Short-Term Outcomes After Hysterectomy for Endometrial Cancer/EIN With Concomitant Pelvic Floor Disorder Surgery.

IMPORTANCE: Endometrial cancer and precancer are common gynecologic problems for many women. A majority of these patients require surgery as the mainstay of treatment. Many of these patients often have concurrent pelvic floor disorders. Despite the prevalence and shared risk, fewer than 3% of women undergo concomitant surgery for PFDs at the time of surgery for endometrial cancer or endometrial intraepithelial neoplasia/hyperplasia. OBJECTIVE: This study aimed to evaluate postoperative morbidity of concomitant pelvic organ prolapse (POP) and/or urinary incontinence (UI) procedures at the time of hysterectomy for endometrial cancer (EC) or endometrial intraepithelial neoplasia/endometrial hyperplasia (EIN/EH). METHODS: This retrospective analysis of women undergoing hysterectomy for EC or EIN/EH between 2017 and 2022 used the American College of Surgeons National Surgical Quality Improvement Program database. The primary outcome was any major complication within 30 days of surgery. Comparisons were made between 2 cohorts: hysterectomy with concomitant pelvic organ prolapse/urinary incontinence procedures (POPUI) versus hysterectomy without concomitant POP or UI procedures (HYSTAlone). A subgroup analysis was performed in patients with EC. A propensity score matching cohort was also created. RESULTS: A total of 23,144 patients underwent hysterectomy for EC or EIN/EH: 1.9% (n = 432) had POP and/or UI procedures. Patients with POPUI were older, were predominantly White, had higher parity, and had lower body mass index with lower American Society of Anesthesiologists class. Patients with POPUI were less likely to have EC (65.7% vs 78.3%, P < 0.0001) and more likely to have their hysterectomy performed by a general obstetrician- gynecologists or urogynecologists. Major complications were low and not significantly different between POPUI and HYSTAlone (3.7% vs 3.6%, P = 0.094). A subgroup analysis of EC alone found that the HYSTAlone subset did not have more advanced cancers, yet the surgeon was more likely a gynecologic oncologist (87.1% vs 68.0%, P < 0.0001). There were no statistically significant differences between the 2 cohorts for the primary and secondary outcomes using propensity score matching analysis. CONCLUSIONS: Concomitant prolapse and/or incontinence procedures were uncommon and did not increase the rate of 30-day major complications for women undergoing hysterectomy for EC/EH.

Association between adherence to posttreatment National Comprehensive Cancer Network (NCCN) surveillance guidelines and detection of recurrent uterine cancer.

OBJECTIVE: To identify correlations between disease recurrence and adherence to NCCN posttreatment surveillance guidelines in patients who develop recurrent uterine cancer. METHODS: Retrospective analysis identified patients (n = 60) with recurrent uterine cancer and at least one surveillance visit with a gynecologic oncologist between 2011 and 2020. Adherence to NCCN guidelines and details of recurrence were recorded. RESULTS: Recurrent uterine cancer was identified in 60 patients with an average time to recurrence (TTR) of 25 months. Of those, 39 (65%) were adherent to NCCN surveillance guidelines and 36 (60%) were symptomatic at the time of recurrence diagnosis. Asymptomatic recurrence was diagnosed by imaging in 11 (46%), physical exam in 7 (29%), and blood work in 6 (25%) patients. Patients who were adherent to NCCN guidelines were diagnosed with recurrence on average 11 months earlier (p = 0.0336). Adherence was an independent predictor of TTR for all patients regardless of symptoms. There was no significant effect of age, race, primary language, or stage of disease on adherence. CONCLUSION: Adherence to NCCN posttreatment surveillance guidelines for uterine cancer is independently associated with an earlier diagnosis of recurrence.

Analysis of Sociodemographic Factors Affecting Ambulatory Surgical Center Discharge Patterns for Endometrial Cancer Hysterectomies.

STUDY OBJECTIVE: Investigate outcomes for patients undergoing minimally invasive hysterectomies (MIHs) performed for endometrial cancer at ambulatory surgery centers (ASCs). DESIGN: Our study aimed to explore the feasibility and discharge outcomes for MIHs for endometrial cancer in an ASC setting by using same-day discharge data. SETTING: The prevalence of MIH for endometrial cancer between 2016 and 2019 was estimated from the Nationwide Ambulatory Surgery Sample. PATIENTS: Patients who underwent MIHs for endometrial cancer at an ASC were included. INTERVENTIONS: N/A MEASUREMENTS MAIN RESULTS: Weighted estimates of prevalence and association between discharge status and sociodemographic factors were explored. Same-day discharge was defined as discharge on the day of surgery, and delayed discharge was defined as discharge after the day of surgery. An estimated 95 041 MIHs for endometrial cancer were performed at ASCs between 2016 and 2019. Notably, 91.9% (n = 87 372) resulted in same-day discharge, 1.2% (n = 1121) had delayed discharge, and 6.9% (n = 6548) had missing discharge information; 78.7% procedures (n = 68 812) were performed at public hospitals. The proportion of delayed discharges were lower in private, not-for profit ASCs (0.8%, p = .03) than public hospitals. Patients who had delayed discharges on average were older (69.7 vs 62.4 years, p <.001), more likely to have comorbid conditions including diabetes (adjusted odds ratio [aOR] 1.48, 95% confidence interval [CI] 1.25-1.75) and overweight or obese body mass indices (aOR 1.18, 95% CI 1.01-1.39), and more likely to have public insurance (aOR 1.78, 95% CI 1.40-2.25). CONCLUSION: MIHs for endometrial cancer are feasible in an ASC. Optimal candidates for receipt of MIHs for endometrial cancer at an ASC are patients who are younger and have less comorbidities, lower body mass index, and private insurance.

Human papillomavirus vaccination receipt and provider counseling rates among high-risk patients.

OBJECTIVE: We describe provider documented counseling patterns and perception regarding HPV vaccination among patients with a history of cervical dysplasia. METHODS: All patients ages 21-45 who underwent colposcopy at a single academic medical center from 2018 to 2020were sent a self-administered survey through the electronic medical record patient portal to assess their attitudes regarding human papillomavirus (HPV) vaccination. Demographic information, HPV vaccination history, and documented obstetrics and gynecology provider counseling at the time of colposcopy were examined. RESULTS: Of 1465patients, 434 (29.6 %) reported or had documented receipt of at least one dose of the human papillomavirus vaccine. The remainder reported they were not vaccinated or had no documentation of vaccination. Proportion of vaccinated patients was higher among White compared to Black and Asian patients (P = 0.02). On multivariate analysis, private insurance (aOR 2.2, 95 % CI 1.4-3.7) was associated with vaccinated status while Asian race (aOR 0.4, 95 % CI 0.2-0.7) and hypertension (aOR 0.2, 95 % CI 0.08-0.7) were less likely to be associated with vaccination status. Among patients with unvaccinated or unknown vaccination status, 112 (10.8 %) received documented counseling regardingcatch-up human papillomavirus vaccination at a gynecologic visit. Patients seen by a sub-specialist obstetrics and gynecologic provider were more likely to have documented provider counseling regarding vaccination compared to those seen by a generalist obstetric/gynecologist provider (26 % vs 9.8 %, p < 0.001). Patients cited lack of physician discussion (53.7 %) and the belief that they were too old to receive the HPV vaccine (48.8 %) as the main reasons for remaining unvaccinated. CONCLUSION: HPV vaccination and the rate of obstetric and gynecologic provider counseling regarding HPV vaccination among patients undergoing colposcopy remains low. When surveyed, many patients with a history of colposcopy cited provider recommendation as afactor in their decision to undergo adjuvant HPV vaccination, demonstrating the importance of provider counseling in thisgroup.

Diagnostic Utility of Endocervical Curettage During Colposcopy Among Patients of Varying Risk Factors.

OBJECTIVE: Endocervical curettage (ECC) during colposcopy is recommended in certain circumstances; however, diagnostic use remains unclear. We evaluate the utility of ECC among patients with non-fully visualized squamocolumnar junction (SCJ) and certain patient socioeconomic factors. METHODS: Retrospective chart analysis was completed for patients aged older than 21 years who underwent a colposcopy at 2 study sites between 2012 and 2021. Demographics and histopathologic results were analyzed. RESULTS: A total of 1,516 colposcopies were reviewed; 73.8% (n = 1,119) had an ECC with colposcopy. Of those, 92.1% (n = 1,031) had benign ECC whereas 13.9% (n = 156) had a positive ECC at time of colposcopy. Most patients with benign ECC had benign/low-grade squamous intraepithelial lesion pathology on colposcopy biopsy (82.3%; n = 914; p < .001), and most patients with high-grade squamous intraepithelial lesion (HSIL) on ECC had HSIL on colposcopy biopsy (63.4%; n = 52; p < .001) However, when looking at patients with high-grade pathology on colposcopy biopsy, it was seen that most had benign or low-grade squamous intraepithelial lesion on ECC (79.5%; n = 205; p < .001). Most patients with adequately visualized SCJ on colposcopy were noted to have HSIL on biopsy and negative ECC (73%; n = 81; p < .001). This result was similar in patients with non-fully visualized SCJ, although not statistically significant. When stratified by socioeconomic status, most patients with high-grade lesions had a benign ECC. CONCLUSIONS: Endocervical curettage has been described to increase the identification of high-grade lesions at time of colposcopy. This descriptive study shows that many high-grade lesions at time of excisional procedure had a benign ECC on colposcopy, with no demonstrated clear additional utility in high-risk groups.

Misfolded proteins impose a dosage-dependent fitness cost and trigger a cytosolic unfolded protein response in yeast.

Evolving lineages face a constant intracellular threat: most new coding sequence mutations destabilize the folding of the encoded protein. Misfolded proteins form insoluble aggregates and are hypothesized to be intrinsically cytotoxic. Here, we experimentally isolate a fitness cost caused by toxicity of misfolded proteins. We exclude other costs of protein misfolding, such as loss of functional protein or attenuation of growth-limiting protein synthesis resources, by comparing growth rates of budding yeast expressing folded or misfolded variants of a gratuitous protein, YFP, at equal levels. We quantify a fitness cost that increases with misfolded protein abundance, up to as much as a 3.2% growth rate reduction when misfolded YFP represents less than 0.1% of total cellular protein. Comparable experiments on variants of the yeast gene orotidine-5'-phosphate decarboxylase (URA3) produce similar results. Quantitative proteomic measurements reveal that, within the cell, misfolded YFP induces coordinated synthesis of interacting cytosolic chaperone proteins in the absence of a wider stress response, providing evidence for an evolved modular response to misfolded proteins in the cytosol. These results underscore the distinct and evolutionarily relevant molecular threat of protein misfolding, independent of protein function. Assuming that most misfolded proteins impose similar costs, yeast cells express almost all proteins at steady-state levels sufficient to expose their encoding genes to selection against misfolding, lending credibility to the recent suggestion that such selection imposes a global constraint on molecular evolution.

Circulating hormone adrenomedullin and its binding protein protect neural cells from hypoxia-induced apoptosis.

BACKGROUND: Brain ischemia is the underlying cause of neuron death during stroke and brain trauma. Neural cells exposed to ischemia can undergo apoptosis. Adrenomedullin (AM) in combination with its enhancing binding protein, AMBP-1, has been shown to reduce tissue damage in inflammation. METHODS: To evaluate a beneficial effect of AM/AMBP-1 administration in brain ischemia, we employed an in vitro model of neuronal hypoxia using differentiated human neuroblastoma SH-SY5Y cells. RESULTS: After exposure to 1% O(2) for 20 h, neural cells were injured with decreased ATP levels and increased LDH release. Pre-administration of AM/AMBP-1 significantly reduced hypoxia-induced cell injury. Moreover, AM/AMBP-1 treatment reduced the number of TUNEL-positive cells and activation of caspase-3, compared to cells exposed to hypoxia alone. AM/AMBP-1 prevented a reduction of cAMP levels and protein kinase A (PKA) activity in neural cells after hypoxia exposure. Correspondingly, an elevation of cAMP levels by forskolin protected neural cells from hypoxia-induced injury. Inhibition of PKA by KT5720 abolished the protective effect of AM/AMBP-1 on hypoxia-induced apoptosis. CONCLUSIONS: AM/AMBP-1 elevates cAMP levels, followed by activating PKA, to protect neural cells from the injury caused by hypoxia. GENERAL SIGNIFICANCE: AM/AMBP-1 may be used as therapeutic agents to prevent neuron damage from brain ischemia.

The double danger of ethanol and hypoxia: their effects on a hepatoma cell line.

Alcohol use has become far too prevalent in our society. Alcohol kills 6.5 times more youth than all other illicit drugs combined. In combination with traumatic and hemorrhagic injuries, alcohol results in a much higher mortality rate. Alcohol, alone and in high dosages, also causes great damage to the body, often leading to death as well. Thus, it is of utmost importance that research is conducted to help explain the pathological mechanism of high fatalities and injuries associated with alcohol use. In order to simulate this complex situation in vitro, a rat hepatoma cell line (H-II-4-E) was exposed to various concentrations of ethanol as well as the condition of hypoxia. Hypoxia mimics the primary level of tissue damage caused by hemorrhage after impact in a car accident. In this way, we tested the hypothesis that the presence of ethanol in combination with hypoxia causes greater cellular damage compared to conditions of ethanol or hypoxia alone. Ethanol, alone and in high concentrations, was found to greatly affect cell function as shown by decreased cellular ATP levels, increased LDH release, and a downregulated expression of CYP2E1 gene. By adding the condition of hypoxia to low concentrations of ethanol, cellular damage increased dramatically as well. Decreased gene expression and protein levels of CYP2E1 correlated with increased hepatocyte injury and thus, this enzyme may significantly contribute to the severity of cellular damage. These results provide useful information for future research on the effects of ethanol in combination with hemorrhage on cells in vitro, simulating the condition of driving while intoxicated and binge drinking.