Gender Disparity Among Surgical Peer-Reviewed Literature.

BACKGROUND: Women remain under-represented in academic surgery despite increasing percentages of female surgeons and surgery residents. Publications and leadership positions are used for hiring and promoting academic surgeons. We sought to determine the disparity of female authorship when compared with male authors in surgical peer-reviewed publications. METHODS: PubMed was searched for surgical publications from the United States. Obstetrics and gynecology was selected as a control specialty owing to its history of high female representation. Thirteen other surgical specialties were randomly selected from the Accreditation Council for Graduate Medical Education specialty list. Manuscripts from four time periods, 2000-2005, 2006-2010, 2011-2015, and 2016-2017, were randomly selected, and the gender of the first and last authors was determined. The Accreditation Council for Graduate Medical Education and Association of American Medical Colleges databases were used to determine women representation in surgery. Trends were assessed using the Cochran-Armitage test. RESULTS: In total, 560 manuscripts in 14 specialties were reviewed. In the control specialty, 51% of first authors were female compared with 18% of those in study specialties, and 39% of last authors were female compared with 11% of those in study specialties. No difference was found when comparing the gender of first (P-value = 0.393) and/or last authors (P-value = 0.281) with the proportion of female residents and attendings. CONCLUSIONS: Women surgeons publish research at a rate proportional to the number of females involved in that specialty. Disparities in leadership roles are unlikely explained by differences in publications. Instead, disparities are likely due to other reasons such as failure to attract women to academic surgery and failure to promote and mentor women surgeons into leadership positions.

Is the American College of Surgeons Online Communities a safe and useful venue to ask for surgical advice?

BACKGROUND: Many surgeons rely on the American College of Surgeons (ACS) Community Forums for advice on managing complex patients. Our objective was to assess the safety and usefulness of advice provided on the most popular surgical forum. METHODS: Overall, 120 consecutive, deidentified clinical threads were extracted from the General Surgery community in reverse chronological order. Three groups of three surgeons (mixed academic and community perspectives) evaluated the 120 threads for unsafe or dangerous posts. Positive and negative controls for safe and unsafe answers were included in 20 threads, and reviewers were blinded to their presence. Reviewers were free to access all online and professional resources. RESULTS: There were 855 unique responses (median 7, 2-15 responses per thread) to the 120 clinical threads/scenarios. The review teams correctly identified all positive and negative controls for safety. While 58(43.3%) of threads contained unsafe advice, the majority (33, 56.9%) were corrected. Reviewers felt that a there was a standard of care response for 62/120 of the threads of which 50 (80.6%) were provided by the responses. Of the 855 responses, 107 (12.5%) were considered unsafe/dangerous. CONCLUSION: The ACS Community Forums are generally a safe and useful resource for surgeons seeking advice for challenging cases. While unsafe or dangerous advice is not uncommon, other surgeons typically correct it. When utilizing the forums, advice should be taken as a congregate, and any single recommendation should be approached with healthy skepticism. However, social media such as the ACS Forums is self-regulating and can be an appropriate method for surgeons to communicate challenging problems.

Expectant Management of Patients with Ventral Hernias: 3 Years of Follow-up.

BACKGROUND: The safety and effectiveness of expectant management (e.g., watchful waiting or initially managing non-operatively) for patients with a ventral hernia is unknown. We report our 3-year results of a prospective cohort of patients with ventral hernias who underwent expectant management. METHODS: A hernia clinic at an academic safety-net hospital was used to recruit patients. Any patient undergoing expectant management with symptoms and high-risk comorbidities, as determined by a surgeon based on institutional criteria, would be included in the study. Patients unlikely to complete follow-up assessments were excluded from the study. Patient-reported outcomes were collected by phone and mailed surveys. A modified activities assessment scale normalized to a 1-100 scale was used to measure results. The rate of operative repair was the primary outcome, while secondary outcomes include rate of emergency room (ER) visits and both emergent and elective hernia repairs. RESULTS: Among 128 patients initially enrolled, 84 (65.6%) completed the follow-up at a median (interquartile range) of 34.1 (31, 36.2) months. Overall, 28 (33.3%) patients visited the ER at least once because of their hernia and 31 (36.9%) patients underwent operative management. Seven patients (8.3%) required emergent operative repair. There was no significant change in quality of life for those managed non-operatively; however, substantial improvements in quality of life were observed for patients who underwent operative management. CONCLUSIONS: Expectant management is an effective strategy for patients with ventral hernias and significant comorbid medical conditions. Since the short-term risk of needing emergency hernia repair is moderate, there could be a safe period of time for preoperative optimization and risk-reduction for patients deemed high risk.

Nitric oxide modulates µ-opioid receptor function in vitro.

Painful diabetic neuropathy (PDN) is a type of peripheral neuropathic pain that develops as a consequence of prolonged hyperglycaemia-induced injury to the long nerves. Apart from pain, PDN is also characterized by morphine hyposensitivity. Intriguingly, in streptozotocin (STZ)-induced diabetic rats exhibiting marked morphine hyposensitivity, dietary administration of the nitric oxide (NO) precursor, L-arginine at 1 g/d, progressively rescued morphine efficacy and potency over an 8-week treatment period. In earlier work, single bolus doses of the furoxan nitric oxide (NO) donor, PRG150 (3-methylfuroxan-4-carbaldehyde), evoked dose-dependent pain relief in STZ-diabetic rats but the efficacious doses were 3-4 orders of magnitude higher in advanced diabetes than that required in early STZ diabetes. Together, these findings suggested a role for NO in the modulation of µ-opioid (MOP) receptor signalling. Therefore, the present study was designed to assess a role for NO released from PRG150, in modulating MOP receptor function in vitro. Here, we show an absolute requirement for the MOP receptor, but not the δ-opioid (DOP) or the κ-opioid (KOP) receptor, to transduce the cellular effects of PRG150 on forskolin-stimulated cAMP responses in vitro. PRG150 did not interact with the classical naloxone-sensitive binding site of the MOP receptor, and its effects on cAMP responses in HEK-MOP cells were also naloxone-insensitive. Nevertheless, the inhibitory effects of PRG150 on forskolin-stimulated cAMP responses in HEK-MOP cells were dependent upon pertussis toxin (PTX)-sensitive Gi/o proteins as well as membrane lipid rafts and src kinase. Together, our findings implicate a role for NO in modulating MOP receptor function in vivo.

The furoxan nitric oxide donor, PRG150, evokes dose-dependent analgesia in a rat model of painful diabetic neuropathy.

Painful diabetic neuropathy (PDN) is a type of peripheral neuropathic pain that is often intractable. Elevated nitric oxide (NO) from neuronal and non-neuronal sources in the somatosensory system is implicated in the pathobiology of peripheral neuropathic pain. However, in diabetes, nitrergic nerve degeneration to deplete NO bioactivity appears causal in the pathogenesis of irreversible autonomic neuropathy, another long term complication of diabetes. Hence, this study hypothesized that progressive NO depletion may underpin the pathobiology of PDN and that NO donors may alleviate PDN. Diabetes was induced in rats with intravenous streptozotocin (STZ) at 70 mg/kg and confirmed if blood glucose levels (BGLs) on day 10 post-STZ were ≥15 mmol/L. Analgesic efficacy of subcutaneous (s.c.) bolus doses of the furoxan NO donor, PRG150 was assessed in the STZ-diabetic rat model of PDN at 10-, 14- and 24-weeks post-STZ relative to the sydnominine NO donor, SIN-1 and its prodrug, molsidomine. PRG150 produced dose-dependent analgesia in STZ-diabetic rats whereas SIN-1 and molsidomine evoked neuro-excitatory side-effects, but not analgesia. The 1000-fold larger doses of PRG150 needed to produce analgesia at 14- and 24-weeks (800 pmol/kg) c.f. 10-weeks (8 fmol/kg) post-STZ in rats, suggest that progressive NO depletion is also causal in PDN. Importantly, doses of PRG150 up to 10 000 fold higher than the analgesic dose did not produce hypotension in rats. The 50-fold greater release of NO by SIN-1 c.f. PRG150 in vitro, may underpin the neuro-excitatory rather than analgesic effects of SIN-1/molsidomine. PRG150 is worthy of further investigation as a potential novel analgesic for PDN.

Cardiovascular Disease and Dementia: Exploring Intersections, Risks, and Therapeutic Challenges.

This review examines the complex bidirectional relationship between cardiovascular disease and various dementia subtypes, including Alzheimer's disease, vascular dementia, Lewy body dementia, and frontotemporal dementia. Traditional cardiovascular risk factors such as hypertension, coronary artery disease, arrhythmia, and diabetes mellitus are strongly linked to the development of dementia. Emerging evidence indicates that cognitive decline can exacerbate cardiovascular risks through heightened inflammatory responses and compromised autonomic regulation. Additionally, this review explores trials that investigate the impact of cardiovascular medications, such as antihypertensive and statin therapies, on cognitive outcomes, as well as studies examining how dementia treatments like anticholinesterases affect cardiovascular health. This review emphasizes the importance of early identification of at-risk individuals, integrated care approaches, and lifestyle interventions aimed at reducing both cardiovascular disease and dementia risk, ultimately aiming to enhance patient outcomes and quality of life.

The vascular complications of diabetes: a review of their management, pathogenesis, and prevention.

INTRODUCTION: This review highlights the pathogenesis of both microvascular and macrovascular complications of diabetes and how these mechanisms influence both the management and preventative strategies of these complications. The cumulative data shown in this review suggest hyperglycemic and blood pressure control remain central to this intricate process. AREAS COVERED: We reviewed the literature including retrospective, prospective trials as well as meta-analysis, and post hoc analysis of randomized trials on microvascular andmacrovascular complications. EXPERT OPINION: Further research is needed to explore the ideal intervention targets and preventative strategies needed to prevent macrovascular complications. Furthermore, as the data for trials looking at microvascular complications lengthen more long-term data will further elucidate the role that the duration of diabetes has on these complications. Additionally, trials looking to maximize hyperglycemic control with multiple agents in diabetes, such as metformin, SGL2isand GLP-1 receptor agonists are currently in process, which will have implications for rates of microvascular as well as macrovascular complications.

Massive Hemorrhage Following Spontaneous Mediastinal Inflammatory Myofibroblastic Tumor Rupture: A Case Report.

A 45-year-old male in a hypertensive emergency was admitted with complaints of frontal headache, progressive chest discomfort, shortness of breath, dysphagia, and right upper quadrant abdominal pain radiating across the epigastrium and to the back that increases in intensity with deep inspiration. He denied any history of abdominal pain, vomiting, dyspnea, nausea, and weight loss. A computed tomography (CT) scan of the chest showed a posterior mediastinal mass between the esophagus and descending aorta. A magnetic resonance imaging (MRI) scan revealed a non-enhancing posterior mediastinal mass possibly compressing both the esophagus and the airway. A 30-degree thoracoscope was inserted in the chest cavity revealing a large hemothorax from a possibly ruptured inflammatory myofibroblastic tumor (IMT) encompassing nearly the entire pleural space with both fresh and clotted blood. Two liters of fresh blood was removed via a right thoracotomy procedure. Once removed, a large fibrinous clot-filled mass was resected entirely and sent to pathology. Postoperative recovery was uneventful; dysphagia and shortness of breath resolved. The patient gradually resumed his regular diet.

Acute Bacterial Tenonitis and Conjunctivitis following Intravitreal Injection.

A 73-year-old man presented 3 days after intravitreal injection (IVI) with bevacizumab for treatment of neovascular age-related macular degeneration with pain and redness around the injection site. Examination showed conjunctival edema and injection around the injection site and a central infiltrate at the injection site consistent with infection of Tenon's capsule and the conjunctiva. Infection of a vitreous wick was considered, but vitreous inflammation was not present. Acute bacterial tenonitis and conjunctivitis were diagnosed, and the patient was prescribed topical antibiotic drops. The patient's symptoms were resolved within 48 h following the use of topical antibiotic drops, so a culture was not performed. The patient did not develop endophthalmitis. To our knowledge, this is the first reported case of acute bacterial tenonitis and conjunctivitis of the injection site following IVI. Even with the use of betadine, infection of Tenon's capsule and the conjunctiva may occur after IVI and must be differentiated from other causes of postinjection ocular redness such as chemical irritation of the ocular surface, corneal abrasions, and endophthalmitis.

Gender Disparity in Authorship of Peer-Reviewed Medical Publications.

BACKGROUND: Women are underrepresented in medicine despite increases in the percentage of female physicians. It is unknown if academic productivity contributes to these differences. We sought to determine whether gender disparity exists in peer-reviewed literature authorship in the United States from 2000 to 2017. METHODS: Medical and surgical peer-reviewed research articles from the United States were retrospectively reviewed using PubMed from 2000 to 2017. Manuscripts were randomly selected within 4 different time periods: 2000-2005, 2006-2010, 2011-2015 and 2016-2017. The gender of the first and last authors was determined and the journal's impact factor recorded. The Accreditation Council for Graduate Medical Education (ACGME) and Association of American Medical Colleges (AAMC) databases were used to determine the percent of female residents, attendings and academic leadership positions. Primary outcome was the prevalence of female authors in peer-reviewed literature. Secondary aims were differences in disparity in medical versus surgical specialties, differences in publications' impact factor among gender and the association between gender and mentoring. RESULTS: Within 1,120 articles reviewed, 31.6% of first authors and 19.4% of last authors were women. Female first and last authors increased over time and authorship was proportional to the number of women in the studied specialties at that specific time period (P = 0.78). There was no difference in the journal's impact factors between gender (P = 0.64). On subgroup analysis of medical and surgical subspecialties, results remained unchanged. CONCLUSIONS: Women publish research at a rate proportional to the number of academic female physicians. Disparities in leadership roles are unlikely explained by differences in publications. While gender disparities in medicine have improved, substantial disparities in leadership persist.

Role of the PACAP system of the extended amygdala in the acoustic startle response in rats.

Anxiety-related disorders are the most prevalent mental disorders in the world and they are characterized by abnormal responses to stressors. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide highly expressed in the extended amygdala, a brain macrostructure involved in the response to threat that includes the central nucleus of the amygdala (CeA) and the bed nucleus of the stria terminalis (BNST). The aim of this series of experiments was to systematically elucidate the role of the PACAP system of the CeA and BNST under both control, unstressed conditions and after the presentation of a stressor in rats. For this purpose, we used the acoustic startle response (ASR), an unconscious response to sudden acoustic stimuli sensitive to changes in stress which can be used as an operationalization of the hypervigilance present in anxiety- and trauma-related disorders. We found that infusion of PACAP, but not the related peptide vasoactive intestinal peptide (VIP), into either the CeA or the BNST causes a dose-dependent increase in ASR. In addition, while infusion of the antagonist PACAP(6-38) into either the CeA or the BNST does not affect ASR in non-stressed conditions, it prevents the sensitization of ASR induced by an acute footshock stress. Finally, we found that footshock stress induces a significant increase in PACAP, but not VIP, levels in both of these brain areas. Altogether, these data show that the PACAP system of the extended amygdala contributes to stress-induced hyperarousal and suggest it as a potential novel target for the treatment of stress-related disorders.

Gender Disparity in Surgery: An Evaluation of Surgical Societies.

Background: The percentage of female surgeons and surgery residents has increased slowly to 24% and 35%, respectively. However, women remain under-represented in surgical leadership positions (<20%). Society awards and leadership positions are used for hiring and promoting surgeons. We hypothesized that within the Surgical Infection Society (SIS), females are under-represented. Methods: The SIS website and databases were consulted for the number of female members, awardees, and leaders. Representation was divided into four time periods: 2000-2005, 2006-2010, 2011-2015, and 2016-2017 and compared for changes over time utilizing a Χ2 test. In addition, we reviewed the council members of five other surgical societies and compared the percentage of female representation in leadership positions. Results: Since the SIS was founded, there have been 587 members of whom only 135 (23%) are female. There has been an increase in female membership over time (p < 0.001). The number of female awardees rose from 37% during the first two study periods to more than 50% in the last two periods (p = 0.002). However, female representation in leadership positions decreased from 26% in 2000-2005 to less than 15% in the last three study periods (p = 0.234). Similar disparities emerged when comparing the SIS with other surgical societies: Women have represented only 24% (range 8%-42%) of leaders and 4% (range 0-11%) of society presidents. Conclusions: Female surgeons are under-represented in the SIS membership and leadership positions. Whereas the number of female surgeons and residents has increased, these trends have not occurred with council membership and leadership within the SIS. There is a need to address this gender disparity.

The oncogenic gene fusion TMPRSS2: ERG is not a diagnostic or prognostic marker for ovarian cancer.

TMPRSS2:ERG is a gene fusion resulting from the chromosomal rearrangement of the androgen-regulated TMPRSS2 gene and the ETS transcription factor ERG, leading to the over-expression of the oncogenic molecule ERG. This gene rearrangement has been found in approximately half of all prostate cancers and ERG overexpression is considered as a novel diagnostic marker for prostate carcinoma. However, little is known about the role of the TMPRSS2:ERG gene fusion in ovarian cancer. The purpose of this study was to test ERG expression in ovarian cancer and its potential as a diagnostic marker for ovarian carcinoma progression. A tissue microarray containing 180 ovarian cancer tissues of various pathological types and grades were examined by immunohistochemical analysis for expression of ERG. We also used 40 prostate carcinoma tissues and 40 normal tissues for comparison in parallel experiments. ERG-positive expression was detected in 40% of the prostate tumor cancer, as well as in internal positive control endothelial cells, confirming over-expression of ERG in prostate cancer at relatively the same rate observed by others. In contrast, all of the ovarian tumor patient tissues of varying histologic types were ERG-negative, despite some positivity in endothelial cells. These results suggest that the oncogenic gene fusion TMPRSS2:ERG does not occur in ovarian cancer relative to prostate cancer. Therefore, development of ERG expression profile would not be a useful diagnostic or prognostic marker for ovarian cancer patient screening.

Comparison of the pharmacokinetics of oxycodone and noroxycodone in male dark agouti and Sprague--Dawley rats: influence of streptozotocin-induced diabetes.

PURPOSE: The aims of this study are to evaluate whether cytochrome P450 (CYP)2D1/2D2-deficient dark agouti (DA) rats and/or CYP2D1/2D2-replete Sprague-Dawley (SD) rats are suitable preclinical models of the human, with respect to mirroring the very low plasma concentrations of metabolically derived oxymorphone seen in humans following oxycodone administration, and to examine the effects of streptozotocin-induced diabetes on the pharmacokinetics of oxycodone and its metabolites, noroxycodone and oxymorphone, in both rodent strains. METHODS: High-performance liquid chromatography-electrospray ionization-tandem mass spectrometry was used to quantify the serum concentrations of oxycodone, noroxycodone, and oxymorphone following subcutaneous administration of bolus doses of oxycodone (2 mg/kg) to groups of nondiabetic and diabetic rats. RESULTS: The mean (+/-SEM) areas under the serum concentration vs. time curves for oxycodone and noroxycodone were significantly higher in DA relative to SD rats (diabetic, p<0.05; nondiabetic, p<0.005). Serum concentrations of oxymorphone were very low (<6.9 nM). CONCLUSIONS: Both DA and SD rats are suitable rodent models to study oxycodone's pharmacology, as their systemic exposure to metabolically derived oxymorphone (potent micro-opioid agonist) is very low, mirroring that seen in humans following oxycodone administration. Systemic exposure to oxycodone and noroxycodone was consistently higher for DA than for SD rats showing that strain differences predominated over diabetes status.