Small Molecule Benzothiophene with In Vivo Efficacy in a Mouse Model of Drug-Resistant Enterococcus faecium Infection.

Hospital-acquired infections, caused by ESKAPE bacteria, are a challenging global public health concern, in part due to the emergence of drug-resistant strains. While profiling a diverse set of compounds for in vitro activity versus this class of bacteria, we noted that the benzothiophene JSF-2827 exhibited promising antibacterial activity against Enterococcus faecium. A hit evolution campaign ensued, involving the design, synthesis, and biological assay of analogues designed to address early issues such as a short mouse liver microsome half-life and a modest mouse pharmacokinetic profile. Among these derivatives, JSF-3269 was found to exhibit an enhanced profile and in vivo efficacy in an immunocompetent mouse model of acute, drug-resistant E. faecium infection. The findings suggest a rationale for the further evolution of this promising series to afford a novel therapeutic strategy to treat drug-resistant E. faecium infection.

Supradiaphragmatic origin of the celiac trunk leading to median arcuate ligament syndrome with superior mesenteric artery involvement.

Median arcuate ligament (MAL) syndrome (MALS) is a rare condition caused by compression of the celiac artery by the MAL. Symptoms include abdominal pain, nausea, and weight loss. Rarely, the MAL can compress both the celiac artery and the superior mesenteric artery (SMA). We describe the case of a young man with MALS involving the celiac artery and SMA. Laparoscopic release of the MAL was performed, and the patient had resolution of his symptoms at 6 months of follow-up. A review of the literature identified only six cases of MALS involving the SMA and celiac artery, making this a rare occurrence.

Landscape of Centralized Otolaryngology Research Efforts Grant Recipients Over the Past Decade.

OBJECTIVE: To investigate the demographics of CORE grant recipients (Centralized Otolaryngology Research Efforts) over the last decade and evaluate disparity among recipients as compared with otolaryngology overall. To assess whether procurement of a grant predicts pursuit of an academic career. STUDY DESIGN: Analysis of grant recipients' bibliometrics. SETTING: Academic medical center. METHODS: The list of recipients of grants from 2010 to 2019 was obtained from the website of the American Academy of Otolaryngology-Head and Neck Surgery. Demographics of recipients were collected through an internet search, including gender, race, residency program, and h-index. Recipients from 2010 were searched to determine current academic faculty rank. Univariate and multivariate analyses were used to compare these factors with otolaryngology overall. RESULTS: The distribution of gender among recipients over the last decade remained nearly constant, with no significant difference versus residents in otolaryngology (P > .05). However, there were significantly more female recipients when adjusted for gender differences in the field overall (P < .01). Asians were relatively overrepresented, while Black and Hispanic residents were underrepresented (P < .01). Many recipients (52.6%) trained at institutions recognized as the best training programs with reputations for quality research output. The h-index of recipients decreased over the last decade (P < .01). The h-index of duplicate winners was significantly higher than those of nonduplicate winners (P < .01). After adjusting for gender and rank, recipients were significantly more likely to hold academic positions (P < .01). CONCLUSION: CORE grants are favorably distributed as related to gender and racial disparities, and recipients frequently go on to achieve high levels of academic success.

Facial paralysis and vaccinations: a vaccine adverse event reporting system review.

BACKGROUND: Vaccinations are a cornerstone of preventative medicine in the USA. However, growing concerns regarding facial nerve palsy following vaccination exist. OBJECTIVE: This study aims to assess the occurrence of facial palsy as reported by the Vaccine Adverse Event Reporting System (VAERS) database. METHODS: A retrospective analysis of the VAERS database was performed for cases of 'Facial Palsy', 'Bell's Palsy', 'Facial Paralysis' and 'Ramsay Hunt Syndrome' between 2009 and 2018. Subgroup analysis was performed to determine gender, age, history of facial palsy, type of vaccine used, number of days until onset of symptoms and overall facial palsy rate. RESULTS: Nine hundred and forty-four entries met our inclusion criteria with 961 vaccine administrations resulting in facial paralysis. Facial palsy following vaccinations was evenly distributed across all age cohorts with two peaks between 60 and 74 years old and between 0 and 14 years old. Most patients were female (N = 526, 55.7%) without a reported history of facial palsy (N = 923, 97.8%). In 2009, reported incidence rate was 0.53%, as compared with 0.23% in 2018. The influenza vaccine had the greatest number of cases (N = 166, 17.3%), followed by the varicella (N = 87, 9.1%) and human papillomavirus vaccines (N = 47, 4.9%). CONCLUSIONS: With the SARS-CoV-2 pandemic and recent approvals of the vaccinations, there is growing concern of facial palsy following vaccination. Although it is a known adverse event following vaccination, the likelihood of facial palsy following vaccination is low, with only 0.26% of overall reported cases over a 10-year span.

Adverse Events Associated with Intranasal Sprays: An Analysis of the Food and Drug Administration Database and Literature Review.

BACKGROUND: Intranasal sprays (INSs) are commonly used medications for the treatment of many rhinologic conditions. Despite their popularity, an analysis of a nationwide reporting database and comparison to the available literature has never been performed. METHODS: The Food and Drug Administration Adverse Event Reporting System (FAERS) database was accessed to obtain adverse event (AE) records from 2014 to 2019 for varying INSs, including: 10 corticosteroids, 1 alpha adrenergic, and 3 antihistamines. The Proportional Reporting Ratios (PRR) and Reporting Odds Ratios (ROR) were calculated for dyspnea, anosmia, ageusia/dysgeusia, epistaxis, and headache. A PRR ≥ 2 or ROR ≥ 1 was considered significant. RESULTS: Corticosteroids had 98 864 total reported AEs to the database, followed by antihistamines (7011) and alpha adrenergics (2071). In total, dyspnea was reported 5843 times, followed by headache (4230), epistaxis (1205), ageusia/dysgeusia (920), and anosmia (312). Overall, PRR and ROR values for dyspnea ranged from 0.51 to 4.25 and 0.51 to 4.49; for dysgeusia/ageusia from 0.56 to 6.09 and 0.56 to 6.12; and for epistaxis from 1.03 to 27.24 and 1.03 to 30.76, respectively. All medications which listed anosmia within the top AEs had PRR and ROR values exceeding 2 and 1, respectively. The PRR for headache exceeded 2 for 1 medication and the ROR exceeded 1 in 7 medications. CONCLUSION: The AEs of dyspnea, anosmia, ageusia/dysgeusia, epistaxis, and headache are reported within the FAERS database for commonly prescribed INSs. When compared against the existing scientific literature, the clinical significance of this reporting tool from the FDA for these classes of medications remains unvalidated.

Adverse Events Associated With Botox as Reported in a Food and Drug Administration Database.

BACKGROUND: Botulinum toxin treatment is the most frequently performed noninvasive cosmetic procedure performed in the USA. Because of its widespread use, an analysis of the adverse event (AE) profile of Botox injections is needed. METHODS: The FDA Adverse Event Report System was queried using an online web-based tool to determine the top 15 adverse events reported for four Botox brand names: Botox/Botox Cosmetic, Dysport, and Xeomin. The proportional reporting ratios (PRR) and relative odds ratios (ROR) were determined. A literature review was performed for eight AEs of clinical significance: eyelid/eyebrow ptosis, asthenia, muscular weakness, facial paresis, dysphagia, botulism, and death. RESULTS: Botox/Botox Cosmetic had 38367 AEs. Dysport had 3582 AEs. Xeomin had 1405 AEs. All drugs with reported cases of eyelid and eyebrow ptosis had significant PRR and ROR values. The PRR and ROR values for asthenia were not significant in any of the drugs and only reached significance for Dysport for muscular weakness and dysphagia. Both Botox/Botox Cosmetic and Dysport had elevated PRRs and RORs for facial paresis and botulism. While all drugs had at least one reported case of death related to Botox injection use, none of the PRR or ROR values were significant. CONCLUSION: Known AEs for Botox injection use include eyelid/brow ptosis and muscular weakness. Feared but rare complications of Botox injection use include dysphagia, botulism, and possibly death, owing to systemic spread of the toxin. This is the first study to analyze the AE data reported to the FDA on Botox injection use. EBM LEVEL: III.

Integrating the Bleeding Control Basic course into medical school curriculum.

BACKGROUND: The American College of Surgeons has pioneered hemorrhage control through its lifesaving bleeding control (BCon) basics course. A gap exists in teaching these skills to medical students. We sought to integrate BCon into the medical school curriculum. METHODS: BCon programs taught to entering Year 1 medical students in Academic Years 2017-2018. Post-course surveys assessed effectiveness of teaching and learner confidence in performing skills. Refreshers in Year 2 and Year 3 of study were implemented to reinforce skills. RESULTS: Post-course surveys (n = 348) showed that 98% of students felt that they were effectively taught how to stop bleeding and 92% felt comfortable using these skills. CONCLUSION: The BCon program is feasible to implement in medical school. It is easily integrated into pre-existing curricula in addition to other life support skills taught to medical students. SUMMARY: Bleeding control is increasingly a topic of national concern with mass casualty incidents. We used a peer training model to teach BCon techniques to all our medical students on entry into medical school and these skills were refreshed longitudinally in the next two years. Combining BCon training with other basic life support skills training is feasible and medical students find this training effective.

Outdoor particulate matter (PM) and associated cardiovascular diseases in the Middle East.

Air pollution is a widespread environmental concern. Considerable epidemiological evidence indicates air pollution, particularly particulate matter (PM), as a major risk factor for cardiovascular diseases (CVD) in the developed countries. The main objective of our review is to assess the levels and sources of PM across the Middle East area and to search evidence for the relationship between PM exposure and CVD. An extensive review of the published literature pertaining to the subject (2000-2013) was conducted using PubMed, Medline and Google Scholar databases. We reveal that low utilization of public transport, ageing vehicle fleet and the increasing number of personal cars in the developing countries all contribute to the traffic congestion and aggravate the pollution problem. The annual average values of PM pollutants in the Middle East region are much higher than the World Health Organization 2006 guidelines (PM2.5 = 10 µg/m(3), PM10 = 20 µg/m(3)). We uncover evidence on the association between PM and CVD in 4 Middle East countries: Iran, Kingdom of Saudi Arabia, Qatar and the United Arab Emirates. The findings are in light of the international figures. Ambient PM pollution is considered a potential risk factor for platelet activation and atherosclerosis and has been found to be linked with an increased risk for mortality and hospital admissions due to CVD. This review highlights the importance of developing a strategy to improve air quality and reduce outdoor air pollution in the developing countries, particularly in the Middle East. Future studies should weigh the potential impact of PM on the overall burden of cardiac diseases.

Sodium lauryl sulfate impedes drug release from zinc-crosslinked alginate beads: switching from enteric coating release into biphasic profiles.

The aim of this research is to investigate the effects of sodium lauryl sulfate (SLS) on ionotropically cross-linked alginate beads. Different levels of SLS were mixed with sodium alginate and chlorpheniramine maleate (as loaded model drug). The resulting viscous solutions were dropped onto aqueous solutions of zinc or calcium ions for ionotropic curing. The generated beads were assessed by their drug releasing profiles, infrared and differential scanning colorimetery (DSC) traits. SLS was found to exert profound concentration-dependent impacts on the characteristics of zinc-crosslinked alginate beads such that moderate modifications in the levels of SLS switched drug release from enteric coating-like behavior to a biphasic release modifiable to sustained-release by the addition of minute amounts of xanthan gum. Calcium cross-linking failed to reproduce the same behavior, probably due to the mainly ionic nature of calcium-carboxylate bonds compared to the coordinate character of their zinc-carboxylate counterparts. Apparently, moderate levels of SLS repel water penetration into the beads, and therefore minimize chlorpheniramine release. However, higher SLS levels seem to discourage polymeric cross-linking and therefore allow biphasic drug release.