Safety and efficacy of responsive neurostimulation in the pediatric population: Evidence from institutional review and patient-level meta-analysis.

BACKGROUND: Responsive neurostimulation (RNS) is a novel technology for drug-resistant epilepsy rising from bilateral hemispheres or eloquent cortex. Although recently approved for adults, its safety and efficacy for pediatric patients is under investigation. METHODS: A comprehensive literature search (Pubmed/Medline, Scopus, Cochrane) was conducted for studies on RNS for pediatric epilepsy (<18 y/o) and supplemented by our institutional series (4 cases). Reduction in seizure frequency at last follow-up compared to preoperative baseline comprised the primary endpoint. RESULTS: A total of 8 studies (49 patients) were analyzed. Median age at implant was 15 years (interquartile range [IQR] 12-17) and 63% were males. A lesional MRI was noted in 64% (14/22). Prior invasive EEG recording was performed in the majority of patients (90%) and the most common modality was stereoelectroencephalography (57%). The most common implant location (total of 94 RNS leads) was the frontal lobe (27%), followed by mesial temporal structures (23%) and thalamus (17%). At a median follow-up of 22 months, median seizure frequency reduction was 75% (IQR: 50-88%) and 80% were responders (>50% seizure reduction). Responses ranged from 50% for temporal lobe epilepsy to 81-93% for frontal, parietal, and multilobar epilepsy. Four infections were observed (8%) and there were no hematomas or postoperative neurological deficits. CONCLUSION: Current evidence, albeit limited by potential publication bias, supports the promising safety and efficacy profile of RNS for medically refractory pediatric epilepsy. Randomized controlled trial data are needed to further establish the role of this intervention in preoperative discussions with patients and their families.

Comparison of Genes Associated with Thoracic and Abdominal Aortic Aneurysms.

Aneurysms impacting the ascending thoracic aorta and the abdominal aorta affect patient populations with distinct clinical characteristics. Through a literature review, this paper compares the genetic associations of ascending thoracic aortic aneurysm (ATAA) with abdominal aortic aneurysms (AAA). Genes related to atherosclerosis, lipid metabolism, and tumor development are associated specifically with sporadic AAA, while genes controlling extracellular matrix (ECM) structure, ECM remodeling, and tumor growth factor ß function are associated with both AAA and ATAA. Contractile element genes uniquely predispose to ATAA. Aside from known syndromic connective tissue disease and poly-aneurysmal syndromes (Marfan disease, Loeys-Dietz syndrome, and Ehlers-Danlos syndrome), there is only limited genetic overlap between AAA and ATAA. The rapid advances in genotyping and bioinformatics will elucidate further the various pathways associated with the development of aneurysms affecting various parts of the aorta.

Liver transplantation during COVID-19: Adaptive measures with future significance.

Following the outbreak of coronavirus disease 2019 (COVID-19), a disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the field of liver transplantation, along with many other aspects of healthcare, underwent drastic changes. Despite an initial increase in waitlist mortality and a decrease in both living and deceased donor liver transplantation rates, through the implementation of a series of new measures, the transplant community was able to recover by the summer of 2020. Changes in waitlist prioritization, the gradual implementation of telehealth, and immunosuppressive regimen alterations amidst concerns regarding more severe disease in immunocompromised patients, were among the changes implemented in an attempt by the transplant community to adapt to the pandemic. More recently, with the advent of the Pfizer BNT162b2 vaccine, a powerful new preventative tool against infection, the pandemic is slowly beginning to subside. The pandemic has certainly brought transplant centers around the world to their limits. Despite the unspeakable tragedy, COVID-19 constitutes a valuable lesson for health systems to be more prepared for potential future health crises and for life-saving transplantation not to fall behind.

The Synergistic Role of Irreversible Electroporation and Chemotherapy for Locally Advanced Pancreatic Cancer.

Irreversible electroporation (IRE) is a local ablative technique used in conjunction with chemotherapy to treat locally advanced pancreatic cancer (LAPC). The combination of IRE and chemotherapy has showed increased overall survival when compared to chemotherapy alone, pointing towards a possible facilitating effect of IRE on chemotherapeutic drug action and delivery. This review aims to present current chemotherapeutic regimens for LAPC and their co-implementation with IRE, with an emphasis on possible molecular augmentative mechanisms of drug delivery and action. Moreover, the potentiating mechanism of IRE on immunotherapy, M1 oncolytic virus and dendritic cell (DC)-based treatments is briefly explored. Investigating the synergistic effect of IRE on currently established treatment regimens as well as newer ones, may present exciting new possibilities for future studies seeking to improve current LAPC treatment algorithms.

Prevalence of abnormal liver biochemistry and its impact on COVID-19 patients' outcomes: a single-center Greek study.

Background: Abnormalities in aminotransferases are frequently observed in hospitalized COVID-19 patients, but their clinical impact is poorly characterized. Methods: A total of 1046 patients hospitalized to the non-intensive care unit ward with documented COVID-19 were included retrospectively. Demographic, clinical and laboratory characteristics on admission and during hospital stay, including the presence of liver injury (LI), defined as aspartate aminotransferase (AST) >200 IU/L, were recorded. Results: On admission, 363 (34.7%) and 269 (25.7%) patients had abnormal AST and ALT values (i.e., >40 IU/L), respectively, while during hospitalization 53 (5%) patients fulfilled the criteria for LI. In multivariate logistic regression analysis, AST (odds ratio [OR] 1.023, 95% confidence interval [CI] 1.016-1.029; P<0.001), and ferritin (OR 1.01, 95%CI 1.001-1.02; P<0.001) were the baseline factors independently associated with the development of LI during hospital stay. One hundred twenty-three (11.7%) patients died during hospitalization. The independent variables associated with mortality were: age (hazard ratio [HR] 1.043, 95%CI 1.029-1.056; P<0.001), ferritin (HR 1.1, 95%CI 1.05-1.2; P<0.001), platelets (HR 0.996, 95%CI 0.994-0.999; P=0.003), and administration of remdesivir (HR 0.50, 95%CI 0.30-0.85; P=0.009). The patients with abnormal baseline AST (i.e., >40 IU/L), compared to those with normal AST values, had worse outcomes (log rank test: 8.8, P=0.003). Conclusions: Elevated aminotransferases are commonly seen in COVID-19 patients. They possibly reflect disease severity and may be associated with in-hospital mortality.