Imaging the effective networks associated with cortical function through intracranial high‐frequency stimulation

Direct electrical stimulation (DES) is considered to be the gold standard for mapping cortical function. A careful mapping of the eloquent cortex is key to successful resective or ablative surgeries, with a minimal postoperative deficit, for treatment of drug‐resistant epilepsy. There is accumulating evidence suggesting that not only local, but also remote activations play an equally important role in evoking clinical effects. By introducing a new intracranial stimulation paradigm and signal analysis methodology allowing to disambiguate EEG responses from stimulation artifacts we highlight the spatial extent of the networks associated with clinical effects. Our study includes 26 patients that underwent stereoelectroencephalographic investigations for drug‐resistant epilepsy, having 337 depth electrodes with 4,351 contacts sampling most brain structures. The routine high‐frequency electrical stimulation protocol for eloquent cortex mapping was altered in a subtle way, by alternating the polarity of the biphasic pulses in a train, causing the splitting the spectral lines of the artifactual components, exposing the underlying tissue response. By performing a frequency‐domain analysis of the EEG responses during DES we were able to capture remote activations and highlight the effect''s network. By using standard intersubject averaging and a fine granularity HCP‐MMP parcellation, we were able to create local and distant connectivity maps for 614 stimulations evoking specific clinical effects. The clinical value of such maps is not only for a better understanding of the extent of the effects'' networks guiding the invasive exploration, but also for understanding the spatial patterns of seizure propagation given the timeline of the seizure semiology.     

Immunogenicity Following Administration of BNT162b2 and Ad26.COV2.S COVID-19 Vaccines in the Pregnant Population during the Third Trimester

Globally, COVID-19 vaccines are currently being used to prevent transmission and to reduce morbidity and death associated with SARS-CoV-2 infection. Current research reveals that vaccines such as BNT162b2 and Ad26.COV2.S are highly immunogenic and have high short-term effectiveness for most of the known viral variants. Clinical trials showed satisfying results in the general population, but the reluctance in testing and vaccinating pregnant women left this category with little evidence regarding the safety, efficacy, and immunogenicity following COVID-19 vaccination. With the worldwide incidence of COVID-19 remaining high and the possibility of new transmissible SARS-CoV-2 mutations, data on vaccination effectiveness and antibody dynamics in pregnant patients are critical for determining the need for special care or further booster doses. An observational study was developed to evaluate pregnant women receiving the complete COVID-19 vaccination scheme using the BNT162b2 and Ad26.COV2.S, and determine pregnancy-related outcomes in the mothers and their newborns, as well as determining adverse events after vaccination and immunogenicity of vaccines during four months. There were no abnormal findings in pregnancy and newborn characteristics comparing vaccinated versus unvaccinated pregnant women. COVID-19 seropositive pregnant women had significantly higher spike antibody titers than seronegative patients with similar characteristics, although they were more likely to develop fever and lymphadenopathy following vaccination. The same group of pregnant women showed no statistically significant differences in antibody titers during a 4-month period when compared with case-matched non-pregnant women. The BNT162b2 and Ad26.COV2.S vaccines are safe to administer during the third trimester of pregnancy, while their safety, efficacy, and immunogenicity remain similar to those of the general population.     

Update on the clinical use of kinase inhibitors in melanoma

The identification of targetable molecules in cellular signaling pathways represents a milestone in the treatment of melanoma. Selective inhibitors of these molecules, known as phosphokinases, allow for individual signaling pathways to be “switched off”. This is of particular importance for tumors in which these pathways are constitutively activated by mutations in genes encoding said molecules. Especially patients with BRAF‐mutated melanomas significantly benefit from kinase inhibitor therapies, with the current standard of combined BRAF and MEK inhibition providing very good long‐term disease control. Such regimens have been shown to achieve a progression‐free survival of more than ten months and an overall survival of more than two years, along with good quality of life. Given that the majority of patients develop secondary resistance during long‐term kinase inhibitor therapy, current clinical trials are geared towards finding suitable drug combinations including inhibitors of other signaling pathways as well as immune checkpoint inhibitors. The present review highlights targeted therapies for melanoma currently available as well as potential future options presently under clinical investigation.     

HE4 Expression in Plasma Correlates with Surgical Outcome and Overall Survival in Patients with First Ovarian Cancer Relapse

Background

Epithelial ovarian cancer (EOC) remains the main cause of mortality due to gynecological malignancies. Optimal tumor debulking and platinum response are the most important prognostic factors for overall survival (OS) in primary EOC. In the setting of recurrence, the role of cytoreduction is not clear. A critical point is to predict preoperatively the subgroup of patients with optimal surgical outcome. The aim of the study was to analyze the predictive role of HE4 for surgical outcome and platinum response in EOC patients experiencing a first relapse. Secondary aims were the prognostic role of HE4 for OS and progression-free survival (PFS).

Methods

Plasma was obtained before secondary cytoreduction from 73 EOC patients. A total of 66.7 % underwent a total macroscopic tumor clearance; 86.3 % of the patients had disease that responded to platinum therapy. HE4 was detected by enzyme-linked immunosorbent assay. For statistical analysis, the chi-square test, Fisher’s exact test, Kendall’s tau b, and Mann-Whitney U test were used. OS, PFS rates, and respective 95 % confidence intervals (CI) were estimated according to the Kaplan–Meier method.

Results

At a HE4 cutoff value of 250 pMk, a sensitivity of 52 % and a specificity of 93.8 % (p = 0.001, 95 % CI 0.601–0.861) were reached in predicting total macroscopic tumor clearance. Plasma HE4 concentrations together with platinum response were the only independent prognostic factors for OS (p < 0.001, hazard ratio [HR] 18.77, 95 % CI 4.68–75.25; and p = 0.044, HR 3.33, 95 % CI 1.03–10.7, respectively). Together with ascites, HE4 was the only independent predictive factor for surgical outcome (p = 0.029, odds ratio [OR] 7.2, 95 % CI 1.22–42.19 and p = 0.036, OR 10.18, 95 % CI 1.16–88.69, respectively).

Conclusions

HE4 is an independent predictive marker for surgical outcome and OS in patients with recurrent EOC. Larger population studies are needed to validate these results.     

The role of capsule endoscopy in suspected Crohn's disease

Capsule endoscopy (CE) revolutionized the small bowel examination. We emphasize the role of CE in suspected Crohn's disease, studying 24 investigations performed in the Institute of Gastroenterology and Hepatology. The global diagnostic yield was 54%, the specific diagnostic yield for Crohn's disease was 37.5%, the specificity was 100% and the retention rate was 4.1%. For maximum accuracy and efficiency, unitary administration and diagnostic criteria are needed, and for minimising the risk of complications, specific prior investigations would be suitable.     

Biochemical and Metabolical Pathways Associated with Microbiota-Derived Butyrate in Colorectal Cancer and Omega-3 Fatty Acids Implications: A Narrative Review

Knowledge regarding the influence of the microbial community in cancer promotion or protection has expanded even more through the study of bacterial metabolic products and how they can modulate cancer risk, which represents an extremely challenging approach for the relationship between intestinal microbiota and colorectal cancer (CRC). This review discusses research progress on the effect of bacterial dysbiosis from a metabolic point of view, particularly on the biochemical mechanisms of butyrate, one of the main short chain fatty acids (SCFAs) with anti-inflammatory and anti-tumor properties in CRC. Increased daily intake of omega-3 polyunsaturated fatty acids (PUFAs) significantly increases the density of bacteria that are known to produce butyrate. Omega-3 PUFAs have been proposed as a treatment to prevent gut microbiota dysregulation and lower the risk or progression of CRC.     

Comparative Study on Nutrition and Lifestyle of Information Technology Workers from Romania before and during COVID-19 Pandemic

The study aimed to evaluate lifestyle factors among Information Technology (IT) workers from Romania before and during the pandemic. We used an online applied questionnaire, filled in by 1638 respondents, that assessed nutrition status-Body Mass Index (BMI), weight and diet change, physical activity, alcohol consumption, number of hours working in front of the computer, stress, and sleep. Multivariate logistic regression was used to establish the lifestyle factors that lead to weight gain. Although the level of physical activity (PA) was low before the pandemic, the results of our study showed a further decrease in physical activity. In total, 61.1% of men and 71.1% of women performed PA for less than 30 min per day. Weight gain was reported in 50.5% of men and 45.3% of women (mean weight gain was 5.11 ± 3.52 kg) as a result of increased screen time (with a mean of 3.52 ± 4.29 for females and 3.05 ± 2.09 for males, p > 0.05 h per day) and the reported changes in diet. Despite the popularity of home-cooked foods, the intake of vegetables and fruit remained low. The quality of sleep was poor for 55.7% of the respondents. Public health and corporation policies are required to encourage a healthy lifestyle and avoid chronic diseases.