Cenobamate, a Sodium Channel Inhibitor and Positive Allosteric Modulator of GABAA Ion Channels, for Partial Onset Seizures in Adults: A Comprehensive Review and Clinical Implications

Medical management of epilepsy seeks to eliminate or to reduce the frequency of seizures, help patients maintain a normal lifestyle, and maintain psychosocial and occupational activities, while avoiding the negative side effects of long-term treatment. Current FDA approved drugs have been shown to have similar efficacy; however, they all share a commonality of having side effects that have the potential to significantly reduce a patient’s quality of life. Cenobamate, a newly-FDA approved drug used to treat partial-onset seizures in adult patients, has demonstrated promise in that it works on two proposed mechanisms that are commonly associated with epilepsy. Cenobamate acts as a positive allosteric modulator of the GABAA ion channels and is effective in reducing repetitive neuronal firing by inhibition of voltage-gated sodium channels, although the complete mechanism of action is currently unknown. The efficacy of Cenobamate with its low toxicity and adverse drug reaction profile emphasizes the need to further evaluate antiepileptic therapies containing sulfamoylphenyl and/or carbamate moieties in their chemical structure. Recent studies have found more patients to be seizure free during the maintenance period when compared to placebo. The most common side effects reported in with Cenobamate are somnolence, dizziness, headache, nausea, and fatigue. There are currently ongoing phase III studies looking to further evaluate the long-term benefits of Cenobamate and investigate adverse events

Immune Checkpoint Inhibitors Have Clinical Activity in Patients With Recurrent Chordoma

The aim of this study is to evaluate the outcomes and tolerance of immune checkpoint inhibitors (ICIs) for patients with recurrent chordoma. We reviewed the records of 17 patients with recurrent chordomas who received ICIs for progressing disease as part of their treatment between 2016 and 2020. Response was assessed using response evaluation criteria in solid tumors 1.1 criteria. The Kaplan-Meier method was used to estimate the duration of response, progression-free survival (PFS), and overall survival (OS). Clinical benefit was defined as having stable disease (SD), a partial response, or a complete response. The median follow-up from the start of ICIs was 29 months [interquartile range (IQR): 13-35 m]. The majority received pembrolizumab (n=9, 53%), and the median number of cycles delivered was 8 (IQR: 7-12). The 1-year OS was 87%, and the 1-year PFS was 56% with a median PFS of 14 months (95% CI, 5-17 mo). After ICI initiation, most patients (n=15, 88%) had clinical benefit consisting of a complete response (n=1, 6%), partial response (n=3, 18%), and stable disease (n=11, 65%). Among all responders (n=15), the median duration of response was 12 months. Toxicities were limited: 2 (12%) patients having grade 3/4 immune-related toxicities (colitis, grade 3; myocarditis, grade 4). We observed a high rate of clinical benefit and favorable durability from ICI use for patients with recurrent chordoma. These data provide support for the integration of ICIs as a standard first-line systemic therapy option for patients with recurrent chordoma. Prospective studies are warranted to further evaluate efficacy and enhance response rates

Henry Versus Thompson Approach for Fixation of Proximal Third Radial Shaft Fractures: A Multicenter Study

Objective: To compare the volar Henry and dorsal Thompson approaches with respect to outcomes and complications for proximal third radial shaft fractures. Design: Multicenter retrospective cohort study. Patients/Participants: Patients with proximal third radial shaft fractures ± associated ulna fractures (OTA/AO 2R1 ± 2U1) treated operatively at 11 trauma centers were included. Intervention: Patient demographics and injury, fracture, and surgical data were recorded. Final range of motion and complications of infection, neurologic injury, compartment syndrome, and malunion/nonunion were compared for volar versus dorsal approaches. Main Outcome: The main outcome was difference in complications between patients treated with volar versus dorsal approach. Results: At an average follow-up of 292 days, 202 patients (range, 18–84 years) with proximal third radial shaft fractures were followed through union or nonunion. One hundred fifty-five patients were fixed via volar and 47 via dorsal approach. Patients treated via dorsal approach had fractures that were on average 16 mm more proximal than those approached volarly, which did not translate to more screw fixation proximal to the fracture. Complications occurred in 11% of volar and 21% of dorsal approaches with no statistical difference. Conclusions: There was no statistical difference in complication rates between volar and dorsal approaches. Specifically, fixation to the level of the tuberosity is safely accomplished via the volar approach. This series demonstrates the safety of the volar Henry approach for proximal third radial shaft fractures

Serotonin Reduction in Post-acute Sequelae of Viral Infection

Post-acute sequelae of COVID-19 (PASC, Long COVID ) pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction. Here, we propose a mechanism that links all four hypotheses in a single pathway and provides actionable insights for therapeutic interventions. We find that PASC are associated with serotonin reduction. Viral infection and type I interferon-driven inflammation reduce serotonin through three mechanisms: diminished intestinal absorption of the serotonin precursor tryptophan; platelet hyperactivation and thrombocytopenia, which impacts serotonin storage; and enhanced MAO-mediated serotonin turnover. Peripheral serotonin reduction, in turn, impedes the activity of the vagus nerve and thereby impairs hippocampal responses and memory. These findings provide a possible explanation for neurocognitive symptoms associated with viral persistence in Long COVID, which may extend to other post-viral syndromes

How Does Health Impact Happiness? Overall, Mental and Physical Health and Happiness

Objective. This study was conducted to determine if overall health, mental health or physical health have a significant association with happiness in Americans. Background. Research performed in Kuwait has shown that mental health has a significant association with happiness. This study aimed to see if there is a similar association in the United States. Methods. Data was collected from the General Social Survey, a bi-annual personal interview survey by the National Opinion Research Center. A univariate analysis, bivariate analysis, logistic regression and odds ratio were conducted to analyze the data. Results. There are statistically significant associations between overall health and happiness, mental health and happiness, and physical health and happiness. For overall health and happiness, the percentage of happiness differed by χ 2 (9,2292)=248.76, p= 2 (9, 1416) = 155.98, p = 2 (9,699) = 25.31, p = 0.0026. Logistic regression showed χ 2= 93.48, p \u3c 0.0001, therefore a significant prediction based on mental health can be made regarding happiness. The odds ratio of mental health and happiness showed OR 8.25 95%CI (3.02-21.79). Therefore, if exposed to 30 days of poor mental health, one is 8.25x more likely of being unhappy. Conclusion. There is a significant association between overall health, mental health, physical health and happiness. Health professionals should focus on improving patients’ mental health to improve their happiness. Grants. Not applicable

Is Morgellons an organic disease? structural and functional abnormalities implicated in the pathophysiology of delusional infestation

Little is known about the pathophysiology of delusional infestation (DI), a psychodermatologic condition in which patients have a fixed, false belief of being infested with parasites or inanimate material in their skin, despite lack of objective evidence. Because some delusional states, such as schizophrenia and psychotic state in bipolar disorder have been found to be associated with brain structural and functional abnormalities, a literature review was conducted to summarize available data on structural and functional abnormalities that are found to be associated with DI. A review of the literature found cases of brain imaging studies in patients with primary DI, as well as patients with secondary DI. Accumulating evidence from the studies reviewed suggests that dysfunction of the fronto-striato-thalamo-parietal network may explain how delusions manifest in DI and suggest that DI has an organic etiology. Abnormalities in the striato-thalamo-parietal network may cause false sensations of infestation through dysfunction in visuo-tactile regulation, whereas abnormalities in the frontal region may impair judgement. Delusional infestation patients also exhibit increased activation of brain structures implicated in itch processing. Furthermore, patients at high risk for cerebrovascular disease who present with secondary DI may benefit from brain imaging studies to rule out brain ischemic insult

Is Morgellons an organic disease? structural and functional abnormalities implicated in the pathophysiology of delusional infestation

Little is known about the pathophysiology of delusional infestation (DI), a psychodermatologic condition in which patients have a fixed, false belief of being infested with parasites or inanimate material in their skin, despite lack of objective evidence. Because some delusional states, such as schizophrenia and psychotic state in bipolar disorder have been found to be associated with brain structural and functional abnormalities, a literature review was conducted to summarize available data on structural and functional abnormalities that are found to be associated with DI. A review of the literature found cases of brain imaging studies in patients with primary DI, as well as patients with secondary DI. Accumulating evidence from the studies reviewed suggests that dysfunction of the fronto-striato-thalamo-parietal network may explain how delusions manifest in DI and suggest that DI has an organic etiology. Abnormalities in the striato-thalamo-parietal network may cause false sensations of infestation through dysfunction in visuo-tactile regulation, whereas abnormalities in the frontal region may impair judgement. Delusional infestation patients also exhibit increased activation of brain structures implicated in itch processing. Furthermore, patients at high risk for cerebrovascular disease who present with secondary DI may benefit from brain imaging studies to rule out brain ischemic insult

The role of hydrogen peroxide in hip arthroplasty: A narrative review.

Hydrogen peroxide has become more commonly used in hip arthroplasties due to high risk of periprosthetic infections. Its purported roles include irrigation, haemostasis, reduction of aseptic loosening and attachment of antibiotics. However, current literature does not provide conclusive evidence on the efficacy of hydrogen peroxide in preventing aseptic loosening, with some controversy around whether it in fact contributes to aseptic loosening. The complications of hydrogen peroxide across medicine are well distinguished; however, the risks within orthopaedic surgery and hip arthroplasties are not well known. Beyond cytotoxicity, the most dangerous reported risk associated with hydrogen peroxide in hip arthroplasties was an oxygen embolism in an unvented femoral canal and acrylic bone cement, consequentially leading to cardiac arrest. However, it may be inappropriate to solely attribute the oxygen embolism to the use of hydrogen peroxide and thus if used appropriately, hydrogen peroxide may have a justifiable role in hip arthroplasty surgery. In this narrative review, we present the current uses of hydrogen peroxide while evaluating its associated risks. We have summarised the key indications and aggregated recommendations to provide guidelines for the use of hydrogen peroxide in hip arthroplasty

A Systematic Review of ‘Fair’ AI Model Development for Image Classification and Prediction

Abstract Purpose The new challenge in Artificial Intelligence (AI) is to understand the limitations of models to reduce potential harm. Particularly, unknown disparities based on demographic factors could encrypt currently existing inequalities worsening patient care for some groups. Methods Following PRISMA guidelines, we present a systematic review of ‘fair’ deep learning modeling techniques for natural and medical image applications which were published between year 2011 to 2021. Our search used Covidence review management software and incorporates articles from PubMed, IEEE, and ACM search engines and three reviewers independently review the manuscripts. Results Inter-rater agreement was 0.89 and conflicts were resolved by obtaining consensus between three reviewers. Our search initially retrieved 692 studies but after careful screening, our review included 22 manuscripts that carried four prevailing themes; ‘fair’ training dataset generation (4/22), representation learning (10/22), model disparity across institutions (5/22) and model fairness with respect to patient demographics (3/22). We benchmark the current literature regarding fairness in AI-based image analysis and highlighted the existing challenges. We observe that often discussion regarding fairness are limited to analyzing existing bias without further establishing methodologies to overcome model disparities. Conclusion Based on the current research trends, exploration of adversarial learning for demographic/camera/institution agnostic models is an important direction to minimize disparity gaps for imaging. Privacy preserving approaches also present encouraging performance for both natural and medical image domain