Therapies for Parkinson's disease and the gut microbiome: evidence for bidirectional connection.

The gut brain axis (GBA), a bidirectional communication pathway has often been linked to health and disease, and gut microbiota (GM), a key component of this pathway shown to be altered in Parkinson's disease (PD), are suggested to contribute to the pathogenesis of PD. There are few studies that report the impact of oral medication therapy on GM, however, there are even fewer studies that discuss the impact of other treatments such as device assisted therapies (DAT) including deep brain stimulation (DBS), levodopa-carbidopa intestinal gel infusion (LCIG) and photobiomodulation (PBM) and how these might impact GM. Here, we review the literature and summarize findings of the potential contributions of GM to the heterogenous clinical response to pharmaceutical therapies among individuals with PD. We also discuss the potential interactions between the GM and DATs such as DBS and LCIG and present evidence for alterations in GM in response to DATs. Given the complexity and highly individual nature of the GM of patients with PD and the potential influence that other external factors such as diet, lifestyle, medications, stage of the disease and other comorbidities, further investigations into the response of GM to therapies are worthy of future study in prospective, controlled trials as well as medication naïve individuals. Such detailed studies will help us further comprehend the relationship between GM in PD patients, and will help investigate the potential of targeting GM associated changes as a treatment avenue for PD.

Identity-related experiences of Asian American trainees in gynecologic oncology.

Background: Anti-Asian violence increased during the COVID-19 pandemic. Asian American/Pacific Islanders (AAPI) represent a diverse population experiencing a long history of stereotyping and exclusionism; however, this group is often left out of diversity/inclusion conversations. In academic medicine, AAPI are under-represented in leadership. We characterized the personal/professional experiences of AAPI gynecologic oncology trainees and assessed the impact of a virtual panel discussion with leaders in the field. Methods: An anonymous survey was disseminated online to trainees in/interested in gynecologic oncology fellowship who identified as AAPI, using modified snowball sampling. A virtual session with AAPI leaders in gynecologic oncology discussed themes emerging from survey responses. Session attendees completed an anonymous follow-up survey. Results were assessed quantitatively and qualitatively. Results: 44/59 (75%) respondents participated in the pre-survey; 23 (39%) participated in the virtual session. All session participants (23/23, 100%) completed the post-session survey. Participants reported increased identity-related thoughts with the COVID-19 pandemic (88% during, 61% prior). Sixty-eight percent reported that identity-related thoughts/awareness changed during the pandemic. Presence of AAPI colleagues was associated with higher perceived identity-related support from their department. Of those without AAPI coworkers, none (0%) felt 'moderately' or 'extremely well supported.' Qualitative analysis demonstrated that the panel discussion created a sense of community and encouragement, combating previously reported isolation and self-consciousness. Participants reported more connection with their heritage and identified more personal/professional topics that might be related to their cultural backgrounds. Discussion: This intervention demonstrates the opportunity to provide a supportive network for mentorship and professional development in a culturally inclusive way.

ERAS implementation in an urban patient population undergoing gynecologic surgery.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols improve outcomes. We investigated ERAS implementation in a population with comorbid conditions, inadequate insurance, and barriers to healthcare undergoing gynecologic surgery. OBJECTIVE: To investigate ERAS implementation in publicly insured/uninsured patients undergoing gynecologic surgery on hospital length of stay (LOS), 30-day hospital readmission rates, opioid administration, and pain scores. STUDY DESIGN: Data were obtained pre- and post-ERAS implementation. Patients undergoing gynecologic surgery with private insurance, public insurance, and uninsured were included (N = 589). LOS, readmission <30 days, opioid administration, and pain scores were assessed. RESULTS: Implementation of ERAS led to shorter LOS 1.75 vs. 1.49 days (p = 0.008). Average pain scores decreased from 3.07 pre-ERAS vs. 2.47 post-ERAS (p = <0.001). Opioid use decreased for ERAS patients (67.22 vs. 33.18, p = <0.001). Hospital readmission rates were unchanged from 8.2% pre-ERAS vs. 10.3% post-ERAS (p = 0.392). CONCLUSIONS: ERAS decreased pain scores and opioid use without increasing LOS or readmissions.

Equity in visual representation of vulvar conditions in major gynecology textbooks.

OBJECTIVES: To evaluate images of vulvar conditions (VCs) in major gynecologic textbooks and describe the skin tone representation. METHODS: Images of VCs in gynecological textbooks for medical students, obstetrics and gynecology (OBG) residents, and fellows were compiled. Texts were categorized into education levels (medical student, resident, or fellow) and selected based on the recommendations of OBG attendings and fellows at LSUHSCNew Orleans. Skin tones were scored according to the Fitzpatrick Scale (FS) and categorized as benign, infectious, inflammatory, and dysplasia/cancerous. Publishing and primary author demographics were collected. Proportional odds regression (POR) predicted FS based on image pathologies and book titles. RESULTS: Of 512 images selected from 21 textbooks, 77.0% [N = 395] were lighter skin tones (FS I-III). VCs were represented by the darkest skin tone (FS of VI) in 19.6% of images in texts targeting residents, compared to 8.5% and 4.5% in fellow and student textbooks, respectively (p <0.001). Compared to a cornerstone surgical atlas, the pediatric and adolescent gynecology text consisted of lighter skin tones. A prominent general gynecology text used darker skin tones. Images of infectious conditions were more likely to be darker skin tones than other VCs (p = 0.010). CONCLUSIONS: Most textbook images of VCs represent lighter skin tones, and women with darker skin are more underrepresented in texts geared at fellows and students. Inadequate exposure to the appearance of VCs on darker skin promotes and propagates racial inequities in healthcare. Medical textbooks should present visually diverse images of vulvar pathologies to train physicians to be well versed in caring for patients of all skin tones.

The Current and Future States of Screening in Gynecologic Cancers.

Gynecologic cancers contribute to a significant portion of cancer morbidity and mortality among women in the United States and across the globe. This article provides a comprehensive review of current screening guidelines and novel techniques that have promise in the prevention and early detection of gynecologic cancers in the future. The authors anticipate a move toward less invasive testing modalities, use of cancer biomarkers, and the prevention and treatment of high-risk factors such as human papilloma virus infection and obesity.

International Gynaecological Cancer Society (IGCS) 2020 Annual Global Meeting: Twitter activity analysis.

OBJECTIVES: Twitter is the most frequently used social media platform by healthcare practitioners, at medical conferences. This study aimed to analyze Twitter conversations during the virtual International Gynecological Cancer Society 2020 conference to understand the interactions between Twitter users related to the conference. METHODS: Tweets using the hashtag '#IGCS2020' were searched using the Twitter Search Application Programming Interface (API) during the period 10-13 September 2020. NodeXL Pro was used to retrieve data. The Clauset-Newman-Moore cluster algorithm clustered users into different groups or 'clusters' based on how users interacted. RESULTS: There were 2009 registrants for the virtual IGCS 2020 conference. The total number of users within the network was 168, and there were 880 edges connecting users. Five types of edges were identified as follows: 'replies to' (n=18), 'mentions' (n=221), 'mentions in retweets' (n=375), retweets (n=198), and tweets (n=68). The most influential account was that of the IGCS account itself (@IGCSociety). The overall network shape resembled a community where distinct groups formed within the network. Our current analyses demonstrated that less than 10% of the total members interacted on Twitter. CONCLUSION: This study identified the most influential Twitter users within the '#IGCS2020' community. he results also confirmed the community network shape of the #IGCS2020 hashtag and found that the most frequent co-related words were 'ovarian' and 'cancer' (n=39).

Technique for inguino-femoral lymph node dissection in vulvar cancer: an international survey.

BACKGROUND: Vulvar cancer is a rare disease and despite broad adoption of sentinel lymph node mapping to assess groin metastases, inguino-femoral lymph node dissection still plays a role in the management of this disease. Inguino-femoral lymph node dissection is associated with high morbidity, and limited research exists to guide the best surgical approach. OBJECTIVE: To determine international practice patterns in key aspects of the inguino-femoral lymph node dissection technique and provide data to guide future research. METHODS: A survey addressing six key domains of practice patterns in performing inguino-femoral lymph node dissection was distributed internationally to gynecologic oncology surgeons between April and October 2020. The survey was distributed using the British Gynecological Cancer Society, the Society of Gynecologic Oncology, authors' direct links, the UK Audit and Research in Gynecology Oncology group, and Twitter. RESULTS: A total of 259 responses were received from 18 countries. The majority (236/259, 91.1%) of respondents reported performing a modified oblique incision, routinely dissecting the superficial and deep inguino-femoral lymph nodes (137/185, 74.1%) with sparing of the saphenous vein (227/258, 88%). Most respondents did not routinely use compression dressings/underwear (169/252 (67.1%), used prophylactic antibiotics at the time of surgery only (167/257, 65%), and closed the skin with sutures (192 74.4%). Also, a drain is placed at the time of surgery by 243/259 (93.8%) surgeons, with most practitioners (144/243, 59.3%) waiting for drainage to be less than 30-50 mL in 24 hours before removal; most respondents (66.3%) routinely discharge patients with drain(s) in situ. CONCLUSION: Our study showed that most surgeons perform a modified oblique incision, dissect the superficial and deep inguino-femoral lymph nodes, and spare the saphenous vein when performing groin lymphadenectomy. This survey has demonstrated significant variability in inguino-femoral lymph node dissection in cases of vulvar cancer among gynecologic oncology surgeons internationally.

Antioxidants Associated With Oncogenic Human Papillomavirus Infection in Women.

BACKGROUND: Human papillomavirus (HPV) infection is a major cause of cervical cancer. Studies showed the onset of HPV carcinogenesis may be induced by oxidative stress affecting the host immune system. The association between antioxidants and oncogenic HPV remains unclear. In this study, we aim to identify antioxidants associated with vaginal HPV infection in women. METHODS: The associations between the 15 antioxidants and vaginal HPV infection status (no, low-risk [LR], and high-risk [HR] HPV) were evaluated using 11 070 women who participated in the 2003-2016 National Health and Nutrition Examination Survey (NHANES). RESULTS: We identified serum albumin and 4 dietary antioxidants (vitamin A, B2, E, and folate) inversely associated with HR-HPV infection. Women with a low level of albumin (≤39 g/L) have a significantly higher risk of HR-HPV (odds ratio [OR] = 1.4, P = .009 vs >44 g/L). A Nutritional Antioxidant Score (NAS) was developed based on these 4 dietary antioxidants. The women with the lowest quartile NAS had a higher chance of HR-HPV (OR = 1.3, P = .030) and LR-HPV (OR = 1.4, P = .002) compared with the women with the highest quartile NAS. CONCLUSIONS: We identified 5 antioxidants negatively associated with vaginal HR-HPV infection in women. Our findings provide valuable insights into understanding antioxidants' impact on HPV carcinogenesis.

An Update on Screening and Prevention for Breast and Gynecological Cancers in Average and High Risk Individuals.

Breast and gynecological cancers affect almost 900,000 women and therefore most health care providers will be involved at some point in the management of women with cancer. As the prognosis of all cancers is much more favorable when diagnosed in early stages, it is imperative that all health care providers are familiar not only with current screening guidelines for the average population, but also with the identification of high risk individuals who may benefit from more intense screening as well as available interventions to prevent disease or decrease risk. The purpose of this review article is to provide relevant information to physicians and other health care providers to aid in identifying patients that are classified as "high risk" for developing breast or a gynecologic cancer, outlining what interventions exist for adequate screening and risk reduction strategies, and to provide an update on current screening guidelines for individuals at average and high risk.

Sentinel Lymph Node Ultra-staging as a Supplement for Endometrial Cancer Intraoperative Frozen Section Deficiencies.

For endometrial cancer (EC), most surgeons rely on intraoperative frozen section (IFS) to determine the risk of nodal metastasis and necessity of lymphadenectomy. IFS remains a weak link in this practice due to its susceptibility to diagnostic errors. As a less invasive alternative, sentinel lymph node (SLN) mapping and ultra-staging have gradually gained acceptance for EC. We aimed to establish the SLN success rate, negative predictive value, and whether SLNs provide useful information for cases misdiagnosed on IFS. From 2013 to 2017, 100 patients (63 low-risk and 37 high-risk EC) underwent hysterectomy, bilateral salpingo-oophorectomy, and SLN. Among them, 56 had additional pelvic lymphadenectomy. A total of 337 SLNs were obtained in 86 cases: 55 bilaterally and 31 unilaterally. The remaining 14 cases failed because of patient obesity or leiomyoma. Pathology ultra-staging detected 2 positive SLNs from 2 patients (1 with isolated tumor cells, 1 with micrometastases). One of 773 nonsentinel pelvic nodes was positive on the contralateral hemi-pelvis in a patient who was mapped unilaterally, resulting in negative predictive value of 100%. During IFS, tumor grade and/or depth of myometrial invasion was misdiagnosed in 22 cases (22%). These errors would have resulted in under-staging in 10 high-risk patients or over-staging in 4 low-risk patients. SLNs were mapped in these misestimated patients, with one revealing metastases. SLN provides invaluable information on nodal status while detecting occult metastases in cases misdiagnosed on IFS. Our findings justify the incorporation of SLN in initial surgery for EC as an offset to IFS diagnostic errors, minimizing their negative impact on patient care.

Hysterectomy at the time of risk-reducing surgery in BRCA carriers.

In this study, women at risk for BRCA were surveyed to understand their choice of prophylactic surgery and associated risk of uterine cancers. The study was conducted as an anonymous online web-based survey that assessed personal and family histories and choice of prophylactic surgery. Respondents were targeted through social media groups that bring awareness to hereditary breast and ovarian cancer. The study cohort included an international group of 601 respondents. The majority were female (99.3%), in their 40s (34.2%), and had completed college or graduate school (68.8%). 87% of respondents carry BRCA gene mutation. Of 339 respondents who underwent risk-reducing salpingo-oophorectomy (RRSO), 55.8% had a hysterectomy at time of RRSO. Most common reasons for hysterectomy at time of RRSO included: 39% provider recommendation, 27.6% personal desire, 9.7% benign indications, 1.6% cancer in uterus, 1.1% precancerous uterine lesion, and 21.1% other (N = 185). In this cohort, nine were diagnosed with uterine cancer. Three were diagnosed after risk-reducing surgery. Both patients with uterine serous carcinoma were BRCA1 carriers. Two thirds of BRCA carriers surveyed had undergone RRSO. Of these, more than half had hysterectomy at time of RRSO. One third chose to have hysterectomy based on surgeon recommendation. <1% (2 out of 258) of BRCA1 gene mutation carriers reported being diagnosed with uterine serous carcinomas. While this incidence is low, it may be an underestimate based on the limitations of this study. Additional studies are needed to select which patients will benefit from concurrent hysterectomy and RRSO.

Georgia Primary Care Providers' Knowledge of Hereditary Breast and Ovarian Cancer Syndrome.

Hereditary breast and ovarian cancer syndrome (HBOC) is an inherited condition associated with mutations in the BRCA1 or BRCA2 (BRCA) genes. Identification of individuals with HBOC requires that primary care providers understand the genetic principles required to appropriately collect family history and refer individuals for genetic evaluation. A survey was developed and administered to primary care providers in Georgia to assess their existing knowledge of HBOC and direct targeted educational efforts.We found that Georgia providers demonstrate some knowledge of basic genetic principles but were unable to consistently identify individuals at risk for HBOC. Knowledge deficits included lack of understanding of inheritance patterns and failure to recognize the significance of ovarian cancer history. Strategies for improving identification of patients with HBOC include increasing provider knowledge and integrating HBOC risk assessment tools into practice. Identification of individuals at risk is the critical first step in the process of reducing incidence of breast and ovarian cancer associated with BRCA mutations.

Genomic Analysis of Uterine Lavage Fluid Detects Early Endometrial Cancers and Reveals a Prevalent Landscape of Driver Mutations in Women without Histopathologic Evidence of Cancer: A Prospective Cross-Sectional Study.

BACKGROUND: Endometrial cancer is the most common gynecologic malignancy, and its incidence and associated mortality are increasing. Despite the immediate need to detect these cancers at an earlier stage, there is no effective screening methodology or protocol for endometrial cancer. The comprehensive, genomics-based analysis of endometrial cancer by The Cancer Genome Atlas (TCGA) revealed many of the molecular defects that define this cancer. Based on these cancer genome results, and in a prospective study, we hypothesized that the use of ultra-deep, targeted gene sequencing could detect somatic mutations in uterine lavage fluid obtained from women undergoing hysteroscopy as a means of molecular screening and diagnosis. METHODS AND FINDINGS: Uterine lavage and paired blood samples were collected and analyzed from 107 consecutive patients who were undergoing hysteroscopy and curettage for diagnostic evaluation from this single-institution study. The lavage fluid was separated into cellular and acellular fractions by centrifugation. Cellular and cell-free DNA (cfDNA) were isolated from each lavage. Two targeted next-generation sequencing (NGS) gene panels, one composed of 56 genes and the other of 12 genes, were used for ultra-deep sequencing. To rule out potential NGS-based errors, orthogonal mutation validation was performed using digital PCR and Sanger sequencing. Seven patients were diagnosed with endometrial cancer based on classic histopathologic analysis. Six of these patients had stage IA cancer, and one of these cancers was only detectable as a microscopic focus within a polyp. All seven patients were found to have significant cancer-associated gene mutations in both cell pellet and cfDNA fractions. In the four patients in whom adequate tumor sample was available, all tumor mutations above a specific allele fraction were present in the uterine lavage DNA samples. Mutations originally only detected in lavage fluid fractions were later confirmed to be present in tumor but at allele fractions significantly less than 1%. Of the remaining 95 patients diagnosed with benign or non-cancer pathology, 44 had no significant cancer mutations detected. Intriguingly, 51 patients without histopathologic evidence of cancer had relatively high allele fraction (1.0%-30.4%), cancer-associated mutations. Participants with detected driver and potential driver mutations were significantly older (mean age mutated = 57.96, 95% confidence interval [CI]: 3.30-∞, mean age no mutations = 50.35; p-value = 0.002; Benjamini-Hochberg [BH] adjusted p-value = 0.015) and more likely to be post-menopausal (p-value = 0.004; BH-adjusted p-value = 0.015) than those without these mutations. No associations were detected between mutation status and race/ethnicity, body mass index, diabetes, parity, and smoking status. Long-term follow-up was not presently available in this prospective study for those women without histopathologic evidence of cancer. CONCLUSIONS: Using ultra-deep NGS, we identified somatic mutations in DNA extracted both from cell pellets and a never previously reported cfDNA fraction from the uterine lavage. Using our targeted sequencing approach, endometrial driver mutations were identified in all seven women who received a cancer diagnosis based on classic histopathology of tissue curettage obtained at the time of hysteroscopy. In addition, relatively high allele fraction driver mutations were identified in the lavage fluid of approximately half of the women without a cancer diagnosis. Increasing age and post-menopausal status were associated with the presence of these cancer-associated mutations, suggesting the prevalent existence of a premalignant landscape in women without clinical evidence of cancer. Given that a uterine lavage can be easily and quickly performed even outside of the operating room and in a physician's office-based setting, our findings suggest the future possibility of this approach for screening women for the earliest stages of endometrial cancer. However, our findings suggest that further insight into development of cancer or its interruption are needed before translation to the clinic.