Immune Dysregulation, Inflammation in Characterizing Women with Vulvodynia, Depression, and Both.

Background: Depression and vulvodynia are often comorbid. The onset of depression and vulvodynia may be immune and/or stress/environmentally induced. We explored whether vulvodynia, depression, or both occur in response to a Th1-mediated versus Th2-mediated immune response. Materials and Methods: We analyzed data from a case-control study of clinically confirmed vulvodynia and history of depression determined through structured clinical interviews. Immune dysregulation and inflammation were categorized based on the following self-reported conditions: rheumatoid arthritis, Sjogren's disease, scleroderma, systemic lupus erythematosus, inflammatory bowel disease, fibromyalgia, osteoarthritis, polycystic ovarian syndrome, diabetes mellitus, uterine fibroids, asthma, atopic dermatitis, and allergic rhinitis. Logistic regression analyses were adjusted for marital status, body mass index, age, and pack years. Results: Women with systemic immune dysregulation had higher odds of depression (adjusted odds ratio [aOR] = 1.61, confidence interval [95% CI]: 0.65-3.98), vulvodynia (aOR = 2.45, 95% CI: 1.00-5.96), and comorbid depression and vulvodynia (aOR = 4.93, 95% CI: 2.19-11.10) versus neither condition. Women reporting local immune dysregulation had similar odds of depression (aOR = 1.89, 95% CI: 0.99-3.59), vulvodynia (aOR = 2.12, 95% CI: 1.08-4.18), and comorbid depression and vulvodynia (aOR = 1.96, 95% CI: 0.98-3.90). Women with Th2 inflammation had similar odds of depression (aOR = 2.23, 95% CI: 1.05-4.77) and vulvodynia (aOR = 2.56, 95% CI: 1.20-5.49). Women with Th1 or Th2 inflammation had similar odds of comorbid depression and vulvodynia (aOR = 3.03, 95% CI: 1.48-6.19; aOR = 3.14, 95% CI: 1.49-6.60, respectively). Conclusions: Our results suggest that an imbalance of cytokines, indicated by the presence of one or more immune-related health conditions, is associated with an increased risk of vulvodynia and/or depression.

African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans.

BACKGROUND: Asthma is the most common chronic disease in children, occurring at higher frequencies and with more severe disease in children with African ancestry. METHODS: We tested for association with haplotypes at the most replicated and significant childhood-onset asthma locus at 17q12-q21 and asthma in European American and African American children. Following this, we used whole-genome sequencing data from 1060 African American and 100 European American individuals to identify novel variants on a high-risk African American-specific haplotype. We characterized these variants in silico using gene expression and ATAC-seq data from airway epithelial cells, functional annotations from ENCODE, and promoter capture (pc)Hi-C maps in airway epithelial cells. Candidate causal variants were then assessed for correlation with asthma-associated phenotypes in African American children and adults. RESULTS: Our studies revealed nine novel African-specific common variants, enriched on a high-risk asthma haplotype, which regulated the expression of GSDMA in airway epithelial cells and were associated with features of severe asthma. Using ENCODE annotations, ATAC-seq, and pcHi-C, we narrowed the associations to two candidate causal variants that are associated with features of T2 low severe asthma. CONCLUSIONS: Previously unknown genetic variation at the 17q12-21 childhood-onset asthma locus contributes to asthma severity in individuals with African ancestries. We suggest that many other population-specific variants that have not been discovered in GWAS contribute to the genetic risk for asthma and other common diseases.

State-of-the-art diagnostic evaluation of common variable immunodeficiency.

OBJECTIVE: To summarize the current understanding of diagnostic and postdiagnostic evaluation of common variable immunodeficiency (CVID). DATA SOURCES: PubMed Central database. STUDY SELECTIONS: Original research articles and review articles from 2015 to 2020 including seminal articles that shaped the diagnostic and postdiagnostic evaluation of CVID were incorporated. This work focuses on initial diagnosis of CVID, genetic evaluations, and postdiagnostic assessment of respiratory, gastrointestinal, and hepatobiliary diseases including spleen and lymph node enlargement. RESULTS: CVID presents not only with frequent infections but also with noninfectious complications such as autoimmunity, gastrointestinal disease, chronic lung disease, granulomas, liver disease, lymphoid hyperplasia, splenomegaly, or malignancy. The risk of morbidity and mortality is higher in patients with CVID and noninfectious complications. Detailed diagnostic approaches, which may incorporate genetic testing, can aid characterization of individual CVID cases and shape treatment in some instances. Moreover, continued evaluation after CVID diagnosis is key to optimal management of this complex disorder. These postdiagnostic evaluations include pulmonary function testing, radiologic studies, and laboratory evaluations that may be conducted at frequencies determined by disease activity. CONCLUSION: Although the diagnosis can be achieved similarly in all patients with CVID, those with noninfectious complications have distinct concerns during clinical evaluation. State-of-the-art workup of CVID with noninfectious complications typically includes genetic analysis, which may shape precision therapy, and thoughtful application of postdiagnostic tests that monitor the presence and progression of disease in the myriad of tissues that may be affected. Even with recent advancements, knowledge gaps in diagnosis, prognosis, and treatment of CVID persist, and continued research efforts are needed.

Transgender individuals' cancer survivorship: Results of a cross-sectional study.

BACKGROUND: Transgender individuals' cancer prevalence and transgender cancer survivors' health needs have received scarce attention. The current study compared transgender and cisgender individuals' cancer prevalence and described the health needs of transgender cancer survivors. METHODS: The authors used Behavioral Risk Factor Surveillance System data on 95,800 cisgender and transgender individuals who self-reported a cancer diagnosis. Using multiple logistic regression, they estimated cancer prevalence and calculated odds ratios with 95% confidence intervals of physical, psychological, overall health, and health behaviors of transgender survivors compared with cisgender survivors. RESULTS: After adjusting for confounders, transgender men had a significantly higher (>2-fold) number of cancer diagnoses compared with cisgender men, but not cisgender women. Cancer prevalence among gender nonconforming individuals and transgender women was not significantly different from that of cisgender men and cisgender women. Gender nonconforming survivors had significantly greater physical inactivity, heavy episodic alcohol use, and depression compared with cisgender men and cisgender women. Transgender men survivors were significantly more likely to report poor physical health and greater medical comorbidities and were less likely to report smoking compared with cisgender men and cisgender women. Transgender women survivors were significantly more likely to report diabetes compared with cisgender men and cisgender women and were more likely to report cardiovascular disease compared with cisgender women. CONCLUSIONS: Clinicians should be aware of the higher prevalence of cancer among transgender men and a potential survivorship bias among transgender individuals. Transgender survivors have considerable variation in their risk profile. Clinicians and health services can target gender nonconforming survivors' depression and health behaviors to improve survival and should address the complex comorbidities of transgender men and transgender women.

Cancer survivors' access to care and quality of life: Do sexual minorities fare worse than heterosexuals?

BACKGROUND: Adults with poor access to care are known to have worse quality of life (QOL). The purpose of the current study was to determine differences in cancer survivors' access to care by sexual orientation and to examine the association between access to care and QOL. METHODS: The current secondary data analysis used 4 years of Behavioral Risk Factor Surveillance System data regarding adult men and women who self-reported a history of cancer. Among the 70,524 cancer survivors, a total of 1931 self-identified as sexual minorities, defined as lesbian, gay, bisexual, or other nonheterosexual orientation. RESULTS: Sexual minority women had significantly more access deficits compared with heterosexual women (42.7% vs 28.0%; P < .0001), whereas men of different sexual orientations had similar access to care. Among sexual minority women, those with access deficits had higher odds of poor physical QOL compared with heterosexual women (odds ratio [OR], 2.0 [95% CI, 1.2-3.4] vs OR, 1.3 [95% CI, 1.2-1.5]), poor mental QOL (OR, 1.8 [95% CI, 1.1-3.1] vs OR, 1.5 [95% CI, 1.3-1.7]), and difficulties concentrating (OR, 2.0 [95% CI, 1.2-3.5] vs OR, 1.7 [95% CI, 1.4-1.9]). Sexual minority men with access deficits had greater odds of difficulty concentrating compared with heterosexual men (OR, 4.3 [95% CI, 2.0-9.3] vs OR, 1.5 [95% CI, 1.2-1.9]). Among men, sexual minority status increased the odds of poor mental QOL (OR, 1.49 [95% CI, 1.11-2.01]). CONCLUSIONS: Access to care among sexual minority cancer survivors needs improvement. Sexual minority women should be a focus of future research because their poor access to care more strongly relates to worse QOL.

The Sexual Health of Women in Lebanon: Are There Differences by Sexual Orientation?

PURPOSE: From studies conducted in Western countries (United States, United Kingdom, and Australia), we know that the sexual health of sexual minority women (SMW) differs in key ways from that of heterosexual women (HSW). To date, the sexual health of SMW living in the Middle East and North Africa region has not been studied. The purpose of this study was to compare the sexual health of SMW and HSW living in Lebanon. METHODS: SMW and HSW living in Lebanon (N = 95) completed an anonymous, self-administered survey. SMW's risk perceptions and health promoting and sexual behaviors were compared to those of HSW. We examined differences by sexual orientation by using t tests and Fisher's exact tests. RESULTS: The 45 SMW and 50 HSW had similar demographic characteristics. Significantly more SMW had heard of human papillomavirus, but only 22% of women from both groups knew of its association with abnormal Papanicolaou tests. Cervical cancer screening rates were similar in SMW and HSW, although remarkably low (42%) compared with rates in Western countries. Significantly more SMW (18%) reported difficulty with access to care than HSW (0%). Forty-four percent of SMW reported discomfort in disclosing their sexual orientation to their healthcare provider and 61% reported that healthcare providers lacked sensitivity toward lesbian, gay, bisexual, and transgender needs. Unwanted sexual contact occurred more frequently in SMW (53%) than HSW (23%). CONCLUSION: The sexual health of women is affected by sociocultural factors. SMW living in Lebanon have unique health needs that should be addressed within their sociocultural context.