-day mortality. We used a Bayesian multilevel logistic regression stratified by hospitals and adjusted for key confounders to estimate the association between income groups and mortality. RESULTS: Among 1016 patients, the number of patients in each income group was 765 (75.3%) in HIC, 142 (14.0%) in UMIC, and 109 (10.7%) in LLMIC. The management of 200 (19.8%) patients changed from usual care, most commonly delayed surgery. Within 30 days after surgery, 14 (1.4%) patients had a COVID-19 diagnosis and 39 (3.8%) patients died. In the multivariable model, LLMIC was associated with increased mortality (odds ratio 2.83, 95% credible interval 1.37-5.74) compared to HIC. CONCLUSIONS: The first wave of the pandemic had a significant impact on surgical decision-making. While the incidence of SARS-CoV-2 infection within 30 days after surgery was low, there was a disparity in mortality between countries and this warrants further examination to identify any modifiable factors.

Differential aspects of stroke and congestive heart failure in quality of life reduction: a case series with three comparison groups.

BACKGROUND: To assess QOL of patients with stroke in comparison to other groups (caregivers and CHF patients), to identify which items of QOL are more affected on each group and what is the functional profile of patients with stroke. METHODS: Consecutive stroke or congestive heart failure (CHF) patients were evaluated and compared to their caregivers (caregivers). The NIH Stroke Scale (NIHSS) and EuroQoL-5D (EQ-5D) scale were applied. RESULTS: We evaluated 67 patients with stroke, 62 with CHF and 67 caregivers. For stroke patients, median NIHSS score was four. EQ-5D score was significantly worse in stroke, as compared to CHF and caregivers (0.52, 0.69 and 0.65, respectively). Mobility and usual activity domains were significantly affected in stroke and CHF patients as compared to caregivers; and self-care was more affected in stroke as compared with the other two groups. CONCLUSIONS: Despite a mild neurological deficit, there was a significantly worse QOL perception in stroke as compared to CHF patients, mostly in their perception of self-care.

Validation of the National Institutes of Health Stroke Scale, modified Rankin Scale and Barthel Index in Brazil: the role of cultural adaptation and structured interviewing.

BACKGROUND: We aimed to validate three widely used scales in stroke research in a multiethnic Brazilian population. METHODS: The National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index (BI) were translated, culturally adapted and applied by two independent investigators. The mRS was applied with or without a previously validated structured interview. Interobserver agreement (kappa statistics) and intraclass correlation coefficients were calculated. RESULTS: 84 patients underwent mRS (56 with and 28 without a structured interview), 57 BI and 62 NIHSS scoring. Intraclass correlation coefficient was 0.902 for NIHSS and 0.967 for BI. For BI, interobserver agreement was good (kappa = 0.70). For mRS, the structured interview improved interobserver agreement (kappa = 0.34 without a structured interview; 0.75 with a structured interview). CONCLUSION: The NIHSS, BI and mRS show good validity when translated and culturally adapted. Using a structured interview for the mRS improves interobserver concordance rates.

Balanced Crystalloids Versus Saline for Perioperative Intravenous Fluid Administration in Children Undergoing Neurosurgery: A Randomized Clinical Trial.

BACKGROUND: Balanced crystalloid solutions induce less hyperchloremia than normal saline, but their role as primary fluid replacement for children undergoing surgery is unestablished. We hypothesized that balanced crystalloids induce less chloride and metabolic derangements than 0.9% saline solutions in children undergoing brain tumor resection. METHODS: In total, 53 patients (age range, 6 mo to 12 y) were randomized to receive balanced crystalloid (balanced group) or 0.9% saline solution (saline group) during and after (for 24 h) brain tumor resection. Serum electrolyte and arterial blood gas analyses were performed at the beginning of surgery (baseline), after surgery, and at postoperative day 1. The primary trial outcome was the absolute difference in serum chloride concentrations (post-preopΔCl) measured after surgery and at baseline. Secondary outcomes included the post-preopΔ of other electrolytes and base excess (BE); hyperchloremic acidosis incidence; and the brain relaxation score, a 4-point scale evaluated by the surgeon for assessing brain edema. RESULTS: Saline infusion increased post-preopΔCl (6 [3.5; 8.5] mmol/L) compared with balanced crystalloid (0 [-1.0; 3.0] mmol/L; P<0.001). Saline use also resulted in increased post-preopΔBE (-4.4 [-5.0; -2.3] vs. -0.4 [-2.7; 1.3] mmol/L; P<0.001) and hyperchloremic acidosis incidence (6/25 [24%] vs. 0; P=0.022) compared with balanced crystalloid. Brain relaxation score was comparable between groups. CONCLUSIONS: In children undergoing brain tumor resection, saline infusion increased variation in serum chloride compared with balanced crystalloid. These findings support the use of balanced crystalloid solutions in children undergoing brain tumor resection.

Caudal Zona Incerta/VOP Radiofrequency Lesioning Guided by Combined Stereotactic MRI and Microelectrode Recording for Posttraumatic Midbrain Resting-Kinetic Tremor.

OBJECTIVE: Reporting the outcome of two patients who underwent unilateral ablative stereotactic surgery to treat pharmacologic resistant posttraumatic tremor (PTT). METHODS: We present two patients (31 and 47 years old) with refractory PTT severely affecting their quality of life. Under stereotactic guidance, refined by T2-weighted magnetic resonance imaging and double-channel multiunit microelectrode recording (MER), three sequential radiofrequency lesions were performed in the caudal zona incerta (cZi) up to the base of thalamus (VOP). Effects of cZi/VOP lesion were prospectively rated with a tremor rating scale. RESULTS: Both patients demonstrated intraoperative tremor suppression with sustained results up to 18 months follow-up, with improvement of 92% and 84%, respectively, on the tremor rating scale. Tremor improvement was associated with enhancement functionality and quality of life for the patients. The patients returned to their work after the procedure. No adverse effects were observed up to the last follow-up. CONCLUSION: Radiofrequency lesion of the cZi/VOP target was effective for posttraumatic tremor in both cases. The use of T2-weighted images and MER was found helpful in increasing the precision and safety of the procedure, because it leads the RF probe by relying on neighbor structures based on thalamus and subthalamic nucleus.

Chagas disease is independently associated with brain atrophy.

Chagas disease (CD) remains a major cause of cardiomyopathy and stroke in developing countries. Brain involvement in CD has been attributed to left ventricular dysfunction, resulting in chronic brain ischemia due to hypoperfusion and/or embolic infarcts. However, cognitive impairment in CD may occur independently of cardiac disease. Therefore, we aimed to investigate head computed tomography (CT) findings in patients with Chagas disease cardiomyopathy (CDC) in comparison with other cardiomyopathies (OC). We studied 73 patients with CDC (n = 41) or OC (n = 32) matched for age and gender. These patients underwent head CT, rated by an investigator blinded to all clinical information. Head CT was rated for the presence of lacunar or territorial infarcts, as well as for measuring the total volumes of the brain, cerebellum and ventricles. Total brain volume was smaller in CDC as compared to OC patients (1,135 +/- 150 vs. 1,332 +/- 198 cm(3), P < 0.001). Cerebellar and ventricular volumes did not differ between the groups. The prevalence of brain infarcts did not differ significantly between the groups. Chagas disease was the only independent predictor of brain atrophy in the multivariable analysis (OR = 1.38; 95% CI = 1.06-1.79, P = 0.017). Chagas disease is associated with brain atrophy independent of structural cardiac disease related to cardiomyopathy. Brain atrophy, rather than multiple infarcts, may represent the main anatomical substrate of cognitive impairment in Chagas disease.