McGree, Michaela E.

ABSTRACT Objective To evaluate long‐term failure rates and complications after retropubic and transobturator midurethral sling procedures for primary stress urinary incontinence (SUI). Design Retrospective cohort study. Setting Academic medical centre. Population A previously described cohort of patients ( n = 1881) who underwent midurethral sling procedures (2002–2012) and a covariate‐matched cohort of patients with retropubic ( n = 570) or transobturator ( n = 317) slings. Methods Health record review with follow‐up extended by 9 years (through December 31, 2022). Main Outcome Measures Treatment failure (reoperation for recurrent SUI) and procedure‐associated complications. Results The duration of assessment was extended by 6.9 years for the retropubic group and by 6.4 years for the transobturator group. The median (IQR) follow‐up was 11.1 (5.1–14.5) years (retropubic, 11.4 [5.9–14.6]; transobturator, 9.6 [2.6–13.7]). Higher risk of reoperation was observed with transobturator (8.8%) than retropubic (4.4%) slings (unadjusted hazard ratio [HR], 2.29 [95% CI, 1.49–3.54]; p < 0.001; covariate‐matched analysis HR, 1.91 [95% CI, 1.15–3.17]; p = 0.01). The increased risk of reoperation with a transobturator sling was higher when the procedure was combined with prolapse repair (unadjusted HR, 6.34 [95% CI, 3.09–13.02]; p < 0.001; covariate‐matched analysis HR, 3.96 [95% CI, 1.35–11.58]; p = 0.01). Higher rates of reoperation for urinary retention were observed for the retropubic group than for the transobturator group (covariate‐matched analysis HR, 8.39 [95% CI, 1.11–63.22]; p = 0.04). Conclusion In this long‐term follow‐up study, midurethral slings had a low failure rate. Women with SUI undergoing transobturator sling placement plus prolapse repair had a greater risk of reoperation. However, women with retropubic slings had a greater risk of urinary retention requiring intervention.

Background/Objectives: Our objective was to describe the use of intraoperative radiation therapy (IORT) for the treatment of recurrent/persistent cervical or endometrial cancer and assess predictors of postoperative complications and 3-year mortality. Methods: In this multi-site retrospective study, data were abstracted for recurrent/persistent endometrial or cervical cancer patients who underwent IORT from June 2004 to May 2021. Complications were graded on the six-point Accordion scale. Variables associated with complications were analyzed with univariate logistic regression, while variables associated with death within 3 years were analyzed with Cox proportional hazards modeling. Survival was analyzed with the Kaplan–Meier method. Results: Eighty patients had planned IORT for recurrent/persistent endometrial (n = 35) or cervical cancer (n = 45). The mean age of the cohort was 56.8 years (SD = 13.7), and the median disease-free interval from primary disease to recurrence was 20.0 months (IQR 10.0–63.1). The overall survival at 3 years was 48.6% (95% CI: 38.3–61.6%) with a median survival of 2.8 years. Within 30 days postoperative, 16 patients (20.1%) had grade 3–5 complications and one death (1.3%) occurred. Factors associated with grade 3+ complication included ECOG PS 2–3 (OR 18.00, p = 0.04), neoadjuvant chemotherapy and/or immunotherapy (OR 6.98, p < 0.01), and pelvic sidewall involvement (OR 8.80, p = 0.04). Factors associated with death within 3 years of surgery included ECOG PS 2–3 (HR 8.97, p < 0.01), neoadjuvant chemotherapy and/or immunotherapy (HR 2.34, p = 0.03), whether exenteration was performed (HR 2.64, p = 0.01), and positive resection margin (HR 3.37, p < 0.01). Conclusions: In well-selected patients, IORT is a feasible and safe option for the treatment of recurrent/persistent gynecologic malignancy with an appreciable survival benefit.

Abstract Obesity accelerates the onset and progression of age-related conditions. In preclinical models, obesity drives cellular senescence, a cell fate that compromises tissue health and function, in part through a robust and diverse secretome. In humans, components of the secretome have been used as senescence biomarkers that are predictive of age-related disease, disability, and mortality. Here, using biospecimens and clinical data from two large and independent cohorts of older adults, we tested the hypothesis that the circulating concentrations of senescence biomarkers are influenced by body mass index. After adjusting for age, sex, and race, we observed significant increases in activin A, Fas, MDC, PAI1, PARC, TNFR1, and VEGFA, and a significant decrease in RAGE, from normal weight, to overweight, to obesity body mass index categories by linear regression in both cohorts (all p &lt; .05). These results highlight the influence of body mass index on circulating concentrations of senescence biomarkers.

5546 Background: Advanced ovarian cancer (OC) is managed with cytoreductive surgery and platinum-based chemotherapy. Prehabilitation is a multimodal intervention to improve physical and mental health prior to oncologic surgery. This study evaluates baseline differences in clinical characteristics, functional status, and patient-reported outcomes (PROs) between patients undergoing primary cytoreductive surgery (PCS) versus neoadjuvant chemotherapy (NACT) who enrolled in a prospective prehabilitation trial. Methods: This was a single-institution, non-randomized prospective behavioral intervention trial of patients with suspected advanced stage (IIIC/IV) OC. Baseline functional testing included the Short Physical Performance Battery (SPPB), Fried Frailty Index (FFI), gait speed, and grip strength. Patient-Reported Outcomes Measurement Information System (PROMIS) metrics, the Mindfulness Attention Awareness Scale (MAAS), and the Perceived Stress Scale (PSS-10) were used to evaluate PROs. Comparisons between cohorts utilized two-sample t-test or Kruskal Wallis test for continuous variables and chi-square or Fisher’s exact test for categorical variables. T-scores were obtained for PROMIS data using the HealthMeasures Scoring Service; validated cut points for PROMIS, MAAS, and PSS-10 were used for categorization. Results: Amongst the 53 enrolled patients, physical and emotional distress was higher amongst OC patients compared to population means. When compared to PCS patients, NACT patients were more likely to report “severe” in at least one PROMIS domain (emotional distress and anxiety, pain interference, physical function, and fatigue, p<0.01). NACT patients reported significantly higher levels of perceived stress (p<0.01). NACT patients were more likely to have stage IV disease, albumin <3.5 g/dL, and lower gait speed and grip strength (all p<0.01). Despite differences in clinical variables and PROs including physical function, there were no measurable differences in physical function based on SPPB and FFI. Conclusions: Advanced OC patients have high psychosocial needs, with NACT patients reporting severe perceived symptoms on PRO measures. The PSS-10 may be a valuable screening tool for patients undergoing NACT to prioritize supportive care services. Clinical trial information: NCT05047926 . [Table: see text]

We investigated the impact of sarcopenia on adjuvant chemotherapy dosing in advanced epithelial ovarian cancer (EOC). The chemotherapy dosing and toxicity of 173 eligible patients who underwent cytoreductive surgery and adjuvant chemotherapy at a single institution were analyzed. Patients with a skeletal muscle index less than 39 cm2/m2 measured on a CT scan were considered sarcopenic. Sarcopenic and non-sarcopenic patients were compared with regard to relative dose intensity (RDI), completion of scheduled chemotherapy, toxicity, and survival. A total of 62 (35.8%) women were sarcopenic. Sarcopenic women were less likely to complete at least six cycles of chemotherapy (83.9% vs. 95.5%, p = 0.02). The mean RDI for both carboplatin (80.4% vs. 89.4%, p = 0.03) and paclitaxel (91.9% vs. 104.1%, p = 0.03) was lower in sarcopenic patients compared to non-sarcopenic patients. Despite these differences in chemotherapy, there was no difference in neutropenia or median overall survival (3.99 vs. 4.57 years, p = 0.62) between the sarcopenic and non-sarcopenic women, respectively. This study highlights the importance of considering lean body mass instead of body weight or surface area in chemotherapy dosing formulas for sarcopenic women with advanced EOC. Further research is needed to optimize chemotherapy strategies based on individual body composition, potentially leading to improved dosing strategies in this population.

Objective Ceramides have been associated with several ageing-related conditions but have not been studied as a general biomarker of multimorbidity (MM). Therefore, we determined whether ceramide levels are associated with the rapid development of MM. Design Retrospective cohort study. Setting Mayo Clinic Biobank. Participants 1809 persons in the Mayo Clinic Biobank ≥65 years without MM at the time of enrolment, and with ceramide levels assayed from stored plasma. Primary outcome measure Persons were followed for a median of 5.7 years through their medical records to identify new diagnoses of 20 chronic conditions. The number of new conditions was divided by the person-years of follow-up to calculate the rate of accumulation of new chronic conditions. Results Higher levels of C18:0 and C20:0 were associated with a more rapid rate of accumulation of chronic conditions (C18:0 z score RR: 1.30, 95% CI: 1.10 to 1.53; C20:0 z score RR: 1.26, 95% CI: 1.07 to 1.49). Higher C18:0 and C20:0 levels were also associated with an increased risk of hypertension and coronary artery disease. Conclusions C18:0 and C20:0 were associated with an increased risk of cardiometabolic conditions. When combined with biomarkers specific to other diseases of ageing, these ceramides may be a useful component of a biomarker panel for predicting accelerated ageing.

Objective: Using a triage algorithm for primary cytoreductive surgery (PCS) reduces perioperative mortality, however, nonlethal complications are common. This study identified procedures associated with postoperative complications in triage-appropriate women, with the aim of guiding the next steps to foster surgical quality improvement. Materials and Methods: Consecutive triage-appropriate women with stage IIIC/IV ovarian cancer undergoing PCS, from January 2012 to April 2018, were included. The expanded Accordion scale was used to grade complications. Adjusted risk ratios ( RRs ) were calculated to quantify the association between concomitant procedures and risk of 30-day grade 3+ (G3+) complications by fitting Poisson regression models adjusted for performance status and age. Population-attributable risk (PAR) was calculated based on the adjusted RR s and prevalence of each procedure. Results: Of 214 women, 82.7% had intermediate- or high-complexity surgery, 68.7% had complete gross resection, 3.7% had residual disease >1 cm, and 18.7% experienced G3+ complications. In univariate analysis, operative time, surgical complexity, splenectomy, and bowel resection (any and extent of) were associated with G3+ complications. Operative time, bowel resection (any, extent of, and large) were associated with G4+ complications. In the adjusted analysis for G4+ complications, bowel resection (any, extent of, and large) had statistically significant PAR values of 60.7%, 54.7%, and 50.8%, respectively. PAR values associated with G3+ complications were 27.4% and 26.8% for any and multiple bowel resections, respectively. Conclusions: Bowel resection, upper abdominal procedures, and longer operative times are essential for PCS, but each contributes to the relatively constant rates of postoperative morbidity despite triage to prevent frail patients from undergoing PCS. Surgical-improvement research should focus on improving the safety of these procedures. (J GYNECOL SURG 39:123)

Abstract Data evaluating change in body composition during treatment of advanced cancer are limited. Here we evaluated computed tomography (CT)–based changes in muscle mass during treatment for advanced ovarian cancer (OC) and association with outcomes. We analyzed the preoperative and posttreatment skeletal muscle index (SMI), skeletal muscle area normalized for height of 109 patients with advanced OC who underwent primary surgery and platinum-based chemotherapy from 2006 to 2016. Based on an SMI less than 39 cm2/m2, 54.1% of patients were never sarcopenic, 24.8% were sarcopenic on both CT scans, and 21.1% were newly sarcopenic upon treatment completion. Patients who lost muscle during treatment had the worst survival of the 3 groups identified: median survival 2.6 years vs 4.6 years if sarcopenic on both CT scans and 4.8 years if never sarcopenic. Loss of muscle portends a poor prognosis among patients with OC. Additional research is needed to better understand and best mitigate these changes.

Objectives To study the association between multi-morbidity percentiles, which is a measure of clinical aging, and interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α. Methods Participants 50 to 95 years of age from the Mayo Clinic Study of Aging were assigned age- and sex-specific multi-morbidity percentiles using look-up tables that were reported previously (n = 1646). Percentiles were divided into quintiles for analysis. Plasma IL-6, IL-10, and TNF-α levels were measured in 1595 participants. Median inflammatory marker levels were compared across multi-morbidity quintiles using nonparametric tests. Results People with higher multi-morbidity percentiles had significantly higher IL-6 and TNF-α levels compared with those with lower multi-morbidity percentiles. Tests for trend across five multi-morbidity quintiles were significant among women for IL-6 and among participants 70 years of age or older for IL-6 and TNF-α. IL-10 was not associated with multi-morbidity percentiles. Conclusions Multi-morbidity percentiles may be a useful clinical index of biological age for future studies, particularly in women and people 70 years of age and older.