Atypical Spitz tumor with SQSTM1::NTRK2 fusion: Report of a case with unique spindled cell features.

A host of signature genetic alterations have been demonstrated in Spitz neoplasms, most notably fusions of kinase genes (including BRAF, ALK, ROS1, NTRK1, NTRK3, RET, MET, MAP3K8) or variants in HRAS. While there are multiple reports of rearrangements involving NTRK1 and NTRK3 in Spitz tumors, there are very few reports of NTRK2-rearranged Spitz nevi in the literature. This report presents an NTRK2-rearranged atypical Spitz tumor with spindled cell features. The patient was a 6-year-old female with a growing pigmented papule on the back. Histopathological evaluation revealed an asymmetric, biphasic, compound proliferation of melanocytes featuring an epithelioid cell population arranged as variably sized nests and single cells along the basal layer with extension down adnexa, as well as a population of spindled melanocytes with desmoplastic features and loss of Melan-A expression in the dermis. There was partial loss of p16 expression in the epidermal component and diffuse loss in the dermal component. Immunohistochemistry for PRAME, ALK, NTRK1, HRAS Q61R, p53, and BRAF V600E were negative. A SQSTM1::NTRK2 fusion was identified by RNA sequencing. No TERT promoter hotspot variants were detected. This case report expands the known histopathologic spectrum of genetic alterations in Spitz neoplasms.

Mapping Community-Engaged Implementation Strategies with Transgender Scientists, Stakeholders, and Trans-Led Community Organizations.

PURPOSE OF REVIEW: Pre-exposure prophylaxis (PrEP) represents one of the most effective methods of prevention for HIV, but remains inequitable, leaving many transgender and nonbinary (trans) individuals unable to benefit from this resource. Deploying community-engaged PrEP implementation strategies for trans populations will be crucial for ending the HIV epidemic. RECENT FINDINGS: While most PrEP studies have progressed in addressing pertinent research questions about gender-affirming care and PrEP at the biomedical and clinical levels, research on how to best implement gender-affirming PrEP systems at the social, community, and structural levels remains outstanding. The science of community-engaged implementation to build gender-affirming PrEP systems must be more fully developed. Most published PrEP studies with trans people report on outcomes rather than processes, leaving out important lessons learned about how to design, integrate, and implement PrEP in tandem with gender-affirming care. The expertise of trans scientists, stakeholders, and trans-led community organizations is essential to building gender-affirming PrEP systems.

Behaviors associated with HIV transmission risk among rural sexual and gender minority and majority residents.

Multiple rural states and communities experience elevated rates of human immunodeficiency virus (HIV), often associated with diminished healthcare access and increased drug use. Though a substantial proportion of rural populations are sexual and gender minorities (SGM), little is known of this group regarding substance use, healthcare utilization, and HIV transmission behaviors. During May-July 2021, we surveyed 398 individuals across 22 rural Illinois counties. Participants included cisgender heterosexual males (CHm) and females (CHf) (n = 110); cisgender non-heterosexual males and females (C-MSM and C-WSW; n = 264); and transgender individuals (TG; n = 24). C-MSM participants were more likely to report daily-to-weekly alcohol and illicit drug use prescription medication misuse (versus CHf; aOR = 5.64 [2.37-13.41], 4.42 [1.56-12.53], and 29.13 [3.80-223.20], respectively), and C-MSM participants more frequently reported traveling to meet with romantic/sex partners. Further, more C-MSM and TG than C-WSW reported healthcare avoidance and denial due to their orientation/identity (p < 0.001 and p = 0.011, respectively); 47.6% of C-MSM and 58.3% of TG had not informed their provider about their orientation/identity; and only 8.6% of C-MSM reported ever receiving a pre-exposure prophylaxis (PrEP) recommendation. More work is needed to explore the substance use and sexual behaviors of rural SGM, as well as their healthcare interactions, to better target health and PrEP engagement campaigns.

Changes in Sexual Behaviors Due to Mpox: a Cross-Sectional Study of Sexual and Gender Minority Individuals in Illinois.

The spread of the monkeypox virus (mpox) in 2022 primarily within the sexual networks of men who have sex with men (MSM) triggered a potentially stigmatizing public health response in the USA. Despite mpox being primarily spread through skin-to-skin contact, most messaging has promoted abstinence and/or reduction in sexual risk behaviors. More research is needed on decreases in sexual risk behaviors among sexual and gender minority (SGM) youth and young adults (YYA) related to the most recent mpox epidemic and whether there are factors associated with these decreases in sexual risk behavior. Participants within an ongoing cohort study of SGM YYA who reside in Illinois were offered the opportunity to participate in an mpox survey between September 10th and September 20th, 2022. Analyses looked at demographic factors associated with sexual activity since the start of the outbreak, as well as associations with two sexual risk reduction factors. Survey participation was 68.7% (322/469). Three-quarters of participants (82.6%) reported sexual activity since June 1st. Most sexually active participants (83.5%) adopted at least one sexual risk reduction behavior due to mpox. Black and Latinx individuals were less likely to be sexually active but more likely to report risk reduction behaviors (31.3% and 22.6%, respectively). Participants who received the mpox vaccine were more likely to report sexual activity. SGM YYA in Illinois reported that their sexual behaviors were impacted by the mpox outbreak. However, associations between vaccination and sexual behavior demonstrate that those who are vaccinated do adopt protective methods despite not decreasing sexual activity. Therefore, sex-positive communications and harm reduction messaging may be more appropriate as opposed to abstinence-only prevention, which can further stigmatize an already marginalized group.

Trends in heroin use and injection drug use among high school students in five urban school districts in the US (2005-2017).

Background. We describe the prevalence of and changes in heroin use and injection drug use (IDU) among high school students in five large, urban school districts in the US (2005-2017); nearly three-fourths of the students were Black and/or Hispanic/Latino.Methods. Data are from the Centers for Disease Control and Prevention's "Youth Risk Behavior Survey" program, which includes biennial surveys in urban school districts. We pooled data across districts and survey years, and then generated weighted prevalence estimates (and 95% CIs) for any lifetime heroin use and IDU. Joinpoint regression modeling was used to estimate changes in prevalence over the study period.Results. Biennial prevalence estimates (2005-2017) for heroin use and IDU were above 1.8% for all seven timepoints. In 2017, prevalence of heroin use and IDU were 2.9% and 2.5%, respectively. Both heroin use and IDU were higher among boys than girls. There were statistically significant increases in heroin use and IDU among girls from 2005-2009, whereas changes over time were stable among boys.Conclusions. High school students in large, urban school districts may have higher rates of heroin use and IDU than US high school students in general, and there is little evidence of increases since 2009. This study suggests that adolescence may be a critical period for initiation of heroin use among adolescents in large urban school districts, the majority of whom are Black and/or Latino.Supplemental data for this article is available online at https://doi.org/10.1080/15332640.2021.1992327 .

Proteobacteria abundance during nursing predicts physical growth and brain volume at one year of age in young rhesus monkeys.

Over the last decade, multiple studies have highlighted the essential role of gut microbiota in normal infant development. However, the sensitive periods during which gut bacteria are established and become associated with physical growth and maturation of the brain are still poorly defined. This study tracked the assembly of the intestinal microbiota during the initial nursing period, and changes in community structure after transitioning to solid food in infant rhesus monkeys (Macaca mulatta). Anthropometric measures and rectal swabs were obtained at 2-month intervals across the first year of life and bacterial taxa identified by 16S rRNA gene sequencing. At 12 months of age, total brain and cortical regions volumes were quantified through structural magnetic resonance imaging. The bacterial community structure was dynamic and characterized by discrete maturational phases, reflecting an early influence of breast milk and the later transition to solid foods. Commensal microbial taxa varied with diet similar to findings in other animals and human infants; however, monkeys differ in the relative abundances of Lactobacilli and Bifidobacteria, two taxa predominant in breastfed human infants. Higher abundances of taxa in the phylum Proteobacteria during nursing were predictive of slower growth trajectories and smaller brain volumes at one year of age. Our findings define discrete phases of microbial succession in infant monkeys and suggest there may be a critical period during nursing when endogenous differences in certain taxa can shift the community structure and influence the pace of physical growth and the maturational trajectory of the brain.

HIV Response Interventions that Integrate HIV Molecular Cluster and Social Network Analysis: A Systematic Review.

Due to improved efficiency and reduced cost of viral sequencing, molecular cluster analysis can be feasibly utilized alongside existing human immunodeficiency virus (HIV) prevention strategies. The goal of this paper is to elucidate how HIV molecular cluster and social network analyses are being integrated to implement HIV response interventions. We searched PubMed, Scopus, PsycINFO, and Cochrane Library databases for studies incorporating both HIV molecular cluster and social network data. We identified 32 articles that combined analyses of HIV molecular sequences and social or sexual networks. All studies were descriptive. Six studies described network interventions informed by molecular and social data but did not fully evaluate their efficacy. There is no current standard for incorporating molecular and social network analyses to inform interventions or data demonstrating its utility. More research must be conducted to delineate benefits and best practices for leveraging molecular data for network-based interventions.

RESUMEN: Debido a mejor eficiencia y costo reducido de la secuenciación viral, el análisis de complejos moleculares se puede utilizar de manera factible junto con las estrategias de prevención del virus de inmunodeficiencia humana (VIH) existentes. El objetivo de este repaso es de aclarar como integrar los análisis de las redes sociales y de los complejos moleculares del VIH para implementar intervenciones para controlar el VIH. Buscamos en las bases de datos de PubMed, Scopus, PsycINFO y Cochrane Library por estudios que incorporaran datos de redes sociales y grupos moleculares del VIH. Identificamos 32 estudios que combinaban análisis de secuencias moleculares del VIH y datos de redes sociales. Todos los estudios fueron descriptivos. Seis estudios describieron intervenciones informadas por datos moleculares y sociales, pero no evaluaron completamente su eficacia. No existe un estándar actual para incorporar análisis moleculares y sociales para informar intervenciones o datos que demuestren su eficacia. Se deben realizar más investigaciones para delinear los beneficios y las mejores prácticas de aplicar los datos moleculares y sociales para crear intervenciones del VIH.

Associations between HIV Testing and Consent Policies among Sexually Active Adolescents: Differences by Sexual Behavior.

HIV incidence remains high among US youth, especially among sexual minority youth. However, only half of youth with HIV are aware of their status. One potential explanation for low HIV testing rates is that restrictive policies may prevent minors from access HIV testing due to parental consent requirements. Using pooled data from the local Youth Risk Behavior Survey, we assessed whether state HIV testing laws, including age restrictions and explicit inclusion of HIV in STI testing consent laws, were associated with differences in HIV testing rates; differences by sexual behavior were also examined. Among female youth, policies were not associated with HIV testing. However, among male youth, both the presence of age restrictions and explicit inclusion in STI services were significantly associated with increased odds of HIV testing. Results indicate that policy changes may be effective at increasing testing among male youth who have sex with other males.

A retrospective analysis of diagnostic testing in a large North American cohort of patients with epidermolysis bullosa.

BACKGROUND: Accurate diagnosis of epidermolysis bullosa (EB) has significant implications for prognosis, management, and genetic counseling. OBJECTIVE: To describe diagnostic testing patterns and assess diagnostic concordance of transmission electron microscopy (TEM), immunofluorescence mapping (IFM), and genetic analysis for EB. METHODS: A retrospective cohort included patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2004, to July 8, 2019. Tests concluding the same EB type (EB simplex, junctional EB, dominant dystrophic EB, and recessive dystrophic EB) were considered concordant; those concluding different EB types were considered discordant; and those with nonspecific/nondefinitive results were equivocal. RESULTS: A total of 970 diagnostic tests were conducted from 1984 to 2018 in 771 patients. Genetic analyses were performed chronologically later than IFM or TEM (P < .001). The likelihood of undergoing genetic analysis was greater for junctional EB and recessive dystrophic EB, and the same for dominant dystrophic EB as compared with EB simplex. TEM results in 163 patients were equivocal (55%), concordant (42%), and discordant (3%). IFM results in 185 patients were equivocal (54%), concordant (42%), and discordant (4%). LIMITATIONS: Retrospective design. CONCLUSIONS: Diagnostic testing has shifted in favor of genetic analysis. TEM and IFM frequently offer equivocal findings when compared to the specificity afforded by genetic analysis.

Someone to talk to: the association of mentorship and cyberbullying with suicidality among US high school students.

OBJECTIVE: Suicide is the second-leading cause of death in youth. We tested whether having a mentoring relationship associated with lower risks for suicidality, particularly among youth at higher risk due to cyberbullying. METHODS: This study pooled the 2017 Youth Risk Behavior Survey (YRBS) data from five jurisdictions that asked students if there was at least one teacher or other adult in their school that they could talk with, if they have a problem (mentorship). Students self-reported cyberbullying exposure and suicidality in the past 12 months. Odds of suicidal ideation, planning, and attempts were estimated using multivariable weighted logistic regression in overall and sex-stratified stepwise models. Interactions between mentorship and cyberbullying were also tested. RESULTS: Of the 25,527 student respondents, 87% reported having a mentoring relationship. Mentoring relationships were associated with lower odds of suicidal ideation (aOR, 0.44; 95% CI 0.33-0.57), planning (aOR, 0.59; 95% CI 0.41-0.85), and suicide attempts (aOR, 0.42; 95% CI 0.31-0.56). Stratified analyses showed a significant interaction between cyberbullying and mentorship with suicidal attempts among males, and a near-significant association between cyberbullying and mentorship with suicidal thoughts among females. Compared to male students with no cyberbullying and no mentorship, odds of attempting suicide were lower for males with no cyberbullying and mentorship (aOR, 0.55, 95% CI 0.32-0.92), higher for males with cyberbullying and no mentorship (aOR, 7.78, 95% CI 3.47-17.47), but not significantly different for males with cyberbullying and mentoring relationships (aOR, 1.49, 95% CI 0.86-2.48). Similarly, compared with females with no cyberbullying and no mentorship, odds of having suicidal thoughts were lower for females with no cyberbullying and mentorship (aOR, 0.40, 95% CI 0.28-0.57), and higher for females with cyberbullying and no mentorship (aOR, 2.54, 95% CI 1.59-4.07). CONCLUSION: School-based mentoring may mitigate risk of suicidality among adolescents and limit the toxic effects of cyberbullying.

Network Analysis of Organizations Providing HIV Services in Chicago: Toward an Integrated Response to the HIV Epidemic.

CONTEXT: The public health response to the HIV epidemic has increasingly centered on the uptake of and adherence to biomedical interventions (eg, pre-exposure prophylaxis [PrEP], treatment as prevention [TasP]). Traditionally, various community and health care organizations have worked to address different stages of PrEP or TasP care. OBJECTIVE: To understand the importance of how HIV prevention organizations providing these services interact to provide the comprehensive care needed for successful HIV and PrEP continuum outcomes. DESIGN: Utilizing an Organizational Network Survey, network ties were examined between formal and informal partnerships among community agencies. SETTING: This study examined community agencies in the current HIV prevention system in Chicago. PARTICIPANTS: Seventy-two community agencies across the Chicago metropolitan area. MAIN OUTCOME MEASURES: Using network analysis, this study examined ties between community agencies and assessed perceptions of collaboration and competitiveness in the current HIV prevention system in Chicago. RESULTS: Overall, respondents reported that the current environment of HIV prevention in Chicago was extremely (18.8%), moderately (37.5%), or somewhat collaborative (37.5%) and extremely (68.8%) or moderately competitive (25.0%). The majority of partnerships reported were informal, with less than a quarter being formalized. That said, those who reported formal partnerships reported being satisfied with those relationships. There was a significantly negative association between density and perceived collaboration-grantees experiencing a more collaborative also reported less dense networks. CONCLUSION: These findings indicate that, despite perceived competitiveness, agencies are willing to work together and create a cohesive HIV prevention and treatment system. However, more work should be done to foster an environment that can support the formation of partnerships, to improve a coordinated response to providing HIV care, and sustain mutually beneficial relationships.

Compositional shifts in root-associated bacterial and archaeal microbiota track the plant life cycle in field-grown rice.

Bacterial communities associated with roots impact the health and nutrition of the host plant. The dynamics of these microbial assemblies over the plant life cycle are, however, not well understood. Here, we use dense temporal sampling of 1,510 samples from root spatial compartments to characterize the bacterial and archaeal components of the root-associated microbiota of field grown rice (Oryza sativa) over the course of 3 consecutive growing seasons, as well as 2 sites in diverse geographic regions. The root microbiota was found to be highly dynamic during the vegetative phase of plant growth and then stabilized compositionally for the remainder of the life cycle. Bacterial and archaeal taxa conserved between field sites were defined as predictive features of rice plant age by modeling using a random forest approach. The age-prediction models revealed that drought-stressed plants have developmentally immature microbiota compared to unstressed plants. Further, by using genotypes with varying developmental rates, we show that shifts in the microbiome are correlated with rates of developmental transitions rather than age alone, such that different microbiota compositions reflect juvenile and adult life stages. These results suggest a model for successional dynamics of the root-associated microbiota over the plant life cycle.

Evaluation of a Text Messaging-Based Human Papillomavirus Vaccination Intervention for Young Sexual Minority Men: Results from a Pilot Randomized Controlled Trial.

BACKGROUND: Men who have sex with men (MSM) are at high risk for human papillomavirus (HPV) infection and HPV-related anal cancer. Although a safe and effective vaccine is available to prevent HPV infection, HPV vaccine uptake among young MSM remains low. PURPOSE: This pilot randomized controlled trial tested the acceptability, feasibility, and preliminary efficacy of a text messaging-based HPV vaccination intervention for young sexual minority men. METHODS: In 2018, unvaccinated sexual minority men aged 18-25 years were recruited from Chicago to participate in a 9 month sexual health program called txt2protect. Participants (N = 150) were randomized to the intervention or control condition. Intervention condition messages focused primarily on HPV vaccination, with only a brief mention of other sexual health practices (e.g., condom use and HIV testing), while control condition messages focused on a variety of sexual health practices with only a brief mention of HPV vaccination. Participants received daily text messages for the first 3 weeks and monthly text messages for the remaining ~8 months of the trial. Participants completed surveys at baseline and 3 week and 9 month follow-ups. RESULTS: Participants reported high satisfaction with the intervention. Although trial retention was high (with over 88% completing the 9 month survey), the study fell short of meeting its recruitment goal. HPV vaccine series initiation was significantly higher among intervention participants (19.4%) compared to control participants (6.6%), odds ratio = 3.43, 95% confidence interval: 1.17, 10.08. CONCLUSIONS: Findings suggest that txt2protect is an acceptable and potentially promising intervention for increasing HPV vaccine initiation among young sexual minority men. CLINICAL TRIAL REGISTRATION: NCT02994108.

Structural Interventions for HIV Prevention and Care Among US Men Who Have Sex with Men: A Systematic Review of Evidence, Gaps, and Future Priorities.

The preponderance of HIV interventions have been behavioral, targeting individual, dyadic, or group dynamics. However, structural-level interventions are required to decrease HIV transmission and increase engagement in care, especially for men who have sex with men (MSM), particularly Black and Latinx MSM. A systematic literature review was conducted to assess the current state of structural interventions; only two studies detailing structural interventions related to HIV for Black and Latinx MSM in the US were identified. An additional 91 studies which discussed structural-level barriers to optimal HIV outcomes among MSM, yet which did not directly evaluate a structural intervention, were also identified. While this paucity of findings was discouraging, it was not unexpected. Results of the systematic review were used to inform guidelines for the implementation and evaluation of structural interventions to address HIV among MSM in the U.S. These include deploying specific interventions for multiply marginalized individuals, prioritizing the deconstruction of structural stigma, and expanding the capacity of researchers to evaluate "natural" policy-level structural interventions through a standardization of methods for rapid evaluative response, and through universal application of sex, sexual orientation, and gender identity demographic measures.

Dermatologic infections in cancer patients treated with checkpoint inhibitors.

BACKGROUND: The incidence of dermatologic infections in patients receiving checkpoint inhibitors (CPIs) has not been systematically described. OBJECTIVE: Identify the incidence of dermatologic infections in patients who received CPIs. METHODS: Retrospective review of dermatologic infections in patients who received CPIs between 2005 and 2020 and were evaluated by dermatologists at Memorial Sloan Kettering Cancer Center. RESULTS: Of 2061 patients in the study, 1292 were actively receiving CPIs (≤ 90 days since the last dose) and 769 had previously been on CPIs (> 90 days since the last dose). The dermatologic infection rate was significantly higher in patients with active CPI treatment (17.5%) than in patients not actively being treated (8.2%; P < .0001). In patients on CPIs, 82 (36.2%), 78 (34.5%), and 48 (21.2%) had bacterial, fungal, and viral infections, respectively, and 18 (8.0%) had polymicrobial infections. Anti-cytotoxic T-lymphocyte-associated antigen-4 monotherapy was associated with the highest risk of infection (hazard ratio, 2.93; 95% confidence interval, 1.87 to 4.60; P < .001). LIMITATIONS: Retrospective design and sample limited to patients referred to dermatology. CONCLUSIONS: Patients actively receiving CPIs are more susceptible to dermatologic infections, with anti-cytotoxic T-lymphocyte-associated antigen-4 monotherapy carrying the highest risk, suggesting that the index of suspicion for infections should be increased in these patients to minimize morbidity and optimize care.

Associations Between LGBTQ-Affirming School Climate and Intimate Partner Violence Victimization Among Adolescents.

Intimate partner violence (IPV) impacts sexual minority adolescents at rates equal to or greater than the rate it impacts heterosexual adolescents. We investigated whether reports of physical and sexual IPV were less frequent in school jurisdictions with more affirming climates for lesbian, gay, bisexual, transgender, and queer (LGBTQ) students; and whether these associations varied for sexual orientation subgroups. We combined student-level data from the 2015 Youth Risk Behavior Surveys on demographics and experiences with physical and sexual IPV with jurisdiction-level data from the 2014 School Health Profiles on LGBTQ-affirming school climate. Multilevel logistic regression models examined associations between LGBTQ-affirming school climates and IPV. We stratified our data by sex and examined whether these associations differed by sexual orientation subgroups using cross-level interaction terms between school climate and sexual orientation (assessed via sexual identity and behavior). Sexual minority youth were more likely to report experiencing past-year physical and sexual IPV than their heterosexual counterparts. Attending schools with more LGBTQ-affirming climates reduced the likelihood of reporting physical IPV, but not sexual IPV, for female students. More LGBTQ-affirming school climates increased risk for sexual IPV among gay male students. Establishing LGBTQ-affirming school climates may reduce physical IPV for female students, but may have unintended consequences on sexual IPV prevalence for gay male students. More work is necessary to ensure that these climates are affirming for all sexual minority students and to address sexual violence prevention.

Lifetime Asthma Prevalence and Correlates Among US Youths by Sexual Identity and Race/Ethnicity, 2009-2017.

Objectives. To comprehensively assess asthma disparities and identify correlates in youths at the intersections of sex, sexual identity, and race/ethnicity in the United States.Methods. We obtained a diverse sample of youths (n = 307 073) from the Centers for Disease Control and Prevention's Youth Risk Behavior Survey. We pooled data across 107 jurisdiction-years (2009-2017). We calculated lifetime asthma prevalence by sexual identity, race/ethnicity, and their intersections-stratified by sex. We developed multivariable weighted logistic regression models to examine the impact of selected correlates on lifetime asthma prevalence.Results. Lesbian, gay, and bisexual youths have significant disparities in asthma prevalence compared with heterosexual peers. Moreover, across sex, higher prevalence of lifetime asthma was seen for most sexual identity and race/ethnicity subpopulations (27 of 30) when compared with White heterosexual sex-matched participants. Selected traditional risk factors (overweight, obese, and smoking) and bullying tended to attenuate odds among groups, especially those with a minority sexual identity.Conclusions. Asthma inequities at the intersection of sexual identity and race/ethnicity are substantive. Future studies should investigate the mechanisms contributing to these disparities to promote health equity among vulnerable youth populations. (Am J Public Health. Published online ahead of print May 21, 2020: e1-e8. doi:10.2105/AJPH.2020.305664).

Landscape of HIV Implementation Research Funded by the National Institutes of Health: A Mapping Review of Project Abstracts.

In 2019, the requisite biomedical and behavioral interventions to eliminate new HIV infections exist. "Ending the HIV Epidemic" now becomes primarily a challenge of will and implementation. This review maps the extent to which implementation research (IR) has been integrated into HIV research by reviewing the recent funding portfolio of the NIH. We searched NIH RePORTER for HIV and IR-related research projects funded from January 2013 to March 2018. The 4629 unique studies identified were screened using machine learning and manual methods. 216 abstracts met the eligibility criteria of HIV and IR. Key study characteristics were then abstracted. NIH currently funds HIV studies that are either formally IR (n = 109) or preparatory for IR (n = 107). Few (13%) projects mentioned a guiding implementation model, theory, or framework, and only 56% of all studies explicitly mentioned measuring an implementation outcome. Considering the study aims along an IR continuum, 18 (8%) studies examined barriers and facilitators, 43 (20%) developed implementation strategies, 46 (21%) piloted strategies, 73 (34%) tested a single strategy, and 35 (16%) compared strategies. A higher proportion of formal IR projects involved established interventions (e.g., integrated services) compared to newer interventions (e.g., pre-exposure prophylaxis). Prioritizing HIV-related IR in NIH and other federal funding opportunity announcements and expanded training in implementation science could have a substantial impact on ending the HIV pandemic. This review serves as a baseline by which to compare funding patterns and the sophistication of IR in HIV research over time.

Immune checkpoint inhibitors to treat cutaneous malignancies.

As the incidence of cutaneous malignancies continues to rise and their treatment with immunotherapy expands, dermatologists and their patients are more likely to encounter immune checkpoint inhibitors. While the blockade of immune checkpoint target proteins (cytotoxic T-lymphocyte-associated protein-4, programmed cell death-1, and programmed cell death ligand-1) generates an antitumor response in a substantial fraction of patients, there is a critical need for reliable predictive biomarkers and approaches to address refractory disease. The first article of this Continuing Medical Education series reviews the indications, efficacy, safety profile, and evidence supporting checkpoint inhibition as therapeutics for metastatic melanoma, cutaneous squamous cell carcinoma, and Merkel cell carcinoma. Pivotal studies resulting in the approval of ipilimumab, pembrolizumab, nivolumab, cemiplimab, and avelumab by regulatory agencies for various cutaneous malignancies, as well as ongoing clinical research trials, are discussed.

Immune checkpoint inhibitor-related dermatologic adverse events.

Immune checkpoint inhibitors have emerged as a pillar in the management of advanced malignancies. However, nonspecific immune activation may lead to immune-related adverse events, wherein the skin and its appendages are the most frequent targets. Cutaneous immune-related adverse events include a diverse group of inflammatory reactions, with maculopapular rash, pruritus, psoriasiform and lichenoid eruptions being the most prevalent subtypes. Cutaneous immune-related adverse events occur early, with maculopapular rash presenting within the first 6 weeks after the initial immune checkpoint inhibitor dose. Management involves the use of topical corticosteroids for mild to moderate (grades 1-2) rash, addition of systemic corticosteroids for severe (grade 3) rash, and discontinuation of immunotherapy with grade 4 rash. Bullous pemphigoid eruptions, vitiligo-like skin hypopigmentation/depigmentation, and psoriasiform rash are more often attributed to programmed cell death-1/programmed cell death ligand-1 inhibitors. The treatment of bullous pemphigoid eruptions is similar to the treatment of maculopapular rash and lichenoid eruptions, with the addition of rituximab in grade 3-4 rash. Skin hypopigmentation/depigmentation does not require specific dermatologic treatment aside from photoprotective measures. In addition to topical corticosteroids, psoriasiform rash may be managed with vitamin D3 analogues, narrowband ultraviolet B light phototherapy, retinoids, or immunomodulatory biologic agents. Stevens-Johnson syndrome and other severe cutaneous immune-related adverse events, although rare, have also been associated with checkpoint blockade and require inpatient care as well as urgent dermatology consultation.