Uterine Collagen Cross-Linking: Biology, Role in Disorders, and Therapeutic Implications.

Collagen is an essential constituent of the uterine extracellular matrix that provides biomechanical strength, resilience, structural integrity, and the tensile properties necessary for the normal functioning of the uterus. Cross-linking is a fundamental step in collagen biosynthesis and is critical for its normal biophysical properties. This step occurs enzymatically via lysyl oxidase (LOX) or non-enzymatically with the production of advanced glycation end-products (AGEs). Cross-links found in uterine tissue include the reducible dehydro-dihydroxylysinonorleucine (deH-DHLNL), dehydro-hydroxylysinonorleucine (deH-HLNL), and histidinohydroxymerodesmosine (HHMD); and the non-reducible pyridinoline (PYD), deoxy-pyridinoline (DPD); and a trace of pentosidine (PEN). Collagen cross-links are instrumental for uterine tissue integrity and the continuation of a healthy pregnancy. Decreased cervical cross-link density is observed in preterm birth, whereas increased tissue stiffness caused by increased cross-link density is a pathogenic feature of uterine fibroids. AGEs disrupt embryo development, decidualization, implantation, and trophoblast invasion. Uterine collagen cross-linking regulators include steroid hormones, such as progesterone and estrogen, prostaglandins, proteoglycans, metalloproteinases, lysyl oxidases, nitric oxide, nicotine, and vitamin D. Thus, uterine collagen cross-linking presents an opportunity to design therapeutic targets and warrants further investigation in common uterine disorders, such as uterine fibroids, cervical insufficiency, preterm birth, dystocia, endometriosis, and adenomyosis.

Surgical and oncologic outcomes in surgically treated women 80 years and older with endometrioid endometrial cancer as a function of their comorbidities.

Objective: To describe the surgical and oncologic outcomes in surgically treated oldest old women (≥80 years) with endometrioid endometrial cancer as a function of their comorbidities. Methods: In this retrospective cohort study, patients aged 80-99 years who underwent surgical management of stage I endometrioid endometrial cancer between 2006 and 2018 were included. Low- and high-intermediate risk disease was defined using the Gynecologic Oncology Group-99 criteria. The validated, Combined Age-Charlson Comorbidity Index (CA-CCI) was used to quantify comorbidity burden. Logistic regression was used to identify the independent predictors of various surgical and oncologic outcomes. Kaplan-Meier survival analysis was performed to compare survival distributions based on mortality cause and comorbidity status. Results: We identified 64 women who met the eligibility criteria. Median age was 84 years (IQR 80, 94 years). Among oldest old women undergoing a hysterectomy with or without lymph node dissection, women with a CA-CCI score of ≥7 had an 8 times higher risk of postoperative infections compared with oldest old women with a <7 score (95% CI 1.53-48.91, P = 0.015). Women with a CA-CCI score of ≥8 were 45% less likely to survive at 3 years (aRR 0.55, 95% CI 0.004-0.87; P = 0.039) than those with a lower CA-CCI score (three-year overall survival 73% vs 96%). Conclusion: Surgical and oncologic outcomes in oldest old women with early stage endometrioid endometrial cancer are largely determined by comorbidity status. Less comorbid women (CA-CCI score < 8) had a significantly higher five-year survival at 87% than their more comorbid counterparts. Use of age-comorbidity risk scoring such as CA-CCI, preoperative optimization, and careful selection for and counseling of patients about surgical treatment are paramount in providing optimal recovery and survival advantages in the oldest old.

Uterine Transcriptome: Understanding Physiology and Disease Processes.

In recent years, transcriptomics has enabled us to gain a deeper understanding of fundamental reproductive physiology, including the menstrual cycle, through a more precise molecular analysis. The endometrial mRNA transcript levels fluctuate during the normal menstrual cycle, indicating changes in the relative recruitment and abundance of inflammatory cells, as well as changes in the receptivity and remodeling of the endometrium. In addition to providing a more comprehensive understanding of the molecular underpinnings of pathological gynecological conditions such as endometriosis, leiomyomas, and adenomyosis through RNA sequencing, this has allowed researchers to create transcriptome profiles during both normal menstrual cycles and pathological gynecological conditions. Such insights could potentially lead to more targeted and personalized therapies for benign gynecological conditions. Here, we provide an overview of recent advances in transcriptome analysis of normal and pathological endometrium.

Oxidative Stress and Antioxidants in Uterine Fibroids: Pathophysiology and Clinical Implications.

In the last few decades, our understanding of the complex pathobiology of uterine fibroid development has grown. While previously believed to be a purely neoplastic entity, we now understand that uterine fibroids possess different and equally important aspects of their genesis. An increasing body of evidence suggests that oxidative stress, the imbalance between pro- and antioxidants, is an important factor in fibroid development. Oxidative stress is controlled by multiple, interconnecting cascades, including angiogenesis, hypoxia, and dietary factors. Oxidative stress in turn influences fibroid development through genetic, epigenetic, and profibrotic mechanisms. This unique aspect of fibroid pathobiology has introduced several clinical implications, both diagnostic and therapeutic, that can aid us in managing these debilitating tumors by using biomarkers as well as dietary and pharmaceutical antioxidants for diagnosis and treatment. This review strives to summarize and add to the current evidence revealing the relationship between oxidative stress and uterine fibroids by elucidating the proposed mechanisms and clinical implications.

Association of Surgical Start Time with Outcomes of Benign Hysterectomy.

STUDY OBJECTIVE: To evaluate whether surgical start time is associated with clinical and financial outcomes of hysterectomies performed for benign indications. DESIGN: Retrospective cohort study. SETTING: University 5-hospital healthcare system. PATIENTS: Women who underwent benign hysterectomy between 2014 and 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed demographic, operative, and financial data to evaluate the relationships between surgical start time and perioperative outcomes including operating room time, estimated blood loss, length of stay, same-day discharge, and adverse perioperative events. Additionally, we evaluated the impact of surgical start time on total hysterectomy charges. Descriptive statistics and multivariate logistic and linear regressions were performed adjusting for confounders. Our study identified 2894 women who underwent benign hysterectomy, with 1910 hysterectomies starting prior to 12 pm (am group) and 984 hysterectomies starting after 12 pm (pm group). A pm start time was associated with higher estimated blood loss (Median 100, interquartile range 50, 200 in the am group vs Median 125, interquartile range 75, 250), increased length of stay, and decreased likelihood of same-day discharge. No significant differences were noted in the rates of adverse perioperative events between the 2 groups. Surprisingly, an afternoon start time was associated with decreased total hospital charges (median am $14 055.30 versus median pm $11 724.80). These cost differences persisted after multivariate linear regression, and when stratified by hysterectomy surgical approach, remained significant in the open and laparoscopic cohorts. CONCLUSION: Afternoon hysterectomy start time is associated with increased blood loss and length of stay with decreased rates of same-day discharge; however, there was no associated increase in perioperative adverse events or mortality. Awareness regarding surgical start time and outcomes can guide surgical scheduling and optimize same-day discharge.

Cardiometabolic profile of women with uterine leiomyoma: a cross-sectional study.

BACKGROUND: 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 aimed to determine the association of cardiometabolic comorbidities and cardiometabolic medication use with a leiomyoma diagnosis. METHODS: In this cross-sectional study, aggregate-level data from 2013-2020 were collected using the SlicerDicer feature of Epic (Epic, Verona, WI, USA) electronic medical record system. Women ≥18 years with at 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 prespecified 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. RESULTS: 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). CONCLUSIONS: 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.

Perioperative opioid dispensing and persistent use after benign hysterectomy: a systematic review and meta-analysis.

OBJECTIVE: 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 from study inception to 25 March 2022. STUDY ELIGIBILITY CRITERIA: 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 units. METHODS: The random-effects model was used to pool the mean differences or odds ratios and the corresponding 95% confidence intervals. RESULTS: A total of 8 studies presenting data on 377,569 women undergoing benign hysterectomy were included. Of these women, 83% (95% confidence interval, 81-84) were dispensed opioids during the perioperative period. The average amount of perioperatively dispensed opioids was 143.5 morphine milligram equivalents (95% confidence interval, 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% confidence interval, 2-8). Younger patient age (odds ratio, 1.38; 95% confidence interval, 1.17-1.63), smoking history (odds ratio, 1.87; 95% confidence interval, 1.67-2.10), alcohol use (odds ratio, 3.16; 95% confidence interval, 2.34-4.27), back pain (odds ratio, 1.50; 95% confidence interval, 1.10-2.05), and fibromyalgia (odds ratio, 1.60; 95% confidence interval, 1.39-1.83) were significantly associated with a higher risk of persistent opioid use after benign hysterectomy. However, there was no significant effect of hysterectomy route and operative complexity on persistent opioid use postoperatively. CONCLUSION: Perioperative opioid dispensing was significantly dependent on the route of hysterectomy, with the lowest dispensed morphine milligram equivalents 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.

Climate change and cardiovascular disease: implications for global health.

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.

Impact of Obesity on Clinical and Financial Outcomes of Minimally Invasive Hysterectomy for Benign Conditions.

OBJECTIVE: 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 (BMI <30 kg/m2), class I (BMI 30-34 kg/m2), class II (BMI 35-39 kg/m2), and class III (BMI >40 kg/m2). Descriptive statistics and multivariate logistic and linear regressions were performed. RESULTS: A 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/m2, and total charges were US $13 928 ± $5954. Each additional minute in the OR increased costs by US $47.89 (P < 0.001). Compared with patients without obesity, OR time and EBL were significantly higher among patients with class I or II obesity and highest among patients with class III obesity (P < 0.001). Obesity did not affect LOS or occurrence of adverse perioperative events. Although obesity appeared to be a significant predictor of hysterectomy charges, after adjusting for covariates, charges for laparoscopic and robotic hysterectomy did not differ significantly by BMI. CONCLUSION: Obesity 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.

Predictors of new persistent opioid use after benign hysterectomy in the United States.

BACKGROUND: 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. OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Predictors of same-day discharge after minimally invasive hysterectomy for benign indications.

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.

Clinical characteristics and cardiovascular outcomes among young patients with acute myocardial infarction in Kerala, India: A secondary analysis of ACS QUIK trial.

Background: Limited data exist on the risk profile and outcomes among young patients with acute myocardial infarction(AMI) in low-and middle-income countries(LMICs). This study explored differences in the clinical characteristics, medical care, and outcomes of AMI in young adults in India with a subanalysis focusing on sex disparities amongst the young. Methods: Using the Acute Coronary Syndrome Quality Improvement in Kerala trial database, we compared baseline characteristics, management, and outcomes amongst the young patients(≤50 years) and their older counterparts. The primary outcomes were the rates of in-hospital and 30-day composite of in-hospital major adverse cardiovascular events(MACE). Results: Of the 21,374 adults enrolled, 4762(22%) were young, of which 614 (12.9%) were females. Young patients with AMI were more likely to be smokers(41.9% vs. 27.8%;P < 0.001) and undergo coronary angiography (66.3%vs.57.3%;P < 0.001) and percutaneous coronary intervention (PCI)(57.5% vs. 47.0%;P < 0.001), compared to older patients. After adjustment for potential confounders, younger patients had a lower likelihood of in-hospital (RR = 0.49; 95%CI 0.40-0.61;P < 0.001) and 30-day MACE (RR = 0.54; 95%CI 0.46-0.64;P < 0.001). Subgroup analysis comparing young males and females revealed worse cardiovascular risk profile among young women except for smoking. In-hospital MACE(RR = 1.60; 95%CI, 1.0-2.45;P = 0.048) were higher for young women compared to men. Conclusion: Young AMI patients had higher prevalence of modifiable risk factors, were more likely to receive reperfusion therapy, and had better short and intermediate outcomes, compared to older patients. Compared to young men with AMI, young women had worse cardiovascular risk profile, were less likely to be treated with diagnostic angiography or PCI and experienced higher in-hospital death and MACE.

Challenges in treatment of renal echinococcosis with gross hydatiduria and unsalvageable kidney: a case report.

INTRODUCTION: Renal echinococcosis is of rare occurrence, and although often asymptomatic, it can present with various mild to drastic presentations, of which hydatiduria is pathognomonic. Diagnosis can be preliminarily established by imaging, and treatment is primarily surgical. We present a patient with renal echinococcosis treated successfully with exclusive antiparasitic pharmacotherapy after refusing surgery despite extensive renal involvement. We hope through this report to help establish future solid guidelines regarding this uncommon therapeutic approach. CASE PRESENTATION: This is a case of a 49-year-old Syrian shepherd presenting with flank pain and passage of grape-skin-like structures in urine. A diagnosis of renal echinococcosis with hydatiduria and significant parenchymal destruction was established based on exposure history, positive serology, imaging findings, and renal scintigraphy. After proper counseling, the patient refused nephrectomy and was therefore started on dual pharmacotherapy (albendazole and praziquantel) and is having an uneventful follow-up and a satisfactory response to treatment. CONCLUSION: This case embodies the daily challenges physicians navigate as they uphold the ethical principles of their practice and support their patients' autonomy while delivering the best standards of care and consulting the scientific evidence. Although surgery is the cornerstone of renal echinococcosis treatment, treating physicians should be prepared to tackle situations where surgery cannot be done and offer the best next available option for patients who refuse surgery. As data on exclusive pharmacotherapy are limited, future research should thoroughly investigate the efficacy of this uncommon approach and outline reliable recommendations, facilitating future clinical decision-making in this avenue.

Diet and Nutrition in Gynecological Disorders: A Focus on Clinical Studies.

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.

Vascular biology of uterine fibroids: connecting fibroids and vascular disorders.

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.

Role of inflammation in benign gynecologic disorders: from pathogenesis to novel therapies†.

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.

Primary Headache Disorder Among School Students in Kuwait.

Background: Primary headaches are remarkably prevalent worldwide and are increasingly reported among children. However, the exact trend in this age group, particularly in the Gulf region, remains largely unknown. 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 the 2018/2019 academic year. Prevalence and attributable burden of headaches, definite and probable migraines, definite and probable tension-type headaches, chronic headaches (≥15 days/month), and probable medication-overuse headaches were assessed using the Headache-Attributed Restriction, Disability, Social Handicap, and Impaired Participation (HARDSHIP) questionnaire for children and adolescents. Results: Of 1,485 questionnaires that were distributed, 1,089 students completed the questionnaire with a respondent rate of 73.4%. The study population consisted of 420 boys (38.56%) and 669 girls (61.43%) students with a mean age of 11.5 ± 2.11 years. The 1-year prevalence of primary headache disorders was 42.78%, with more middle schoolers reporting headaches than primary schoolers (50.37 vs. 30.48%; p < 0.02). The mean age of students with primary headaches was 11.98 ± 2.03 years in both genders. When stratified according to diagnostic criteria, migraine headaches were the most frequently reported (20.75%), followed by tension type headaches (18.8%), chronic headaches (2.75%), and probable medication-overuse headaches (0.46%). Primary headaches were significantly higher in girls compared to boys among middle schoolers (66.46 vs. 38.49%; p < 0.001); however, no significant difference between genders was noted among primary school students (33.12 vs. 22.33%; p < 0.118). Conclusion: Primary headaches are remarkably common in Kuwaiti school students, with migraine headaches being the most frequently reported type. Age and female gender may play a role in the development of primary headaches. These findings necessitate the direction of health services and research efforts toward this age group and warrant the need for further epidemiological studies.

Predictors of the cost of hysterectomy for benign indications.

INTRODUCTION: Hysterectomy is a commonly performed procedure with widely variable costs. As gynecologists divert from invasive to minimally invasive approaches, many factors come into play in determining hysterectomy cost and efforts should be sought to minimize it. Our objective was to identify the predictors of hysterectomy cost. MATERIALS AND METHODS: This was a retrospective cohort study where women who underwent hysterectomy for benign conditions at the University of Texas Medical Branch from 2009 to 2016 were identified. We obtained and analyzed demographic, operative, and financial data from electronic medical records and the hospital finance department. RESULTS: We identified 1,847 women. Open hysterectomy was the most frequently practiced (35.8 %), followed by vaginal (23.7 %), laparoscopic (23.6 %), and robotic (16.9 %) approaches. Multivariate regression demonstrated that hysterectomy charges can be significantly predicted from surgical approach, patient's age, operating room (OR) time, length of stay (LOS), estimated blood loss, insurance type, fiscal year, and concomitant procedures. Charges increased by $3,723.57 for each day increase in LOS (P <0.001), by $76.02 for each minute increase in OR time (P <0.001), and by $48.21 for each one-year increase in age (P 0.037). Adjusting for LOS and OR time remarkably decreased the cost of open and robotic hysterectomy, respectively when compared with the vaginal approach. CONCLUSION: Multiple demographic and operative factors can predict the cost of hysterectomy. Healthcare providers, including gynecologists, are required to pursue additional roles in proper resource management and be acquainted with the cost drivers of therapeutic interventions. Future efforts and policies should target modifiable factors to minimize cost and promote value-based practices.

Impact of Puberty in Girls on Prevalence of Primary Headache Disorder Among Female Schoolchildren in Kuwait.

Background: The prevalence of primary headaches in the pediatric population is shaped by many factors, of which pubertal status may possibly play a substantial role. Epidemiological studies in the pediatric population in the gulf region remain scarce. Aims and objectives: To examine the impact of puberty on the prevalence of primary headache disorders among female schoolchildren in Kuwait. Methods: We conducted a cross-sectional study that included Kuwaiti primary and middle schoolgirls in randomly selected schools located in two governorates in Kuwait during the academic year 2018/2019. Prevalence of headache was assessed using the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire for children and adolescents. Female students were asked about their menarchal status and whether they attained menarche before or after experiencing headaches. Results: The questionnaire was completed by 669 girls with a mean age of 11.44 ± 2.14 years. The 1-year prevalence of migraine headache disorder among girls was 23.62%, and the lifetime prevalence of any headache was 84.9%, whereas the 1-year prevalence of primary headache disorders was 47.98%. The mean age of girls with headaches was 11.44 ± 2.14 years. With respect to diagnostic criteria, migraine headache was the most frequently reported (23.62%), followed by tension-type headaches (20.93%), chronic headaches (2.99%), and probable medication-overuse headaches (0.45%). Postpubertal females were at significantly higher risk of having primary headaches compared to their prepubertal counterparts (64.26 vs. 34%; p < 0.0001). All types of primary headaches were more significantly prevalent among postpubertal girls compared to those who are prepubertal. Conclusion: Migraine headache is commonly reported among Kuwaiti schoolgirls. Postpubertal females are at higher risk of developing primary headaches compared to prepubertal females. Pubertal transition and female sex hormones may play a significant role in the pathophysiology of headaches, migraines in particular, and further research is therefore needed to investigate the underlying mechanisms.

Association of demographic, clinical, and hospital-related factors with use of robotic hysterectomy for benign indications: A national database study.

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.