HIV, inflammation, and initiation of methamphetamine use in sexual and gender minorities assigned male at birth.

Methamphetamine use and HIV disproportionately affect sexual and gender minority (SGM) people assigned male at birth. Identifying risk factors for methamphetamine use is crucial to inform preventive interventions. In this cohort study with 1,296 SGM people assigned male at birth, ages 16 to 29, and who resided in Chicago, Poisson regression analyses indicated the prevalence of methamphetamine use increased from 2015 to 2023 [Incidence Rate Ratio (IRR) = 1.07; 95% CI = 1.01 to 1.13; P = 0.02]. This increase was most pronounced among those ages 25 or older at baseline (IRR = 2.20; 95% CI = 1.33 to 3.63; P = 0.002), and 23.9 [Interquartile Range (IQR) = 22.1 to 26.9] was the median age of first-time methamphetamine use. In 826 participants with a prior HIV diagnosis or previous inflammatory measurements, Cox proportional-hazards models examined risk factors for incident, first-time methamphetamine use. Adjusting for other substance use, the rate of incident, first-time methamphetamine use was two-fold greater after HIV diagnosis [adjusted hazard ratio (aHR) = 2.02; 95% CI = 1.27 to 3.23; P = 0.003]. For each SD higher C-reactive protein, the rate of incident, first-time methamphetamine use was 18% greater (aHR = 1.18; 95% CI, 1.05 to 1.34; P = 0.008). HIV seroconversion and inflammation could increase the risk of initiating methamphetamine use in SGM people assigned male at birth.

Mpox: The Reemergence of an Old Disease and Inequities.

Mpox, previously known as monkeypox, is caused by an Orthopoxvirus related to the variola virus that causes smallpox. Prior to 2022, mpox was considered a zoonotic disease endemic to central and west Africa. Since May 2022, more than 86,000 cases of mpox from 110 countries have been identified across the world, predominantly in men who have sex with men, most often acquired through close physical contact or during sexual activity. The classical clinical presentation of mpox is a prodrome including fever, lethargy, and lymphadenopathy followed by a characteristic vesiculopustular rash. The recent 2022 outbreak included novel presentations of mpox with a predominance of anogenital lesions, mucosal lesions, and other features such as anorectal pain, proctitis, oropharyngeal lesions, tonsillitis, and multiphasic skin lesions. We describe the demographics and clinical spectrum of classical and novel mpox, outlining the potential complications and management.

Racial disparity in prostate cancer: an outlook in genetic and molecular landscape.

Prostate cancer (PCa) incidence, morbidity, and mortality rates are significantly impacted by racial disparities. Despite innovative therapeutic approaches and advancements in prevention, men of African American (AA) ancestry are at a higher risk of developing PCa and have a more aggressive and metastatic form of the disease at the time of initial PCa diagnosis than other races. Research on PCa has underlined the biological and molecular basis of racial disparity and emphasized the genetic aspect as the fundamental component of racial inequality. Furthermore, the lower enrollment rate, limited access to national-level cancer facilities, and deferred treatment of AA men and other minorities are hurdles in improving the outcomes of PCa patients. This review provides the most up-to-date information on various biological and molecular contributing factors, such as the single nucleotide polymorphisms (SNPs), mutational spectrum, altered chromosomal loci, differential gene expression, transcriptome analysis, epigenetic factors, tumor microenvironment (TME), and immune modulation of PCa racial disparities. This review also highlights future research avenues to explore the underlying biological factors contributing to PCa disparities, particularly in men of African ancestry.

Immunogenicity and protective capacity of a CpG ODN adjuvanted alum adsorbed bivalent meningococcal outer membrane vesicle vaccine.

Invasive meningococcal disease (IMD) is caused by Neisseria meningitidis, with the main serogroups responsible for the disease being A, B, C, W, X, and Y. To date, several vaccines targeting N. meningitidis have been developed albeit with a short-lived protection. Given that MenW and MenB are the most common causes of IMD in Europe, Turkey, and the Middle East, we aimed to develop an outer membrane vesicle (OMV) based bivalent vaccine as the heterologous antigen source. Herein, we compared the immunogenicity, and breadth of serum bactericidal activity (SBA) assay-based protective coverage of OMV vaccine to the X serotype with existing commercial meningococcal conjugate and polysaccharide (PS) vaccines in a murine model. BALB/c mice were immunized with preclinical batches of the W + B OMV vaccine, either adjuvanted with Alum, CpG ODN, or their combinations, and compared with a MenACYW conjugate vaccine (NimenrixTM, Pfizer), and a MenB OMV-based vaccine (Bexsero®, GSK), The immune responses were assessed through enzyme-linked immunosorbent assay (ELISA) and SBA assay. Antibody responses and SBA titers were significantly higher in the W + B OMV vaccine when adjuvanted with Alum or CpG ODN, as compared to the control groups. Moreover, the SBA titers were not only significantly higher than those achieved with available conjugated ACYW vaccines but also on par with the 4CMenB vaccines. In conclusion, the W + B OMV vaccine demonstrated the capacity to elicit robust antibody responses, surpassing or matching the levels induced by licensed meningococcal vaccines. Consequently, the W + B OMV vaccine could potentially serve as a viable alternative or supplement to existing meningococcal vaccines.

Spatial profiling reveals tissue-specific neuro-immune interactions in gastroenteropancreatic neuroendocrine tumors.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous malignancies that arise from complex cellular interactions within the tissue microenvironment. Here, we sought to decipher tumor-derived signals from the surrounding microenvironment by applying digital spatial profiling (DSP) to hormone-secreting and non-functional GEP-NETs. By combining this approach with in vitro studies of human-derived organoids, we demonstrated the convergence of cell autonomous immune and pro-inflammatory proteins that suggests their role in neuroendocrine differentiation and tumorigenesis. DSP was used to evaluate the expression of 40 neural- and immune-related proteins in surgically resected duodenal and pancreatic NETs (n = 20) primarily consisting of gastrinomas (18/20). A total of 279 regions of interest were examined between tumors, adjacent normal and abnormal-appearing epithelium, and the surrounding stroma. The results were stratified by tissue type and multiple endocrine neoplasia I (MEN1) status, whereas protein expression was validated by immunohistochemistry (IHC). A tumor immune cell autonomous inflammatory signature was further evaluated by IHC and RNAscope, while functional pro-inflammatory signaling was confirmed using patient-derived duodenal organoids. Gastrin-secreting and non-functional pancreatic NETs showed a higher abundance of immune cell markers and immune infiltrate compared with duodenal gastrinomas. Compared with non-MEN1 tumors, MEN1 gastrinomas and preneoplastic lesions showed strong immune exclusion and upregulated expression of neuropathological proteins. Despite a paucity of immune cells, duodenal gastrinomas expressed the pro-inflammatory and pro-neural factor IL-17B. Treatment of human duodenal organoids with IL-17B activated NF-κB and STAT3 signaling and induced the expression of neuroendocrine markers. In conclusion, multiplexed spatial protein analysis identified tissue-specific neuro-immune signatures in GEP-NETs. Duodenal gastrinomas are characterized by an immunologically cold microenvironment that permits cellular reprogramming and neoplastic transformation of the preneoplastic epithelium. Moreover, duodenal gastrinomas cell autonomously express immune and pro-inflammatory factors, including tumor-derived IL-17B, that stimulate the neuroendocrine phenotype. © 2024 The Pathological Society of Great Britain and Ireland.

Morbidity and mortality risks associated with valproate withdrawal in young adults with epilepsy.

Valproate is the most effective treatment for idiopathic generalized epilepsy. Current guidance precludes its use in females of childbearing potential, unless other treatments are ineffective or not tolerated, because of high teratogenicity. This risk was recently extended to males. New guidance will limit use both in males and females aged <55 years, resulting in withdrawal of valproate from males already taking it, as occurs for females. Whether there are risks of personal harm (including injury or death) associated with valproate withdrawal has not yet been quantified for males or females ON valproate, meaning clinicians cannot reliably counsel either sex when discussing valproate withdrawal with them, despite that this concern may be at the forefront of patients' and clinicians' minds. We assessed whether there are any morbidity or mortality risks associated with valproate withdrawal in young males and females. We performed a retrospective cohort study of internationally derived electronic health data within the TriNetX Global Collaborative Network. Included were males and females aged 16-54 years with ≥1 epilepsy disease or symptom code between 1 December 2017 and 1 December 2018, and ≥2 valproate prescriptions over the preceding 2 years (1 January 2015-30 November 2017). Five-year propensity-matched risks of mortality and a range of morbidity outcomes were compared between those remaining ON versus withdrawn from valproate during the 1 December 2017-1 December 2018 recruitment period, regardless of whether switched to another antiseizure medication. Survival analysis was undertaken using Cox-proportional hazard models, generating hazard ratios (HRs) with 95% confidence intervals (CIs). In total, 8991 males and 5243 females taking valproate were recruited. Twenty-eight per cent of males and 36% of females were subsequently withdrawn from valproate. Valproate withdrawal was associated with significantly increased risks of emergency department attendance [HRs overall: 1.236 (CI 1.159-1.319), males: 1.181 (CI 1.083-1.288), females: 1.242 (CI 1.125-1.371)], hospital admission [HRs overall: 1.160 (CI 1.081-1.246), males: 1.132 (CI 1.027-1.249), females: 1.147 (CI 1.033-1.274)], falls [HRs overall: 1.179 (CI 1.041-1.336), males: 1.298 (CI 1.090-1.546)], injuries [HRs overall: 1.095 (CI 1.021-1.174), males: 1.129 (CI 1.029-1.239)], burns [HRs overall: 1.592 (CI 1.084-2.337)] and new-onset depression [HRs overall 1.323 (CI 1.119-1.565), females: 1.359 (CI 1.074-1.720)]. The risk of these outcomes occurring was 1%-7% higher in those withdrawn from valproate than in those remaining ON valproate. Overall, valproate withdrawal was not associated with increased mortality. These results may help patients and clinicians have a more informed discussion about personal safety when considering valproate withdrawal.

A Systematic Review of Implementation Research on Determinants and Strategies of Effective HIV Interventions for Men Who Have Sex with Men in the United States.

Men who have sex with men (MSM) are disproportionately affected by HIV, accounting for two-thirds of HIV cases in the United States despite representing ∼5% of the adult population. Delivery and use of existing and highly effective HIV prevention and treatment strategies remain suboptimal among MSM. To summarize the state of the science, we systematically review implementation determinants and strategies of HIV-related health interventions using implementation science frameworks. Research on implementation barriers has focused predominantly on characteristics of individual recipients (e.g., ethnicity, age, drug use) and less so on deliverers (e.g., nurses, physicians), with little focus on system-level factors. Similarly, most strategies target recipients to influence their uptake and adherence, rather than improving and supporting implementation systems. HIV implementation research is burgeoning; future research is needed to broaden the examination of barriers at the provider and system levels, as well as expand knowledge on how to match strategies to barriers-particularly to address stigma. Collaboration and coordination among federal, state, and local public health agencies; community-based organizations; health care providers; and scientists are important for successful implementation of HIV-related health innovations.

Pathogenic variant detection rate varies considerably in male breast cancer families and sporadic cases: minimal additional contribution beyond BRCA2, BRCA1 and CHEK2.

BACKGROUND: Male breast cancer (MBC) affects around 1 in 1000 men and is known to have a higher underlying component of high and moderate risk gene pathogenic variants (PVs) than female breast cancer, particularly in BRCA2. However, most studies only report overall detection rates without assessing detailed family history. METHODS: We reviewed germline testing in 204 families including at least one MBC for BRCA1, BRCA2, CHEK2 c.1100DelC and an extended panel in 93 of these families. Individuals had MBC (n=118), female breast cancer (FBC)(n=80), ovarian cancer (n=3) or prostate cancer-(n=3). Prior probability of having a BRCA1/2 PV was assessed using the Manchester Scoring System (MSS). RESULTS: In the 204 families, BRCA2 was the major contributor, with 51 (25%) having PVs, followed by BRCA1 and CHEK2, with five each (2.45%) but no additional PVs identified, including in families with high genetic likelihood on MSS. Detection rates were 85.7% (12/14) in MSS ≥40 and 65.5% with MSS 30-39 but only 12.8% (6/47) for sporadic breast cancer. PV rates were low and divided equally between BRCA1/2 and CHEK2. CONCLUSION: As expected, BRCA2 PVs predominate in MBC families with rates 10-fold those in CHEK2 and BRCA1. The MSS is an effective tool in assessing the likelihood of BRCA1/2 PVs.

Syphilis Prevalence, Incidence, and Demographic Differences in a Longitudinal Study of Young Sexual and Gender Minority Adults Assigned Male at Birth.

BACKGROUND: Syphilis rates in the United States have increased. Few studies have examined syphilis incidence and prevalence prospectively among young sexual and gender minorities (YSGM). METHODS: This study of YSGM assigned male at birth comes from a Chicago-based prospective cohort at 2 visits 6 months apart (N = 882). Syphilis cases were identified through serologic test results and self-reported history. RESULTS: In this sample, 25.1% had a lifetime prevalence, and 3.3% were incident cases with a crude incidence rate of 6.76 per 100 person-years. CONCLUSIONS: Lifetime syphilis and incidence are high in this sample of YSGM relative to general population samples.

How the Orthodox Features of Orthopoxviruses Led to an Unorthodox Mpox Outbreak: What We've Learned, and What We Still Need to Understand.

Orthopoxviruses have repeatedly confounded expectations in terms of the clinical illness they cause and their patterns of spread. Monkeypox virus (MPXV), originally characterized in the late 1950s during outbreaks among captive primates, has been recognized since the 1970s to cause human disease (mpox) in West and Central Africa, where interhuman transmission has largely been associated with nonsexual, close physical contact. In May 2022, a focus of MPXV transmission was detected, spreading among international networks of gay, bisexual, and other men who have sex with men. The outbreak grew in both size and geographic scope, testing the strength of preparedness tools and public health science alike. In this article we consider what was known about mpox before the 2022 outbreak, what we learned about mpox during the outbreak, and what continued research is needed to ensure that the global public health community can detect, and halt further spread of this disease threat.

Accumulation of Immunity in Heavy-Tailed Sexual Contact Networks Shapes Mpox Outbreak Sizes.

Many countries affected by the global outbreak of mpox in 2022 have observed a decline in cases. Our mathematical model accounting for heavy-tailed sexual partnership distributions suggests that mpox epidemics can hit the infection-derived herd immunity threshold and begin to decline, with <1% of sexually active men who have sex with men infected regardless of interventions or behavioral changes. We consistently found that many countries and US states experienced an epidemic peak, with cumulative cases of around 0.1% to 0.5% among men who have sex with men. The observed decline in cases may not necessarily be attributable to interventions or behavioral changes primarily.

Cumulative Detection of Anal High-Grade Squamous Intraepithelial Lesions Over 2-Year Follow-up in Men Who Have Sex With Men Living With Human Immunodeficiency Virus in France.

We assessed cumulative detection and determinants of anal high-grade squamous intraepithelial lesions (HSILs) in men who have sex with men living with human immunodeficiency virus and who underwent 3 visits over 2 years, with cytology and high-resolution anoscopy, within the ANRS-EP57-APACHES study. The cumulative HSIL detection rate was 33% (134 of 410), of which 48% HSILs were detected at baseline. HSIL detection varied considerably by center (from 13% to 51%). The strongest HSIL determinants were baseline human papillomavirus 16 (adjusted odds ratio, 8.2; 95% confidence interval, 3.6-18.9) and p16/Ki67 (4.6 [2.3-9.1]). Repeated annual cytology and high-resolution anoscopy improved HSIL detection but did not fully compensate for between-center heterogeneity.

Characteristics of the Sexual Networks of Men Who Have Sex With Men in Montréal, Toronto, and Vancouver: Insights from Canada's 2022 Mpox Outbreak.

BACKGROUND: The 2022-2023 global mpox outbreak disproportionately affected gay, bisexual, and other men who have sex with men (GBM). We investigated differences in GBM's sexual partner distributions across Canada's 3 largest cities and over time, and how they shaped transmission. METHODS: The Engage Cohort Study (2017-2023) recruited GBM via respondent-driven sampling in Montréal, Toronto, and Vancouver (n = 2449). We compared reported sexual partner distributions across cities and periods: before COVID-19 (2017-2019), pandemic (2020-2021), and after lifting of restrictions (2021-2023). We used Bayesian regression and poststratification to model partner distributions. We estimated mpox's basic reproduction number (R0) using a risk-stratified compartmental model. RESULTS: Pre-COVID-19 pandemic distributions were comparable: fitted average partners (past 6 months) were 10.4 (95% credible interval: 9.4-11.5) in Montréal, 13.1 (11.3-15.1) in Toronto, and 10.7 (9.5-12.1) in Vancouver. Sexual activity decreased during the pandemic and increased after lifting of restrictions, but remained below prepandemic levels. Based on reported cases, we estimated R0 of 2.4 to 2.7 and similar cumulative incidences (0.7%-0.9%) across cities. CONCLUSIONS: Similar sexual partner distributions may explain comparable R0 and cumulative incidence across cities. With potential for further recovery in sexual activity, mpox vaccination and surveillance strategies should be maintained.

Prevalence of Oral Human Papillomavirus Infection Among Urban Gay, Bisexual, and Other Men Who Have Sex With Men in Canada, 2017-2019.

BACKGROUND: Oral human papillomavirus (HPV) infections are a leading cause of oropharyngeal cancers. In 2015 and 2016, HPV vaccines became publicly funded for gay, bisexual, and other men who have sex with men (GBM) under 27 years of age in most Canadian provinces. METHODS: Between 2017 and 2019, sexually-active GBM in Montreal, Toronto, and Vancouver were recruited through respondent-driven sampling. Participants aged 16 to 30 years were invited to self-collect oral rinse specimens for HPV testing. We estimated HPV prevalence in the oral tract overall and compared these by vaccination status. RESULTS: Among the 838 GBM with a valid oral specimen, 36.9% reported receiving ≥1 dose of HPV vaccine. Overall, oral HPV prevalence was 2.6% (95% confidence interval, CI: 1.5, 3.7%) for at least one HPV type and 1.2% (95% CI: 0.5, 1.9%) for any high-risk type. We detected quadrivalent (HPV 6/11/16/18) vaccine-preventable types in 0.3% (95% CI: 0.0, 1.0%) of vaccinated individuals and 1.1% (95% CI: 0.1, 2.0%) in unvaccinated individuals. CONCLUSIONS: Oral HPV prevalence was low in a population of young urban GBM in Canada of whom 37% were vaccinated. Findings serve as a benchmark for monitoring of vaccination impacts on oral HPV infection within this priority population.

The Fading of the Mpox Outbreak Among Men Who Have Sex With Men: A Mathematical Modelling Study.

BACKGROUND: In the Netherlands, the number of mpox cases started declining before mpox vaccination was initiated. Most cases were men who have sex with men (MSM). We investigated whether the decline in mpox could be attributed to infection-induced immunity or behavioral adaptations. METHODS: We developed a transmission model and accounted for possible behavioral adaptations: fewer casual partners and shorter time until MSM with mpox refrain from sexual contacts. RESULTS: Without behavioral adaptations, the peak in modelled cases matched observations, but the decline was less steep than observed. With behavioral adaptations in the model, we found a decline of 16%-18% in numbers of casual partners in June and 13%-22% in July 2022. Model results showed a halving of the time before refraining from sex. When mpox vaccination started, 57% of MSM with very high sexual activity in the model had been infected. Model scenarios revealed that the outbreak could have waned by November 2022 even without vaccination. CONCLUSIONS: The limited duration of the mpox outbreak in the Netherlands can be ascribed primarily to infection-induced immunity among MSM with high sexual activity levels. The decline was accelerated by behavioral adaptations. Immunity among those most sexually active is essential to impede mpox resurgence.

Exploring the Resurgence of a Neglected Disease: Lessons From the 2023-2024 Mpox Outbreak in Rio de Janeiro, Brazil.

Following the 2022 global mpox outbreak, diagnoses decreased worldwide, even in settings with limited vaccine access. In 2023-2024, a new outbreak emerged in Rio de Janeiro, Brazil, highlighting the importance of continuous surveillance, preventive measures such as vaccination in vulnerable populations, and treatment options, emphasizing equitable global health technology distribution.

Effect of testosterone therapy on breast tissue composition and mammographic breast density in trans masculine individuals.

BACKGROUND: The effect of gender-affirming testosterone therapy (TT) on breast cancer risk is unclear. This study investigated the association between TT and breast tissue composition and breast tissue density in trans masculine individuals (TMIs). METHODS: Of the 444 TMIs who underwent chest-contouring surgeries between 2013 and 2019, breast tissue composition was assessed in 425 TMIs by the pathologists (categories of lobular atrophy and stromal composition) and using our automated deep-learning algorithm (% epithelium, % fibrous stroma, and % fat). Forty-two out of 444 TMIs had mammography prior to surgery and their breast tissue density was read by a radiologist. Mammography digital files, available for 25/42 TMIs, were analyzed using the LIBRA software to obtain percent density, absolute dense area, and absolute non-dense area. Linear regression was used to describe the associations between duration of TT use and breast tissue composition or breast tissue density measures, while adjusting for potential confounders. Analyses stratified by body mass index were also conducted. RESULTS: Longer duration of TT use was associated with increasing degrees of lobular atrophy (p < 0.001) but not fibrous content (p = 0.82). Every 6 months of TT was associated with decreasing amounts of epithelium (exp(ß) = 0.97, 95% CI 0.95,0.98, adj p = 0.005) and fibrous stroma (exp(ß) = 0.99, 95% CI 0.98,1.00, adj p = 0.05), but not fat (exp(ß) = 1.01, 95%CI 0.98,1.05, adj p = 0.39). The effect of TT on breast epithelium was attenuated in overweight/obese TMIs (exp(ß) = 0.98, 95% CI 0.95,1.01, adj p = 0.14). When comparing TT users versus non-users, TT users had 28% less epithelium (exp(ß) = 0.72, 95% CI 0.58,0.90, adj p = 0.003). There was no association between TT and radiologist's breast density assessment (p = 0.58) or LIBRA measurements (p > 0.05). CONCLUSIONS: TT decreases breast epithelium, but this effect is attenuated in overweight/obese TMIs. TT has the potential to affect the breast cancer risk of TMIs. Further studies are warranted to elucidate the effect of TT on breast density and breast cancer risk.

Mpox Epidemiology and Vaccine Effectiveness, England, 2023.

Reported mpox cases in England continued at a low but steady frequency during 2023. Of 137 cases reported in 2023, approximately half were acquired overseas and half were in vaccinated persons. Estimated effectiveness of 2-dose vaccine was 80%, and no vaccinated mpox patient was hospitalized.

Pasteurella bettyae Infections in Men Who Have Sex with Men, France.

Pasteurella bettyae is a gram-negative bacillus sporadically involved in human infections; its main reservoirs are cats and dogs. A recent publication suggests the possibility of sexual transmission leading to genital infections in men who have sex with men. We report 9 cases in France of genital infection among this population.

Estimation of Incubation Period of Mpox during 2022 Outbreak in Pereira, Colombia.

We estimated the incubation period for mpox during an outbreak in Pereira, Colombia, using data from 11 confirmed cases. Mean incubation period was 7.1 (95% CI 4.9-9.9) days, consistent with previous outbreaks. Accurately estimating the incubation period provides insights into transmission dynamics, informing public health interventions and surveillance strategies.