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OBJECTIVES: There is a paucity of data on North American cohorts of patients with penile squamous cell carcinoma (pSCC). Herein, we aimed to assess the sensitivity of various modalities to identify human papillomavirus (HPV) status, determine the prevalence of high-risk HPV-positivity, and evaluate the prognostic impact of relevant clinicopathologic variables. METHODS: Patients with pSCC (n = 121) consecutively treated with partial/total penectomy (2000-2022) at a single institution were included. HPV status (based on immunohistochemistry [IHC], in situ hybridization [ISH], and panviral metagenomic sequencing [PMS]), histologic features, and outcomes were reviewed. Outcome events included death due to disease and progression. RESULTS: The majority of patients were white (105/121, 86.8%). Thirty-seven (30.6%) were high-risk HPV-positive, and morphologic evaluation had a sensitivity of 97.3% (95% confidence interval [CI], 86.2-99.5) for predicting high-risk HPV status compared to IHC/ISH/PMS. Disease progression was more common among high-risk HPV-negative compared to high-risk HPV-positive patients (HR 2.74, CI 1.12-8.23, P = 0.03). Moreover, among high-risk HPV-negative patients, those with moderate-poorly differentiated tumors had increased disease-specific mortality (32.6%, CI 17.1-48.1) compared to those with well-differentiated tumors (0%). Among high-risk HPV-positive patients, those with basaloid morphology had lower disease-specific mortality (0% vs 14.4%, CI 0.0-33.1). CONCLUSIONS: We demonstrate high-risk HPV-positivity in approximately one-third of patients with pSCC. Morphologic evaluation alone had a high sensitivity in correctly determining HPV status. Our results suggest that high-risk HPV status and morphologic features (differentiation in high-risk HPV-negative, and basaloid subtype in high-risk HPV-positive pSCC) may have prognostic value.
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Carcinoma de Células Escamosas , Infecciones por Papillomavirus , Neoplasias del Pene , Humanos , Masculino , Neoplasias del Pene/virología , Neoplasias del Pene/patología , Neoplasias del Pene/mortalidad , Persona de Mediana Edad , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/patología , Carcinoma de Células Escamosas/virología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/mortalidad , Anciano , Inmunohistoquímica , Adulto , Hibridación in Situ , Papillomaviridae/aislamiento & purificación , Papillomaviridae/genética , Estudios Retrospectivos , Anciano de 80 o más Años , Factores de Riesgo , Pronóstico , Progresión de la Enfermedad , Valor Predictivo de las Pruebas , Virus del Papiloma HumanoRESUMEN
The staging for pT2/pT3 penile squamous cell carcinoma (pSCC) has undergone major changes. Some authors proposed criteria wherein the distinction between pT2/pT3 was made using the same histopathological variables that are currently utilized to differentiate pT1a/pT1b. In this single-institution, North American study, we focused on (HPV-negative) pT2/3 pSCCs (i.e., tumors invading corpus spongiosum/corpus cavernosum), and compared the prognostic ability of the following systems: (i) AJCC (8th edition) criteria; (ii) modified staging criteria proposed by Sali et al. (Am J Surg Pathol. 2020; 44:1112-7). In the proposed system, pT2 tumors were defined as those devoid of lymphovascular invasion (LVI) or perineural invasion (PNI), and were not poorly differentiated; whereas pT3 showed one or more of the following: LVI, PNI, and/or grade 3. 48 pT2/pT3 cases were included (AJCC, pT2: 27 and pT3: 21; Proposed, pT2: 22 and pT3: 26). The disease-free survival (DFS) and progression-free survival (PFS) did not differ between pT2 and pT3, following the current AJCC definitions (p = 0.19 and p = 0.10, respectively). When the pT2/3 stages were reconstructed using the modified criteria, however, a statistically significant difference was present in both DFS and PFS between pT2 and pT3 (p = 0.004 and p = 0.003, respectively). The proposed staging system has the potential to improve the prognostication of pT2/pT3 tumors in pSCC. Each of these histopathologic variables has been shown to have a significant association with outcomes in pSCC, which is an advantage. Further studies are needed to demonstrate the utility of this modified staging system in patient populations from other geographic regions.
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Carcinoma de Células Escamosas , Estadificación de Neoplasias , Neoplasias del Pene , Humanos , Neoplasias del Pene/patología , Neoplasias del Pene/virología , Masculino , Estadificación de Neoplasias/métodos , Estadificación de Neoplasias/normas , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Persona de Mediana Edad , Anciano , Adulto , Pronóstico , América del Norte , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is the second most common hepatic malignancy and has a poor prognosis. Surgical resection is the standard of care for patients with resectable disease, representing 30-40% of cases. Increasingly, neoadjuvant systemic therapy is being utilized in patients due to high-risk anatomic or biologic considerations. However, data on the clinical effect of this approach are limited. We performed a cohort study to evaluate the effect of neoadjuvant therapy in patients with oncologically high-risk iCCA. METHODS: iCCA patients (n = 181) between the years 2014-2020 were reviewed for clinical, histopathologic, treatment, and outcome-related data. Tumor regression grade was scored per CAP criteria for gastrointestinal carcinomas. RESULTS: 47 iCCA patients received neoadjuvant therapy and 72 did not. Neoadjuvant treatment led to objective response and tumor regression by CAP score. After adjustment for age, clinical stage, and tumor size, the outcomes of patients who had neoadjuvant therapy followed by surgery were not significantly different from those patients who had surgery first. DISCUSSION: In conclusion, neoadjuvant therapy in iCCA facilitated surgical care. The progression-free and overall survival for surgical patients with and without neoadjuvant therapy were not significantly different suggesting this approach needs further exploration as an effective treatment paradigm.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Terapia Neoadyuvante , Humanos , Colangiocarcinoma/terapia , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Neoplasias de los Conductos Biliares/terapia , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/cirugía , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Hepatectomía , Resultado del TratamientoRESUMEN
The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.hpb.2024.04.011. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.
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Severe hypercholesterolemia/possible familial hypercholesterolemia (FH) is relatively common but underdiagnosed and undertreated. We investigated whether implementing clinical decision support (CDS) was associated with lower low-density lipoprotein cholesterol (LDL-C) in patients with severe hypercholesterolemia/possible FH (LDL-C ≥ 190 mg/dL). As part of a pre-post implementation study, a CDS alert was deployed in the electronic health record (EHR) in a large health system comprising 3 main sites, 16 hospitals and 53 clinics. Data were collected for 3 months before ('silent mode') and after ('active mode') its implementation. Clinicians were only able to view the alert in the EHR during active mode. We matched individuals 1:1 in both modes, based on age, sex, and baseline lipid lowering therapy (LLT). The primary outcome was difference in LDL-C between the two groups and the secondary outcome was initiation/intensification of LLT after alert trigger. We identified 800 matched patients in each mode (mean ± SD age 56.1 ± 11.8 y vs. 55.9 ± 11.8 y; 36.0% male in both groups; mean ± SD initial LDL-C 211.3 ± 27.4 mg/dL vs. 209.8 ± 23.9 mg/dL; 11.2% on LLT at baseline in each group). LDL-C levels were 6.6 mg/dL lower (95% CI, -10.7 to -2.5; P = 0.002) in active vs. silent mode. The odds of high-intensity statin use (OR, 1.78; 95% CI, 1.41-2.23; P < 0.001) and LLT initiation/intensification (OR, 1.30, 95% CI, 1.06-1.58, P = 0.01) were higher in active vs. silent mode. Implementation of a CDS was associated with lowering of LDL-C levels in patients with severe hypercholesterolemia/possible FH, likely due to higher rates of clinician led LLT initiation/intensification.
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OBJECTIVES: There is an unmet need for therapeutically relevant biomarkers for advanced penile squamous cell carcinoma (pSCC). Proposed immunohistochemistry (IHC)-based biomarkers include programmed death-ligand 1 (PD-L1), trophoblast cell-surface antigen 2 (TROP2), and nectin-4; however, there is a paucity of data pertaining to these biomarkers. Herein, we investigated the expression of PD-L1, TROP2, and nectin-4 in a well-annotated cohort of pSCCs. METHODS: A single-institution pathology archive was queried for patients who had a partial or total penectomy for pSCC between January 2000 and December 2022. Whole-slide sections were stained with antibodies against PD-L1 (22C3), TROP2, and nectin-4. Expression in tumor cells was quantified using H-scores (0-300). Associations between IHC expression, human papilloma virus (HPV) status, clinicopathologic findings, and outcome parameters were evaluated. RESULTS: This study included 121 patients. For PD-L1, the median combined positive and H-scores were 1 and 0, respectively; 32.7 % of the cases had an H-score>0. Compared to PD-L1-negative tumors, PD-L1-positive tumors had higher pT stage and grade. The median TROP2 and nectin-4 H-scores were 230 and 140, respectively, with high TROP2 and nectin-4, defined by an H-score>200, noted in 80.7 % and 10.9 % of cases, respectively. High-risk HPV-positive cases had higher TROP2 and nectin-4 scores compared to HPV-negative cases. Patients with high TROP2 expression had significantly more disease progression, and patients with high nectin-4 expression had significantly fewer deaths due to disease. CONCLUSIONS: High expression of TROP2 and nectin-4 in pSCC support evaluation of these markers as therapeutic targets pending validation of our findings.
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Carcinoma de Células Escamosas , Infecciones por Papillomavirus , Neoplasias del Pene , Masculino , Humanos , Antígeno B7-H1/metabolismo , Nectinas , Infecciones por Papillomavirus/complicaciones , Carcinoma de Células Escamosas/metabolismo , Biomarcadores , Neoplasias del Pene/cirugía , Neoplasias del Pene/patología , Biomarcadores de Tumor/metabolismoRESUMEN
CONTEXT.: Clinical testing for Wilson disease (WD) is potentially challenging. Measuring the fraction of labile bound copper (LBC) to total copper may be a promising alternative diagnostic tool with better sensitivity and specificity than some current biomarker approaches. A dual filtration-based inductively coupled mass spectrometry (ICP-MS) assay to measure LBC in serum was developed. OBJECTIVE.: To establish a reference interval for LBC and LBC to total copper (LBC fraction) in a healthy adult population, and to examine associations between total copper, LBC, and LBC fraction with age, sex, menopausal status, hormone replacement therapy, and supplement use. DESIGN.: Serum samples were collected from healthy male (n = 110) and female (n = 104) patients between the ages of 19 and 80 years. Total copper and LBC were analyzed using ICP-MS. Results were used to calculate the LBC fraction. Reference intervals were calculated for the 2.5th and 97.5th percentiles for both LBC and LBC fraction. RESULTS.: The reference intervals for LBC were determined to be 13 to 105 ng/mL and 12 to 107 ng/mL for female and male patients, respectively. The reference intervals for the LBC fraction were 1.0% to 8.1% and 1.2% to 10.5% for female and male patients, respectively. No significant associations were found regarding age, menopausal status, hormone replacement therapy, or vitamin and supplement use. CONCLUSIONS.: Sex-specific reference intervals have now been established for LBC and LBC fraction. These data in conjunction with further testing of WD populations can be used to assess the sensitivity and specificity of LBC fraction in screening, monitoring, and diagnosis.
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Smoking is associated with an increased risk of multiple sclerosis (MS), and smoking and early menopause are related to poor outcomes in MS. Smoking is also associated with early menopause. To explore this intricate relationship between smoking status, age at menopause and disease course in MS, 137 women with MS and 396 age-matched controls were included in this case-control study. Age at menopause (median 49.0 vs. 50.0 years; p = 0.79) and smoking status (40.3% vs. 47.6%; p = 0.15) were similar among MS and control women. Relapsing MS onset was earlier in ever-smoker women with early menopause compared to the rest of the women (median 30.4 vs. 37.0 years; p = 0.02) and also compared to ever-smoker women with normal age at menopause (median 30.4 vs. 41.0 years; p = 0.008) and never-smoker women with early menopause (median 30.4 vs. 41.5 years; p = 0.004). Progressive MS onset was also earlier in ever-smoker women with early menopause compared to ever-smoker women with normal age at menopause (median 41.1 vs. 49.4 years; p = 0.05) and never-smoker women with early menopause (median 41.1 vs. 50.1 years; p = 0.12). Our results suggest that smoking and menopause associate with MS disease course, including the onset of relapsing and progressive MS in women.
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Menopausia Prematura , Esclerosis Múltiple , Humanos , Femenino , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/etiología , Estudios de Casos y Controles , Factores de Riesgo , Fumar/efectos adversos , Menopausia , Progresión de la EnfermedadRESUMEN
OBJECTIVE: There is limited information on the prevalence of premature and early menopause. Therefore, we studied the frequency and type of premature (age < 40 years) or early (age 40-44 years) menopause in a geographically-defined American population. METHODS: We studied a random sample of women aged 18 to 50 years who resided in Olmsted County, MN between 1988 and 2007. Women were followed through December 2021, and age at cessation of menses was assessed via review of the medical records included in a medical records-linkage system. Menopause was defined as cessation of menses due to spontaneous or induced ovarian insufficiency. RESULTS: 1015 women (71.3 %) underwent spontaneous menopause, 138 (9.7 %) underwent bilateral oophorectomy, 17 (1.2 %) had antecedent chemotherapy or radiation therapy, and 254 (17.8 %) underwent hysterectomy or endometrial ablation. The median age at cessation of menses was 51.0 years (IQR, 49.0-52.0) for spontaneous menopause, 46.0 years (IQR, 41.0-49.0) for menopause induced by oophorectomy, chemotherapy, or radiation therapy, and 38.0 years (IQR, 33.0-44.0) for hysterectomy. Considering both spontaneous and induced menopause, the frequency was 3.1 % (95 % CI, 2.2-4.2) for premature and 6.2 % (95 % CI, 5.0-7.8) for early menopause. Considering only spontaneous menopause, the frequency reduced to 0.4 % (95 % CI, 0.2-1.0) for premature and 5.2 % (95 % CI, 4.0-6.8) for early menopause. However, considering all types of cessations of menses, the frequency was 12.2 % (95 % CI, 10.6-14.0) for premature and 9.7 % (95 % CI, 8.3-11.3) for early cessation of menses. DISCUSSION: Approximately 3 % of women in the general population experienced either spontaneous or induced premature menopause. The most common cause of premature menopause was bilateral oophorectomy.
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Menopausia Prematura , Insuficiencia Ovárica Primaria , Femenino , Humanos , Factores de Riesgo , Menopausia , Ovariectomía , Minnesota/epidemiologíaRESUMEN
There is increasing evidence that sex hormones may impact the development of obstructive lung disease (OLD). Therefore, we studied the effect of bilateral oophorectomy (oophorectomy) on the development of OLD. Women were identified from the Mayo Clinic Cohort Study of Oophorectomy and Aging-2. Data were collected using the Rochester Epidemiology Project records-linkage system. A total of 1653 women who underwent oophorectomy and 1653 referent women of similar age were assessed for OLD using diagnostic codes and medical record abstraction. Women who underwent oophorectomy had an overall higher risk of all OLD, all chronic obstructive pulmonary disease (COPD), emphysema, and chronic bronchitis but not of all asthma, confirmed asthma, or confirmed COPD. The association with all OLD was stronger in women who were age ≤45 years at oophorectomy, never smokers, non-obese, and in women with benign indications; however, the interactions were not statistically significant. There was an increased risk of all asthma in women age ≤45 years at oophorectomy who took estrogen therapy. Never smokers of all ages had a stronger association of oophorectomy with all asthma and all COPD, whereas smokers had a stronger association of oophorectomy with emphysema and chronic bronchitis. Non-obese women of all ages had a stronger association of oophorectomy with all COPD, emphysema, and chronic bronchitis. The results of this study combined with the increased risk of several chronic diseases reported in previous studies suggest that oophorectomy in premenopausal women should be avoided unless there is clear evidence of a high genetic risk of ovarian cancer.
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Asma , Bronquitis Crónica , Enfisema , Enfermedad Pulmonar Obstructiva Crónica , Femenino , Humanos , Persona de Mediana Edad , Estudios de Cohortes , Bronquitis Crónica/etiología , Ovariectomía/efectos adversos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Factores de Riesgo , Asma/epidemiología , Asma/etiología , Enfisema/etiologíaRESUMEN
Importance: The association of premenopausal bilateral oophorectomy with parkinsonism and Parkinson disease (PD) remains controversial. Objective: To assess whether women who underwent premenopausal bilateral oophorectomy were at increased risk of parkinsonism and PD and whether the associations varied by age at oophorectomy and by receipt of estrogen replacement therapy. Design, Setting, and Participants: This cohort study used data from a combination of 2 independent cohort studies, the Mayo Clinic Cohort Study of Oophorectomy and Aging 1 and 2, which were based on the Rochester Epidemiology Project medical records-linkage system. A population-based sample of 5499 women from Olmsted County, Minnesota, were included; of those, 2750 women underwent bilateral oophorectomy for a benign indication before spontaneous menopause between January 1, 1950, and December 31, 2007 (oophorectomy cohort), and 2749 age-matched women who did not undergo bilateral oophorectomy were randomly sampled from the general population (reference cohort). Data were analyzed from March 1 to April 30, 2022. The date of oophorectomy was considered the index date for both groups. Exposures: Medical record documentation of bilateral oophorectomy abstracted from a medical records-linkage system (Rochester Epidemiology Project). Main Outcomes and Measures: Incidence and risk of parkinsonism or PD, with diagnoses confirmed by in-person examination or medical record review. Results: Among 5499 participants (median [IQR] age, 45.0 [40.0-48.0] years; 5312 [96.6%] White), 2750 women (2679 White [97.4%]) underwent bilateral oophorectomy at a median age of 45.0 years (IQR, 40.0-48.0 years), and 2749 women (2633 White [95.8%]) with a median age of 45.0 years (IQR, 40.0-48.0 years) at the index date were included in the reference cohort. Bilateral oophorectomy was associated with an increased risk of parkinsonism overall (hazard ratio [HR], 1.59; 95% CI, 1.02-2.46) and in women younger than 43 years at oophorectomy (HR, 7.67; 95% CI, 1.77-33.27). There was a pattern of increasing risk with younger age at the time of oophorectomy using 4 age strata (≥50 years: HR, 1.43 [95% CI, 0.50-4.15]; 46-49 years: HR, 1.55 [95% CI, 0.79-3.07]; 40-45 years: HR, 1.36 [95% CI, 0.64-2.89]; <40 years: HR, 8.82 [95% CI, 1.08-72.00]; P = .02 for trend). The number needed to harm was 53 women overall and 27 women younger than 43 years at the time of oophorectomy. Bilateral oophorectomy was also associated with an increased risk of PD in women younger than 43 years at oophorectomy (HR, 5.00; 95% CI, 1.10-22.70), with a number needed to harm of 48 women. Among women who underwent oophorectomy at 45 years and younger, the risk was lower in women who received estrogen after the procedure and through age 50 years compared with women who did not. For parkinsonism, the HRs were 1.72 (95% CI, 0.54-5.53) vs 2.05 (95% CI, 0.80-5.23); for PD, the HRs were 1.53 (95% CI, 0.29-8.23) vs 2.75 (95% CI, 0.84-9.04). However, the differences were not significant. Conclusions and Relevance: In this study, premenopausal women who underwent bilateral oophorectomy before age 43 years had an increased risk of parkinsonism and PD compared with women who did not undergo bilateral oophorectomy. These findings suggest that a reduction in the practice of prophylactic bilateral oophorectomy in premenopausal women at average risk of ovarian cancer may have substantial benefit for reducing the risk of parkinsonism and PD.
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Enfermedad de Parkinson , Humanos , Femenino , Adulto , Persona de Mediana Edad , Estudios de Cohortes , Enfermedad de Parkinson/epidemiología , Factores de Edad , Factores de Riesgo , Ovariectomía/efectos adversos , EstrógenosRESUMEN
Background: Contemporary prevalence, awareness, and control of severe hypercholesterolemia (SH) and familial hypercholesterolemia (FH) and the associated atherosclerotic cardiovascular disease risk in the US are unknown. Method: Using electronic health records, we assessed the burden of SH and FH in Olmsted County, Minnesota, US, between 2004 and 2015. We defined SH as low-density lipoprotein cholesterol (LDL-C) level ≥190 mg/dl without secondary causes of hypercholesterolemia and FH as a Dutch Lipid Clinic Network score ≥6. Controls were age- and sex-matched individuals with LDL-C level <190 mg/dl. Results: The age- and sex-adjusted point and period prevalence (age-recursive method) of SH was 4.44% and 8.95%, respectively; 1 in 21 had FH (â¼1:233 adults), and 46.2% had a recorded diagnosis. Guideline recommended targets (LDL-C <100 mg/dl and <70 mg/dl in the primary and secondary prevention settings, respectively) were achieved in 33.1% and 21.2% of SH cases, with less women overall achieving the target than men (18.6% vs. 23.7%, p=0.022). After adjustment for conventional risk factors, the hazard ratio for incident coronary heart disease (CHD) in those with SH was 1.21 (1.05-1.39; p=0.010), in those with SH and a family history of CHD was 2.16 (1.57-2.96; p<0.001) and in those with FH was 4.61 (2.66-7.97; p<0.001). The association of SH with CHD was modified by age (p-interaction = 0.015), such that the risk was greater at younger ages. Conclusions: SH was prevalent and an independent risk factor for incident CHD. Awareness and control were low, highlighting a treatment gap (more prominent in women) that needs to be addressed.
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PURPOSE: We compared new cases detected per index case in familial hypercholesterolemia (FH) families with or without an identifiable monogenic etiology. METHODS: We enrolled 52 FH probands with a pathogenic variant (FHg+) in LDLR, APOB, or PCSK9 and 73 probands without such a variant (FHg-). After direct contact by the study team, family members (FMs) of FHg+ probands could opt-in for genetic testing and FMs of FHg- probands were asked to provide a lipid profile. New cases were defined as presence of a pathogenic variant in FHg+ families and as low-density lipoprotein cholesterol ≥155 mg/dL in FHg- families. RESULTS: Of 71 FHg+ probands seen by a genetic counselor, 52 consented and identified 253 FMs (111 consented and were tested, yielding 48 new cases). Of 101 FHg- probands who received counseling, 73 consented and identified 295 FMs (63 consented and were tested, yielding 17 new cases). New case detection per index case was significantly greater in FHg+ than in FHg- families (0.92 vs 0.23), a result of higher cascade testing uptake (43.9 vs 21.4%) and yield (43.2 vs 27.0%) in the former. CONCLUSION: New case detection rate was significantly higher in FH families with a monogenic etiology than in those without such an etiology owing to greater uptake and yield of cascade testing.
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Hiperlipoproteinemia Tipo II , Proproteína Convertasa 9 , Humanos , Proproteína Convertasa 9/genética , Receptores de LDL/genética , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , LDL-ColesterolRESUMEN
OBJECTIVE: To study the trajectories of metabolic parameters after bilateral oophorectomy. STUDY DESIGN: This population-based cohort study included a random sample of all premenopausal women who underwent bilateral oophorectomy at or before age 45 years from 1988 to 2007 in Olmsted County, Minnesota, and their age-matched (±1 year) referent women who did not undergo bilateral oophorectomy. MAIN OUTCOME MEASURES: The medical records of all women were reviewed to collect the metabolic parameters over a 10-year period. We compared three groups of women: 1) referent women (n = 270), 2) women who underwent bilateral oophorectomy and received estrogen therapy (n = 163), and 3) women who underwent bilateral oophorectomy and did not receive estrogen therapy (n = 107). RESULTS: Over 10 years of follow-up, the three groups had significantly different mean values of diastolic blood pressure, weight, body mass index (BMI), total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C). However, women with and without bilateral oophorectomy were already different at baseline for hyperlipidemia, systolic blood pressure, weight, and BMI. Nevertheless, the trajectories of change over 10 years were significant for weight (group by time interaction p = 0.03), BMI (p = 0.03), and HDL-C (p = 0.004). The changes occurred primarily in the initial 4-5 years. Women who received estrogen therapy after bilateral oophorectomy were comparable to the referent women with respect to the weight and BMI trends, and they experienced an increase in HDL-C over time. CONCLUSION: Women who underwent bilateral oophorectomy before menopause experienced unfavorable changes in some metabolic parameters possibly increasing their cardiovascular risk.
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Estrógenos , Lipoproteínas HDL , Factores de Edad , Colesterol , Estudios de Cohortes , Estrógenos/uso terapéutico , Femenino , Humanos , Ovariectomía/efectos adversos , Factores de Riesgo , TriglicéridosRESUMEN
BACKGROUND: Vaccine nonresponse during the coronavirus disease 2019 (COVID-19) pandemic has considerable individual and societal risks. OBJECTIVE: To investigate the clinical characteristics of patients with lack of seroconversion after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Demographic and clinical data were collected from 805 patients who had validated antibody assays against the SARS-CoV-2 spike protein at least 14 days after completion of their COVID-19 vaccination. Clinical characteristics from patients with a negative (< 0.4 U/mL) antibody response were assessed and summarized. RESULTS: A total of 622 (77.3%) patients attained seroconversion as defined by a titer of greater than or equal to 0.4 U/mL, whereas 183 out of 805 (22.7%) patients exhibited no seroconversion after vaccination against SARS-CoV-2. Univariately, older age (P = .02) and male sex were associated with a lower likelihood of seroconversion (P = .003). Therapy with immunosuppressive drugs was noted in 93 (50.8%) of seronegative patients with most (n = 83/93, 89.2%) receiving ongoing immunosuppressive therapy at the time of vaccination. Among the 134 (73.2%) seronegative patients with immunodeficiency, 110 (82.1%) had primary immunodeficiency. Cancer (n = 128, 69.9%), B cell depletion therapy (n = 90/115, 78.3%), and immunosuppressant steroid use (n = 71/93 on immunosuppressants, 76.3%) were the other common characteristics among the vaccine nonresponders. More importantly, our study did not evaluate the actual efficacy of COVID-19 vaccination. CONCLUSION: Vaccine responses vary by age and sex, with men showing lower rates of seroconversion as compared with women. Primary immunodeficiency along with active malignancy and ongoing immunosuppression with steroids or B cell depletion therapy appeared to be the most common characteristics for those with a lack of vaccine seroconversion after COVID-19 vaccination.
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Vacunas contra la COVID-19 , COVID-19 , Seroconversión , Anticuerpos Antivirales , COVID-19/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Femenino , Humanos , Masculino , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/inmunología , VacunaciónRESUMEN
OBJECTIVE: To evaluate trends in the incidence of premenopausal unilateral and bilateral oophorectomy between 1950 and 2018. METHODS: The Rochester Epidemiology Project medical records-linkage system was used to identify all women aged 18-49 years who were residents of Olmsted County, Minnesota, and underwent unilateral or bilateral oophorectomy before spontaneous menopause between January 1, 1950, and December 31, 2018. Population denominators were derived from the U.S. Decennial Censuses for the years 1950-2010, and intercensal year population denominators were linearly interpolated. For 2011-2018, the annual population denominators were obtained from the U.S. Census projections. Where appropriate, overall incidence rates were age-adjusted to the total U.S. female population from the 2010 Census. RESULTS: There were 5,154 oophorectomies in Olmsted County across the 69-year period between 1950 and 2018, and 2.9% showed malignant disease on pathology. A total of 2,092 (40.6%) women underwent unilateral oophorectomy, and 3,062 (59.4%) women underwent bilateral oophorectomy. More than half (n=1,750, 57.2%) of the bilateral oophorectomies occurred between 1990 and 2009. Until 1975-1979, the incidence of unilateral oophorectomy was mostly higher than bilateral oophorectomy. From 1980-1984 until 2000-2004, the incidence of bilateral oophorectomy more than doubled and the incidence of unilateral oophorectomy declined. After 2005, both procedures declined and converged to a similar incidence in 2015-2018. The decline in premenopausal bilateral oophorectomy over the past 14 years (2005-2018) was most pronounced for women who underwent oophorectomy concurrently with hysterectomy or did not have any ovarian indication. CONCLUSION: The incidence rates of unilateral and bilateral oophorectomy have varied greatly across the 69-year period of this study. In the past 14 years, the incidence of premenopausal unilateral and bilateral oophorectomy has decreased. These trends reflect the effects of the initial 2005-2006 publications and the subsequent expanding body of evidence against the practice of oophorectomy for noncancer indications.
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Histerectomía , Premenopausia , Femenino , Humanos , Incidencia , Masculino , Ovariectomía , OvarioRESUMEN
OBJECTIVE: To determine trends in amputations and revascularizations for peripheral artery disease (PAD) in a well-defined population. METHODS: A population-based cohort study of Olmsted County, Minnesota, residents with PAD undergoing amputation or revascularization was conducted between January 1, 1990, and December 31, 2009. Population-level 5-year incidence trends for endovascular, open surgical, and hybrid revascularizations and major and minor amputations were determined. Limb-specific outcomes after revascularization, including major adverse limb events and amputation-free survival, were compared between initial surgical and endovascular or hybrid revascularization groups using Kaplan-Meier analysis. RESULTS: We identified 773 residents who underwent 1906 limb-procedures, including 689 open revascularizations, 685 endovascular or hybrid revascularizations, and 220 major amputations. During the 20-year study period, the incidence of endovascular and hybrid revascularizations increased, whereas the incidence of open surgical revascularizations and major amputations decreased. Incidence of revascularizations for chronic limb-threatening ischemia (CLTI) did not change. Among residents with CLTI undergoing their first revascularization on a limb, endovascular revascularization was associated with more major adverse limb events and major amputations compared with surgical revascularization during the ensuing 15 years. CONCLUSION: The rising incidence of endovascular and hybrid revascularizations and the decreasing incidence of open surgical revascularizations for PAD were associated with a decreasing incidence of major amputations in this population between 1990 and 2009, despite a stable incidence of revascularizations for CLTI. With more major adverse limb events and major amputations after endovascular revascularization, these trends suggest that additional emphasis should be placed on improving limb salvage efforts beyond just mode of revascularization.
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Procedimientos Endovasculares , Enfermedad Arterial Periférica , Amputación Quirúrgica/efectos adversos , Estudios de Cohortes , Procedimientos Endovasculares/efectos adversos , Humanos , Isquemia , Extremidad Inferior/irrigación sanguínea , Enfermedad Arterial Periférica/epidemiología , Enfermedad Arterial Periférica/cirugía , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Electronic health records (EHRs) are a rich source of longitudinal patient data. However, missing information due to clinical care that predated the implementation of EHR system(s) or care that occurred at different medical institutions impedes complete ascertainment of a patient's medical history. OBJECTIVE: This study aimed to investigate information discrepancies and to quantify information gaps by comparing the gynecological surgical history extracted from an EHR of a single institution by using natural language processing (NLP) techniques with the manually curated surgical history information through chart review of records from multiple independent regional health care institutions. METHODS: To facilitate high-throughput evaluation, we developed a rule-based NLP algorithm to detect gynecological surgery history from the unstructured narrative of the Mayo Clinic EHR. These results were compared to a gold standard cohort of 3870 women with gynecological surgery status adjudicated using the Rochester Epidemiology Project medical records-linkage system. We quantified and characterized the information gaps observed that led to misclassification of the surgical status. RESULTS: The NLP algorithm achieved precision of 0.85, recall of 0.82, and F1-score of 0.83 in the test set (n=265) relative to outcomes abstracted from the Mayo EHR. This performance attenuated when directly compared to the gold standard (precision 0.79, recall 0.76, and F1-score 0.76), with the majority of misclassifications being false negatives in nature. We then applied the algorithm to the remaining patients (n=3340) and identified 2 types of information gaps through error analysis. First, 6% (199/3340) of women in this study had no recorded surgery information or partial information in the EHR. Second, 4.3% (144/3340) of women had inconsistent or inaccurate information within the clinical narrative owing to misinterpreted information, erroneous "copy and paste," or incorrect information provided by patients. Additionally, the NLP algorithm misclassified the surgery status of 3.6% (121/3340) of women. CONCLUSIONS: Although NLP techniques were able to adequately recreate the gynecologic surgical status from the clinical narrative, missing or inaccurately reported and recorded information resulted in much of the misclassification observed. Therefore, alternative approaches to collect or curate surgical history are needed.
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Registros Electrónicos de Salud , Procesamiento de Lenguaje Natural , Algoritmos , Estudios de Cohortes , Femenino , Procedimientos Quirúrgicos Ginecológicos , HumanosRESUMEN
OBJECTIVES: Population-based epidemiologic data for paraneoplastic neurologic syndromes (PNSs) in the United States are lacking. Our objective was to evaluate the incidence, prevalence, and associated morbidity of PNS. METHODS: We performed a population-based epidemiology study in Olmsted County, Minnesota, with patients identified between January 1, 1987, and December 31, 2018, using the medical records linkage system of the Rochester Epidemiology Project (REP) who met the definite/probable 2021 PNS criteria and 2004 PNS criteria. Patients with dermatomyositis and myasthenia gravis with underlying tumors were included. Age- and sex-specific population counts were obtained from REP resources for January 1, 2014 (prevalence denominator) and annually for 1987-2018 (incidence denominator). Morbidity was estimated using disability-adjusted life years (DALYs; years lived with disability [YLD] plus years of life lost [YLL]). RESULTS: There were 28 patients with PNS identified (50% female) residing in Olmsted County, Minnesota, with median age at diagnosis of 54.5 (IQR 46.5-69.0) years. All patients had a cancer diagnosis, and 18 (64%) patients were neural autoantibody positive including antineuronal nuclear autoantibody type 1 (ANNA-1/anti-Hu; n = 1), ANNA-2/anti-Ri (n = 1), muscle-type acetylcholine receptor (AChR; n = 6), Purkinje cell cytoplasmic antibody type 1 (PCA-1/anti-Yo; n = 1), kelch-like protein 11 (KLH11; n = 3), collapsin response mediator protein 5 (CRMP-5/anti-CV2; n = 2), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (n = 1), neurofilament light chain (n = 1), leucine zipper 4 (LUZP4; n = 1), and unclassified neural antibodies (n = 1). PNS incidence was 0.6/100,000 person-years and increased over time from 0.4/100,000 person-years (1987-2002) to 0.8/100,000 person-years (2003-2018) (p = 0.06). Prevalence was 5.4/100,000 people. The median follow-up period after PNS diagnosis was 3.1 years (IQR, 1.1-9.9 years). Total disability-adjusted life years (DALYs) for 28 patients with PNS were 472.7 years, based on total years of life lost (YLL) for patients dying between 1987 and 2018 (n = 15) of 445.3 years plus years lived with disability (YLD) 27.4 years. DISCUSSION: PNSs are rare neurologic disorders but are associated with severe morbidity and mortality. The estimated number of prevalent PNS cases in the United States is 17,099, and predicted DALY for all US PNS cases is 292,393 years. Their apparent increasing rate of detection is attributable to increasing physician awareness and availability of serologic testing.
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Años de Vida Ajustados por Discapacidad , Neoplasias/epidemiología , Síndromes Paraneoplásicos del Sistema Nervioso/epidemiología , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Minnesota/epidemiología , Neoplasias/complicaciones , Neoplasias/mortalidad , Síndromes Paraneoplásicos del Sistema Nervioso/etiología , Síndromes Paraneoplásicos del Sistema Nervioso/mortalidad , Prevalencia , Adulto JovenRESUMEN
BACKGROUND: Hysterectomy is one of the most frequent gynecologic surgeries in the United States. Women undergoing hysterectomy are commonly offered bilateral oophorectomy for ovarian and breast cancer prevention. Although bilateral oophorectomy may dramatically reduce the risk of gynecologic cancers, some studies suggested that bilateral oophorectomy may be associated with an increased risk of other types of cancer, such as lung cancer and colorectal cancer. However, the results are conflicting. OBJECTIVE: To study the association between bilateral oophorectomy and the risk of subsequent cancer of any type. STUDY DESIGN: This population-based cohort study included all premenopausal women who underwent bilateral oophorectomy for a nonmalignant indication before the age of 50, between January 1, 1988 and December 31, 2007 in Olmsted County, Minnesota, and a random sample of age-matched (±1 year) referent women who did not undergo bilateral oophorectomy. Women with cancer before oophorectomy (or index date) or within 6 months after the index date were excluded. Time-to-event analyses were performed to assess the risk of de novo cancer. Cancer diagnosis and type were confirmed using medical record review. RESULTS: Over a median follow-up of 18 years, the risk of any cancer did not significantly differ between the 1562 women who underwent bilateral oophorectomy before natural menopause and the 1610 referent women (adjusted hazard ratio, 0.82; 95% confidence interval, 0.66-1.03). However, women who underwent bilateral oophorectomy had a decreased risk of gynecologic cancers (adjusted hazard ratio, 0.15; 95% confidence interval, 0.06-0.34) but not of nongynecologic cancers (adjusted hazard ratio, 0.99; 95% confidence interval, 0.78-1.26). In particular, the risk of breast cancer, gastrointestinal cancer, and lung cancer did not differ between these 2 cohorts. Use of estrogen therapy through the age of 50 years in women who underwent bilateral oophorectomy did not modify the results. CONCLUSION: Women who underwent bilateral oophorectomy before menopause have a reduced risk of gynecologic cancer but not of other types of cancer including breast cancer. Women at average risk of ovarian cancer should not consider bilateral oophorectomy for the prevention of breast cancer or other nongynecologic cancers.