Clinicopathologic and genetic analysis of invasive breast carcinomas in women with germline CHEK2 variants.

PURPOSE: Germline pathogenic variants in checkpoint kinase 2 (CHEK2) are associated with a moderately increased risk of breast cancer (BC). The spectrum of clinicopathologic features and genetics of these tumors has not been fully established. METHODS: We characterized the histopathologic and clinicopathologic features of 44 CHEK2-associated BCs from 35 women, and assessed responses to neoadjuvant chemotherapy. A subset of cases (n = 23) was additionally analyzed using targeted next-generation DNA sequencing (NGS). RESULTS: Most (94%, 33/35) patients were heterozygous carriers for germline CHEK2 variants, and 40% had the c.1100delC allele. Two patients were homozygous, and five had additional germline pathogenic variants in ATM (2), PALB2 (1), RAD50 (1), or MUTYH (1). CHEK2-associated BCs occurred in younger women (median age 45 years, range 25-75) and were often multifocal (20%) or bilateral (11%). Most (86%, 38/44) were invasive ductal carcinomas of no special type (IDC-NST). Almost all (95%, 41/43) BCs were ER + (79% ER + HER2-, 16% ER + HER2 + , 5% ER-HER2 +), and most (69%) were luminal B. Nottingham grade, proliferation index, and results of multiparametric molecular testing were heterogeneous. Biallelic CHEK2 alteration with loss of heterozygosity was identified in most BCs (57%, 13/23) by NGS. Additional recurrent alterations included GATA3 (26%), PIK3CA (226%), CCND1 (22%), FGFR1 (22%), ERBB2 (17%), ZNF703 (17%), TP53 (9%), and PPM1D (9%), among others. Responses to neoadjuvant chemotherapy were variable, but few patients (21%, 3/14) achieved pathologic complete response. Most patients (85%) were without evidence of disease at time of study (n = 34). Five patients (15%) developed distant metastasis, and one (3%) died (mean follow-up 50 months). CONCLUSION: Almost all CHEK2-associated BCs were ER + IDC-NST, with most classified as luminal B with or without HER2 overexpression. NGS supported the luminal-like phenotype and confirmed CHEK2 as an oncogenic driver in the majority of cases. Responses to neoadjuvant chemotherapy were variable but mostly incomplete.

A Survey of Louisiana Pediatricians' Approach to Parenting Teens and Adolescent Reproductive Health.

OBJECTIVE: The American Academy of Pediatrics recommends that pediatricians provide a medical home for adolescent parents, and this study sought to determine pediatricians' compliance with this recommendation within the context of other adolescent reproductive health services provided. METHODS: An Internet-based survey was administered to Louisiana pediatricians. The survey contained 17 Likert scale questions relating to sexual and reproductive health services provided to female and male adolescents, and ascertaining their comfort and experience with issues related to the care of adolescents, including adolescent mothers. Respondents also had the option of describing why they do or do not provide care to adolescent mothers. Lastly, the survey collected demographic characteristics modeled after the American Academy of Pediatrics Periodic Survey of Fellows. RESULTS: There were 101 survey respondents. Seventy-nine percent of pediatricians reported that they provide care to adolescent mothers and they were similar to those who did not with respect to sex, age, race and ethnicity, and training, but they differed by practice community and payer mix. Almost 30% of pediatricians never/rarely test their patients for pregnancy, and nearly 50% never/rarely prescribe contraception. Fifty-four percent agreed that adolescent mothers should continue receiving nonobstetric medical care from their pediatricians, and 70% believed that adolescent fathers should continue receiving medical care from their pediatricians. CONCLUSIONS: Our study suggests that most Louisiana pediatricians provide care to adolescent mothers; however, knowledge gaps and misconceptions related to adolescent reproductive health persist among pediatricians, including those who refuse care to adolescent mothers. Research into provider-level barriers may inform interventions that improve adolescent parents' access to a pediatric medical home.

TRPC5 is required for the NO-dependent increase in dendritic Ca2+ and GABA release from chick retinal amacrine cells.

GABAergic signaling from amacrine cells (ACs) is a fundamental aspect of visual signal processing in the inner retina. We have previously shown that nitric oxide (NO) can elicit release of GABA independently from activation of voltage-gated Ca2+ channels in cultured retinal ACs. This voltage-independent quantal GABA release relies on a Ca2+ influx mechanism with pharmacological characteristics consistent with the involvement of the transient receptor potential canonical (TRPC) channels TRPC4 and/or TRPC5. To determine the identity of these channels, we evaluated the ability of NO to elevate dendritic Ca2+ and to stimulate GABA release from cultured ACs under conditions known to alter the function of TRPC4 and 5. We found that these effects of NO are phospholipase C dependent, have a biphasic dependence on La3+, and are unaffected by moderate concentrations of the TRPC4-selective antagonist ML204. Together, these results suggest that NO promotes GABA release by activating TRPC5 channels in AC dendrites. To confirm a role for TRPC5, we knocked down the expression of TRPC5 using CRISPR/Cas9-mediated gene knockdown and found that both the NO-dependent Ca2+ elevations and increase in GABA release are dependent on the expression of TRPC5. These results demonstrate a novel NO-dependent mechanism for regulating neurotransmitter output from retinal ACs. NEW & NOTEWORTHY Elucidating the mechanisms regulating GABAergic synaptic transmission in the inner retina is key to understanding the flexibility of retinal ganglion cell output. Here, we demonstrate that nitric oxide (NO) can activate a transient receptor potential canonical 5 (TRPC5)-mediated Ca2+ influx, which is sufficient to drive vesicular GABA release from retinal amacrine cells. This NO-dependent mechanism can bypass the need for depolarization and may have an important role in processing the visual signal by enhancing retinal amacrine cell GABAergic inhibitory output.

Fine needle aspiration biopsy in low- and middle-income countries.

Fine needle aspiration biopsy (FNAB) in low- and middle-income countries (LMIC), can provide minimally invasive, cost-effective tissue diagnosis with rapid assessment and specimen triage, which is advantageous in these resource-limited settings. Nevertheless, challenges such as equipment shortages, reagents, and lack of trained personnel exist. This article discusses the effectiveness of FNAB for diagnosis of malignant and inflammatory conditions across various organs, such as lymph nodes, breast, soft tissue, and thyroid and advocates for increased training opportunities and collaboration with academic centers to enhance diagnostic accuracy and access to pathology services.

A comprehensive review of anal cancer-with a special focus on anal cytology.

The diagnosis of anal cancer is relatively uncommon, but its incidence has been steadily increasing in high-risk populations. In the 2001 Bethesda System for Reporting Cervical Cytology, anal cytology was introduced as a component. Since then, it has been recognized as a potential tool for screening anal cancer, often in conjunction with high-resolution anoscopy. There are notable similarities between anal cancer and cervical cancer, including the causative role of human papillomavirus. However, there are also significant differences, particularly in terms of disease prevalence. Anal cytology may be used as a primary screening test, and in the event of abnormalities, patients are subsequently directed for high-resolution anoscopy. However, the best approach for anal cancer screening is yet to be determined and uniformly implemented. This comprehensive review article provides an in-depth analysis of the epidemiology and incidence of anal precursor and malignant lesions. It explores the various methods of sample procurement, preparation, interpretation (including sensitivity and specificity), and reporting terminology in anal cytology. The article also addresses the significance of concurrent high-risk human papillomavirus screening in anal cytology and its role in screening programs. Furthermore, it discusses the follow-up, prevention, and subsequent management strategies for anal cancers. By synthesizing current knowledge in these areas, this review aims to provide a comprehensive understanding of anal cytology and its implications in the early detection, prevention, and management of anal neoplasia and cancer.

Systems Analysis by a Cross-sector Workgroup to Address Housing Insecurity in Cancer Survivorship.

BACKGROUND: Cancer survivors face many financial burdens that generate additional stress such as housing insecurity or homelessness. Because this leads to worse health outcomes, it is essential for health care and housing organizations to begin mobilizing resources to support this vulnerable population. OBJECTIVES: Create a "Housing in Cancer" workgroup to conduct systems-led analysis of housing insecurity in cancer survivorship in the Greater New Orleans area. METHODS: A cross-sector workgroup employed a systems analysis toolkit to explore the system. The group engaged in systems analysis exercises and generated observations on the current system. RESULTS: The problem was discerned into three components. Through reflection, the group created a new focus to support housing policies in cancer survivors and one group member was awarded a grant to provide financial assistance to cancer survivors. CONCLUSIONS: The workgroup's insights identified systemic policies and additional funding for sponsoring organizations who expressed authority over this issue.

Utility and performance of cell blocks in urine cytology: Experience at three teaching hospitals.

BACKGROUND: The use of cell block (CB) preparation is underused in urine cytology (UC) and varies among hospitals. In addition to confirming a diagnosis, CBs can be useful in cases of metastatic disease, diagnoses requiring immunohistochemical (IHC) staining, and for ancillary studies. The role of this study is to examine the performance of CBs for UC at three affiliated teaching hospitals. MATERIALS AND METHODS: A retrospective review of UC cases with a CB was conducted at a county hospital, Veterans Affairs hospital, and tertiary university-based hospital. For each specimen, patient demographics, specimen type, volume, original diagnosis, and IHC stains were recorded. Each case was reviewed for diagnosis based on ThinPrep alone, diagnosis based on ThinPrep and CB, utility of CB for diagnosis, and CB cellularity. RESULTS: A total of 250 UC specimens with CB from 186 patients was identified. Bladder washes were the most common (72.1%). IHC stains were performed on 17.2% of cases. On blinded review, CB preparation was deemed useful in 61.2% of cases, with the highest rate for suspicious for high-grade urothelial carcinoma (SHGUC) cases (87.0%). The diagnosis based on ThinPrep review changed with incorporation of CB in 13.2% of cases, with the highest rate for SHGUC cases (43.5%). CONCLUSIONS: The results demonstrate that use of CB in UC confirms the final diagnosis in more than one-half of cases and changes the diagnosis in a subset of cases. Use of CB was most helpful in the SHGUC category. Further evaluation of the types of cases in which CB are prepared is warranted.

Urine cytology in patients with gender confirmation surgery and hormone therapy: evaluation of urine cytology performance in an underserved patient population.

INTRODUCTION: There is a practice gap and educational need regarding urine cytology (UC) performance in patients with history of gender confirmation surgery (GCS) and/or hormone therapy (HT). This potentially impacts diagnostic accuracy in this medically underserved population. We report a methodology that identifies relevant cases and evaluates the performance of UC in this cohort. MATERIALS AND METHODS: Two institutional pathology archives from 2000 to 2021 were searched using relevant keywords to identify UC specimens from patients with GCS and/or HT for this retrospective study. For each specimen, patient demographics, relevant clinical history, and history of HT and/or GCS were noted. Each case was blindly reviewed by a cytopathologist according to The Paris System. RESULTS: A total of 32 UC specimens from 15 patients with history of GCS and/or HT were identified. There were 13 male to female and 2 female to male transgender patients. The original diagnosis was negative for high-grade urothelial carcinoma (NHGUC) in 24 of 32 (75%) and atypical urothelial cells (AUC) in 8 of 32 (25%) cases. The most common atypical features were irregular nuclear membranes and prominent small nucleoli in 7 of 8 (87.5%). Degenerative changes were present in 5 of 8 (62.5%). On re-review, with relevant clinical history, 100% of cases were re-classified as NHGUC. CONCLUSIONS: The original diagnosis of AUC in these cases likely reflects reactive changes post GCS and/or HT. This cohort may be at risk of AUC overdiagnosis, particularly if the pathologist is unaware of this clinical history. Pathologists need to recognize reactive cytomorphologic changes in these patients. Further multi-institutional studies are warranted to expand knowledge about UC performance in these patients.

Five overlooked dimensions of campus wellness: Qualitative lessons from a Health Sciences Center's wellness program evaluation.

Objective: Successful university wellness programs approach wellness holistically and regularly assess for improvements to program offerings. This case-study reports five lessons learned from a university wellness program evaluation that must be considered when developing wellness programming. Participants: Faculty, staff, and students at a public university health sciences center. Methods: A 23-question electronic survey with open-ended questions was administered to measure feedback on current and future wellness programming. Responses were analyzed with an open coding approach into five themes for program improvement to more holistically address wellness. Results: The five improvements to wellness programming identified by respondents were: wellness offering awareness, workplace culture and environment, racial representation, wellness programming policy enforcement, and creating an environmentally friendly campus. Conclusions: Themes identified in this case-study require additional attention by university wellness programs to ensure they are equitably accessible and comprehensive in their offerings.

Louisiana Pharmacies' Availability of Emergency Contraception and Counseling Accuracy to Adolescent and Physician Callers.

STUDY OBJECTIVE: Adolescents face many barriers to obtaining emergency contraception (EC), despite it being an approved and recommended method to prevent unintended pregnancy. This study examined pharmacy-related barriers to adolescents' access to EC in Louisiana. DESIGN: Prospective, telephone-call secret shopper study to pharmacies to assess same-day EC availability and barriers to purchase. SETTING: A total of 182 pharmacies in 5 Louisiana cities. PARTICIPANTS: Responses provided by pharmacists or other pharmacy staff assessed between July 2018 and November 2019. INTERVENTIONS: Collected data from secret shopper phone calls and compared responses provided to callers between male and female callers and physician and adolescent callers. MAIN OUTCOME MEASURES: Same-day levonorgestrel (LNG) availability, same-day ulipristal acetate (UPA) availability, age restrictions on purchase, requirement of parental consent for purchase, and type of staff member that advised the caller. RESULTS: Of 364 calls to 182 pharmacies, 66% of pharmacists or other pharmacy staff reported same-day LNG access and 5% reported same-day UPA access. An inaccurate age restriction regarding EC purchase was reported in 15% of calls. Female callers were cited this age restriction more frequently than their male counterparts (20% vs 10%). Pharmacists were more likely than other pharmacy staff to counsel female callers compared to male callers (52% vs 27%) and physician callers compared to adolescents (50% vs 30%). CONCLUSIONS: Many pharmacies in Louisiana have limited same-day availability of EC and often report inconsistent and inaccurate age and consent regulations for its use. Continued outreach and education to pharmacies is necessary to address these barriers to adolescent EC access.

Population Geography and Emergency Contraception Access in Louisiana.

We assessed the same-day availability of oral emergency contraception (EC) in five Louisiana communities, and evaluated this data for relationships between availability and local population demographics. Researchers called all retail pharmacies in five municipalities of varying sizes in order to inquire about the same-day stockage of EC products and their availability to teens. Individual pharmacies were then geolocated to a census tract, and call data was analyzed against neighborhood census data regarding population size, income, gender, race, family structure, and educational level. A multivariable logistic regression model was performed to predict the same-day availability of emergency contraception. EC was available on the same day in 66% of all pharmacies. The same-day availability of EC decreased with the local population size (p < 0.001), and the availability increased with higher levels of educational attainment (p = 0.0015). The largest census level predictor of access to same-day EC was the city population, with the availability increasing by 6.6% for every 10,000 person increase in population. Despite changing to over-the-counter sales in 2013, EC is still not widely available in all geographic areas. Its availability is partially predictable by local population demographics, and this difference may represent a health disparity for teens and women seeking EC.