Impact of COVID-19 on U.S. and Canadian neurologists’ therapeutic approach to multiple sclerosis: a survey of knowledge,attitudes, and practices

Journal of Neurology - To report the understanding and decision-making of neuroimmunologists and their treatment of patients with multiple sclerosis (MS) during the early stages of the SARS-CoV-2...     

COVID-19 and hemolysis,elevated liver enzymes and thrombocytopenia syndrome in pregnant women - association or causation?

Pregnant women are among the high-risk population for severe coronavirus disease 2019 (COVID-19) with unfavorable peripartum outcomes and increased incidence of preterm births. Hemolysis, the elevation of liver enzymes, and low platelet count (HELLP) syndrome and severe preeclampsia are among the leading causes of maternal mortality. Evidence supports a higher odd of pre-eclampsia in women with COVID-19, given overlapping pathophysiology. Involvement of angiotensin-converting enzyme 2 receptors by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for the entry to the host cells and its downregulation cause dysregulation of the renin-angiotensin-aldosterone system. The overexpression of Angiotensin II mediated via p38 Mitogen-Activated Protein Kinase pathways can cause vasoconstriction and uninhibited platelet aggregation, which may be another common link between COVID-19 and HELLP syndrome. On PubMed search from January 1, 2020, to July 30, 2022, we found 18 studies on of SARS-COV-2 infection with HELLP Syndrome. Most of these studies are case reports or series, did not perform histopathology analysis of the placenta, or measured biomarkers linked to pre-eclampsia/HELLP syndrome. Hence, the relationship between SARS-CoV-2 infection and HELLP syndrome is inconclusive in these studies. We intend to perform a mini-review of the published literature on HELLP syndrome and COVID-19 to test the hypothesis on association vs causation, and gaps in the current evidence and propose an area of future research.     

A Survey of Practices in the United States Regarding Hepatitis C Screening in Pregnant Women

PurposeHepatitis C virus (HCV) cases have increased in the past decade, with many cases in pregnant patients. However, recommendations for HCV screening during pregnancy vary by professional organization.MethodsPrenatal care providers were surveyed via e-mail about factors affecting choice of HCV screening.FindingsA total of 86 completed surveys were received. Providers using risk-based screening valued guidance from obstetrics and gynecology societies and risk for vertical transmission. Providers using universal screening valued availability of curative treatment in addition to guidance from the Centers for Disease Control and Prevention/infectious diseases societies and obstetrics and gynecology societies.ImplicationsThe results highlight the need for consensus guidelines on HCV screening as a part of prenatal care.     

The generation and analyses of a novel combination of recombinant adenovirus vaccines targeting three tumor antigens as an immunotherapeutic

Phenotypic heterogeneity of human carcinoma lesions, including heterogeneity in expression of tumor-associated antigens (TAAs), is a well-established phenomenon. Carcinoembryonic antigen (CEA), MUC1, and brachyury are diverse TAAs, each of which is expressed on a wide range of human tumors. We have previously reported on a novel adenovirus serotype 5 (Ad5) vector gene delivery platform (Ad5 [E1-, E2b-]) in which regions of the early 1 (E1), early 2 (E2b), and early 3 (E3) genes have been deleted. The unique deletions in this platform result in a dramatic decrease in late gene expression, leading to a marked reduction in host immune response to the vector. Ad5 [E1-, E2b-]-CEA vaccine (ETBX-011) has been employed in clinical studies as an active vaccine to induce immune responses to CEA in metastatic colorectal cancer patients. We report here the development of novel recombinant Ad5 [E1-, E2b-]-brachyury and-MUC1 vaccine constructs, each capable of activating antigen-specific human T cells in vitro and inducing antigen-specific CD4⁺ and CD8⁺ T cells in vaccinated mice. We also describe the use of a combination of the three vaccines (designated Tri-Ad5) of Ad5 [E1-, E2b-]-CEA, Ad5 [E1-, E2b-]-brachyury and Ad5 [E1-, E2b-]-MUC1, and demonstrate that there is minimal to no “antigenic competition” in in vitro studies of human dendritic cells, or in murine vaccination studies. The studies reported herein support the rationale for the application of Tri-Ad5 as a therapeutic modality to induce immune responses to a diverse range of human TAAs for potential clinical studies.     

Is There a Role for the Incretin System in Blood Pressure Regulation?

Incretin-based therapies are now well established for diabetes management and are among the frontline agents for control of hyperglycemia. In addition to their antihyperglycemic effects, evidence is emerging on the role of these agents on blood pressure regulation, cardioprotective and renoprotective properties. Because of the pleiotropic nature of these affects, these agents could offer significant benefits with regards to the cardiorenal metabolic complications that are part of the diabetes and obesity epidemic in the United States and worldwide. We review the various known mechanisms or pathways by which incretin based therapy exerts its regulation of blood pressure with emphasis on novel mechanisms such as inflammation/immunomodulation and oxidative stress.     

Involved surgical margins in oral and oropharyngeal carcinoma—an anatomical problem?

A previous audit conducted in the West of Scotland (WoS) suggested that anatomical factors accounted for a substantial proportion of invaded surgical margins after resection of an oral or oropharyngeal squamous cell carcinoma (SCC). Since then a number of technical improvements have taken place, the most important of which has been advanced digital imaging that has enabled better surgical planning. In this study we compare the incidence of involved surgical margins in a recent group with those found in the earlier audit. The earlier (WoS) group comprised a consecutive series of patient operated on for a primary SCC of the oral cavity or oropharynx between November 1999 and November 2001 (n = 296). The later series comprised 178 patients operated on for oral or oropharyngeal SCC at the Southern General Hospital (SGH), Glasgow, between 2006 and 2009. A total of 245 patients in the WoS cohort had information available on the invasion of the margins of whom 68 (28%) had an invaded margin. Of 177 patients in the SGH group, 9 (5%) had an invaded margin (p = 0.001). An anatomical approach to the resection of oral and oropharyngeal SCC is appropriate, as it results in a rate of invaded margins of less than 10% irrespective of size and site of the primary lesion.     

Live Attenuated Influenza Vaccine: Is Past Performance a Guarantee of Future Results?

Live attenuated influenza vaccine (LAIV) has had a tumultuous recent history that can be difficult for many to follow and understand. Prior to 2013, LAIV had a record of accomplishment of providing equal or superior protection against influenza in children. Since 2013, concerns about the lack of protection with LAIV against pandemic H1N1 strains led to the withdrawal of any recommendation for use in the US by the Advisory Committee on Immunization Practices (ACIP). After some significant changes to the content, evaluation and production of LAIV, it has been be recommended again for use in the US in 2018-19. This commentary reviews the origin of LAIV, the events and circumstances that led to the withdrawal of any recommendation for LAIV use by the ACIP, the merits, shortcomings and repercussions of that decision and finally offers some thoughts about the future of LAIV.