Juvenile dermatomyositis (JDM) is a rare form of childhood autoimmune myositis that presents with proximal muscle weakness and skin rash. B cells are strongly implicated in the pathogenesis of the ...disease, but the underlying mechanisms are unknown. Therefore, the main objective of our study was to investigate mechanisms driving B cell lymphocytosis and define pathological features of B cells in JDM patients. Patients were recruited through the UK JDM Cohort and Biomarker study. Peripheral blood B cell subpopulations were immunophenotyped by flow cytometry. The results identified that immature transitional B cells were significantly expanded in active JDM, actively dividing, and correlated positively with disease activity. Protein and RNAseq analysis revealed high interferon alpha (IFNα) and TLR7-pathway signatures pre-treatment. Stimulation of B cells through TLR7/8 promoted both IL-10 and IL-6 production in controls but failed to induce IL-10 in JDM patient cells. Interrogation of the CD40-CD40L pathway (known to induce B cell IL-10 and IL-6) revealed similar expression of IL-10 and IL-6 in B cells cultured with CD40L from both JDM patients and controls. In conclusion, JDM patients with active disease have a significantly expanded immature transitional B cell population which correlated with the type I IFN signature. Activation through TLR7 and IFNα may drive the expansion of immature transitional B cells in JDM and skew the cells toward a pro-inflammatory phenotype.
The inflammatory cytokine TNF-... has been recognized as a critical tumor promoter, but the effector cells that mediate its action have not been fully characterized. Because B cells regulate squamous ...and prostate carcinogenesis, and Tnf... mice harbor B-cell defects, we investigated the hypothesis that B cells are important effector cells for TNF-α-mediated promotion of cancer development. Using an adoptive transfer strategy and the 7,12-dimethylbenzαanthracene/terephthalic acid (DMBA/TPA) two-stage model of skin carcinogenesis, we found that both B cells and TNF-... are critical for the development of DMBA/TPA-induced papilloma. Transfer of B cells from DMBA/TPA-treated wild-type mice to Tnf... mice rescued papilloma development to a wild-type level, a result not observed when B cells from Tnf... mice were transferred to Rag2... mice or when TNF-α was eliminated selectively in B cells. Resistance to papilloma development in Tnf... mice was associated with increased IFN-... and CD8+ T cells in skin and a significant reduction in IL-10-producing B regulatory cells alongside an increase in IFN-...-producing CD8+ T cells in the spleen. These data indicate that during DMBA/TPA-induced squamous carcinogenesis TNF-α mediates tumor-promoting activity via regulatory B cells that repress antitumor immunity. (ProQuest: ... denotes formulae/symbols omitted.)
The inflammatory cytokine TNF-α has been recognized as a critical tumor promoter, but the effector cells that mediate its action have not been fully characterized. Because B cells regulate squamous ...and prostate carcinogenesis, and Tnfâ»/â» mice harbor B-cell defects, we investigated the hypothesis that B cells are important effector cells for TNF-α-mediated promotion of cancer development. Using an adoptive transfer strategy and the 7,12-dimethylbenzαanthracene/terephthalic acid (DMBA/TPA) two-stage model of skin carcinogenesis, we found that both B cells and TNF-α are critical for the development of DMBA/TPA-induced papilloma. Transfer of B cells from DMBA/TPA-treated wild-type mice to Tnfâ»/â» mice rescued papilloma development to a wild-type level, a result not observed when B cells from Tnfâ»/â» mice were transferred to Rag2â»/â» mice or when TNF-α was eliminated selectively in B cells. Resistance to papilloma development in Tnfâ»/â» mice was associated with increased IFN-γ and CD8⺠T cells in skin and a significant reduction in IL-10-producing B regulatory cells alongside an increase in IFN-γ-producing CD8⺠T cells in the spleen. These data indicate that during DMBA/TPA-induced squamous carcinogenesis TNF-α mediates tumor-promoting activity via regulatory B cells that repress antitumor immunity.
Prostate cancer treatments disrupt receptive anal intercourse (RAI) for gay and bisexual men (GBM). Sexual dysfunction following prostate cancer treatment may include severe pain in the anorectum ...during RAI (i.e., anodyspareunia). The purpose of this study was to explore the impact of prostate cancer and its treatments on RAI among GBM. Data were from a cross-sectional online survey of 100 GBM prostate cancer survivors who reported pleasurable RAI prior to treatment. Approximately 47% of the sample reported recent RAI, which was more common among GBM in long-term relationships. RAI was also associated with engagement in other sexual behaviors (e.g., oral and insertive anal sex). Anodyspareunia was reported by 23% of the men who had attempted recent RAI. Anodyspareunia was negatively associated with mental health, performing oral sex on a partner, and bowel function. The overwhelming majority received no information from their healthcare providers about loss of RAI function prior to prostate cancer treatment. Culturally responsive cancer survivorship care may need to address the loss of RAI function for GBM prostate cancer survivors.
Objective
Prostate cancer is the most common invasive cancer in gay and bisexual men (GBM). Despite the unique sexual and urinary concerns of this group, studies of prostate cancer rehabilitation ...have primarily focused on heterosexual men. GBM also have high prevalence of human immunodeficiency virus (HIV), which may be associated with lower health‐related quality of life (HRQOL). We examined the association between HIV status and HRQOL in a cohort of GBM with prostate cancer.
Methods
Data from the Restore study, a cross‐sectional online survey of GBM treated for prostate cancer, were used to examine this association. The Expanded Prostate Cancer Index Composite (EPIC) assessed function, bother, and summary measures in four domains: urinary, sexual, bowel, and hormone. Overall physical and mental HRQOL was assessed using the Short‐Form Health Survey (SF‐12). Multivariate analysis of variance and linear regression were used to evaluate the association between HIV status and HRQOL scores after adjustment for demographic and sexual characteristics.
Results
Of 192 participants, 24 (12.4%) reported an HIV diagnosis. After adjustment for covariates, HIV‐positive status was associated with lower scores on the EPIC urinary (mean difference MD: −13.0, 95% CI, −21.4 to −4.6), sexual (MD: −12.5, 95% CI, −21.9 to −3.2), and bowel (MD: −5.9, 95% CI, −11.7 to −0.2) domains. No significant associations were observed between HIV status and other outcomes.
Conclusions
HIV status may be associated with poorer urinary, sexual, and bowel HRQOL in GBM prostate cancer survivors.
Background/aims:
Sexual minorities are small and under-researched populations that are at disproportionate risk for cancer and poor cancer outcomes. Described as a “hidden population,” the principal ...research challenge has been to develop effective methods to identify and recruit such cancer patients into cancer studies. Online recruitment strategies, as well as targeted clinic recruitment using patient-entered sexual orientation and gender identity data from electronic medical records have potential to transform recruitment, but studies testing the effects of how to recruit using these have not been published.
Methods:
In 2019, we conducted a naturalistic, three-arm, stratified prospective study to compare three recruitment strategies: (a) clinic based recruitment of prostate cancer patients from gay health and urology clinics; (b) directly from the gay community; and (c) online recruitment (through cancer support, sex/dating, and social sites). For each strategy, we estimated time, workload, and direct costs involved. To study how recruitment strategy may affect sampling, we tested for retention rates, demographic and outcome differences across sites. Using these methods, we successfully recruited 401 gay and bisexual prostate cancer patients into a randomized, controlled, 24-month trial testing an online sexual and urinary rehabilitation curriculum tailored for this population.
Results:
There were seven key results. First, it is possible to recruit substantial numbers of sexual minority men into prostate cancer studies provided online recruitment methods are used. Second, we observed big differences in dropout during study onboarding by recruitment source. Third, within online recruitment, the online sex/dating application (app) was the most successful and efficient, followed by the cancer support site, and then the social networking site. Fourth, while clinics were the cheapest source of recruitment, they were time intensive and low in yield. Fifth, the cancer support site and sex/dating app recruits differed by several characteristics, with the former being more rehabilitation-focused while the latter were younger and more sexually active. Sixth, we found almost no differences in outcomes across the three online recruitment sites. Seventh, because retention in online studies has been a concern, we confirm very low attrition at 3- and 6 months into the trial.
Conclusion:
For sexual minority cancer research, more research on how to use sexual orientation and gender identity electronic medical record data for clinic-based recruitment is needed. For other small or hard-to-reach populations, researchers should compare and publish online versus offline recruitment strategies.
•Sexual orientation outness is situational in gay/bisexual prostate cancer survivors.•Participants disclosed sexual orientation to their primary care provider the most.•If out, surgeons and ...urologists were more likely to discuss sexual side effects.•Sexual side effects among men who have sex with men were infrequently discussed.
In this study, we investigated if outness is more a situational or a consistent characteristic in gay, bisexual, and other men who have sex with men (GBM) treated for prostate cancer and how the disclosure of sexual orientation impacts provider discussions of sexual side effects.
Data came from Restore, an online cross-sectional survey of 193 GBM prostate cancer survivors living in North America and were analyzed using various statistical models.
Disclosure of sexual orientation and of living with prostate cancer were not significantly correlated. Participants who were out regarding sexual orientation were more likely to report that their surgeons and urologists discussed the sexual side effects of treatment.
Outness appears to be a situational phenomenon. GBM prostate cancer survivors who were out regarding sexual orientation received more discussion surrounding sexual side effects of prostate cancer treatment from their providers.
It is important for healthcare providers to inquire about patient’s sexual orientation to provide holistic care to these patients to address health disparities within this group.
Existing measures of sexual functioning in prostate cancer survivors focus primarily on erectile function and do not adequately measure the experiences of sexual minority men.
To develop and ...psychometrically evaluate a new scale to measure sexual functioning among sexual minority men with prostate cancer.
Sexual minority prostate cancer patients (n = 401) completed an online battery of urinary and sexual functioning tests in 2019, including a new 37-item instrument about their sexual functioning post-treatment for prostate cancer.
We used confirmatory factor analysis to determine the construct validity of a new scale including five subscales: a four-factor model for all participants (n = 401) evaluated Sexual Satisfaction, Sexual Confidence, Frequency of Sexual Problems, and Urinary Incontinence in Sex. A single-factor model completed only by participants who had attempted or desired receptive anal sex (n = 255) was evaluated in the fifth subscale: Problematic Receptive Anal Sex. To evaluate criterion validity, we calculated the intercorrelations between each Sexual Minorities and Prostate Cancer Scale (SMACS) subscale and four related scales: the Expanded Prostate Cancer Index Composite-50 (EPIC), the Functional Assessment of Cancer Therapy-Prostate, the Brief Symptom Inventory-18, and the International Consultation on incontinence questionnaire. Cronbach's alphas were calculated to measure internal consistency (ie, reliability).
Cronbach's alpha values ranged from 0.64 to 0.89. Loadings (0.479-0.926) and model fit indices were strong (Root Mean Square Error of Approximation: 0.085, Standardized root mean squared residual: 0.063, comparative fit index: 0.927, Tucker-Lewis Index: 0.907). For criterion validity, Sexual Satisfaction, Sexual Confidence, and Frequency of Sexual Problems were moderately correlated with EPIC function and bother scores (r = 0.50-0.72) and Urinary incontinence in sex correlated moderately with EPIC Urinary Function and International Consultation on incontinence questionnaire scores (0.45-0.56).
The SMACS can be used by clinicians and researchers to comprehensively measure sexual functioning in sexual minority men, in conjunction with existing scales.
This new scale is validated in a large, geographically diverse cohort of sexual minority cancer survivors and fills an important gap in existing measures of sexual functioning. Limitations include a lack of a validation sample.
The SMACS is a valid and reliable new scale that measures sexual minority men's experience of urinary incontinence in sex, problematic receptive anal sex, and sexual distress. Polter EJ, Kohli N, Rosser BRS, et al. Creation and Psychometric Validation of the Sexual Minorities and Prostate Cancer Scale (SMACS) in Sexual Minority Patients-The Restore-2 Study. J Sex Med 2022;19:529-540.
Gay and bisexual men (GBM) with prostate cancer experience worse sexual and mental health outcomes following prostate cancer treatment than heterosexual men. Emerging evidence suggests that GBM may ...change their role-in-sex in response to treatment effects. The purpose of this study was to describe the impact of prostate cancer treatment on role-in-sex, to estimate the prevalence of such changes, and to determine the impact on quality of life and mental health. We conducted semi-structured interviews with 30 sexual minority prostate cancer patients. Then, we recruited 401 gay and bisexual prostate cancer patients into a study assessing the effects of rehabilitation. Qualitative data were analyzed using descriptive thematic analysis. Differences in quality of life and mental health outcomes were analyzed using multivariate analyses of variance. Prostate cancer treatment resulted in loss of role-in-sex for many patients. When changes in role-in-sex occurred, the shifts were predominantly from tops to bottoms. Those with a current top role-in-sex had significantly better sexual and mental health outcomes than either versatiles or bottoms. Clinical implications include the need for providers to ask about role-in-sex in order to address disparities in health outcomes by sexual orientation and to provide culturally appropriate care to sexual minority patients.
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