To mesh or not mesh "apical prolapse," that is the question!

Surgical approaches for pelvic organ prolapse have evolved over the last 30 years and is a popular topic for debate, particularly when discussing apical prolapse. Transvaginal native tissue repairs remain the mainstay of POP surgeries, however, transabdominal approaches continue to evolve. Use of interposition material, such as synthetic polypropylene mesh, is the standard when performing an abdominal sacrocolpopexy, however, use of autologous fascia can be considered. This debate article provides an overview of this subject and highlights the value of different approaches to apical prolapse. The authors were asked to support their approach in various scenarios including:extremes of age, prior hysterectomy and intact uterus, desire to avoid mesh, sexual activity, and presence of comorbidities. In discussing common patient scenarios, ultimate decision making on specific POP surgeries is determined by patient preference and goals.

Remotely monitored physical activity from older people with cardiac devices associates with physical functioning.

INTRODUCTION: Accelerometer-derived physical activity (PA) from cardiac devices are available via remote monitoring platforms yet rarely reviewed in clinical practice. We aimed to investigate the association between PA and clinical measures of frailty and physical functioning. METHODS: The PATTErn study (A study of Physical Activity paTTerns and major health Events in older people with implantable cardiac devices) enrolled participants aged 60 + undergoing remote cardiac monitoring. Frailty was measured using the Fried criteria and gait speed (m/s), and physical functioning by NYHA class and SF-36 physical functioning score. Activity was reported as mean time active/day across 30-days prior to enrolment (30-day PA). Multivariable regression methods were utilised to estimate associations between PA and frailty/functioning (OR = odds ratio, ß = beta coefficient, CI = confidence intervals). RESULTS: Data were available for 140 participants (median age 73, 70.7% male). Median 30-day PA across the analysis cohort was 134.9 min/day (IQR 60.8-195.9). PA was not significantly associated with Fried frailty status on multivariate analysis, however was associated with gait speed (ß = 0.04, 95% CI 0.01-0.07, p = 0.01) and measures of physical functioning (NYHA class: OR 0.73, 95% CI 0.57-0.92, p = 0.01, SF-36 physical functioning: ß = 4.60, 95% CI 1.38-7.83, p = 0.005). CONCLUSIONS: PA from cardiac devices was associated with physical functioning and gait speed. This highlights the importance of reviewing remote monitoring PA data to identify patients who could benefit from existing interventions. Further research should investigate how to embed this into clinical pathways.

Care after premenopausal risk-reducing salpingo-oophorectomy in high-risk women: Scoping review and international consensus recommendations.

Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease.

Factors influencing genetic counseling and testing for hereditary breast and ovarian cancer syndrome in a large US health care system.

Investigate whether disparities and other factors influence referral to genetic counseling and testing for hereditary breast and ovarian cancer syndrome (HBOC) in a large health care system. Examination of clinical, demographic, and socioeconomic factors from electronic health records associated with genetic referral and testing within 12 months after a new cancer diagnosed between August 1, 2013 and December 31, 2018. For patients meeting institutional criteria for HBOC testing, 60.6% were referred for genetic counseling, 88% of whom underwent germline testing; at least one pathogenic variant was found in 15.3%. Referral rates for patients with breast (69%) or ovarian cancer (65.7%) were much higher than for metastatic prostate (11.1%, p < 0.0001) or pancreatic cancer (22.3%, p < 0.0001); referral criteria were implemented more recently for the latter two cancers. Younger age, family history, and chemotherapy were associated with referral. Higher Elixhauser comorbidity score and prior cancer were associated with non-referral. No other factors were associated with genetic referral for all eligible cancers combined, although differences were seen in specific cancers. Race was a significant factor only for breast cancer, with fewer Asians than Whites referred. Health disparities in referral to genetics for HBOC cancers are mitigated in a comprehensive integrated health care system.

Management of ovarian and breast cancer risk in non-BRCA HBOC pathogenic variant carriers in a large California health care system.

PURPOSE: To describe breast and ovarian cancer risk reduction strategies in the clinical management of women who test positive for non-BRCA hereditary breast and ovarian cancer (HBOC) pathogenic variants compared to those who test positive for pathogenic BRCA variants or have negative germline panel testing. METHODS: Examination of imaging and preventive surgeries in women undergoing HBOC genetic testing from 1/1/2015 to 12/31/2018, with follow up to 03/31/2020 in Kaiser Permanente Northern California. RESULTS: A total of 13,271 tests which included HBOC genes were identified. Rate of bilateral salpingo-oophorectomy after genetic testing were similar for BRCA and the non-BRCA moderate risk ovarian pathogenic variants (PVs) (47.4% vs 54%, p = 0.25). Rates were lower for low risk or unknownrisk non-BRCA PVs (12.8%, p < 0.001, 5.3% (p < 0.001). Rates of surveillance for ovarian cancer with ultrasound and CA 125 in the first year was 63.3% and 64.7% for BRCA PV, 37.5% and 27.1%, for non-BRCA moderate risk PVs and 13.7% and 4.6%, for low-risk PVs. Bilateral mastectomy rates were 19.7% for BRCA PV, 10.1% (p = 0.028) for non-BRCA breast high risk PVs, for moderate risk PVs 7.7% (p < 0.001) and for unknown risk 0.4% (p < 0.001). MRI surveillance rates in the first year similarly were 47.4% for non-BRCA BRCA PV, 43% for breast high risk PV, 39.4% for moderate risk and 4.9% for unknown risk PV. CONCLUSION: Surgical and surveillance strategies are underutilized for HBOC PV, however there is concordance of uptake of preventive strategies with specific risk associated with non-BRCA PVs.

Arterial Atherosclerosis: Vascular Surgery Interventions.

Atherosclerotic vascular disease is a leading cause of death worldwide. Atherosclerotic stenosis of the internal carotid or intracranial arteries causes up to 15% of strokes. Peripheral artery disease affects up to one in five people in the United States who are 60 years and older and nearly one-half of those who are 85 years and older. Renal artery stenosis may affect up to 5% of people with isolated hypertension and up to 40% of people with other atherosclerotic diseases. All patients with atherosclerotic vascular disease should receive a comprehensive program of guideline-directed medical therapy, including structured physical activity and lifestyle modification, an antiplatelet agent, a statin, antihypertensive therapy, and smoking cessation counseling. The U.S. Preventive Services Task Force recommends one-time screening for abdominal aortic aneurysm with ultrasonography in men 65 to 75 years of age who have smoked at least 100 cigarettes, but screening is not recommended for carotid, peripheral, and renal disease. Surgical revascularization decreases adverse outcomes and mortality in selected patients with advanced vascular disease. Endovascular repair has become more common for patients younger than 70 years because of decreased short-term mortality. Carotid revascularization with carotid endarterectomy or carotid artery stenting is recommended for symptomatic patients with greater than 50% internal carotid artery stenosis. Carotid artery stenting is preferred in patients with multiple comorbidities, tracheostomy, or previous neck radiation or dissection. In patients older than 70 years, carotid endarterectomy is associated with a lower risk of periprocedural stroke or death than carotid artery stenting. Revascularization is a reasonable treatment option for patients with lifestyle-limiting claudication and an inadequate response to guideline-directed therapies. Revascularization is indicated for patients with critical limb ischemia and is emergently indicated for acute limb ischemia. Renal artery revascularization offers no proven clinical benefit when added to optimal medical therapy.

Ovarian cancer surveillance in the clinical follow up of women with known BRCA1 or BRCA2 pathogenic variants in a large health care system.

OBJECTIVE: To assess CA 125 and transvaginal ultrasound surveillance in women with BRCA1 or BRCA2 pathogenic variants in a pragmatic clinical setting with>1 year follow up. METHODS: Retrospective cohort study in a large integrated health care system of women identified from 1/1/2003 to 12/31/2017 with a BRCA1 or BRCA2 pathogenic variant with at least one intact ovary. Demographic and clinical data were collected from date of genetic testing until oophorectomy, an ovarian cancer diagnosis, or 7/1/2019. Primary outcome was frequency and findings of CA 125 tests and ultrasounds performed; secondary outcome was epithelial ovarian cancers diagnosed. RESULTS: There were 1418 women, age ≥ 30 years with a BRCA1 or BRCA2 pathogenic variant with at least one intact ovary. Of the total of 1683 ultrasounds and 2437 CA 125 tests done, 1022 ultrasounds and 1709 CA 125 tests were performed for surveillance in 771 women followed >1 year. Of these women 241 (31%) women had no surveillance, and 530 (69%) women underwent any surveillance. Only 108 (20%) underwent regular surveillance. The number who underwent regular surveillance declined each year. Twenty-one women underwent surveillance indicated surgery with only 2 ovarian cancers found by surveillance. CONCLUSIONS: Many women with BRCA1 or BRCA2 pathogenic variants undergo ultrasound and CA 125 surveillance testing but abnormal surveillance testing led to diagnosis of ovarian cancer in only two cases. These findings question the use of CA 125 and ultrasound surveillance in the clinical setting for ovarian cancer detection in women with BRCA1 or BRCA2 pathogenic variants.

Caring for the psychosocial needs of the acutely traumatized patient.

ABSTRACT: Support for a patient in the aftermath of a potentially traumatic event is enhanced when clinicians understand the normal reactions that may occur during the traumatization process. This article discusses recommendations from international and national guidelines as well as best practices from the medical and psychiatric literature to help guide clinicians providing care for acutely traumatized patients.

Cytological sampling of fallopian tubes using a hysteroscopic catheter: A multi-center study.

OBJECTIVE: To assess the feasibility of a novel hysteroscopic catheter to collect fallopian tube cytologic samples and to correlate cytologic findings with histopathology. METHODS: This was a prospective, multicenter, single-arm pilot study. Women undergoing salpingo-oophorectomy for a pelvic mass suspicious for malignancy or for prevention of cancer for BRCA mutation carriers were recruited from 3 gynecologic oncology centers (October 2016-August 2017). Cytologic samples were collected from the fallopian tube using a novel FDA-cleared hysteroscopic catheter and evaluated by a pathologist blinded to surgical or pathologic findings. The correlation between cytologic results and final surgical pathology was assessed. RESULTS: Of the 50 patients enrolled, 42 were eligible. Hysteroscopies were completed in 40 patients with 78 fallopian tubes, of which 65 ostia (83%) were identified. Of these, 61 (72%) were successfully catheterized resulting in 44 (68%) cytology samples adequate for further evaluation: 5 were classified as positive (3 neoplastic and 2 malignant) and 39 as negative (34 benign and 5 reactive/atypical). A comparison of cytology results with fallopian tube histopathology showed a concordance rate of 95% (42/44). Of the two samples with discordant results, both had positive cytology but negative tubal pathology, and both were stage I ovarian cancers with malignant ovary histology. CONCLUSIONS: Deployment of the device yielded an evaluable cytologic sample in 68% of cases with a high rate of concordance with histopathology. Further evaluation of the device's ability to detect malignancy in high risk populations is warranted.

Development of a longitudinal two-biomarker algorithm for early detection of ovarian cancer in women with BRCA mutations.

OBJECTIVE: To develop a longitudinal algorithm combining two biomarkers, CA125 and HE4, for early detection of ovarian cancer in women with BRCA mutations. METHODS: Women with BRCA mutations and intact ovaries were invited to participate in a novel ovarian cancer early detection prospective study. The Risk of Ovarian Cancer Algorithm (ROCA) identifying significant increases above each woman's baseline in serum CA125 and HE4 was performed every four months; abnormal risks triggered a subsequent ultrasound. The study first used a risk algorithm for only CA125, a second algorithm was developed for HE4 and finally a risk algorithm combining the two biomarkers was implemented. The ROCA strategy was compared to Standard of Care (SOC) surveillance strategy. RESULTS: A total of 149 women enrolled in the ROCA arm while 43 women enrolled in the SOC arm. Abnormal scores were found in 24% of ROCA CA125 tests, 16% if ROCA CA125 or the novel ROCA HE4 were used independently and reduced to 8% using the new two-marker ROCA, significantly lower than the 15% of abnormal tests seen in the SOC arm (p = 0.042). The average false positive rate among women without ovarian cancer for two-marker ROCA for referral to ultrasound was 6.6% (specificity 93.4%), and for the two-marker ROCA plus ultrasound for referral to surgical consultation was 1.7% (specificity 98.3%). CONCLUSION: A newly developed two-marker ROCA administered every 4 months had lower call-back rates than SOC surveillance. Having established high specificity, the two-marker ROCA score deserves further evaluation for sensitivity in a larger trial.

Streamlining genetic testing for women with ovarian cancer in a Northern California health care system.

OBJECTIVE: Referral to Genetics for pre-testing counseling may be inefficient for women with ovarian cancer. This study assesses feasibility of gynecologic oncologists directly offering genetic testing. METHODS: A prospective pilot study was conducted at two gynecologic oncology hubs in an integrated healthcare system from May 1 to November 6, 2019. Gynecologic oncologists offered multigene panel testing to women with newly diagnosed ovarian cancer, followed by selective genetic counseling. Outcomes were compared between study participants and women from other hubs in the health system. RESULTS: Of ovarian cancer patients at study sites, 40 participated and all underwent genetic testing. Of 101 patients diagnosed at other sites, 85% were referred to genetics (p = .0061 compared to pilot participants) and 67% completed testing (p < .0001). The time from diagnosis to blood draw and notification of result was 18.5 and 34 days for the pilot group compared to 25.5 and 53 days at other sites. Panel testing detected 9 (22.5%) and 7 (10.3%, p = .08) pathogenic mutations in each group, respectively. Patients and providers were highly satisfied with the streamlined process. CONCLUSION: Genetic testing performed at the gynecologic oncology point of care for patients with ovarian cancer is feasible, increases uptake of testing, and improves time to results.

Comparison of two Lynch screening strategies in endometrial cancer in a California health system.

OBJECTIVE: Compare detection of Lynch syndrome in endometrial cancer between regions of a health care system with different screening strategies. METHODS: A retrospective study of endometrial cancer (EC) cases from 2 regions of an integrated health care system (Kaiser Permanente Northern (KPNC) and Southern (KPSC) California). Within KPNC, immunohistochemistry tumor screening (IHC) was physician ordered and risk-based; within KPSC, IHC was universal and automated. Clinical risk factors associated with abnormal IHC and Lynch Syndrome (LS) were identified. RESULTS: During the study, there were 2045 endometrial cancers: 1399 in the physician-order group and 646 in the universal testing group. In the physician-order group: among women < age 60, 34% underwent IHC; 9.6% were abnormal, and 3% were possible LS after methylation testing; among women ≥60, 11% underwent IHC, 3% were abnormal and <1% were possible LS. In the universal group, 87% of women age <60 had IHC, 19.4% were abnormal, and 6% were possible LS; Among women age ≥60, 82% underwent IHC, 26% were abnormal, and 2% were possible LS. There were no differences in LS cases between the physician-order group and the universal group in either age strata (<60: 3% vs. 3.6%, p=0.62; ≥60: <1% vs. 1%, p=0.63) Factors associated with LS were younger age (odds ratio (OR) 0.11, 95% confidence interval (CI) 0.04-0.29) and lower body mass index (BMI), (OR 0.38 95% CI 0.18-0.80). CONCLUSIONS: Universal IHC screening did not result in increased LS detection in EC.

Feasibility, patient compliance and acceptability of ovarian cancer surveillance using two serum biomarkers and Risk of Ovarian Cancer Algorithm compared to standard ultrasound and CA 125 among women with BRCA mutations.

OBJECTIVE: We assessed the feasibility, patient acceptability of and compliance of a new surveillance strategy for ovarian cancer surveillance in women with BRCA mutations, based on assessments of serum CA125 and HE4 every 4 months (Risk of Ovarian Cancer Algorithm (ROCA) arm), compared to Standard of Care (SOC) surveillance with CA125 blood tests and pelvic ultrasounds every 6 months. METHODS: Women were recruited 6/13/16-9/11/17 from an integrated health care system in California for this non-randomized prospective cohort study. Women were invited to participate in a novel serum biomarker surveillance strategy using ROCA or they could opt to be in the standard of care control arm with ultrasound and CA 125 every 6 months. Outcomes assessed included compliance, self-reported distress using the Impact of Event Scale (IES) and cancer anxiety using the Cancer Worry Scale. RESULTS: There were 159 women in the ROCA arm and 43 in the SOC arm. Overall, compliance was higher in the ROCA arm (83.2%) than in SOC (51.9%), p < 0.0001. Based on the IES, ROCA arm women reported less feelings about intrusion and avoidance at 12 months compared to baseline; the difference approached significance for intrusion (7.6% vs 4.1% severe, p = 0.057) and was statistically significant for avoidance (20.8% vs 9.9% severe, p = 0.034). CONCLUSIONS: This pilot demonstrated that compliance was high with blood tests performed every four months for ovarian cancer surveillance. Moreover, ROCA women had lower stress scores over time than SOC women. Given the lack of clinical utility and poor compliance shown with traditional ultrasound and CA125 tests, further investigation is warranted of longitudinal biomarker surveillance for early detection of ovarian cancer.

Sexual function, menopausal symptoms, depression and cancer worry in women with BRCA mutations.

OBJECTIVES: Assess sexual function, menopausal symptoms, and depression in women with BRCA mutations associated with oophorectomy and menopause status. METHODS: Women age 40 and older with BRCA mutations completed a questionnaire with validated measures of sexual activity, menopausal symptoms, depression, and cancer worry. These measures were compared between those with intact ovaries and those who had undergone pre- or post-menopausal risk-reducing salpingo-oophorectomy (RRSO). RESULTS: Of the 244 women, 21 had intact ovaries and 223 had undergone RRSO. Women with intact ovaries had less menopausal symptoms (Menopausal Symptom Checklist (MSCL) score 14 versus 23, P = .01) but more cancer worry than women who had undergone RRSO (median Cancer Worry Scale (CWS) score 5 versus 4, P < .0001) with no significant difference in sexual activity or function. Compared with women with postmenopausal RRSO, women with premenopausal RRSO were more likely to be sexually active (56.3% versus 42.0%, P =.04) but had similar sexual functioning, including frequency, pleasure and discomfort. Women with premenopausal RRSO were also more likely to report menopausal symptoms (MSCL score 26 versus 19, P = .04) and depression (PHQ-8 score 4 versus 2, P < .001). Factors associated with sexual activity included younger age, lower BMI, living with a partner, and lower depression scores. Higher current depression score was associated with history of depression and more menopausal symptoms. CONCLUSIONS: Risk-reducing surgery decreases cancer risk and worry in women with BRCA mutations. Among women undergoing oophorectomy, factors such as age and history of depression were related to reduced sexual activity and increased depression, but menopausal status was not related.

Question 5: Magnesium Sulphate for Acute Asthma in children.

Most children who present to the emergency department with acute asthma, respond well to inhaled ß2-agonists (spacer or nebuliser), oxygen (if required) and systemic steroids. Guidelines across the world agree on this simple, straight forward evidenced based approach. In children with more severe asthma attacks and those who do not respond to initial treatment, the evidence base for the secondary level treatment is less clear. Many regimens exist for the next step. Intravenous Magnesium Sulphate (MgSO4) is now used frequently in these situations and some centres are starting to use nebulized MgSO4 as part of the initial maximal inhaled therapy options. This paper examines the role of MgSO4 in acute asthma in children. It focusses on how MgSO4 might work, what are the current recommendations for use and then what is the current evidence base to support its use. We have presented the evidence for the use of both nebulized and intravenous MgSO4. At the end of the paper we have suggested future directions for research in this area. Our aim is to present a synthesis of the current role of MgSO4 in the management of an acute asthma attack.

Clinical characteristics and outcomes in elderly women with BRCA1 and BRCA2 mutations.

OBJECTIVE: Describe clinical characteristics and risk reducing strategies utilized among women with a BRCA mutation who lived to age 75 and above. METHODS: A retrospective study of women with BRCA mutations identified from 1995 to 2015 in a California health care system. From a database of 1189 women, 69 participants were identified who lived to age 75 or older. Demographic and clinical characteristics were recorded, as well as cancer history and risk-reducing strategies utilized. Descriptive and bivariate analyses were used to analyze the cohort. RESULTS: The median age of the cohort at study entry was 78 (IQR: 76-84) and the median age at time of genetic testing was 73 (IQR 68-79). Fifty (72%) women had a prior history of breast cancer and 27 (39%) had a history of ovarian cancer. Three of 19 (16%) women with no history of breast cancer elected to undergo a risk-reducing mastectomy (RRM) after their positive genetic test. Among 30 women with ovaries still in place, 14 (47%) underwent a risk-reducing salpingo-oophorectomy (RRSO); six were age 70 or older at the time of surgery. Four (6%) women in the cohort developed BRCA-related cancer after testing, one developed breast cancer and three developed pancreatic cancer. CONCLUSIONS: Most women with BRCA mutations surviving beyond age 75 received their genetic test result at an older age and had a history of BRCA-related cancer. Women continued surveillance and risk reducing surgeries at an older age. Pancreatic cancer was the most common new cancer diagnosed in older BRCA mutation carriers.

Lower Extremity Peripheral Artery Disease: Diagnosis and Treatment.

Lower extremity peripheral artery disease (PAD) affects 12% to 20% of Americans 60 years and older. The most significant risk factors for PAD are hyperlipidemia, hypertension, diabetes mellitus, chronic kidney disease, and smoking; the presence of three or more factors confers a 10-fold increase in PAD risk. Intermittent claudication is the hallmark of atherosclerotic lower extremity PAD, but only about 10% of patients with PAD experience intermittent claudication. A variety of leg symptoms that differ from classic claudication affects 50% of patients, and 40% have no leg symptoms at all. Current guidelines recommend resting ankle-brachial index (ABI) testing for patients with history or examination findings suggesting PAD. Patients with symptoms of PAD but a normal resting ABI can be further evaluated with exercise ABI testing. Routine ABI screening for those not at increased risk of PAD is not recommended. Treatment of PAD includes lifestyle modifications-including smoking cessation and supervised exercise therapy-plus secondary prevention medications, including antiplatelet therapy, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins. Surgical revascularization should be considered for patients with lifestyle-limiting claudication who have an inadequate response to the aforementioned therapies. Patients with acute or limb-threatening limb ischemia should be referred immediately to a vascular surgeon.

Bone health and SATB2-associated syndrome.

SATB2-associated syndrome (SAS) is a rare disorder caused by alterations in the special AT-rich sequence-binding protein 2 (SATB2). Skeletal abnormalities such as tibial bowing, osteomalacia, osteopenia or osteoporosis have been reported suggesting a higher frequency of skeletal complications in SAS. The optimal timing, necessity, and methodology for routine assessment of bone health in individuals with SAS, however, remain unclear. We report molecular and phenotypic features of 7 individuals with SAS documented to have low bone mineral density (BMD) ascertained by dual-energy X-ray absorptiometry (DXA), often preceded by tibial bowing. The lowest BMD Z-scores ranged -2.3 to -5.6. In 4 individuals, total alkaline phosphatase levels were elevated (2 with elevated bone fraction) around the time of low BMD documentation. A clinically significant fracture history and a diagnosis of pediatric osteoporosis were present in 4 individuals. Pamidronate treatment in 2 children improved BMD. In conclusion, low BMD, fractures, and tibial bowing are relatively common skeletal complications in individuals with SAS. DXA is a useful tool when evaluating a child with SAS suspected to have low BMD and the results might alter clinical management.

Risk of cardiovascular disease in women with BRCA1 and BRCA2 mutations.

OBJECTIVE: Estimate the prevalence of cardiovascular disease risk factors and endpoints in women with BRCA mutations. METHODS: Women, age 40 and older, with BRCA mutations identified in Kaiser Permanente Northern California completed a questionnaire and underwent a lipid and fasting glucose panel. Bivariable analysis of clinical and demographic factors was performed. The Atherosclerotic Cardiovascular Disease (ASCVD) calculator was used to predict 10-year risk of a cardiovascular event. RESULTS: Of the 233 women, 19 women had intact ovaries (median age 56.0) and 214 had undergone risk-reducing salpingo-oophorectomy (RRSO). Among the 108 women with RRSO under age 50 (median age 51.0), compared to the 106 women who had RRSO at or over age 50 (median age 63.5) 6.5% vs 10.4% reported diabetes (p = 0.30), 23.2% versus 28.3% had elevated fasting blood glucose (p = 0.39), 21.3% versus 34.0% reported hypertension (p = 0.04) with median systolic blood pressure of 118 mmHg versus 125.5 mmHg (p < 0.009), 25% versus 32% reported hyperlipidemia (p = 0.40), and 42% versus 49% had any abnormal lipid test (p = 0.28). An elevated 10-year ASCVD risk of over 10% was seen in 6.1% versus 24.8% respectively (p = 0.0001). CONCLUSION: Women who underwent RRSO at age of 50 and over, had higher ASCVD 10-year risk than women who underwent RRSO at younger ages most likely owing to older age at study entry. The ASCVD risks for women with BRCA mutation who had RRSO did not suggest increased risk associated with being a BRCA mutation carrier.

Bone loss in women with BRCA1 and BRCA2 mutations.

OBJECTIVE: Estimate the prevalence and identify risk factors for bone loss in women with BRCA mutations. METHODS: Women, age 40 and older, with BRCA mutations identified from the Breast Cancer Surveillance database at Kaiser Permanente Northern California were invited to participate and undergo a dual-energy x-ray absorptiometry scan to assess for bone loss (osteopenia or osteoporosis). Multivariable logistic regression analysis was performed to assess clinical factors associated with bone loss. RESULTS: Of the 238 women in the final cohort, 20 women had intact ovaries (median age 54.5years) and 218 had undergone risk reducing salpingo-oophorectomy (RRSO) (median age 57). The prevalence of bone loss was 55% in the no RRSO group and 72.5% in the RRSO group (P=0.10). In multivariable analysis, only higher body mass index (OR 0.6 per 5kg/m2, 95% CI: 0.4-0.7) and nonwhite race compared to white (OR 0.5, 95% CI: 0.2-0.9) were protective for bone loss while older age (OR 1.5 per 10years, 95% CI: 1.1-2.1) and selective estrogen receptor modulator use (3.1, 95% CI: 1.2-10.1) were associated with increased odds of bone loss. Among women with RRSO, bone loss was more frequent in women who had postmenopausal (n=106) compared to women who had premenopausal RRSO (n=112), (82.1% and 63.4% respectively, P=0.002). In multivariable analysis, only BMI was protective of bone loss (OR 0.5, 95%, CI: 0.4-0.7) but neither age nor menopausal status at RRSO were associated with bone loss. CONCLUSION: Bone loss is common in women with BRCA mutations who undergo RRSO.