Carin Y. Smith

Objective: To compare the long‐term risk of subsequent abdominopelvic surgery in women who underwent hysterectomy with ovarian conservation (H‐OC) versus referent women, and in women who underwent abdominal H‐OC versus vaginal H‐OC. Methods: We conducted a population‐based cohort study in Olmsted County, Minnesota, USA including 1573 women who underwent H‐OC for a benign indication at age 18–44 years between January 1, 1980, and December 31, 2002, and 1573 age‐matched (±1 year) referent women who had not undergone hysterectomy or any oophorectomy as of the matching date. For both the H‐OC women and the referent women, we defined the index date as the H‐OC or matching date plus 6 months. The index date served as the starting point for follow‐up. Results: Overall, we found an increased risk of subsequent lysis of adhesions in women who underwent H‐OC compared to referent women (hazard ratio [HR], 1.57 [95% confidence interval [CI]: 1.09–2.27]). Women undergoing H‐OC also had an increased risk of subsequent gastrointestinal tract procedures (HR, 1.18 [95% CI: 1.05–1.31]) compared to referent women. When comparing surgical route of H‐OC, we identified an increased risk of subsequent adnexal surgeries in women undergoing abdominal compared with vaginal H‐OC (HR, 1.91 [95% CI: 1.40–2.61]). Conclusion: Women who underwent H‐OC have an increased risk of subsequent abdominopelvic surgeries compared to referent women. In addition, women who underwent abdominal H‐OC have an increased risk of subsequent adnexal procedures compared to women who underwent vaginal H‐OC.

Background The impact of early-life traumatic experiences on late-life morbidity, or chronic conditions, remains unclear. We tested the hypothesis that traumatic adverse childhood experiences, such as physical, verbal, emotional, or sexual abuse, experienced during childhood or early adulthood are associated with a higher rate of morbidity later in life in women. Methods We studied 1026 women aged 21-45 years randomly selected from the general population in Olmsted County, Minnesota and used the Rochester Epidemiology Project medical records-linkage system to measure the rate of development of 18 chronic conditions. The women had a median age of 41.0 years at inclusion in the study and were followed historically for a median of 21.0 years. Results Here we show that women who experienced 2 or more adverse childhood experiences have higher incidence of 10 of the 18 chronic conditions considered separately and an accelerated accumulation of chronic conditions measured as a morbidity score compared to women who did not experience any. In addition, women exposed to abuse in childhood or early adulthood have accelerated accumulation of morbidity. We exclude the possible confounding effect of socioeconomic status and explore a series of possible mediation events or characteristics. We also discuss several possible biological and social or behavioral mechanisms underlying these associations. Conclusions We are reporting new evidence that adverse childhood experiences and abuse in childhood or early adulthood have multiple deleterious effects on late-life morbidity. Our findings indicate the importance of protecting children and young adults from abuse and other adverse events.

Objectives: We aimed to assess the expression of biomarkers of response to antibody-drug conjugates (TROP2 and nectin-4) and immune microenvironment (NKG7, PD-L1, and B7-H3) in penile squamous cell carcinoma (pSCC). Methods: Our archive was queried for patients who had a penectomy for pSCC between 2000 and 2022. Primary tumors were immunostained for B7-H3 and NKG7, while metastatic specimens were immunostained for TROP2 and nectin-4. Expression of PD-L1, TROP2, and nectin-4 in primary tumors was previously characterized. H-scores (0-300) were used to quantify expression. Associations between biomarkers, tumor-infiltrating lymphocytes (TILs), and clinicopathologic and outcome parameters were evaluated. Results: For both TROP2 and nectin-4, H-scores within the lymph node metastases were higher compared to those within the primary tumors (mean, 264.5 vs 244.8, P = .0003; mean, 170.6 vs 146.7, P = .05, respectively; 33 paired specimens). For B7-H3 (n = 107), 32.7% of the primary tumors had an H-score of more than 0. In 34.8% of the cases, NKG7 expression was observed in 25% to 50% of the TILs. A significant association was noted between TIL density, B7-H3, NKG7, and PD-L1 expression. Conclusions: Therapeutic strategies targeting TROP2 and nectin-4 hold promise for patients with advanced pSCC. The potential of PD-L1, B7-H3, and NKG7 for predicting response to immunomodulatory treatment warrants further research.

The impact of early-life traumatic experiences on late-life morbidity remains partly unknown. We tested the hypothesis that adverse childhood experiences (ACE) and specifically abuse (physical, verbal or emotional, or sexual) experienced during childhood or early adulthood are associated with a higher rate of accumulation of multi-morbidity in women. Here we show strong evidence in support of the hypothesis. We studied 1,026 women aged 21–45 years randomly selected from the general population in Olmsted County, Minnesota and used the Rochester Epidemiology Project medical records-linkage system to measure the rate of development of 18 chronic conditions. The women had a median age of 41 years at inclusion in the study and were followed historically for a median of 21 years. Women with an ACE score ≥ 2 had higher incidence of 10 of the 18 chronic conditions considered separately and an accelerated accumulation of multi-morbidity measured as a score compared to women with ACE score 0. In addition, women exposed specifically to abuse in childhood or early adulthood had accelerated accumulation of multi-morbidity. We excluded the possible confounding effect of socioeconomic status and explored a series of possible mediation events or characteristics. We discuss several possible biological and social or behavioral mechanisms underlying these associations.

Objectives To report myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) epidemiology in two American regions using 2023 diagnostic criteria. Patients and methods We compared age- and sex-adjusted incidence and prevalence of MOGAD per 2023 diagnostic criteria in Olmsted County (Minnesota [USA]) and Martinique (Caribbean [FR]) (01/01/2003–12/31/2018, prevalence day) using Poisson regression. Archived sera in 68–85% were available for MOG-IgG testing by live cell-based assay at Mayo Clinic. Results Of 21 patients with MOG-IgG positivity identified, 16 fulfilled MOGAD criteria (38% female; median age of 27 years, interquartile-range [IQR 23–42]) and five with low-positive MOG-IgG did not (optic neuritis lacking supportive criteria, 2; alternative diagnosis of multiple sclerosis, 3). MOGAD prevalence was similar in Olmsted County (3.70/100,000, 95% confidence interval [CI] 0.74–6.66]) and Martinique (2.61/100,000; 95% CI 0.85–4.37, P = 0.46). MOGAD incidence was 3.00/million-person-years (95% CI 0.78–5.22) in Olmsted County and 1.18/million-person-years (95% CI 0.30–2.07) in Martinique (P = 0.08). Children represented 29% of MOGAD in Olmsted County and 11% in Martinique. During their disease course the attacks included: optic neuritis (13/16 [81%]); myelitis (6/16 [38%]); and acute disseminated encephalomyelitis (2/16 [13%]). The proportion of MOGAD among incident CNS demyelinating diseases was greater in children (13–14%) than adults (2–4%; P = 0.005). At last follow-up (median, 5 years, IQR 2–9), the median EDSS was 1.0 (IQR 0.5–2.75) with 1/16 (6%) blind in one eye and 9/16 (56%) had relapsing MOGAD. Conclusions This study provides estimates of incidence and prevalence of MOGAD in the USA and Martinique and shows that, although children are predisposed, the disease is spread broadly across the age spectrum and population-based outcomes are favorable.

To examine the risks of long-term de novo psychiatric disease in women with primary infertiltiy compared to age-matched referrent women. Retrospective, population-based cohort of 1,001 women with primary infertility and 1,001 age-matched (± 1 year) referent women aged 18–50. The “index date” was date of first clinical note for infertility and included visits fromJanuary 1, 1980 to December 31, 1999. Baseline characteristics were collected by chart review. Outcome data was evaluated through December 31, 2020. Primary outcomes were baseline prevalence and de novo rates of subsequent psychiatric disorders including depression, anxiety, bipolar disorder, substance abuse, suicidality, and somatization evaluated by Cox proportional hazards modeling. Among women with primary infertility and referent women, the median duration of follow-up was 23.7 years. The risk of de novo psychiatric disorders was not significantly different between groups. Additionally, the risk of de novo psychiatric disorders did not significantly differ between those with isolated male factor versus isolated female factor infertility. Among women with primary infertility, the cumulative incidence of de novo depression and anxiety was significantly higher among women diagnosed with primary infertility in the 1990s compared to the 1980s. Women with primary infertility, in a historical population-based cohort, do not have a significantly different long-term risk of de novo psychiatric diagnoses compared to age-matched referent women. Our findings support the notion that infertility diagnosis and treatment present an acute period of stress and for some psychologic distress, neither of which persist or increase the risk for development of future psychiatric disease.

Background: A dual filtration-based method for determination of serum labile bound copper (LBC) and LBC fraction (LBC/total copper) was developed. Reduced total copper, elevated LBC, and elevated LBC fraction have been reported in Wilson disease (WD). Methods: To evaluate the diagnostic performance of these markers, samples were obtained from 21 WD treatment-naïve (WD-TN, no WD treatment or <28 days of treatment) patients, 46 WD standard-of-care–treated (WD-SOC) patients, along with 246 patients representing other potential disorders of copper status. These were then compared to 213 reference interval population patients. Results: Receiver operating characteristic curves for the reference population vs WD-TN yielded areas under the curve for total copper, LBC, and LBC fraction, of 0.99, 0.81, and 0.98, respectively. Using Youden cutoffs, sensitivity/specificity for WD-TN was 95%/97% for total copper, 71%/85% for LBC, and 95%/94% for LBC fraction. LBC values, but not total copper and LBC fraction, differed substantially between WD-TN and WD-SOC cohorts. We propose a dual model wherein total copper and LBC fraction results must agree to be classified as a “positive” or “negative” result for WD. This correctly classified 19/21 WD-TN patients as positive, and 194/213 reference interval patients as negative. The remaining “indeterminate” patients (representing approximately 9% of the reference and the WD-TN populations) exhibited conflicting total copper and LBC fraction results. When indeterminate results are excluded, this model exhibited apparent 100% sensitivity/specificity. Conclusions: Agreement of total serum copper and LBC fraction classification may constitute an effective “rule-in” and “rule-out” assessment for WD-TN patients.