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Simple Summary: Crimean–Congo haemorrhagic fever (CCHF) is an emerging disease that is spreading across the globe. We originally released a predictive map in 2015, which we now update and improve by extending its coverage to Europe and by incorporating the limiting distributions of its main confirmed or potential tick vectors in Europe: Hyalomma marginatum and Hyalomma lusitanicum. Our new models suggest that the disease risk is now predicted to cover substantial parts of southern and central Europe. These maps can be used to more effectively target surveillance and monitoring. Crimean–Congo haemorrhagic fever (CCHF) is considered to be spreading across the globe, with many countries reporting new human CCHF cases in recent decades including Georgia, Türkiye, Albania, and, most recently, Spain. We update a human CCHF distribution map produced in 2015 to include global disease occurrence records to June 2022, and we include the recent records for Europe. The predicted distributions are based on long-established spatial modelling methods and are extended to include all European countries and the surrounding areas. The map produced shows the environmental suitability for the disease, taking into account the distribution of the most important known and potential tick vectors Hyalomma marginatum and Hyalomma lusitanicum, without which the disease cannot occur. This limits the disease's predicted distribution to the Iberian Peninsula, the Mediterranean seaboard, along with Türkiye and the Caucasus, with a more patchy suitability predicted for inland Greece, the southern Balkans, and extending north to north-west France and central Europe. These updated CCHF maps can be used to identify the areas with the highest probability of disease and to therefore target areas where mitigation measures should currently be focused. [ABSTRACT FROM AUTHOR]

Patients who are treated early typically test RPR-negative within 3 years.2 In patients with syphilis, it is imperative to screen for other STDs, as well as blood-borne viruses, based on patient characteristics and locational demographics if a patient has syphilis, given their increased risk of concurrent STDs. CPD questions Learning objective To gain up-to-date knowledge on both the common and uncommon characteristics of syphilis, and on the common differential diagnoses of cutaneous syphilis. Discussion Syphilis, a sexually transmitted disease, is caused by the spirochaete I T i . [Extracted from the article]

Lay Summary: Pathologists sometimes have great difficulty in determining whether a mole biopsied from the skin of a child is benign or malignant.New molecular technologies have helped pathologists to identify pediatric melanomas, but there are still some atypical moles that cannot be definitively classified as benign or malignant.With further research, it is hoped that the number of these atypical tumors can be decreased and that the treatment for all children with moles and melanoma can be improved. Molecular genetic techniques have broadened our understanding of the diagnostic classification of pediatric melanoma and atypical melanocytic proliferations such as Spitz tumors. These techniques should be incorporated into standard approaches to diagnosing and classifying atypical or malignant pediatric melanocytic lesions. [ABSTRACT FROM AUTHOR]

The coronavirus pandemic greatly disrupted the lives of people. Restrictions introduced worldwide to limit the spread of infection included stay-at-home orders, closure of venues, restrictions to travel and limits to social contacts. During this time, parks and outdoor greenspaces gained prominent attention as alternative location for respite. Population mobility data offers a unique opportunity to understand the impact of the pandemic on outdoor behaviour. We examine the role of the restrictions on park use throughout the full span of the pandemic while controlling for weather and region. This study provides a longitudinal population analysis of park visitation using Google COVID-19 Community Mobility Reports data in the UK. Daily park visitation was plotted and ANOVA analyses tested season and year effects in visitation. Then, regressions examined park visitation beyond weather (temperature and rain), according to COVID-19 restrictions, while controlling for region specificities through unit fixed effect models. Time series and ANOVA analyses documented the significant decrease in park visitation in the spring of 2020, the seasonal pattern in visitation, and an overall sustained and elevated use over nearly three years. Regressions confirmed park visitation increased significantly when temperature was greater and when it rained less. More visitation was also seen when there were fewer COVID-19 cases and when the stringency level of restrictions was lower. Of special interest, a significant interaction effect was found between temperature and stringency, with stringency significantly supressing the effect of higher temperature on visitation. COVID-19 restrictions negatively impacted park visitation on warm days. Given the general health, social, and wellbeing benefits of greenspace use, one should consider the collateral negative impact of restrictions on park visitation. When social distancing of contacts is required, the few remaining locations where it can safely occur should instead be promoted. • High frequency population mobility data on park visitation during COVID-19. • Significant drop in park visitation following the start of the pandemic. • Greater park visitation when temperatures were greater and when it rained less. • COVID-19 restriction suppressed the effect of higher temperature on visitation. [ABSTRACT FROM AUTHOR]

Zika virus was discovered in Uganda in 1947 and is transmitted by Aedes mosquitoes, which also act as vectors for dengue and chikungunya viruses throughout much of the tropical world. In 2007, an outbreak in the Federated States of Micronesia sparked public health concern. In 2013, the virus began to spread across other parts of Oceania and in 2015, a large outbreak in Latin America began in Brazil. Possible associations with microcephaly and Guillain-Barre' syndrome observed in this outbreak have raised concerns about continued global spread of Zika virus, prompting its declaration as a Public Health Emergency of International Concern by the World Health Organization. We conducted species distribution modelling to map environmental suitability for Zika. We show a large portion of tropical and sub-tropical regions globally have suitable environmental conditions with over 2.17 billion people inhabiting these areas. [ABSTRACT FROM AUTHOR]

Dengue is a vector-borne disease that causes a substantial public health burden within its expanding range. Several modelling studies have attempted to predict the future global distribution of dengue. However, the resulting projections are difficult to compare and are sometimes contradictory because the models differ in their approach, in the quality of the disease data that they use and in the choice of variables that drive disease distribution. In this Review, we compare the main approaches that have been used to model the future global distribution of dengue and propose a set of minimum criteria for future projections that, by analogy, are applicable to other vector-borne diseases. [ABSTRACT FROM AUTHOR]

The objectives of this study were to investigate the wellbeing trajectories of university students during the COVID-19 pandemic and identify associated protective factors. Results from the study aimed to inform wellbeing-promotion strategies and crisis-response plans in university settings. Systematic review. A review of articles published in English language was conducted in PubMed, PsycINFO, Scopus, Web of Science, and ERIC databases from 1 December 2019 to 15 December 2022. Longitudinal and repeated cross-sectional studies that assessed wellbeing among university students during the COVID-19 pandemic using a validated instrument were included. Article and data extraction were performed by the primary reviewer, with a random subset verified by a second reviewer. Study quality was assessed using the National Institutes of Health 'Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies'. Of 6651 titles screened without duplicates, 181 underwent full-text review, of which 19 were included in the current study (15 longitudinal and 4 repeated cross-sectional studies, with a total of 19,206 participants). A significant decrease in the wellbeing of university students was observed across studies during the early stages of the pandemic compared to prepandemic times; however, mixed findings were found in later phases of the pandemic, with some studies presenting an improvement in wellbeing, others no change, and two studies finding impairments. Overall, wellbeing was greater among males and was also associated with socioeconomic status, more sleep and physical activity, greater social connectedness, less alcohol use, and less social media activity. The study showed varying wellbeing trajectories across different periods of the COVID-19 pandemic. Results provide relevant information for researchers, public health professionals, and higher education institutions in charge of promoting student wellbeing and crisis preparedness. CRD42022383941. [ABSTRACT FROM AUTHOR]

Highlights: [•] The geography of type-specific global DENV circulation has not been well described. [•] We map the global distribution and co-circulation of each DENV type from 1943 to 2013. [•] Detection of all types has expanded worldwide together with growing hyperendemicity. [•] There remains a dearth of type-specific information in many parts of the world. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cutaneous human papillomaviruses (HPVs) may be associated with cutaneous epithelial lesions and non-melanoma skin cancers. No study has systematically evaluated the presence of genus beta [β]-HPV in male genital skin or external genital lesions (EGLs) Objectives: To examine cutaneous β-HPV types detected on the surface of EGLs in men and describe their presence prior to EGL development. Study design: A retrospective case series was conducted among 69 men with pathologically confirmed EGLs (n =72) who participated in the HPV Infection in Men Study. Archived exfoliated cells collected from the surface of each EGL and normal genital skin specimens 6–12 months preceding EGL development were tested for β-HPV DNA using a type-specific multiplex genotyping assay. Results: β-HPV DNA was detected on 61.1% of all EGLs, with types 38 (16.7%), 5 (15.3%), and 12 (12.5%) most commonly identified. HPV prevalence differed across pathological diagnoses, with the largest number of β-HPV types detected on condylomas. Most β-HPV types were detected on normal genital skin prior to EGL development, though the prevalence was lower on EGLs compared to preceding normal genital skin. Conclusions: EGLs and the normal genital skin of men harbor a large number of β-HPV types; however, it appears that β-HPVs are unrelated to EGL development in men. Despite evidence to support a causal role in skin carcinogenesis at UVR-exposed sites, cutaneous HPV appears unlikely to cause disease at the UVR-unexposed genitals. [Copyright &y& Elsevier]

Abstract: Anemia is common in women of child-bearing age in the Democratic Republic of the Congo (DRC). As part of the 2007 DRC Demographic and Health Survey (DHS), 4638 women of childbearing age (including 526 pregnant women) were tested for HIV and had the hemoglobin content of their blood recorded. We used the leftover dried blood spots to assess malaria prevalence using PCR assays. The DHS provided extensive information on individuals, as well as the geographic coordinates of household clusters which enabled us to derive several variables that characterize the spatial context of these clusters. Multilevel analyses were conducted to determine individual and contextual risk factors for anemia. Prevalence varied geographically; the odds of anemia were associated with both one′s ethnic group and the amount and type of nearby agriculture. The odds were not affected by HIV or malaria status. [Copyright &y& Elsevier]

A significant number (81%) of newly diagnosed melanoma patients are of the thin (ie,51 mm) or melanoma in situ category. Since the staging of cutaneous melanoma has recently been revised to include and exclude pathological parameters dealing with thin melanomas, it is increasingly important to incorporate these changes to reflect correct pathological microstaging. We herein review the current AJCC cancer staging system as is relates to melanoma, highlighting a recent study we conducted that demonstrated how expert dermatopathological review at a high volume center can change the stage and ultimately clinical management in thin melanoma patients. This review will discuss the changes reflected in the most recent revision of the 2010 AJCC staging system for malignant melanoma, including detailed instructions of how to approach, interpret, and accurately microstage cutaneous melanoma. Application of the new staging criteria in newly diagnosed melanoma patients at a tertiary care referral center frequently results in changes to treatment-based decisions including surgical excision margins and the performance of a sentinel lymph node biopsy. Key pathological parameters are either frequently omitted or reported incorrectly outside pathology reports. [ABSTRACT FROM AUTHOR]

A significant number (81%) of newly diagnosed melanoma patients are of the thin (ie,51 mm) or melanoma in situ category. Since the staging of cutaneous melanoma has recently been revised to include and exclude pathological parameters dealing with thin melanomas, it is increasingly important to incorporate these changes to reflect correct pathological microstaging. We herein review the current AJCC cancer staging system as is relates to melanoma, highlighting a recent study we conducted that demonstrated how expert dermatopathological review at a high volume center can change the stage and ultimately clinical management in thin melanoma patients. This review will discuss the changes reflected in the most recent revision of the 2010 AJCC staging system for malignant melanoma, including detailed instructions of how to approach, interpret, and accurately microstage cutaneous melanoma. Application of the new staging criteria in newly diagnosed melanoma patients at a tertiary care referral center frequently results in changes to treatment-based decisions including surgical excision margins and the performance of a sentinel lymph node biopsy. Key pathological parameters are either frequently omitted or reported incorrectly outside pathology reports. [ABSTRACT FROM AUTHOR]

The state of Illinois experienced a large outbreak of illness from the West Nile virus in 2002, with the majority of human infections occurring in the greater Chicago area. Although an outbreak as large as the first has not occurred since then, transmission of the virus to humans has persisted, and relatively large outbreaks of human illness occurred again in 2005 and 2006. During the larger outbreaks, some neighborhoods exhibited significantly higher rates of infection than did others. This study first examines the changing spatial distribution of West Nile virus outbreaks in this area from 2002 to 2006. Multivariate statistical analysis with a spatial dependence term then is used to explore the relationship between rates of human WNV infection and potential explanatory environmental and socioeconomic factors and to compare the risk of WNV across years. Several environmental and socioeconomic characteristics were found to be associated with increased risk for human West Nile virus infection, but differences were found in different years. Overall, predominantly white neighborhoods with lower housing density and a greater amount of post—World War II housing were particularly at risk. This research provides a useful example of how aggregated disease data may be mapped and spatial patterns characterized, as well as how these data may be combined with sociodemographic and environmental variables to analyze risk factors in a spatially explicit manner. [ABSTRACT FROM AUTHOR]

Background: Sexually transmitted infections (STI) have made a resurgence in many rapidly developing regions of southern China, but there is little understanding of the social changes that contribute to this spatial distribution of STI. This study examines county-level socio-demographic characteristics associated with syphilis and gonorrhea in Guangdong Province. Methods/Principal Findings: This study uses linear regression and spatial lag regression to determine county-level (n = 97) socio-demographic characteristics associated with a greater burden of syphilis, gonorrhea, and a combined syphilis/ gonorrhea index. Data were obtained from the 2005 China Population Census and published public health data. A range of socio-demographic variables including gross domestic product, the Gender Empowerment Measure, standard of living, education level, migrant population and employment are examined. Reported syphilis and gonorrhea cases are disproportionately clustered in the Pearl River Delta, the central region of Guangdong Province. A higher fraction of employed men among the adult population, higher fraction of divorced men among the adult population, and higher standard of living (based on water availability and people per room) are significantly associated with higher STI cases across all three models. Gross domestic product and gender inequality measures are not significant predictors of reported STI in these models. Conclusions/Significance: Although many ecological studies of STIs have found poverty to be associated with higher reported STI, this analysis found a greater number of reported syphilis cases in counties with a higher standard of living. Spatially targeted syphilis screening measures in regions with a higher standard of living may facilitate successful control efforts. This analysis also reinforces the importance of changing male sexual behaviors as part of a comprehensive response to syphilis control in China. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic data on malaria are scant in many high-burden countries including the Democratic Republic of the Congo (DRC), which suffers the second-highest global burden of malaria. Malaria control efforts in regions with challenging infrastructure require reproducible and efficient surveillance. We employed new high-throughput molecular testing to characterize the state of malaria control in the DRC and estimate childhood mortality attributable to excess malaria transmission. Methods and Findings: The Demographic and Health Survey was a cross-sectional, population-based cluster household survey of adults aged 15-59 years in 2007 employing structured questionnaires and dried blood spot collection. Parasitemia was detected by real-time PCR, and survey responses measured adoption of malaria control measures and under-5 health indices. The response rate was 99% at the household level, and 8,886 households were surveyed in 300 clusters; from 8,838 respondents molecular results were available. The overall prevalence of parasitemia was 33.5% (95% confidence interval [C.I.] 32-34.9); P. falciparum was the most prevalent species, either as monoinfection (90.4%; 95% C.I. 88.8-92.1) or combined with P. malariae (4.9%; 95% C.I. 3.7-5.9) or P. ovale (0.6%; 95% C.I. 0.1-0.9). Only 7.7% (95% CI 6.8-8.6) of households with children under 5 owned an insecticide-treated bednet (ITN), and only 6.8% (95% CI 6.1-7.5) of under-fives slept under an ITN the preceding night. The overall under-5 mortality rate was 147 deaths per 1,000 live births (95% C.I. 141- 153) and between clusters was associated with increased P. falciparum prevalence; based on the population attributable fraction, 26,488 yearly under-5 deaths were attributable to excess malaria transmission. Conclusions: Adult P. falciparum prevalence is substantial in the DRC and is associated with under-5 mortality. Molecular testing offers a new, generalizable, and efficient approach to characterizing malaria endemicity in underserved countries. [ABSTRACT FROM AUTHOR]

Abstract: This study uses a 2007 population-based household survey to examine the individual and community-level factors that increase an individual’s risk for HIV infection in the Democratic Republic of Congo (DRC). Using the 2007 DRC Demographic Health Surveillance (DHS) Survey, we use spatial analytical methods to explore sub-regional patterns of HIV infection in the DRC. Geographic coordinates of survey communities are used to map prevalence of HIV infection and explore geographic variables related to HIV risk. Spatial cluster techniques are used to identify hotspots of infection. HIV prevalence is related to individual demographic characteristics and sexual behaviors and community-level factors. We found that the prevalence of HIV within 25 km of an individual’s community is an important positive indicator of HIV infection. Distance from a city is negatively associated with HIV infection overall and for women in particular. This study highlights the importance of improved surveillance systems in the DRC and other African countries along with the use of spatial analytical methods to enhance understanding of the determinants of HIV infection and geographic patterns of prevalence, thereby contributing to improved allocation of public health resources in the future. [ABSTRACT FROM AUTHOR]

A 55-year-old man presented for a routine preoperative chest X-ray in preparation for a knee replacement. Imaging revealed an extrapleural paraspinal mass in the region of T8. Fine needle aspiration of the mass was interpreted as melanoma. Neurologic examination was unremarkable. Total body skin examination failed to reveal any suspicious pigmented lesions. The mass was in close connection with the exiting T8 nerve root and somewhat adherent to the sympathetic chain. The mass was removed within an intact capsule. Immunohistochemical staining and electron microscopy of the resected specimen revealed a malignant melanotic schwannoma. The features of melanotic schwannoma, both benign and malignant variants, and their distinction from melanoma are discussed. [ABSTRACT FROM AUTHOR]

BACKGROUND. High-risk cutaneous squamous cell carcinoma (SCC) is an aggressive tumor with a significant rate of metastasis, especially nodal, and deaths yearly. Sentinel lymphadenectomy may be a valuable adjunct in the treatment of patients with cutaneous SCC at high risk for metastases with a clinical N0 status. OBJECTIVE. To report the clinical and pathologic features in nine patients who underwent this procedure at a tertiary-care cancer center. METHODS. Since 1995, a total of nine patients from the Cutaneous Oncology Program at the H. Lee Moffitt Cancer Center received preoperative lymphoscintigraphy and sentinel lymphadenectomy for high-risk cutaneous SCC with a clinical N0 status. RESULTS. Histologically positive nodes were found in 4 of 9 cases (44%). Two of the four patients with positive sentinel nodes died of metastatic disease within 2 years. All five patients with negative sentinel nodes are alive and well at a median follow-up of 8 months (mean of 13 months). Preoperative lymphoscintigraphy and sentinel lymphadenectomy were well tolerated by all patients. CONCLUSION. In this small series of predominantly trunk and extremity high-risk SCCs, sentinel lymph node biopsy was technically feasible with low morbidity. Sentinel lymphadenectomy may prove to have an important role in the management of high-risk cutaneous SCC with a clinical N0 status. [ABSTRACT FROM AUTHOR]

The authors reflect on the value of prognostic information in validating the sentinel lymph node (SLN) biopsy in patients with thinner melanoma. They cite the report of M. Mays and colleagues on the SunBelt Melanoma Trial which assesses the impact of a positive SLN on melanoma survival. The authors believe that the time is right to further investigate the growing cases of thinner melanomas and SLN micrometastases.

The COVID‐19 pandemic control measures substantially impacted the life of university students in the UK. While multiple studies investigated early stages of the pandemic, focusing on risk factors for depression and anxiety, fewer studies assessed later phases of the pandemic or examined positive protective factors for mental wellbeing. Our longitudinal study investigated changes and associations between COVID‐19 experiences, lifestyle behaviours, social connectedness and mental wellbeing in the second year of the pandemic. The validated Warwick–Edinburgh Mental Wellbeing Scale was used to measure the primary outcome mental wellbeing. Self‐reported data from 161 university students (18–35‐year‐old) in England was obtained. Data collection took place across two time points with contrasting COVID‐19 epidemiological and countermeasure attributes. T1 occurred in the spring of 2021, during the tail end of the third national lockdown when indoor household mixing was prohibited and vaccination rates were low among 18–35 year olds. T2 took place 6 months later, in the autumn of 2021, when restrictions had ended and vaccination rates were high. Within‐participant changes in students showed that mental wellbeing significantly improved over 6 months, suggesting positive adjustment. Fear of COVID‐19 and engagement in COVID‐19 protective behaviours significantly decreased as pandemic restrictions eased. Physical activity levels were high and did not change over time, while greenspace visits significantly diminished. Social support remained the same and group membership significantly increased over time. Hierarchal regressions revealed that social support was the most critical contributor to mental wellbeing. We discuss lessons for mental wellbeing promotion strategies: encouraging the use of greenspace as locations for distanced social interaction and physical activity in times of lockdown constraints. [ABSTRACT FROM AUTHOR]

The 2015–17 Zika virus (ZIKV) epidemic in the Americas subsided faster than expected and evolving population immunity was postulated to be the main reason. Herd immunization is suggested to occur around 60–70% seroprevalence, depending on demographic density and climate suitability. However, herd immunity was only documented for a few cities in South America, meaning a substantial portion of the population might still be vulnerable to a future Zika virus outbreak. The aim of our study was to determine the vulnerability of populations to ZIKV by comparing the environmental suitability of ZIKV transmission to the observed seroprevalence, based on published studies. Using a systematic search, we collected seroprevalence and geospatial data for 119 unique locations from 37 studies. Extracting the environmental suitability at each location and converting to a hypothetical expected seroprevalence, we were able to determine the discrepancy between observed and expected. This discrepancy is an indicator of vulnerability and divided into three categories: high risk, low risk, and very low risk. The vulnerability was used to evaluate the level of risk that each location still has for a ZIKV outbreak to occur. Of the 119 unique locations, 69 locations (58%) fell within the high risk category, 47 locations (39%) fell within the low risk category, and 3 locations (3%) fell within the very low risk category. The considerable heterogeneity between environmental suitability and seroprevalence potentially leaves a large population vulnerable to future infection. Vulnerability seems to be especially pronounced at the fringes of the environmental suitability for ZIKV (e.g. Sao Paulo, Brazil). The discrepancies between observed and expected seroprevalence raise the question: "why did the ZIKV epidemic stop with large populations unaffected?". This lack of understanding also highlights that future ZIKV outbreaks currently cannot be predicted with confidence. Author summary: After the ZIKV epidemic in the Americas, it remains unclear if and when a resurgence of the ZIKV could occur. We used publicly available data on environmental suitability of transmission as well as seroprevalence data to estimate future vulnerability to ZIKV outbreaks. Our results show a considerable discrepancy between the observed seroprevalence, from past exposure to the virus on one hand, and the environmental suitability, which raised the question why the epidemic subsided before reaching the expected herd immunization threshold in many locations. This lack of understanding also highlights that future ZIKV outbreaks currently cannot be predicted with confidence. Although we cannot provide an answer to the question why the epidemic subsided when it did, we present a better quantification and geospatial mapping of the potential vulnerability to future outbreaks, which will be crucial for decision makers to prepare for future outbreaks. [ABSTRACT FROM AUTHOR]

Background: Aedes (Stegomyia)-borne diseases are an expanding global threat, but gaps in surveillance make comprehensive and comparable risk assessments challenging. Geostatistical models combine data from multiple locations and use links with environmental and socioeconomic factors to make predictive risk maps. Here we systematically review past approaches to map risk for different Aedes-borne arboviruses from local to global scales, identifying differences and similarities in the data types, covariates, and modelling approaches used. Methods: We searched on-line databases for predictive risk mapping studies for dengue, Zika, chikungunya, and yellow fever with no geographical or date restrictions. We included studies that needed to parameterise or fit their model to real-world epidemiological data and make predictions to new spatial locations of some measure of population-level risk of viral transmission (e.g. incidence, occurrence, suitability, etc.). Results: We found a growing number of arbovirus risk mapping studies across all endemic regions and arboviral diseases, with a total of 176 papers published 2002–2022 with the largest increases shortly following major epidemics. Three dominant use cases emerged: (i) global maps to identify limits of transmission, estimate burden and assess impacts of future global change, (ii) regional models used to predict the spread of major epidemics between countries and (iii) national and sub-national models that use local datasets to better understand transmission dynamics to improve outbreak detection and response. Temperature and rainfall were the most popular choice of covariates (included in 50% and 40% of studies respectively) but variables such as human mobility are increasingly being included. Surprisingly, few studies (22%, 31/144) robustly tested combinations of covariates from different domains (e.g. climatic, sociodemographic, ecological, etc.) and only 49% of studies assessed predictive performance via out-of-sample validation procedures. Conclusions: Here we show that approaches to map risk for different arboviruses have diversified in response to changing use cases, epidemiology and data availability. We identify key differences in mapping approaches between different arboviral diseases, discuss future research needs and outline specific recommendations for future arbovirus mapping. [ABSTRACT FROM AUTHOR]

Scapholunate tears subsequent to wrist trauma may potentially created carpal instability and lead to degenerative arthritis (SLAC wrist) in the late stages. This is why it is necessary to early identify these injuries and possibly treat them in order to prevent arthritis. Arthroscopic examination of the wrist can directly visualize these injuries and then it is possible to treat them under arthroscopy or open. The Ewas classification, which is an evolution of Geissler Classification, has developed in order to define the type of injuries and to identify the site of anatomical damage, which has occurred in each patient. It also allows to choose the more appropriate treatment in each stage. Materials and methods Twenty-one patients affected by SL ligament injuries were treated and examined under arthroscopy. There were 1 stage I, 3 stage II, 4 stage IIIA, 1 stage IIIB, 7 stage IIIC, 2 stage IV and 3 stage V (static instability). Patient affected by stage I and II were treated by immobilisation alone, patients affected by stage IIIA were treated by pinning (acute and chronic), patients affected by stage IIIB and IIIC were treated by pinning in acute cases and capsulodesis (open or arthroscopic) in chronic cases. In stage IV, patients were treated by tendon reconstruction of SL ligament with a modified Brunelli technique. Patients were aged 16–57-year-old. Patients were reviewed at a mean follow-up of 3 years (6 months–9 years) and evaluated with Mayo score and Dash score. Results Twenty patients obtained an excellent or good clinical result, one fair result was obtained in a patient who had a stage 5 with initial radio-scaphoid osteoarthritis (Slac I–II). We had one case of pin-tract infection treated by oral antibiotic for 1 week. The best results were obtained in the early stages. Discussion and conclusion Early detection of SL injuries is important to prevent developement of arthritis and wrist arthroscopy is mandatory for this purpose. Ewas classification seems effective in guiding the treatment in pre-dynamic cases and dynamic cases has given excellent and good results in the great majority of cases. In later stages (static instability), Garcia-Elias criteria are of utmost importance to guide the treatment. [ABSTRACT FROM AUTHOR]

Nivolumab is a programmed cell death receptor-1 ( PD-1) antibody used in the treatment of metastatic or unresectable melanoma. Cutaneous reactions are the most common adverse events reported with these agents and are rarely severe or life-threatening. Here we present a case report describing the clinicopathological findings of a patient with a fatal toxic epidermal necrolysis ( TEN) eruption associated with use of nivolumab for treatment of metastatic melanoma. The patient developed a pruritic, morbiliform eruption, which slowly progressed over 3 months to a tender, exfoliative dermatosis. Histology initially showed interface dermatitis and subsequently revealed full thickness epidermal necrosis. The diagnosis of TEN was made. From initial biopsy to TEN presentation, there was an increase in the number of CD8+ lymphocytes within the dermal-epidermal junction and an increase of programmed death ligand 1 ( PD-L1) expression in both lymphocytes and keratinocytes. Despite treatment with infliximab, high-dose steroids and intravenous immunoglobulin, the patient expired. Herein we describe what we believe is the second case of TEN associated with anti- PD1 therapy reported in the literature. Increased expression of PD-L1 by immunohistochemistry was observed as the eruption progressed to TEN. Early diagnosis and treatment is necessary in these fatal TEN reactions secondary to the anti- PD-1 antibody therapies. [ABSTRACT FROM AUTHOR]

Two months of treatment with doxycycline provided no improvement. A biopsy of the patient's cheek led to a proper diagnosis. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have substantially improved overall survival in patients with advanced melanoma; however, the lack of biomarkers to monitor treatment response and relapse remains an important clinical challenge. Thus, a reliable biomarker is needed that can risk‐stratify patients for disease recurrence and predict response to treatment. Methods: A retrospective analysis using a personalized, tumor‐informed circulating tumor DNA (ctDNA) assay on prospectively collected plasma samples (n = 555) from 69 patients with advanced melanoma was performed. Patients were divided into three cohorts: cohort A (N = 30), stage III patients receiving adjuvant ICI/observation; cohort B (N = 29), unresectable stage III/IV patients receiving ICI therapy; and cohort C (N = 10), stage III/IV patients on surveillance after planned completion of ICI therapy for metastatic disease. Results: In cohort A, compared to molecular residual disease (MRD)‐negative patients, MRD‐positivity was associated with significantly shorter distant metastasis‐free survival (DMFS; hazard ratio [HR], 10.77; p =.01). Increasing ctDNA levels from the post‐surgical or pre‐treatment time point to after 6 weeks of ICI were predictive of shorter DMFS in cohort A (HR, 34.54; p <.0001) and shorter progression‐free survival (PFS) in cohort B (HR, 22; p =.006). In cohort C, all ctDNA‐negative patients remained progression‐free for a median follow‐up of 14.67 months, whereas ctDNA‐positive patients experienced disease progression. Conclusion: Personalized and tumor‐informed longitudinal ctDNA monitoring is a valuable prognostic and predictive tool that may be used throughout the clinical course of patients with advanced melanoma. Personalized and tumor‐informed longitudinal circulating tumor DNA monitoring is a valuable prognostic and predictive tool that can be used throughout the clinical course of patients with advanced melanoma, including post surgery adjuvant therapy, during therapy for metastatic disease, and post therapy surveillance. [ABSTRACT FROM AUTHOR]

Currently accepted principles of surgical management-margin width, use of sentinel node biopsy, performance of radical node dissections for node-positive cases-and some aspects of postoperative management (use of radiation for desmoplastic melanoma primaries and for clinically node-positive disease) will change in the future with the potential widespread adoption of adjuvant and neoadjuvant therapies. [ABSTRACT FROM AUTHOR]

Background: Cutaneous human papillomaviruses (cuHPV) and polyomaviruses (HPyV) have been implicated in skin cancers; however, interpretation of findings across studies is complicated by limited understanding of the natural history of these infections across normal tissue types.Methods: In total, 675 eyebrow hair (EBH) and skin swab (SSW) samples were collected from 71 skin cancer screening patients every 6 months over 2 years and measured for presence of β-HPV, γ-HPV, and HPyV. Incidence, persistence, and clearance of cuHPV/HPyV were estimated, and risk factors associated with infection were examined.Results: Prevalence, incidence, and persistence of β-HPV, γ-HPV, and HPyV were consistently higher in SSW than in EBH, with types 5, 24, 49, 76 and Merkel cell polyomavirus (MCPyV) having incidence rates greater than 20 per 1000 person-months. Prevalent γ-HPV EBH infections persisted more often in women (P = .024), incident β-HPV EBH infections persisted less often among individuals with history of blistering sunburn (P = .019), and prevalent MCPyV SSW infections persisted more often in those with a history of skin cancer (P = .033).Conclusions: Incidence and persistence of cuHPV/HPyV were observed in SSW and EBH; however, none of the risk factors examined were commonly associated with cuHPV/HPyV infections across normal tissue types. [ABSTRACT FROM AUTHOR]

Background. Human papillomavirus (HPV) causes external genital lesions (EGLs) in men, including condyloma and penile intraepithelial neoplasia (PeIN). We sought to determine the incidence of pathologically confirmed EGLs, by lesion type, among men in different age groups and to evaluate the HPV types that were associated with EGL development. Methods. HPV Infection in Men (HIM) study participants who contributed ≥2 visits from 2009-2013 were included in the biopsy cohort. Genotyping by an HPV line-probe assay was performed on all pathologically confirmed EGLs. Age-specific analyses were conducted for incident EGLs, with Kaplan-Meier estimation of cumulative incidence. Results. This biopsy cohort included 2754 men (median follow-up duration, 12.4 months [interquartile range, 6.9-19.2 months]). EGLs (n = 377) were pathologically confirmed in 228 men, 198 of whom had incident EGLs. The cumulative incidence of any EGL was highest among men <45 years old and, for condyloma, decreased significantly over time with age. The genotype-specific incidence of EGL varied by pathological diagnoses, with high- and low-risk genotypes found in 15.6% and 73.2% of EGLs, respectively. Condyloma primarily contained HPV 6 or 11. While PeIN lesions primarily contained HPV 16, 1 PeIN III lesion was positive for HPV 6 only. Conclusion. Low- and high-risk HPV genotypes contribute to the EGL burden. Men remain susceptible to HPV-related EGLs throughout the life span, making it necessary to ensure the longevity of immune protection against the most common causative HPV genotypes. [ABSTRACT FROM AUTHOR]

Background: The significance of tumor‐infiltrating lymphocytes (TILs) in melanoma is debated. This article presents a multicenter, retrospective study assessing the predictive and prognostic value of TILs. Methods: The Sentinel Lymph Node Working Group database was queried from 1993 to 2018 for cases with known TIL data. TILs were categorized as absent or present, which included nonbrisk (NB), brisk (B), and present but unspecified TIL levels. Clinicopathologic factors were correlated with TILs, sentinel lymph node (SLN) status, and melanoma‐specific survival (MSS). Results: Overall, 3203 patients were included. The median thickness was 1.5 mm, and 469 cases had SLN metastases. TILs were present in 2458 cases (76.7%), with NB, B, and unspecified TILs seen in 1691 (68.8%), 691 (28.1%), and 76 (3.1%), respectively. Multivariable analysis showed that the presence of TILs significantly predicted a negative SLN biopsy (P <.05). The median follow‐up was 25.2 months. MSS was significantly better for cases with TILs than cases without TILs (P <.001). According to multivariable analysis, age, gender, thickness, mitotic rate, ulceration, lymphovascular invasion, and SLN status were significantly prognostic of MSS (all P values <.05). Although TILs were not prognostic of MSS, when multiple imputation was used and the SLN status was excluded, the presence of TILs was significantly prognostic of improved MSS (hazard ratio, 0.78; 95% confidence interval, 0.64‐0.95; P =.0154). Conclusions: TILs are a favorable marker because their presence significantly predicts a negative SLN, and the absence of TILs may be a prognostic marker of worse survival in patients with a positive SLN but not a negative SLN. TILs may also serve as a prognostic marker of survival when the SLN status is not considered. The presence of tumor‐infiltrating lymphocytes significantly predicts a negative sentinel lymph node and also predicts improved survival when the sentinel lymph node status is positive or not considered. [ABSTRACT FROM AUTHOR]

Background: Telomeres help maintain chromosomal structure and may influence tumorigenesis. We examined the association between telomere length and skin cancer in a clinic-based case-control study of 198 melanoma cases, 136 squamous cell carcinoma (SCC) cases, 185 basal cell carcinoma (BCC) cases, and 372 healthy controls. Methods: Cases were histologically confirmed patients treated at the Moffitt Cancer Center and University of South Florida Dermatology Clinic in Tampa, FL. Controls self-reported no history of cancer and underwent a skin cancer screening exam at study enrollment to rule out the presence of skin cancer. Quantitative real time PCR was used to measure telomere length in peripheral blood samples. Results: Melanoma patients had longer telomeres than controls (odds ratio (OR) = 3.75; 95% confidence interval (CI): 2.02-6.94 for highest versus lowest tertile) (P for trend = <0.0001). In contrast, longer telomere length was significantly inversely associated with SCC (OR = 0.01; 95% CI: 0.00-0.05 for highest versus lowest tertile) (P for trend = <0.0001) and BCC (OR = 0.10; 95% CI: 0.06-0.19 for highest versus lowest tertile) (P for trend = <0.0001). Conclusion: Telomere length may be involved in the development of skin cancer, although the effect on cancer risk differs for melanoma and nonmelanoma carcinomas. Our findings suggest that long telomere length is positively associated with melanoma while inversely associated with SCC and BCC. [ABSTRACT FROM AUTHOR]

Many advances in the cosmetic industry have increased our ability to enhance youth and beauty. Haircoloring products are one such innovation. Over the past several decades, a significant amount of work has been dedicated to understanding the possible long-term side effects associated with hair-dye use, specifically looking at cancer risk. This paper describes the hair-coloring process, highlights the potentially carcinogenic ingredients in various hair-dying products, and reviews the epidemiological evidence relating personal hair-dye use to the risk of developing several types of malignancies. [ABSTRACT FROM AUTHOR]

Human African Trypanosomiasis (HAT) is a major public health problem in the Democratic Republic of the Congo (DRC). Active and passive surveillance for HAT is conducted but may underestimate the true prevalence of the disease. We used ELISA to screen 7,769 leftover dried blood spots from a nationally representative population-based survey, the 2007 Demographic and Health Survey. 26 samples were positive by ELISA. Three of these were also positive by trypanolysis and/or PCR. From these data, we estimate that there were 18,592 people with HAT (95% confidence interval, 4,883–32,302) in the DRC in 2007, slightly more than twice as many as were reported. Author Summary: Because of weak health surveillance infrastructures in poor countries, estimates of the burdens (numbers of infections) of many tropical diseases may be inaccurate. In particular, current estimates for the global burden of Human African Trypanosomiasis (Sleeping Sickness, HAT) vary widely. Most of the reported HAT cases occur in the Democratic Republic of the Congo, where many barriers to surveillance exist. The best way to generate accurate burden estimates is to use a survey sampled to be representative of the general population. Demographic and Health Surveys (DHS) are a widely used tool to obtain nationally representative health data and have been conducted hundreds of times in developing countries, In this report, we use samples from the 2007 Democratic Republic of the Congo DHS to estimate the burden of HAT. ELISA tests were conducted on 7,769 leftover dried blood spots followed by confirmatory trypanolysis and PCR tests. Our data suggest that there are approximately 18,592 cases of Human African Trypanosomiasis (Sleeping Sickness) in the DRC, close to WHO estimates. [ABSTRACT FROM AUTHOR]

Human African Trypanosomiasis (HAT) is a major public health problem in the Democratic Republic of the Congo (DRC). Active and passive surveillance for HAT is conducted but may underestimate the true prevalence of the disease. We used ELISA to screen 7,769 leftover dried blood spots from a nationally representative population-based survey, the 2007 Demographic and Health Survey. 26 samples were positive by ELISA. Three of these were also positive by trypanolysis and/ or PCR. From these data, we estimate that there were 18,592 people with HAT (95% confidence interval, 4,883-32,302) in the DRC in 2007, slightly more than twice as many as were reported. [ABSTRACT FROM AUTHOR]

The authors have indicated no significant interest with commercial supporters. [ABSTRACT FROM AUTHOR]

Background: This study investigates the impact of tubewell user density on cholera and shigellosis events in Matlab, Bangladesh between 2002 and 2004. Household-level demographic, health, and water infrastructure data were incorporated into a local geographic information systems (GIS) database. Geographically-weighted regression (GWR) models were constructed to identify spatial variation of relationships across the study area. Zero-inflated negative binomial regression models were run to simultaneously measure the likelihood of increased magnitude of disease events and the likelihood of zero cholera or shigellosis events. The aim of this study was to examine the effect of tubewell density on both the occurrence of diarrheal disease and the magnitude of diarrheal disease incidence. Results: In Matlab, households with greater tubewell density were more likely to report zero cholera or shigellosis events. Results for both cholera and shigellosis GWR models suggest that tubewell density effects are spatially stationary and the use of non-spatial statistical methods is appropriate. Conclusions: Increasing the amount of drinking water available to households through increased density of tubewells contributed to lower reports of cholera and shigellosis events in rural Bangladesh. Our findings demonstrate the importance of tubewell installation and access to groundwater in reducing diarrheal disease events in the developing world. [ABSTRACT FROM AUTHOR]

Background: Yellow fever (YF) is an arboviral disease which is endemic to Brazil due to a sylvatic transmission cycle maintained by infected mosquito vectors, non-human primate (NHP) hosts, and humans. Despite the existence of an effective vaccine, recent sporadic YF epidemics have underscored concerns about sylvatic vector surveillance, as very little is known about their spatial distribution. Here, we model and map the environmental suitability of YF's main vectors in Brazil, Haemagogus spp. and Sabethes spp., and use human population and NHP data to identify locations prone to transmission and spillover risk. Methodology/Principal findings: We compiled a comprehensive set of occurrence records on Hg. janthinomys, Hg. leucocelaenus, and Sabethes spp. from 1991–2019 using primary and secondary data sources. Linking these data with selected environmental and land-cover variables, we adopted a stacked regression ensemble modelling approach (elastic-net regularized GLM, extreme gradient boosted regression trees, and random forest) to predict the environmental suitability of these species across Brazil at a 1x1 km resolution. We show that while suitability for each species varies spatially, high suitability for all species was predicted in the Southeastern region where recent outbreaks have occurred. By integrating data on NHP host reservoirs and human populations, our risk maps further highlight municipalities within the region that are prone to transmission and spillover. Conclusions/Significance: Our maps of sylvatic vector suitability can help elucidate potential locations of sylvatic reservoirs and be used as a tool to help mitigate risk of future YF outbreaks and assist in vector surveillance. Furthermore, at-risk regions identified from our work could help disease control and elucidate gaps in vaccination coverage and NHP host surveillance. Author summary: Yellow fever virus (YFV) is an arbovirus transmitted to humans from mosquitoes and can lead to severe disease and death. Recent sporadic outbreaks coupled with low vaccination coverage have highlighted the importance of mosquito surveillance for preventing future outbreaks and potential virus spillover into dense urban areas. Yet, very little is known about the spatial distribution of mosquitoes known to transmit YFV and the factors that contribute to their environmental suitability in Brazil. We compiled an occurrence database of primary and secondary mosquito vectors belonging to Haemagogus and Sabethes species' collected between 1991–2019 and integrated this data with environmental and land-use data to predict their spatial suitability at 1x1km resolution. Using this information, we identified suitable regions for their co-existence. We overlaid this information with human population density and locations of non-human primate host reservoirs to identify areas at risk of transmission and spillover. Our study provides high-resolution mapping tools to assist with mosquito and arbovirus surveillance which is especially useful in low-resource settings. [ABSTRACT FROM AUTHOR]

Sézary syndrome (SS) is a rare and aggressive leukemic variant of cutaneous T-cell lymphoma, with a median overall survival (OS) rate of 2–4 years. Few studies have described the clinical outcome of SS patients since 2012. We retrospectively analyzed 70 patients diagnosed with SS treated at a high-volume tertiary cancer center between 2000 and 2018. Overall survival at 1 and 5 years was 84.1% and 50.7%, respectively. Univariate analyses identified older age (>65 years) and male sex as poor prognostic factors. Five patients presented with circulating large granular lymphocytic proliferation and had a favorable prognosis. Targeted therapies were effective in treating refractory/relapsed SS patients with a durable response. Therapeutic advancements and the comprehensive treatments used in a multidisciplinary clinic improved OS rates. [ABSTRACT FROM AUTHOR]

Background: Studies in women have shown an increased risk of human immunodeficiency virus (HIV) acquisition with prior human papilloma virus (HPV) infection; however, few studies have been conducted among men. Our objective was to assess whether HPV-related external genital lesions (EGLs) increase risk of HIV seroconversion among men.Methods: A total of 1379 HIV-negative men aged 18 to 70 years from the United States, Mexico, and Brazil were followed for up to 7 years and underwent clinical examination for EGLs and blood draws every 6 months. Human immunodeficiency virus seroconversion was assessed in archived serum. Cox proportional hazards and marginal structural models assessed the association between EGL status and time to HIV seroconversion.Results: Twenty-nine participants HIV seroconverted during follow-up. Older age was associated with a lower hazard of HIV seroconversion. We found no significant difference in the risk of HIV seroconversion between men with and without EGLs (adjusted hazard ratio, 0.94; 95% confidence interval, 0.32-2.74). Stratified analyses focusing on men that have sex with men found no association between EGLs and HIV seroconversion risk (hazards ratio, 0.63; 95% confidence interval, 0.00-1.86).Conclusions: External genital lesions were not associated with higher risk for HIV seroconversion in this multinational population, although statistical power was limited as there were few HIV seroconversions. Results may differ in populations at higher risk for HIV. [ABSTRACT FROM AUTHOR]

BACKGROUND. A novel surgical technique based on selective lymphadenectomy was used to stage 132 patients with intermediate and thick cutaneous malignant melanoma. Preoperative and intraoperative lymph node mapping techniques were used to ascertain regional lymph node basins at risk for metastasis, and to identify the first node(s) the afferent lymphatics encounter in the basin, defined as the "sentinel" node(s). It has been shown that the histology of the sentinel node reflects the histology of the rest of the nodal basin, and according to preliminary studies using this technique, the likelihood of bypassing the sentinel node(s) to "higher" level nodes is less than 20%. Epidemiologic studies indicate that the long-term survival of patients with melanomas of intermediate thickness or greater is significantly compromised if regional lymph nodes are involved. Yet, the utility of performing lymph node dissections for the purposes of staging only is controversial, not only because of the morbidity and expense of the procedure, but the lack of proven survival benefit. OBJECTIVE. in the present study, we performed preoperative and intraoperative lymphatic mapping, harvested clinically normal sentinel nodes, and examined them for micrometastasis by light microscopy. Both conventional stains and immunocytochemistry for S-100 protein and HMB-45 antibodies were performed, and only those patients with documented micrometastasis received complete lymph node dissections. RESULTS. The sentinel node(s) was identified in each of the patients. Micrometastatic disease was detected in 31 (23%) of the patients by selective lymphadenectomy, and the sentinel node(s) was the only node involved in 83% of the cases upon subsequent complete nodal dissection. CONCLUSION. Our preliminary results suggest that selective lymphadenectomy following lymphatic mapping is an effective procedure for staging melanoma patients with lesions of intermediate thickness or greater. Our results indicate that sentinel lymph nodes may be successfully identified and harvested in the majority of patients, and that they may be examined for the first evidence of micrometastasis without the need of a complete nodal dissection. Information as to whether micrometastases are present in the sentinel node would be valuable in staging patients, and identifying candidates of complete nodal dissections. We are participating in an national Cancer Institute-sponsored multicenter trial to ascertain whether this surgical approach can impact on the recurrence rate and survival of patients with stage 1 and 2 melanoma. [ABSTRACT FROM AUTHOR]

The world's most important mosquito vector of viruses, Aedes aegypti, is found around the world in tropical, subtropical and even some temperate locations. While climate change may limit populations of Ae. aegypti in some regions, increasing temperatures will likely expand its territory thus increasing risk of human exposure to arboviruses in places like Europe, Northern Australia and North America, among many others. Most studies of Ae. aegypti biology and virus transmission focus on locations with high endemicity or severe outbreaks of human amplified urban arboviruses, such as dengue, Zika, and chikungunya viruses, but rarely on areas at the margins of endemicity. The objective in this study is to explore previously published global patterns in the environmental suitability for Ae. aegypti and dengue virus to reveal deviations in the probability of the vector and human disease occurring. We developed a map showing one end of the gradient being higher suitability of Ae. aegypti with low suitability of dengue and the other end of the spectrum being equal and higher environmental suitability for both Ae. aegypti and dengue. The regions of the world with Ae. aegypti environmental suitability and no endemic dengue transmission exhibits a phenomenon we term 'aegyptism without arbovirus'. We then tested what environmental and socioeconomic variables influence this deviation map revealing a significant association with human population density, suggesting that locations with lower human population density were more likely to have a higher probability of aegyptism without arbovirus. Characterizing regions of the world with established populations of Ae. aegypti but little to no autochthonous transmission of human-amplified arboviruses is an important step in understanding and achieving aegyptism without arbovirus. Author summary: The preeminent vector of arboviruses, Aedes aegypti, is distributed globally and capable of transmitting deadly pathogens to over half the world's population. While most studies focus on areas where Ae. aegypti and human-amplified urban arboviruses such as dengue and Zika viruses are locally established, our study explores the margins of endemicity where Aedes aegypti can be found, but arboviral illness is rare. These areas where we find environmental suitability for the vector but an absence of established arboviral transmission we term 'aegyptism without arbovirus'. This builds on the long-held observation of 'anophelism without malaria' in which some regions having Plasmodium-competent Anopheles spp. mosquitoes but not the associated human malaria. This study uses previously published maps to reveal locations with higher suitability of Ae. aegypti and low suitability of dengue. Additionally, we analyzed the resulting map of deviations between Ae. aegypti and dengue and found significant associations with human population density, Infant Mortality Rate, temperature, and precipitation. To the best of our knowledge, this is the first study to characterize places around the world that exhibit 'aegyptism without arbovirus' which is an important first step in our ongoing battle with human-amplified urban arboviruses. [ABSTRACT FROM AUTHOR]

Patients with primary immunodeficiency are at increased risk for malignancy, especially hematologic neoplasms. This paper reports a unique case of a 47‐year‐old man with X‐linked agammaglobulinemia who presented with progressive asymptomatic violaceous papules and plaques on his face, hands, and trunk for 1 year. Skin biopsies revealed deep, nodular infiltrates of histiocytes and CD8‐positive lymphocytes, with a CD4:CD8 ratio of 1:10. Laboratory studies showed cytopenias. Flow cytometry in the skin, blood, and bone marrow (BM) showed a CD3+/CD8+/CD57+ large granular lymphocyte population. BM biopsy showed 30% involvement with these atypical T‐cells. T‐cell gene rearrangement studies of skin, blood, and BM revealed identical T‐cell clones. He was diagnosed with T‐large granular lymphocyte leukemia (T‐LGLL) with an associated CD8+ cutaneous lymphoproliferation. Skin involvement was suspected to represent infiltration by T‐LGLL. However, co‐existence of two lymphoproliferative disorders (LPDs), T‐LGLL and CD8+ granulomatous LPD, remains a possibility. In general, cutaneous infiltrates associated with LGLL are rare and poorly understood. It has been suggested that they are markers of poor prognosis. Our case report describes skin, blood, and BM findings in an immunosuppressed patient with T‐LGLL in detail. These findings have not yet been reported and their significance requires further investigation. [ABSTRACT FROM AUTHOR]

Background: Melanoma causes the vast majority of deaths attributable to skin cancer, largely due to its propensity for metastasis. To date, few studies have examined molecular changes between primary cutaneous melanoma and adjacent putatively normal skin. To broaden temporal inferences related to initiation of disease, we performed a metabolomics investigation of primary melanoma and matched extratumoral microenvironment (EM) tissues; and, to make inferences about progressive disease, we also compared unmatched metastatic melanoma tissues to EM tissues. Methods: Ultra-high performance liquid chromatography—mass spectrometry-based metabolic profiling was performed on frozen human tissues. Results: We observed 824 metabolites as differentially abundant among 33 matched tissue samples, and 1,118 metabolites as differentially abundant between metastatic melanoma (n = 46) and EM (n = 34) after false discovery rate (FDR) adjustment (p<0.01). No significant differences in metabolite abundances were noted comparing primary and metastatic melanoma tissues. Conclusions: Overall, pathway-based results significantly distinguished melanoma tissues from EM in the metabolism of: ascorbate and aldarate, propanoate, tryptophan, histidine, and pyrimidine. Within pathways, the majority of individual metabolite abundances observed in comparisons of primary melanoma vs. EM and metastatic melanoma vs. EM were directionally consistent. This observed concordance suggests most identified compounds are implicated in the initiation or maintenance of melanoma. [ABSTRACT FROM AUTHOR]

Hypertrophic lupus erythematosus is a variant of discoid lupus erythematosus, which manifests as verrucous plaques and/or keratoacanthoma-like nodules on the face and arms. Diagnosis and treatment of hypertrophic lupus erythematosus can be challenging as it can resemble cutaneous squamous cell carcinoma clinically and histopathologically. Furthermore, cutaneous squamous cell carcinoma is a known complication of discoid lupus erythematosus. We present a diagnostically challenging case of a patient with a rapidly enlarging rhinophymatous mass and multiple keratoacanthoma-like lesions of the bilateral upper extremities whose work-up was initially equivocal. CD123 staining helped to elucidate a final diagnosis of cutaneous squamous cell carcinoma arising in a background of occult hypertrophic lupus erythematosus. [ABSTRACT FROM AUTHOR]

Combination therapy with ipilimumab and nivolumab is an adjuvant treatment approach for metastatic melanoma that boasts increased 3‐year survival when compared with a single immunotherapy agent. Combination therapy, however, is associated with increased toxicities, especially cutaneous side‐effects. Here we present a patient with metastatic melanoma and a sudden eruption of painful nodules on the face and arms 10 days after the administration of the fourth dose of combination ipilimumab/nivolumab. Biopsies demonstrated lymphoid hyperplasia, not clinically or pathologically consistent with an infectious, malignant or autoimmune etiology; a diagnosis of pseudolymphoma secondary to ipilimumab/nivolumab was made. After a steroid taper, the lesions resolved, and the patient was restarted on nivolumab monotherapy 2 weeks later without recurrence of symptoms or disease. [ABSTRACT FROM AUTHOR]

Background: Traditional chemotherapy agents adversely affect wound healing and need to be held prior to or after surgery. Immune checkpoint inhibitors (ICIs) and targeted agents are now standard of care for the several treatment cancers. We hypothesize that ICI and targeted therapy do not have similar adverse effects on perioperative outcomes. Methods: We performed a review of melanoma patients undergoing surgery at an academic hospital between 2011 and 2019. All patients received ICI or targeted therapy ≤ 60 days prior to surgery, including palliative procedures. Preoperative performance status was assessed using Eastern Cooperative Oncology Group score and American Society of Anesthesiologists Classification System. Thirty-day complications were classified by Clavien–Dindo grade. No statistical comparisons were performed. Results: Of 63 patients included in the analysis, 29 (46%) patients received ICI and 34 (54%) received targeted therapy with median of 14 days (IQR 5–27 days) between the last preoperative dose and day of surgery (ICI, median 18 days [IQR 13–34.5]; targeted therapy, median 7 days [IQR 3–22.25]). There were no perioperative mortalities. Among patients treated with ICI, 22 patients (76%) had no complications. Four patients had wound infections (2 readmitted), 1 had reoperation (hematoma) and 2 readmitted for other reasons (fever; volvulus). Among patients treated with targeted therapy, 25 patients (74%) had no complications. Seven patients had wound infections (none readmitted), 1 had reoperation (flap failure) and 1 had dehiscence (not treated). Conclusions: Patients undergoing treatment with ICI or targeted therapies can safely undergo surgery without substantially increased risk of serious intraoperative and postoperative complications. [ABSTRACT FROM AUTHOR]

Acral melanomas arise on the non-hair bearing skin of the palms, soles and in the nail beds. These rare tumors comprise 2–3 % of all melanomas, are not linked to UV-exposure, and represent the most frequent subtype of melanomas in patients of Asian, African and Hispanic origin. Although recent work has revealed candidate molecular events that underlie acral melanoma development, this knowledge is not yet been translated into efficacious local, regional, or systemic therapies. In the current review, we describe the clinical characteristics of acral melanoma and outline the genetic basis of acral melanoma development. Further discussion is given to the current status of systemic therapy for acral melanoma with a focus on ongoing developments in both immunotherapy and targeted therapy for the treatment of advanced disease. [ABSTRACT FROM AUTHOR]

Current management of locoregional and oligometastatic melanoma is typically with surgery; however, some patients are unable to undergo resection due to location/size of their tumors and/or the anticipated morbidity of the surgery. While there are currently no established guidelines for neoadjuvant therapy in melanoma, neoadjuvant BRAF‐targeted therapy may make resection more feasible. A retrospective analysis was conducted of 23 patients with BRAFV600‐mutant, stage III/IV melanoma treated with BRAF‐targeted therapy prior to surgery, with no adjuvant treatment. Surgical specimens, preoperative imaging, and clinical outcomes were evaluated. Results: Ten of 23 patients (44%) attained a pathologic complete response (pCR), with no correlation between RECIST response based on preoperative imaging and pathologic response. After a median of 43‐month follow‐up, only 1 patient (10%) with a pCR recurred, while 8 of 13 (62%) patients without a pCR recurred. Patients with a pCR had significantly improved relapse‐free (RFS) and overall survival (OS) compared to patients with residual tumor. Neoadjuvant BRAF‐targeted therapy is associated with a high pCR rate in patients with stage III‐IV melanoma, which may correlate with improved RFS and OS. [ABSTRACT FROM AUTHOR]