Dietary supplementation with a wheat polar lipid complex improves skin conditions in women with dry skin and mild-to-moderate skin aging.

BACKGROUND: Aging, menopause, and seasonal changes alter the lipid composition of the outermost skin layer, the stratum corneum, resulting in dry and itchy skin. AIMS: This clinical trial aimed at evaluating the effects of a wheat polar lipid complex (WPLC) on skin characteristics in women showing dry and wrinkled skin, investigating its effects in a subgroup of postmenopausal women, and assessing if benefits were maintained after supplementation. METHODS: Seventy-two women with dry and wrinkled skin were recruited in this double-blind, randomized, parallel-group study, and allocated to three groups of 24 subjects, each including at least 10 postmenopausal women. For 56 days, subjects consumed the WPLC supplement (oil or powder), or the placebo. Skin hydration, transepidermal water loss (TEWL), elasticity, and profilometry were evaluated at baseline, after 14, 28, and 56 days of supplementation, and 56 days after the end of supplementation. Additionally, a lipidomic analysis was performed to examine changes in superficial skin layers over 56 days. RESULTS: Dietary supplementation with WPLC rapidly improved all parameters. It increased skin hydration, smoothness, and elasticity while decreasing TEWL, roughness, and wrinkle depth after only 14 days of supplementation. These effects were also observed in the subpopulation of postmenopausal women and led to an improved self-perception of skin. For all the parameters, outcomes were not maintained after the supplementation was stopped. The lipidomic analysis revealed 10 compounds evolving over the 56 days of WPLC supplementation. CONCLUSION: WPLC supplementation improved skin hydration, smoothness, elasticity, and wrinkledness within 14 days and, as expected, did not last after supplementation was stopped.

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.

Breast cancer risk in BRCA mutation carriers after diagnosis of epithelial ovarian cancer is lower than in carriers without ovarian cancer.

OBJECTIVE: Evaluate the incidence and characteristics of breast cancers (BC) diagnosed following an epithelial ovarian cancer (EOC) diagnosis in women with pathogenic BRCA mutations. METHODS: Retrospective cohort study of all women in an integrated healthcare system with BRCA mutations diagnosed with EOC from 1/1/1997-12/31/2018. Primary outcome was rate of subsequent BC diagnosis. Secondary outcomes included risk factors associated with development of BC, median time to detection following EOC, and method of detection. RESULTS: There were 284 women with BRCA-associated EOC identified. Fifty-two women had risk-reducing mastectomy and were excluded. Of the 232 eligible women with a median follow-up of 5.6 years, 33 (14%) women were diagnosed with BC following EOC: 27 (11%) new cases and 6 (3%) recurrences. Twelve (36%) cases of BC were detected on screening mammogram, 4 (12%) on screening MRI, and 9 (27%) on work-up after presenting with a palpable lump. Twenty-nine (87%) were early stage (0-II) disease. Median interval from EOC to BC diagnosis was 80 months (IQR 32, 134) for new and 63 months (IQR 21, 94) for recurrent BCs. There was one death from breast cancer while 12 women died of ovarian cancer. CONCLUSIONS: Most BC following BRCA-associated EOC is early stage and not associated with mortality. Given BC rate similar to general population and median diagnosis at 6.6 years following ovarian cancer, increased BC screening may not be warranted in the early years after EOC diagnosis.

Barrier disruption, dehydration and inflammation: Investigation of the vicious circle underlying dry skin.

OBJECTIVE: Many endogenous or exogenous factors, isolated or combined, can trigger dry skin disorder, leading to a water/lipids-depleted stratum corneum concomitant with uncomfortable rough and scaly skin surface. In a defensive reaction, the alteration of the skin barrier stimulates the production of cytokines to initiate homeostasis restoration but this can also induce an inflammatory response that further weakens the barrier. The two phenomena intertwining one another lead to the creation of a vicious circle, here called Inflamm'dryness, that maintains dry skin state. It is thus very important to investigate biological mechanisms involved in Inflamm'dryness to better manage dry skin. METHODS: A 3D model mimicking dry skin has been developed. Adjustment of tape stripping level allowed to reproduce skin barrier alterations and resulting inflammation involved in dry skin. The effect of Helichrysum stoechas extract on this downward spiral was then investigated to validate the concept. RESULTS: Tape-stripping permitted to successively remove the cell layers of the stratum corneum: the barrier function was altered and skin was inflamed creating a vicious circle, mimicking very dry skin prone to Inflamm'dryness. Helichrysum stoechas extract was not only able to resolve inflammation but also to reverse concurrently adverse tape-stripping effects and imparted significant structural and functional recovery of the barrier (e.g. on NMF and ceramides levels, TEWL, tissue organization). CONCLUSION: This 3D model reproduces Inflamm'dryness vicious circle present in dry skin and highlights the importance of breaking this process to improve dry skin conditions. Helichrysum stoechas extract is a promising active ingredient for the management of dry skin.

OBJECTIF: De nombreux facteurs endogènes ou exogènes, isoles ou combines, peuvent être à l'origine de sècheresse cutanée, conduisant à une peau en manque d'eau et de lipides : la peau tiraille, présente parfois un l'aspect rugueux (voire la présence de squames) et des sensations d'inconfort. Cette altération de la barrière cutanée induit la production de cytokines permettant la restauration de l'homéostasie de la peau mais induisant également une réponse inflammatoire fragilisant davantage la barrière cutanée. Ces deux phénomènes conduisent à la création d'un cercle vicieux, l'Inflamm'dryness, qui entretient l'état de sécheresse de la peau. Il semble donc important d'étudier les mécanismes biologiques impliqués dans le phénomène d'Inflamm'dryness afin de mieux prendre soin des peaux sèches. MÉTHODES: Un modèle 3D mimant une peau sèche a été développé. Un ajustement du nombre de tape-strippings a été nécessaire afin de reproduire les défauts de barrière ainsi que de l'inflammation caractéristiques des peaux sèches. L'effet d'un extrait d'Helichrysum stoechas sur cette spirale négative a ensuite été étudié pour valider le concept. RÉSULTATS: L'étape de tape-stripping a permis de retirer successivement les couches superficielles du stratum corneum: la fonction barrière est altérée et la peau est enflammée créant un cercle vicieux, mimant une peau très sèche sujette à l'Inflamm'dryness. L'extrait d'Helichrysum stoechas est non seulement capable de résoudre l'inflammation, mais également de restaurer la fonction barrière de la peau (quantités de NMF et de céramides, la perte insensible en eau, organisation des tissus…). CONCLUSION: Ce modèle 3D reproduit le cercle vicieux de l'Inflamm'dryness caractéristique des peaux sèches et met en évidence l'importance de rompre ce processus afin de remédier à la sécheresse cutanée. L'extrait d'Helichrysum stoechas développé est un actif prometteur pour le soin des peaux sèches.

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.

Using a resident-led patient safety quality council to educate future QI leaders.

Resident-led councils represent an important initiative to involve trainees in patient safety, but little is known about how to create and sustain one of these councils. We evaluated the impact of a resident-led patient safety council in an internal medicine residency program. We assessed change in resident perception of safety issues over 3 years, scholarship activities, and behavioral choices to participate or lead patient safety activities after residency.The Stony Brook Internal Medicine Residency Program formed the Patient Safety and Quality Council (PSQC) in 2014, consisting of fifteen peer-nominated residents serving a three-year term. Surveys were distributed annually from 2014 to 2017 to measure resident council members' perception of patient safety. The number of safety-related abstract/publications were tracked during and one year after graduation. Additionally, graduates from the council were surveyed to assess the influence of the council on post residency involvement and leadership in safety activities.A total of 18 residents have participated in the council from 2014 to 2017. Overall, resident perception of safety culture improved. A total of 17/18 (94%) PSQC resident members demonstrated scholarship activities in safety during residency: 8/18 (44%) were engaged in an independent Quality Improvement (QI) project, 5/18 (27%) achieved a quality improvement leadership role post residency. A total of 15 of 18 (83%) recent graduates suggest that involvement with the safety council during residency fostered future involvement in patient safety.Implementation of a resident-led safety council can help to improve the safety culture, generate scholarly activities, and encourage continued participation in patient safety after graduation.

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.

Salpingectomy for Sterilization: Change in Practice in a Large Integrated Health Care System, 2011-2016.

OBJECTIVE: To evaluate the utilization rate of salpingectomy for cesarean deliveries and postpartum and interval tubal sterilization procedures. METHODS: This is a retrospective cohort study using the electronic medical record to identify women older than 18 years of age undergoing surgical sterilization from June 2011 to May 2016 in an integrated health care system. The primary objective is to describe the change in utilization rate of salpingectomy for tubal sterilization procedures over time and after a systemwide practice recommendation was issued in 2013. Rates of salpingectomy and tubal occlusion were calculated for each of the five 1-year intervals in the study. Secondary outcomes included blood loss, operating time, length of stay, readmission, and emergency department visits. RESULTS: A total of 10,741 tubal sterilization procedures were identified. There was an increase in salpingectomies from 0.4% (8/1,938; 95% CI 0.2-0.8) to 35.5% (902/2,538; 95% CI 33.7-37.4) of tubal sterilization procedures performed over the study period (test for trend, P<.001). Salpingectomy instead of tubal occlusion increased at cesarean delivery from 0.1% (1/1,141; 95% CI 0.0-0.5) to 9.2% (125/1,354; 95% CI 7.8-10.9) (test for trend, P<.001); postpartum from 0% (0/124; 95% CI 0.0-3.0) to 4.5% (9/201; 95% CI 2.4-8.3) (test for trend, P=.003); and as an interval (nonpartum) tubal sterilization procedure from 1% (7/673; 95% CI 0.5-2.1) to 78% (768/983; 95% CI 75.4-80.6) (test for trend, P<.001). Median operative minutes was increased from 52 (95% CI 51-52) to 61.5 (95% CI 57-64), from 33 (95% CI 32-34) to 50 (95% CI 35-64), and from 30 (95% CI 29-30) to 33 (95% CI 32-33), respectively, for salpingectomy compared with tubal occlusion at cesarean delivery and postpartum and interval sterilization. Median blood loss was similar for salpingectomy and tubal occlusion at cesarean delivery (660 mL; 95% CI 600-700 mL compared with 700 mL; 95% CI 680-700 mL) and interval sterilization (both 5 mL; 95% CI 5-5 mL) but was more for salpingectomy postpartum (250 mL; 95% CI 200-500 mL compared with 200 mL; 95% CI 200-200 mL). CONCLUSION: There was a significant increase in salpingectomy for sterilization from June 2011 to May 2016. In the final year of the study, salpingectomy accounted for 78% of interval laparoscopic tubal sterilization procedures and 9% of intrapartum and postpartum procedures.

Does Surgical Teaching Take Time? Resident Participation in Minimally Invasive Hysterectomy for Endometrial Cancer.

STUDY OBJECTIVE: To determine the association between resident involvement and operative time for minimally invasive surgery (MIS) for endometrial cancer. DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: An integrated health care system in Northern California. PATIENTS: A total of 1433 women who underwent MIS for endometrial cancer and endometrial intraepithelial neoplasia from January 2009 to January 2014. INTERVENTIONS: Resident participation in 430 of 688 laparoscopic cases (62%) and 341 of 745 robotic cases (46%). MEASUREMENTS AND MAIN RESULTS: The primary outcome was the impact of resident involvement on surgical time. When residents were involved in laparoscopic and robotic surgery, there was an increase of 61 minutes (median operative time, 186 vs 125 minutes; p < .001) and 31 minutes (median operative time, 165 vs 134 minutes; p < .001), respectively. Resident participation was associated with increased operative times in all levels of surgical complexity from hysterectomy alone to hysterectomy with pelvic and para-aortic lymph node dissection. Resident participation was also associated with increased major intraoperative complications (3.4% vs 1.8%, p = .02) as well as major postoperative complications (6.4% vs 3.8%, p = .003). CONCLUSION: The presence of a resident was associated with a 32% increase in operative time for minimally invasive cases in gynecologic oncology for endometrial cancer. Because of the retrospective nature, we cannot infer causality of operative outcomes because residents were also involved in more high-risk patients and complex cases. For health care systems using surgical metrics, there may be a need to allocate more time for resident involvement.

Classification of Postoperative Complications in Robotic-assisted Compared With Laparoscopic Hysterectomy for Endometrial Cancer.

STUDY OBJECTIVE: To compare intraoperative and postoperative surgical complications and outcomes between robotic-assisted and laparoscopic surgical management of endometrial cancer using a standardized classification system. DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: An integrated health care system in Northern California. PATIENTS: One thousand four hundred thirty-three women with a diagnosis of complex atypical hyperplasia and endometrial cancer managed by minimally invasive hysterectomy and surgical staging from January 2009 to January 2014. INTERVENTIONS: Seven hundred forty-five robotic-assisted and 688 laparoscopic hysterectomies were evaluated. MEASUREMENTS AND MAIN RESULTS: The primary outcome was intraoperative and postoperative complications within 30 days. All complications were categorized using the Clavien-Dindo classification system. Secondary outcomes included total operative time, estimated blood loss, transfusion rates, length of stay, conversion to laparotomy, and number of pelvic and para-aortic lymph nodes retrieved. The modality of hysterectomy was not associated with either overall intraoperative complications or major postoperative complications (p > .1). However, there were significantly fewer minor postoperative complications with robotic surgery (16.6% vs 25.6%, p < .01). Statistically significant differences were also noted in the following outcomes: decreased median operative time, length of stay, estimated blood loss, conversion to laparotomy, and median number of lymph nodes retrieved in the robotic group when compared with the laparoscopic group. CONCLUSION: There was no difference in the rate of major complication between robotic and laparoscopic surgery using the Clavien-Dindo system of categorizing surgical complications; however, there were clinically significant differences favoring the robotic approach, including a lower rate of minor complications and conversion rate to laparotomy.

Experience With Opportunistic Salpingectomy in a Large, Community-Based Health System in the United States.

OBJECTIVE: To evaluate the trend in uptake of salpingectomy at the time of hysterectomy and assess physicians' attitudes toward the practice. METHODS: This was a retrospective cohort study using the electronic medical record to identify women 18 years of age or older undergoing hysterectomy from June 2011 to May 2014 in a large integrated health care delivery system. The primary outcome was the change in rate of opportunistic salpingectomy over time and after a systemwide practice recommendation was issued in May 2013. Secondary outcomes included data on blood loss, operating time, and length of stay. RESULTS: Of the 12,143 hysterectomies performed over the 3-year study period, 7,498 were performed without oophorectomy. There was a statistically significant rise in rate of salpingectomy over time from 14.7% for June 2011 to May 2012 to 44.6% from June 2012 to May 2013 and to 72.7% from June 2013 to May 2014 (P<.001). Sixty-one percent of laparoscopic hysterectomies were performed with salpingectomy, whereas only 25% of abdominal and 17% of vaginal hysterectomies had salpingectomies. Median estimated blood loss was lower in the salpingectomy group, 100 compared with 150 mL (P<.01). There was a significantly shorter median operating time (147 compared with 154 minutes, P=.002) for laparoscopic hysterectomy with bilateral salpingectomy compared with laparoscopic hysterectomy alone. CONCLUSION: Rates of salpingectomy increased significantly over time, consistent with the high reported acceptance rate reported by health care providers and highlighting the importance of physician education to improve compliance with risk-reducing clinical strategies.

Effect of leukocyte telomere length on total and regional brain volumes in a large population-based cohort.

IMPORTANCE: Telomere length has been associated with dementia and psychological stress, but its relationship with human brain size is unknown. OBJECTIVE: To determine if peripheral blood telomere length is associated with brain volume. DESIGN, SETTING, AND PARTICIPANTS: Peripheral blood leukocyte telomere length and brain volumes were measured for 1960 individuals in the Dallas Heart Study, a population-based, probability sample of Dallas County, Texas, residents, with a median (25th-75th percentile) age of 50 (42-58) years. Global and 48 regional brain volumes were assessed from the automated analysis of magnetic resonance imaging. MAIN OUTCOMES AND MEASURES: Telomere length and global and regional brain volumes. RESULTS: Leukocyte telomere length was associated with total cerebral volume (ß [SE], 0.06 [0.01], P <.001) including white and cortical gray matter volume (ß [SE], 0.04 [0.01], P = .002; ß [SE], 0.07 [0.02], P <.001, respectively), independent of age, sex, ethnicity, and total intracranial volume. While age was associated with the size of most subsegmental regions of the cerebral cortex, telomere length was associated with certain subsegmental regions. Compared with age, telomere length (TL) explained a sizeable proportion of the variance in volume of the hippocampus, amygdala, and inferior temporal region (hippocampus: ßTL [SE], 0.08 [0.02], R2, 0.91% vs ßage [SE], -0.16 [0.02], R2, 3.80%; amygdala: ßTL [SE], 0.08 [0.02], R2, 0.78% vs ßage [SE],-0.19 [0.02], R2,4.63%; inferior temporal: ßTL [SE], 0.07 [0.02], R2, 0.92% vs ßage [SE], -0.14 [0.02], R2, 3.98%) (P <.001 for all). The association of telomere length and the size of the inferior and superior parietal, hippocampus, and fusiform regions was stronger in individuals older than 50 years than younger individuals (inferior parietal: ß>50 [SE], 0.13 [0.03], P <.001 vs ß≤50 [SE], 0.02 [0.02], P = .51, P for interaction = .001; superior parietal: ß>50 [SE], 0.11 [0.03], P <.001 vs ß≤50 [SE], 0.01 [0.02], P = .71, P for interaction = .004; hippocampus: ß>50 [SE], 0.10 [0.03], P = .004 vs ß≤50 [SE], 0.05 [0.02], P = .07, P for interaction = .04; fusiform: ß>50 [SE], 0.09 [0.03], P = .002, ß≤50 [SE], 0.03 [0.02], P = .31, P for interaction = .03). The volume of the hippocampus, amygdala, superior and inferior temporal, precuneus, lateral orbitofrontal, posterior cingulate, thalamus and ventral diencephalon were independently associated with telomere length after adjustment for all covariates (age, gender, ethnicity, total intracranial volume, body mass index, blood pressure, diabetes, smoking status, and APOE genotype). CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first population-based study to date to evaluate telomere length as an independent predictor of global and regional brain size. Future studies are needed to determine how telomere length and anatomic structural changes are related to cognitive function, dementia, and psychological disease.

Risk management options elected by women after testing positive for a BRCA mutation.

OBJECTIVE: To assess the uptake of risk-reducing options for the management of ovarian and breast cancer risk in BRCA mutation carriers in a large community based integrated health system in Northern California. METHODS: A retrospective cohort of deleterious BRCA mutation carriers (1995-2012) was evaluated for consistency with NCCN guidelines for risk reducing salpingo-oophorectomy (RRSO) by age of 35-40, risk reducing mastectomy (RRM), as well as surveillance practices, including pelvic ultrasound, CA 125, mammogram, and breast MRI. Secondary outcomes included the use of chemoprevention and hormone replacement. RESULTS: Of the 305 eligible women, 170 were BRCA1 positive, and 135 were BRCA2 positive. Seventy four percent underwent RRSO with only 17% under age 40, while 44% underwent RRM. The median time from the test to both RRSO and RRM was 6 months. In the first year after BRCA diagnosis, 45% underwent a pelvic ultrasound, dropping to 2.3% by year 5. In year 1, 47% had a CA 125, dropping to 2% by year 5. The number of women undergoing annual MRI and mammogram fell similarly over time. Sixteen percent of BRCA carriers used oral contraceptives (OCPs) and only one patient used tamoxifen for chemoprevention. CONCLUSION: Uptake of RRSO in BRCA carriers in a population based health system is high, however the majority of women do not have RRSO by the NCCN recommended age. Compliance with surveillance is low and rapidly declines even 1 year out from testing. Attention needs to be focused on the earlier identification of BRCA mutation carriers with consolidated and standardized care to improve risk reduction.