Longitudinal changes in global structural brain connectivity and cognitive performance in former hospitalized COVID-19 survivors: an exploratory study.

BACKGROUND: Long-term sequelae of COVID-19 can result in reduced functionality of the central nervous system and substandard quality of life. Gaining insight into the recovery trajectory of admitted COVID-19 patients on their cognitive performance and global structural brain connectivity may allow a better understanding of the diseases' relevance. OBJECTIVES: To assess whole-brain structural connectivity in former non-intensive-care unit (ICU)- and ICU-admitted COVID-19 survivors over 2 months following hospital discharge and correlate structural connectivity measures to cognitive performance. METHODS: Participants underwent Magnetic Resonance Imaging brain scans and a cognitive test battery after hospital discharge to evaluate structural connectivity and cognitive performance. Multilevel models were constructed for each graph measure and cognitive test, assessing the groups' influence, time since discharge, and interactions. Linear regression models estimated whether the graph measurements affected cognitive measures and whether they differed between ICU and non-ICU patients. RESULTS: Six former ICU and six non-ICU patients completed the study. Across the various graph measures, the characteristic path length decreased over time (ß = 0.97, p = 0.006). We detected no group-level effects (ß = 1.07, p = 0.442) nor interaction effects (ß = 1.02, p = 0.220). Cognitive performance improved for both non-ICU and ICU COVID-19 survivors on four out of seven cognitive tests 2 months later (p < 0.05). CONCLUSION: Adverse effects of COVID-19 on brain functioning and structure abate over time. These results should be supported by future research including larger sample sizes, matched control groups of healthy non-infected individuals, and more extended follow-up periods.

Randomized phase II study of axitinib versus physicians best alternative choice of therapy in patients with recurrent glioblastoma.

We conducted a randomized, non-comparative, multi center, phase II clinical trial in order to investigate the efficacy of axitinib, an oral small molecule tyrosine kinase inhibitor with high affinity and specificity for the vascular endothelial growth factor receptors, in patients with recurrent glioblastoma following prior treatment with radiation and temozolomide. Forty-four patients were randomly assigned to receive treatment with axitinib (5 mg BID starting dose; N = 22) or "physicians best alternative choice of therapy" that consisted of bevacizumab (N = 20) or lomustine (N = 2). Six-month progression-free survival served as the primary endpoint. The estimated 6-month progression-free survival rate was 34 % (95 % CI 14-54) for patients treated with axitinib and 28 % (95 % CI 8-48) with best alternative treatment; median overall survival was 29 and 17 weeks, respectively. Objective responses according to RANO criteria were documented in 28 % of patients treated with axitinib and 23 % of patients treated with best alternative therapy. A decrease in maximal uptake of 18F-fluoro-ethyL-tyrosine (18F-FET) by the glioblastoma on PET imaging was documented in 85 % of patients at the time of response on axitinib. Corticosteroid treatment could be stopped in four and tapered in seven out of the 15 patients who were treated with steroids at baseline in the axitinib cohort. Most frequent axitinib related grade ≥3 adverse events consisted of fatigue (9 %), diarrhea (9 %), and oral hyperesthesia (4.5 %). We conclude that axitinib has single-agent clinical activity and a manageable toxicity profile in patients with recurrent glioblastoma.

An observational study of the first experience with bevacizumab for the treatment of patients with recurrent high-grade glioma in two belgian university hospitals.

Background. Bevacizumab (BEV), a humanized immunoglobulin G1 monoclonal antibody that inhibits VEGF has demonstrated activity against recurrent high-grade gliomas (HGG) in phase II clinical trials. Patients and Methods. Data were collected from patients with recurrent HGG who initiated treatment with BEV outside a clinical trial protocol at two Belgian university hospitals. Results. 19 patients (11 M/8 F) were administered a total of 138 cycles of BEV (median 4, range 1-31). Tumor response assessment by MRI was available for 15 patients; 2 complete responses and 3 partial responses for an objective response rate of 26% for the intent to treat population were observed on gadolinium-enhanced T1-weighted images; significant regressions on T2/FLAIR were documented in 10 out of 15 patients (67%). A reduced uptake on PET was documented in 3 out of 4 evaluable patients. The six-month progression-free survival was 21% (95% CI 2.7-39.5). Two patients had an ongoing tumor response and remained free from progression after 12 months of BEV treatment. Conclusions. The activity and tolerability of BEV were comparable to results from previous prospective phase II trials. Reduced uptake on PET suggests a metabolic response in addition to an antiangiogenic effect in some cases with favorable clinical outcome.

Is there any relationship between nCPAP therapy and signs of sinus hyperpneumatization?

OBJECTIVES: Both nasal continuous positive airway pressure (nCPAP) therapy and nose blowing can generate high pressures in the nose and sinuses. Nose blowing generates higher pressures than nCPAP therapy, but the duration of nCPAP therapy is considerably longer than the duration of nose blowing. Therefore, nCPAP could cause bone deformation. The aim of this study was to document the influence of the pressure generated by nCPAP therapy on the structure and dimensions of the sinuses and on the nose-blowing patterns of the patients. METHODOLOGY: The study included nine patients, who had recently been diagnosed with obstructive sleep apnea syndrome (OSAS) and had not received any previous treatment for OSAS. Before nCPAP therapy was started, they all underwent computer tomography (CT) in the prone position with sequential coronal slices followed by pressure measurements during nose blowing. After the initial measurements, nCPAP therapy commenced. All of the patients were treated with a fixed-pressure device and nasal mask for 6 mo. nCPAP therapy compliance was checked after 6 mo. At the end of the 6 mo treatment with nCPAP, coronal CT scans of the sinuses and pressure measurements during nose blowing were repeated. RESULTS AND CONCLUSION: Although CPAP therapy provides continuous positive pressure for several hours at night, bone structure and sinus dimensions appeared to be unchanged after 6 mo of therapy. However, CPAP therapy seemed to have an effect on the nose-blowing pattern of the patients, with a significant decrease in nose blowing pressure after 6 mo of CPAP treatment.

Pituitary microadenomas: diagnosis with dynamic serial CT, conventional CT and T1-weighted MR imaging before and after injection of gadolinium.

PURPOSE: The few studies comparing CT and MR in the diagnosis of pituitary microadenomas give discordant results. This prospective study compares the value of dynamic serial CT (DSCT), conventional CT (CCT), pre-Gd T1-weighted spin echo (T1SE-Gd) and post-Gd T1-weighted SE (T1SE+Gd) in the detection of pituitary microadenomas. METHODS: The value of CT and MR was assessed in 17 cases, with the surgical confirmation as reference. The CTs and MRs were independently and blindly evaluated by two neuroradiologists. Because the finding at MR and/or CT influenced the selection of patients for surgery, the positive predictive value was calculated. The sensitivity calculation applies only for a specific group of postsurgical patients with positive CT and/or MR (marked with an asterisk for these reasons). RESULTS: In this study, the highest sensitivity* (88% and 82%, respectively, for observers I and II) was achieved by DSCT. The T1SE-Gd and T1SE+Gd (evaluated separately) were slightly inferior (sensitivity* of 76% for observer I). The combination of T1SE-Gd with T1SE+Gd improved the sensitivity* to 94% and 82% respectively, for observers I and II. There was also moderate improvement of sensitivity* by combination of DSCT with conventional CT (94% for observer I). CONCLUSION: These results suggest that rapid injection of a large amount of contrast conjointly with a fast scanning through the pituitary is crucial for the confident detection of microprolactinomas. Taking into account the similar results of the combination DSCT + CT and T1SE-Gd + T1SE+Gd in the detection of microprolactinomas, high field MRI is the first step modality in the evaluation of presumed hypophyseal hyperprolactinemia.