Sex-specific lung inflammation and mitochondrial damage in a model of electronic cigarette exposure in asthma.

The prevalence of electronic cigarette (EC) use among adult with asthma has continued to increase over time, in part due to the belief of being less harmful than smoking. However, the extent of their toxicity and the involved mechanisms contributing to the deleterious impact of EC exposure on patients with preexisting asthma have not been delineated. In the present project, we tested the hypothesis that EC use contributes to respiratory damage and worsening inflammation in the lungs of patients with asthma. To define the consequences of EC exposure in established asthma, we used a mouse model with/without preexisting asthma for short-term exposure to EC aerosols. C57/BL6J mice were sensitized and challenged with a DRA (dust mite, ragweed, Aspergillus fumigates, 200 µg/mL) mixture and exposed daily to EC with nicotine (2% nicotine in 30:70 propylene glycol: vegetable glycerin) or filtered air for 2 wk. The mice were evaluated at 24 h after the final EC exposure. After EC exposure in asthmatic mice, lung inflammatory cell infiltration and goblet cell hyperplasia were increased, whereas EC alone did not cause airway inflammation. Our data also show that mitochondrial DNA (mtDNA) content and a key mtDNA regulator, mitochondrial transcription factor A (TFAM), are reduced in asthmatic EC-exposed mice in a sex-dependent manner. Together, these results indicate that TFAM loss in lung epithelium following EC contributes to male-predominant sex pathological differences, including mitochondrial damage, inflammation, and remodeling in asthmatic airways.NEW & NOTEWORTHY Respiratory immunity is dysregulated in preexisting asthma, and further perturbations by EC use could exacerbate asthma severity. However, the extent of their toxicity and the involved mechanisms contributing to the deleterious impact of EC exposure on patients with preexisting asthma have not been delineated. We found that EC has unique biological impacts in lungs and potential sex differences with loss of TFAM, a key mtDNA regulator, in lung epithelial region from our animal EC study.

Gender Distribution of Deans Among US Medical Schools: Towards Equity in Academic Medicine.

BACKGROUND: Less than half of medical school professorships and decanal ranks are held by women. Our study investigates the gender-based geographical distribution and differences in lifetime peer-reviewed publications, H-index, and grant funding by the National Institutes of Health (NIH) of all allopathic medical school deans in the United States (US). METHODS: A cross-sectional cohort study utilizing data from US allopathic medical school websites, PubMed, and the NIH Research Portfolio Online Reporting Tools regarding lifetime peer-reviewed publications and quantity/monetary sum of NIH grants received by medical school deans. Descriptive statistics, independent sample T-tests, and ANOVA were performed with statistical significance defined as P < 0.05. RESULTS: Women occupied 33/157 (21.0%) dean positions overall. Compared to women, men possess higher mean number of lifetime peer-reviewed publications (112.0 vs. 55.2, P = 0.001) and H-index (43.2 vs. 25.7, P = 0.001); however, there are no differences in the mean number of NIH grants (27.5 vs. 19.1, P = 0.323) nor mean total NIH funding received ($18,931,336 vs. $14,289,529, P = 0.524). While significant differences in mean H-index between all US regions were found (P = 0.002), no significant differences exist between major US regions regarding the mean lifetime publication count (P = 0.223), NIH grants received (P = 0.200), nor total NIH funding (P = 0.824) received. CONCLUSION: A significant discrepancy in the gender distribution, lifetime peer-reviewed publications, and H-index of allopathic medical school deans exists across the US, highlighting the need for adequate support for women in academic medicine. Greater implementation of mentorship, increased institutional support, and diversity training can improve the representation of women in medical school decanal positions.

Emergency Resuscitative Thoracotomy for Civilian Thoracic Trauma in the Field and Emergency Department Settings: A Systematic Review and Meta-Analysis.

BACKGROUND: Emergency department resuscitative thoracotomy (ED-RT) or prehospital resuscitative thoracotomy (PH-RT) is performed for trauma patients with impending or full cardiovascular collapse. This systematic review and meta-analysis analyze outcomes in patients with thoracic trauma receiving PH-RT and ED-RT. METHODS: PubMed, JAMA Network, and CINAHL electronic databases were searched to identify studies published on ED-RT or PH-RT between 2000-2020. Patients were grouped by location of procedure and type of thoracic injury (blunt versus penetrating). RESULTS: A total of 49 studies met the criteria for qualitative analysis, and 43 for quantitative analysis. 43 studies evaluated ED-RT and 5 evaluated PH-RT. Time from arrival on scene to PH-RT >5 min was associated with increased neurological complications and time from the initial encounter to PH-RT or ED-RT >10 min was associated with increased mortality. ISS ≥ 25 and absent signs of life were also associated with increased mortality. There was higher mortality in all PH-RT (93.5%) versus all ED-RT (81.8%) (P = 0.02). Among ED-RTs, a significant difference was found in mortality rate between patients with blunt (92.8%) versus penetrating (78.7%) injuries (P < 0.001). When considering only blunt or penetrating injury types, no significant difference in RT mortality rate was found between ED-RT and PH-RT (P = 0.65 and P = 0.95, respectively). CONCLUSIONS: ED-RT and PH-RT are potentially life-saving procedures for patients with penetrating thoracic injuries in extremis and with signs of life. The efficacy of this procedure is time sensitive. Moreover, there appears to be a greater mortality risk for patients with thoracic trauma receiving RT in the PH setting compared to the ED setting. More studies are needed to determine the significance of PH-RT mortality.

Impacts and challenges of the COVID-19 pandemic on emergency medicine physicians in the United States.

BACKGROUND: Emergency medicine (EM) physicians have been on the front line of the COVID-19 pandemic. This study aims to determine the impact of COVID-19 pandemic and other related factors such as resource availability and institutional support on well-being, burnout and job-satisfaction of EM physicians in the United States. METHODS: A cross-sectional survey study of EM physicians was conducted through the Emergency Medicine Practice Research Network of the ACEP. The survey focused on resource adequacy, institutional support, well-being, and burnout. A total of 890 EM physicians were invited to participate. Both descriptive and risk adjusted, and multivariate regressions were performed with a statistical significance defined as p < 0.05. RESULTS: EM physicians' response rate was 18.7% (166) from 39 states. Burnout was reported by 74.7% (124) since the start of the pandemic. Factors contributing included work-related emotional strain and anxiety, isolation from family and friends, and increased workload. Those reporting inadequate resources felt ignored by their institutions (p < 0.0001). Physicians who felt there was inadequate institutional support, were also dissatisfied with patient care resources (p = 0.001). Physicians expressing job dissatisfaction were more likely to report feelings of burnout (p = 0.001). CONCLUSION: EM physicians face greater burnout in the COVID-19 pandemic. This may be compounded by resource scarcity, psychological stress, isolation, and job dissatisfaction. Many of the survey respondents reported inadequate mental health services and resources. The findings of this study may help identify solutions to mitigate these issues.

Venous Thromboembolism Chemoprophylaxis in Trauma and Emergency General Surgery Patients: A Systematic Review.

BACKGROUND: Appropriate venous thromboembolism (VTE) chemoprophylaxis in trauma and emergency general surgery (EGS) patients is crucial. OBJECTIVE: The purpose of this study is to review the recent literature and offer recommendations for VTE chemoprophylaxis in trauma and EGS patients. METHODS: We conducted a literature search from 2000 to 2021 for articles investigating VTE chemoprophylaxis in adult trauma and EGS patients. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. RESULTS: Our search resulted in 34 articles. Most studies showed low-molecular-weight heparin (LMWH) is similar to unfractionated heparin (UFH) for VTE prevention; however, LMWH was more commonly used. Adjusted chemoprophylaxis dosing did not change the VTE rate but the timing did. Direct oral anticoagulants (DOACs) have been shown to be safe and effective in trauma and traumatic brain injury (TBI)/spinal cord injury (SCI). Studies showed VTE prophylaxis in EGS can be inconsistent and improves with guidelines that lower VTE events. CONCLUSIONS: There may be no benefit to receiving LMWH over UFH in trauma patients. In addition, different drugs under the class of LMWH do not change the incidence of VTE. Adjusted dosing of enoxaparin does not seem to affect VTE incidence. The use of DOACs in the trauma TBI and SCI setting has been shown to be safe and effective in reducing VTE. One important consideration with VTE prophylaxis may be the timing of prophylaxis initiation, specifically as it relates to TBI, with a higher likelihood of developing VTE as time progresses. EGS patients are at a high risk of VTE. Improved compliance with clinical guidelines in this population is correlated with decreased thrombotic events.

Let Kids Play: Using Virtual Reality as a Substitute for General Anesthesia for Minor Procedures in Pediatric Population.

BACKGROUND: In the pediatric population, virtual reality (VR) has been used as an adjunct to augment analgesia and reduce the need for opioids. In this study, we review our experience using VR in lieu of anesthesia or sedation to enable minor procedures in children. METHODS: A retrospective chart review study was performed on patients who presented to our institution from 2019 to 2022 for hormone implant placement, exchange, or removal with VR distraction. Demographic and procedure information was recorded. The primary outcome was successful procedure completion without requiring pharmacologic sedation or analgesia. RESULTS: A total of 111 patients underwent the following minor procedures with VR and without anesthesia or sedation. Fourteen patients had multiple encounters resulting in a total of 126 encounters. The median age was 11 [6] years. 43 patients were female, 23 were female to male, 6 were non-binary, 7 were male, and 32 were male to female. 58 % had private insurance. Most common diagnosis was precocious puberty (54 %) followed by gender dysphoria (46 %). Most common procedure was implant placement (72 %). 69 % of procedures were performed in the clinic and 31 % in the OR. All procedures were completed without requiring the administration of additional sedation or anesthesia. None of the patients required intravenous catheter placement for the procedure. No intra-procedural complications were recorded. CONCLUSION: VR is a feasible option that can spare children from sedation or general anesthesia for minor procedures. VR may enable minor procedures in children to be successfully performed in clinic setting.

Vaccination of multiple sclerosis patients during the COVID-19 era: Novel insights into vaccine safety and immunogenicity.

Multiple sclerosis (MS) is an incurable autoimmune disease known to cause widespread demyelinating lesions in the central nervous system (CNS) and a host of debilitating symptoms in patients. The development of MS is believed to be driven by the breakdown of the blood brain barrier, subsequent infiltration by CD4+ and CD8+ T cells, and widespread CNS inflammation and demyelination. Disease modifying therapies (DMTs) profoundly disrupt these processes and therefore compose an essential component of disease management. However, the effects of these therapeutic agents on vaccine safety and immunogenicity in individuals with MS are not yet fully understood. As such, the primary objective of this review article was to summarize the findings of recently conducted studies on vaccine safety and immunogenicity in MS patients treated with DMTs, particularly in the context of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Discussed in this review are vaccinations against influenza, yellow fever, human papillomavirus, measles, mumps, rubella, Streptococcus pneumoniae, hepatitis B, and COVID-19. This article additionally reviews our current understanding of COVID-19 severity and incidence in this patient population, the risks and benefits of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and vaccination guidelines set forth by MS societies and organizations.

Predictive Factors of First Time Pass Rate on the American Board of Surgery Certification in General Surgery Exams: A Systematic Review.

OBJECTIVE: General Surgery residency programs are evaluated on their American Board of Surgery (ABS) Qualifying examination (QE) and Certifying examination (CE) pass rates. This systematic review aims to evaluate predictive factors of ABS QE and CE first time pass rates. DESIGN: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, the following electronic databases were searched: PubMed, Embase, JAMA Network, and Google Scholar. Studies available in the English language published between January 2000 and July 2020 were deemed eligible. Articles that did not assess either of the ABS board examinations performance and pass-rates as outcomes were excluded. The Oxford Centre for Evidence-Based Medicine was used to determine the quality and risk of bias of each study. RESULTS: A total of 31 publications were included for analysis. Undergraduate medical education variables associated with first-time pass rates on the QE and CE include USMLE score, AOA membership, and class rank. Program factors affecting pass rates include program size, geographic location, and Program Director turnover. There is strong correlation between ABSITE and QE. Evidence supports the utility of mock oral examinations (MOEs) in predicting CE success. CONCLUSIONS: ABSITE scores demonstrated higher correlation with QE pass rate than CE pass rate. MOEs have a positive association with first-time CE pass rates. Nonmodifiable factors such as race/ethnicity, marital status, and geographic location were also found to be predictors. Delaying board certification examination beyond 1 year after residency graduation significantly reduces first-time pass rate.

Rare Papillary Breast Carcinoma Incidentally Discovered After Trauma-Induced Hematoma.

Papillary carcinoma of the breast is rare, comprising only 0.5% incidence of all breast cancers. Clinically the disease presents in postmenopausal women as a painless breast lump with possible bloody nipple discharge. Prognosis is favorable due to its slow growth. We present a 61-year-old woman incidentally diagnosed with papillary breast carcinoma after presenting with a trauma-induced hematoma of the right breast. The patient presented to our surgery oncology clinic for persistent right breast swelling secondary to a fall, despite initial incision and drainage (I&D) six weeks prior. She had no history of breast cancer. On presentation, her right breast was distended demonstrating an approximately 20cm ill-defined solid mass with skin changes consistent with a tense hematoma. CT scan demonstrated a large complex cystic and solid breast mass measuring 15.2cmx11.8cmx15.2cm with irregular peripheral solid hyperdense polypoid components. She then underwent a right breast incisional biopsy and hematoma evacuation. Frozen sections of the mass outer cavity wall and papillary projections were consistent with encapsulated papillary carcinoma (EPC). The patient was lost to follow-up and did not obtain definitive treatment. Breast cancer rarely presents as a breast hematoma. However, as in this case, if the hematoma fails to resolve, further investigation is warranted. The prognosis of EPC is excellent when identified and treated appropriately.

Immunogenicity of The Influenza Vaccine in Multiple Sclerosis Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: Multiple sclerosis is a neurodegenerative disease thought to be of autoimmune origin. It can lead to development of neurological symptoms and increase the risk of infection from communicable diseases. Thus, vaccines are endorsed to mitigate this risk. However, it has not yet been confirmed whether the dysfunctional immune system of these patients combined with taking immunosuppressants can lead to a dampened immunity in response to the influenza vaccine. Infection with the influenza virus is a concern for multiple sclerosis patients. Previous research on multiple sclerosis patients who have received the influenza vaccine focuses on safety and relapse rates. Studies that focus on the immune response mounted against the vaccine in this patient cohort are scant. This study serves to provide a comprehensive picture of the immunogenicity of the influenza vaccine in MS patients. METHODS: A systematic review of compiled research was conducted. Data obtained from the research was used in a meta-analysis using risk differences with a 95% confidence interval. RESULTS: Across the various strains incorporated into the influenza vaccine analyzed in this paper, there was no statistical difference in immune response mounted against the influenza vaccine between healthy controls and multiple sclerosis patients. CONCLUSION: The results of this study suggest that multiple sclerosis patients can mount an adequate immune response to the influenza vaccine when compared to healthy controls. Most of the immunotherapies these patients are on do not appear to affect this immune response. Therefore, the influenza vaccine should continue to be recommended to multiple sclerosis patients.

Gender Distribution of Current Surgical Critical Care Fellows, Faculty, and Program Directors.

As women surgeons continue to represent a minority within the surgical field while also holding lower ranked positions, gaining a sub-specialized set of clinical skills through surgical fellowships, like surgical critical care (SCC), is one approach to advance within the surgical field. A cross-sectional analysis was performed investigating the websites of all 106 US-based SCC fellowships. A total of 116 SCC fellows were included in this analysis, comprising 67 (59.3%) men and 46 (40.7%) women. There were 977 SCC fellowship faculty were evaluated, comprising 619 (67.9%) men and 292 (32.1%) women. Additionally, 103 SCC fellowship program directors were analyzed, consisting of 77 (74.8%) men and 26 (25.2%) women. There is a significantly lower proportion of women fellows and faculty members (P < .001) compared to men. SCC programs with female program directors on average have higher proportions of female fellows and faculty compared to programs with male program directors (52% and 36% vs 31% and 29%, respectively). There is a stable yet unbalanced gender distribution throughout all positions in SCC fellowship programs. Actively supporting women surgeons pursuing SCC fellowship and removing barriers to their advancement through effective interventions can disrupt the persistently low prevalence of women SCC fellows, faculty, and program directors.

Gender distribution among surgical journals' editorial boards: Empowering women surgeon scientists.

BACKGROUND: Gender disparities still exist in the field of academic surgery. Women face additional obstacles obtaining high-ranking, surgical academia positions compared to men, and this may extend to the appointment of editorial board members. We aim to evaluate the gender distribution of editorial board members, associate editors, and editors-in-chief of top US surgical journals and to recommend interventions, which can promote equitable gender representation among editorial boards. METHODS: The study is a cross-sectional analysis using publicly available data regarding the number and proportion of female editorial board members, associate editors, and editors-in-chief from 42 US surgical journals. Descriptive statistics and linear regression were performed with significance defined as P < .05. RESULTS: Of 2,836 editorial board members from 42 US surgical journals, 420 (14.8%) were women. Of 881 associate editors, 118 (13.3%) were women. Only 2/42 (4.8%) of editors-in-chief were women. The mean proportions of female editorial board members and associate editors were 14.5% and 19.5%, respectively. No significant associations were found between the 2019 Scimago Journal & Country Rank indicator nor the 2019 impact factor and the proportion of female editorial board members and female associate editors after adjusting for author H-index. CONCLUSION: Gender disparities are evident in academic surgery, and women comprise a minority of US surgical editorial board members, associate editors, and editors-in-chief. The implementation of women mentorship from senior faculty on behalf of senior residents and junior faculty, as well as journal-facilitated pipeline programs, can diversify editorial board members by increasing women representation and reduce disparities in surgical journal editorial boards.

The CLK inhibitor SM08502 induces anti-tumor activity and reduces Wnt pathway gene expression in gastrointestinal cancer models.

The Wnt/ß-catenin signaling pathway is aberrantly activated in colorectal (CRC) and many other cancers, and novel strategies for effectively targeting it may be needed due to its complexity. In this report, SM08502, a novel small molecule in clinical development for the treatment of solid tumors, was shown to reduce Wnt pathway signaling and gene expression through potent inhibition of CDC-like kinase (CLK) activity. SM08502 inhibited serine and arginine rich splicing factor (SRSF) phosphorylation and disrupted spliceosome activity, which was associated with inhibition of Wnt pathway-related gene and protein expression. Additionally, SM08502 induced the generation of splicing variants of Wnt pathway genes, suggesting that its mechanism for inhibition of gene expression includes effects on alternative splicing. Orally administered SM08502 significantly inhibited growth of gastrointestinal tumors and decreased SRSF phosphorylation and Wnt pathway gene expression in xenograft mouse models. These data implicate CLKs in the regulation of Wnt signaling and represent a novel strategy for inhibiting Wnt pathway gene expression in cancers. SM08502 is a first-in-class CLK inhibitor being investigated in a Phase 1 clinical trial for subjects with advanced solid tumors (NCT03355066).

Viscous contact lens system for vitrectomy.

The authors describe a recently developed system for use in vitreoretinal surgery. The system is compatible with a variety of lens choices, including wide-field, equatorial, and high-magnification direct viewing lenses, allowing for visualization of the far peripheral retina and detailed imaging of the macula. Used with autoclavable lenses, the system achieves high-resolution image quality at a cost-effective price.

Hypopyon and pseudoendophthalmitis associated with chronic vitreous hemorrhage.

Infectious endophthalmitis is an uncommon but potentially devastating eye disease. Although the presence of a hypopyon is considered one of the hallmark clinical signs of infectious endophthalmitis, hypopyon associated with non-infectious causes may occur. Two patients with hypopyon and pseudoendophthalmitis secondary to chronic vitreous hemorrhage are described. In both cases, the hypopyon improved without the use of intravitreal antibiotics.

Blast eye injuries: a review for first responders.

As the rate of terrorism increases, it is important for health care providers to become familiar with the management of injuries inflicted by blasts and explosions. This article reviews the ocular injuries associated with explosive blasts, providing basic concepts with which to approach the blast-injured patient with eye trauma. We conducted a literature review of relevant articles indexed in PubMed between 1948 and 2007. Two hundred forty-four articles were reviewed. We concluded that ocular injury is a frequent cause of morbidity in blast victims, occurring in up to 28% of blast survivors. Secondary blast injuries, resulting from flying fragments and debris, cause the majority of eye injuries among blast victims. The most common blast eye injuries include corneal abrasions and foreign bodies, eyelid lacerations, open globe injuries, and intraocular foreign bodies. Injuries to the periorbital area can be a source of significant morbidity, and ocular blast injuries have the potential to result in severe vision loss.

Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration.

PURPOSE: To evaluate the safety and efficacy of intravitreal bevacizumab (Avastin, Genentech Inc.) for the treatment of neovascular age-related macular degeneration (ARMD). METHODS: A retrospective review was performed on consented patients with neovascular ARMD receiving intravitreal bevacizumab therapy. All patients received intravitreal bevacizumab at baseline with additional monthly injections given at the discretion of the treating physician. At each visit, a routine Snellen visual acuity assessment was performed followed by an ophthalmic examination and optical coherence tomography (OCT) imaging. RESULTS: Fifty-three eyes of 50 patients received an intravitreal bevacizumab injection between May and August 2005. Including the month 3 visit, the average number of injections was 2.3 out of a maximum of 4 injections. No serious drug-related ocular or systemic adverse events were identified. Improvements in visual acuity and central retinal thickness measurements were evident by week 1 and continued through month 3. At month 3, the mean visual acuity improved from 20/160 to 20/125 (P < 0.001) and the mean central retinal thickness decreased by 99.6 microm (P < 0.001). CONCLUSION: Off-label intravitreal bevacizumab therapy for neovascular ARMD was well tolerated over 3 months with improvements in visual acuity and OCT central retinal thickness measurements. While the long-term safety and efficacy of intravitreal bevacizumab remain unknown, these short-term results suggest that intravitreal bevacizumab may be the most cost effective therapy for the treatment of neovascular ARMD.