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Emerging evidence suggests that cardiometabolic risk factors contribute to uterine leiomyoma development, but cardiometabolic profiles of women with the tumor remain poorly defined. This study aims to determine the association of cardiometabolic comorbidities and cardiometabolic medication use with a leiomyoma diagnosis.In this cross-sectional study, aggregate-level data from 2013-2020 were collected using the SlicerDicer feature of Epic electronic medical record system. Women ≥18 years with least one visit or hospital encounter at the Johns Hopkins Health System (n=679,981) were assigned as cases or controls according to leiomyoma status. Individual prevalence of each pre-specified cardiometabolic comorbidity and relevant prescription medications was obtained. Prevalence odds ratios were used to assess the association of cardiometabolic comorbidities and medication use with uterine leiomyoma.Women with uterine leiomyoma (n=27,703) were more likely to be obese (2.56; 95% CI, 2.49-2.63), have metabolic syndrome (1.82; 95% CI, 1.51-2.19), essential hypertension (1.45; 95% CI, 1.42-1.49), diabetes mellitus (1.29; 95% CI, 1.24-1.33) and hyperlipidemia (1.23; 95% CI, 1.19-1.26). These associations were stronger among younger women and persisted after excluding those with a hysterectomy. Notably, statins were the only medications associated with a lower leiomyoma risk (0.81; 95% CI, 0.79-0.84).Uterine leiomyoma is associated with a spectrum of cardiometabolic comorbidities and use of associated medications, constituting an unfavorable cardiometabolic profile in women with the tumor. If definitively correlated, prevention and early management of cardiometabolic risk factors may decrease uterine leiomyoma incidence, and screening women with uterine leiomyoma for cardiometabolic comorbidities may aid in cardiovascular disease prevention.

Fibroids are benign tumors caused by the proliferation of myometrial smooth muscle cells in the uterus that can lead to symptoms such as abdominal pain, constipation, urinary retention, and infertility. While traditionally thought of as a disease process intrinsic to the uterus, accumulating evidence suggests that fibroid growth may be linked with the systemic vasculature system, although cell-intrinsic factors are certainly of principal importance in their inception. Fibroids are associated with essential hypertension and preeclampsia, as well as atherosclerosis, for reasons that are becoming increasingly elucidated. Factors such as the renin–angiotensin–aldosterone system, estrogen, and endothelial dysfunction all likely play a role in fibroid pathogenesis. In this review, we lay out a framework for reconceptualizing fibroids as a systemic vascular disorder, and discuss how pharmaceutical agents and other interventions targeting the vasculature may aid in the novel treatment of fibroids.

This meta-analysis was conducted to 1) assess the quantity and dose of perioperatively dispensed opioids for benign hysterectomy by procedure route and 2) identify the predictors of persistent opioid use after the procedure DATA SOURCES: PubMed, Web of Science and Embase were systematically searched up to 25 March 2022.Studies reporting data on opioid dispensing among patients undergoing benign hysterectomy were considered eligible. The primary outcome was the dosage of opioids dispensed perioperatively (from 30 preoperative days to 21 postoperative days). The secondary outcome was the predictors of persistent opioid use after benign hysterectomy (from 3 months to 3 years postoperatively). Total opioid dispensing was measured in morphine milligram equivalents (MME) units.The random-effects model was used to pool the mean differences or odds ratios (ORs) and the corresponding 95% confidence intervals (CIs).Eight studies presenting data on 377,569 women undergoing benign hysterectomy were included. Of these women, 83% (95% CI: 81, 84) were dispensed opioids during the perioperative period. The average amount of perioperatively dispensed opioids was 143.5 MME (95% CI: 40, 247). Women undergoing vaginal hysterectomy were dispensed a significantly lower amount of opioids than those undergoing laparoscopic or abdominal hysterectomies. The overall rate of persistent opioid use after benign hysterectomy was 5% (95% CI: 2, 8). Younger patient age (OR 1.38 [95% CI: 1.17, 1.63]), smoking history (OR 1.87 [95% CI: 1.67, 2.10]), alcohol use (OR 3.16 [95% CI: 2.34, 4.27]), back pain (OR 1.50 [95% CI: 1.10, 2.05]) and fibromyalgia (OR 1.60 [95% CI: 1.39, 1.83]) were significantly associated with a higher risk of persistent opioid use after benign hysterectomy. However, there was no significant impact of hysterectomy route and operative complexity on persistent opioid use postoperatively.Perioperative opioid dispensing is significantly dependent on the route of hysterectomy, with the lowest dispensed MME of opioids for vaginal hysterectomy and the highest for abdominal hysterectomy. Nevertheless, hysterectomy route did not significantly predict persistent opioid use postoperatively, whereas younger age, smoking, alcohol use, back pain and fibromyalgia were significantly associated with persistent opioid use.

Emerging evidence supports the notion that inflammation fosters the development of common benign gynecologic disorders, including uterine leiomyoma, endometriosis, and adenomyosis. Numerous cytokines, chemokines, and growth and transcription factors have indisputable roles in the establishment and maintenance of benign gynecologic disorders by initiating complex cascades that promote proliferation, angiogenesis, and lesion progression. The interaction between inflammation and benign gynecologic disorders is orchestrated by a plethora of factors, including sex steroids, genetics, epigenetics, extracellular matrix, stem cells, cardiometabolic risk factors, diet, vitamin D, and the immune system. The role of inflammation in these disorders is not limited to local pathobiology but also extends to involve clinical sequelae that range from those confined to the reproductive tract, such as infertility and gynecologic malignancies, to systemic complications such as cardiovascular disease. Enhanced understanding of the intricate mechanisms of this association will introduce us to unvisited pathophysiological perspectives and guide future diagnostic and therapeutic implications aimed at reducing the burden of these disorders. Utilization of inflammatory markers, microRNA, and molecular imaging as diagnostic adjuncts may be valuable, noninvasive techniques for prompt detection of benign gynecologic disorders. Further, use of novel as well as previously established therapeutics, such as immunomodulators, hormonal treatments, cardiometabolic medications, and cyclooxygenase-2 and NF-κB inhibitors, can target inflammatory pathways involved in their pathogenesis. In this comprehensive review, we aim to dissect the existing literature on the role of inflammation in benign gynecologic disorders, including the proposed underlying mechanisms and complex interactions, its contribution to clinical sequelae, and the clinical implications this role entails.Summary sentenceReconceptualizing common benign gynecologic disorders as having inherent inflammatory pathobiology will introduce us to previously unvisited perspectives of their development and devise novel clinical implications aimed at reducing their burden.Graphical Abstract

Climate change is the greatest existential challenge to planetary and human health and is dictated by a shift in the Earth's weather and air conditions owing to anthropogenic activity. Climate change has resulted not only in extreme temperatures, but also in an increase in the frequency of droughts, wildfires, dust storms, coastal flooding, storm surges and hurricanes, as well as multiple compound and cascading events. The interactions between climate change and health outcomes are diverse and complex and include several exposure pathways that might promote the development of non-communicable diseases such as cardiovascular disease. A collaborative approach is needed to solve this climate crisis, whereby medical professionals, scientific researchers, public health officials and policymakers should work together to mitigate and limit the consequences of global warming. In this Review, we aim to provide an overview of the consequences of climate change on cardiovascular health, which result from direct exposure pathways, such as shifts in ambient temperature, air pollution, forest fires, desert (dust and sand) storms and extreme weather events. We also describe the populations that are most susceptible to the health effects caused by climate change and propose potential mitigation strategies, with an emphasis on collaboration at the scientific, governmental and policy levels.

Despite substantial reductions in the past decade, prescription opioids continue to cause widespread morbidity and mortality in the United States. Little is known regarding patterns and predictors of opioid use among women undergoing benign hysterectomy.This study aimed to identify the incidence and predictors of new persistent opioid use after benign hysterectomy among opioid-naïve women from a set of demographic, operative, and opioid prescription characteristics of patients.In this retrospective cohort study, we identified women undergoing benign hysterectomy from 2011 to 2016 using a validated national insurance claims database (IBM MarketScan Commercial Database). After excluding women with prevalent opioid use (from 365 to 31 days preoperatively), we identified patients who received a perioperative opioid prescription (30 days before to 14 days after hysterectomy) and evaluated them for new persistent opioid use, defined as at least 1 prescription from 15 to 90 days and at least 1 prescription from 91 to 365 days postoperatively. Multivariate logistic regression was used to examine demographic, clinical, operative, and opioid prescription-related factors associated with new persistent use. International Classification of Diseases, Ninth and Tenth Revisions, and Clinical Classification Software codes were used to identify hysterectomies, preoperative pain and psychiatric diagnoses, surgical indications, and surgical complications included as covariates.We identified 114,260 women who underwent benign hysterectomy and were not prevalent opioid users, of which 93,906 (82.2%) received at least 1 perioperative opioid prescription. Of 93,906 women, 4334 (4.6%) developed new persistent opioid use. Logistic regression demonstrated that new persistent use odds is significantly increased by younger age (18-34 years; adjusted odds ratio, 1.97; 95% confidence interval, 1.69-2.30), southern geographic location (adjusted odds ratio, 2.03; 95% confidence interval, 1.79-2.27), preoperative psychiatric and pain disorders (anxiety: adjusted odds ratio, 1.20 [95% confidence interval, 1.09-1.33]; arthritis: adjusted odds ratio, 1.30 [95% confidence interval, 1.21-1.40]),1 perioperative prescription (adjusted odds ratio, 1.53; 95% confidence interval, 1.24-1.88), mood disorder medication use (adjusted odds ratio, 1.51; 95% confidence interval, 1.40-1.64), tobacco smoking (adjusted odds ratio, 1.65; 95% confidence interval, 1.45-1.89), and surgical complications (adjusted odds ratio, 1.84; 95% confidence interval, 1.69-2.00). Although statistically nonsignificant, total morphine milligram equivalent of ≥300 in the first perioperative prescription increased persistent use likelihood by 9% (95% confidence interval, 1.01-1.17). Dispensing of a first perioperative prescription before the surgery, as opposed to after, increased new persistent use odds by 61% (95% confidence interval, 1.50-1.72). Each additional perioperative day covered by a prescription increased the likelihood of persistent use by 2% (95% confidence interval, 1.02-1.03). In contrast, minimally invasive hysterectomy (laparoscopic: adjusted odds ratio, 0.89 [95% confidence interval, 0.71-0.88]; vaginal: adjusted odds ratio, 0.82 [95% confidence interval, 0.72-0.93]) and a more recent surgery year (2016 vs reference 2011: adjusted odds ratio 0.58; 95% confidence interval, 0.51-0.65) significantly decreased its likelihood.New persistent opioid use after hysterectomy was associated with several patient, operative, and opioid prescription-related factors. Considering these factors may be beneficial in counseling patients and shared decision-making about perioperative prescription to decrease the risk of persistent opioid use.

BackgroundPrimary headache disorders have being increasingly reported in younger populations. They can have significant effects on their quality of life and academic achievement and may cause significant distress to their families.Aims and objectivesTo assess the burden of primary headache disorder and its impact on the quality of life on school student in Kuwait.MethodsAcross-sectional study was conducted among Kuwaiti primary and middle school students of both genders in randomly selected schools located in two governorates in 2018/2019 academic year. Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire for children and adolescents was used to assess the impact of primary headaches on the quality of life.ResultsOne thousand and ninety-one questionnaires were completed by primary and middle school students of both genders; of whom 466 students (girls 321 (68.88%) were diagnosed with primary headache disorders with mean age 11.98 ± 2.03 years. In the month prior to the survey, the effect of the headache was variable. The students lost a mean of 1.99 ± 2.015 days of school while they could not perform their usual activities for a mean of 2.84 ± 4.28 days. Their parents lost a mean of 2 ± 2.03 days of work because of headaches of their children and parents prohibited 5.7% of the students to engage in any activity due to their headaches. Difficulties in concentrations were reported as never sometimes (39.1%), often (24.8%), and always (26%). Majority of the students (51.5%) experienced a feeling of sadness ranging from sometimes to always. Most of the students (67.3%) struggled to cope with the headache and 22.4% were never able to cope. Additionally, 19.4% of students reported they did not want others noticing their headache.ConclusionPrimary headache disorder can have a significant impact on the quality of life in children. It can affect their engagement in activities and academic achievement. Implementing strategies to properly manage schoolchildren with primary headaches can have profound effects on their quality of life.

To evaluate the effect of obesity on clinical and financial outcomes of minimally invasive hysterectomy METHODS: This was a retrospective cohort study of 5 affiliated hospitals. We obtained demographic, operative, and financial characteristics to analyze the effects of obesity on outcomes, including operating room (OR) time, estimated blood loss (EBL), length of stay (LOS), adverse perioperative events, and hospital charges. Obesity was stratified by the following classes: no obesity (BMI30 kg/mA total of 2483 women underwent benign, minimally invasive hysterectomy. Laparoscopic was the most common approach (79.8%), followed by robotic (12.2%), and vaginal (8.0%). Mean BMI was 30.13 ± 6.99 kg/mObesity appears to have a significant effect on clinical outcomes of benign hysterectomy that is approach-dependent and most notable among patients with class III obesity. BMI was not, however, a predictor of financial outcomes.

OBJECTIVE To identify predictors of same-day discharge after benign minimally invasive hysterectomy. METHODS In this retrospective cohort study, we identified women (n = 1084) undergoing benign minimally invasive hysterectomy from 2009 to 2016. Multivariate logistic regression was used to examine demographic, operative, and surgeon factors associated with discharge on postoperative day 0. RESULTS In our study population, 238 women (22%) were discharged on the same day. Robotic hysterectomy (risk ratio [RR] 2.24; 95% confidence interval [CI] 1.13-4.44), shorter operative time (lowest quartile; RR 5.28; 95% CI 2.66-10.46), and minimal blood loss (lowest quartile; RR 3.01; 95% CI 1.68-6.23) were associated with higher same-day discharge likelihood whereas later procedure start time (2-5 pm; RR 0.38; 95% CI 0.17-0.85) and postoperative complications (RR 0.19; 95% CI 0.06-0.55) significantly decreased its likelihood. The strongest predictor was surgeon's number of years in practice, with recently graduated surgeons more likely to discharge their patients on the same day (RR 3.15; 95% CI 2.09-4.77). CONCLUSION Same-day discharge after minimally invasive hysterectomy is determined by several patient, operative, and surgeon factors that can be incorporated into an implementation plan to promote earlier discharge. Most especially, scheduling patients based on perceived case complexity and targeted surgeon education can qualify a larger cohort for same-day discharge.

A healthy lifestyle and a balanced diet play a paramount role in promoting and maintaining homeostatic functions and preventing an array of chronic and debilitating diseases. Based upon observational and epidemiological investigations, it is clear that nutritional factors and dietary habits play a significant role in gynecological disease development, including uterine leiomyoma, endometriosis, polycystic ovary syndrome, and gynecological malignancies. Diets rich in fruits and vegetables, Mediterranean diets, green tea, vitamin D, and plant-derived natural compounds may have a long-term positive impact on gynecological diseases, while fats, red meat, alcohol, and coffee may contribute to their development. Data regarding the association between dietary habits and gynecological disorders are, at times, conflicting, with potential confounding factors, including food pollutants, reduced physical activity, ethnic background, and environmental factors limiting overall conclusions. This review provides a synopsis of the current clinical data and biological basis of the association between available dietary and nutritional data, along with their impact on the biology and pathophysiology of different gynecological disorders, as well as an outlook on future directions that will guide further investigational research.

Study Objective To evaluate the impact of obesity on clinical and financial outcomes of minimally invasive hysterectomy (MIH) for benign indications. Design This is a retrospective cohort study of women who underwent MIH for benign indications. We obtained demographic, operative, and surgeon characteristics to analyze the impact of obesity on various outcomes by hysterectomy approach including operating room (OR) time, estimated blood loss (EBL), length of stay (LOS), adverse perioperative events, and procedure costs. Setting N/A. Patients or Participants All women who underwent MIH for benign indications between 2013-2019 at five affiliated hospitals. Interventions N/A. Measurements and Main Results We identified 2,494 women who underwent MIH for benign indications. Laparoscopic approach was most commonly performed (78.5%) followed by robotic (13.5%) then vaginal (8.0%). Mean total cost was $13,928 (± $5,954), age was 48.04 years (± 9.62), and BMI was 30.13 (± 6.99). OR time and EBL were higher among patients with obesity (BMI 30-39) and highest among patients with class III obesity (BMI > 40) (p 40) was a significant predictor of hysterectomy charges, patients with obesity (BMI of 30-39) had a lower laparoscopic hysterectomy cost by $702.2 compared with non-obese patients. Logistic regression analysis showed no significant impact of obesity on LOS or occurrence of adverse perioperative events. Conclusion Obesity appears to have a significant impact on several clinical and financial outcomes of benign hysterectomy that is approach-dependent and most notable among morbidly obese patients. Increased awareness of this impact should guide gynecologists towards approaches that optimize care of high-risk patients while decreasing procedure costs.

Background: Primary headaches are remarkably prevalent worldwide and increasingly reported among children. However, the exact trend in this age group, particularly in the gulf region, remains scarce. Aims and Objectives: To examine the prevalence of primary headache disorders among primary and middle school students in Kuwait.Methods: We conducted a cross-sectional study that included Kuwaiti primary and middle school children and adolescents of both genders in randomly selected schools located in two governorates in Kuwait in 2018/2019 academic year. Prevalence and attributable burden of headache, definite and probable migraine,definite and probable tension-type headache, chronic headache ≥15 days/month and probable medication over use headache were assessed using the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire for children and adolescents. Results: Of 1485 questionnaires that were distributed, 1089 students completed the questionnaire with a respondent rate of 73.4%. The study population consisted of 420 boys (38.56%) versus 669 girls (61.43%) students with a mean age of 11.5 ± 2.11 years. The lifetime prevalence of any headache was 85.2%. The one-year prevalence of primary headache disorders was 42.71% with more middle schoolers reporting headaches than primary schoolers (50.37% versus 30,48%; p Conclusion: Primary headaches are remarkably common in Kuwaiti school students with migraine headache being the most frequently reported type. Age and female gender pay a role in the development of primary headaches. The results attract attention of health services for those group, the need for further epidemiological researches.

Background We examined the association of patient factors, gynecologic diagnoses, and hospital characteristics with utilization of the robotic approach for benign hysterectomy. Methods We performed cross-sectional study of women (n = 725 050) undergoing hysterectomies in the 2012 to 2014 National Inpatient Sample. Results A total of 725 050 women underwent inpatient hysterectomy for benign indications: 70345 (10%) were performed robotically. Women were more likely to receive robotic hysterectomy at teaching hospitals (RR 1.60 [95% CI 1.54-1.66]) after adjustment for other patient factors, gynecologic diagnoses, and hospital characteristics. They were more likely to undergo robotic hysterectomy at large (RR 1.34 [95% CI 1.29-1.39]) and for-profit hospitals (RR 1.16 [95% CI 1.11-1.22]). Women were less likely to undergo robotic hysterectomy if they were rural (RR 0.68 [95% CI 0.64-0.72]), African-American (RR 0.78 [95% CI 0.74-0.82]), or publicly insured or uninsured (RR 0.55 [95% CI 0.53-0.57]) women. Conclusion Significant geographic and hospital-level disparities exist in access to robotic hysterectomy in the United States.

IMPORTANCE: While it has long been known that polycystic ovarian syndrome (PCOS) is associated with cardiometabolic risk factors, there is emerging evidence that other benign gynecologic conditions, such as uterine leiomyomas, endometriosis, and even hysterectomy without oophorectomy, can be associated with cardiometabolic risk factors. Understanding the evidence and mechanisms of these associations can lead to novel preventive and therapeutic interventions. OBJECTIVE: This article discusses the evidence and the potential mechanisms mediating the association between cardiometabolic risk factors and benign gynecologic disorders. EVIDENCE ACQUISITION: We reviewed PubMed, Embase, Scopus, and Google Scholar databases to obtain plausible clinical and biological evidence, including hormonal, immunologic, inflammatory, growth factor-related, genetic, epigenetic, atherogenic, vitamin D-related, and dietary factors. RESULTS: Cardiometabolic risk factors appear to contribute to uterine leiomyoma pathogenesis. For example, obesity can modulate leiomyomatous cellular proliferation and extracellular matrix deposition through hyperestrogenic states, chronic inflammation, insulin resistance, and adipokines. On the other hand, endometriosis has been shown to induce systemic inflammation, thereby increasing cardiometabolic risks, for example, through inducing atherosclerotic changes. CONCLUSION AND RELEVANCE: Clinical implications of these associations are twofold. First, screening and early modification of cardiometabolic risk factors can be part of a preventive strategy for uterine leiomyomas and hysterectomy. Second, patients diagnosed with uterine leiomyomas or endometriosis can be screened and closely followed for cardiometabolic risk factors and cardiovascular disease.

An amendment to this paper has been published and can be accessed via the original article.

Background/Aims: Prenatal exposure to lipopolysaccharide (LPS) dampens hippocampal neurogenesis. This effect is associated with increased anxiety-like behavior in adult offspring. Furthermore, blocking serotonin transporters (SERT) promotes adult neurogenesis. Previous studies were performed largely in males. Therefore, we explored the impact of prenatal LPS on neurogenesis, SERT expression in the hippocampus, and anxiety-like behavior in female rats during prepubertal and adulthood stages. Materials and Methods: Timed pregnant rats were injected with either saline or LPS (100 µg/kg, i.p.) on gestational days 15, 17, and 19. Newly born neurons were monitored by immunohistochemistry, and anxiety-like behavior was monitored using the elevated plus maze and open-field test. SERT expression in the hippocampus was assessed by Western blot and immunofluorescence. Results: Prenatal LPS led to reduced hippocampal neurogenesis in adult but not in prepubertal female offspring. This reduced neurogenesis was associated with enhanced hippocampal expression of SERT protein. However, there was no significant impact of prenatal LPS on anxiety-like behavior. Conclusions: Prenatal LPS-induced reduction in neurogenesis was dissociated from anxiety-like behavior in adult female rats. Furthermore, the long-lasting impact of prenatal LPS on neurogenesis in female offspring was age-dependent.