Epithelioid hemangioendothelioma: a case report.

Background: Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor with limited clinical data that can guide treatment choices. The diagnosis of EHE is based on its unique histological, immunohistochemical, and molecular characteristics. Differential diagnoses are broad and include autoimmune diseases. Treatments include hepatic resection, liver transplantation, systemic/regional chemotherapy, and radiotherapy. Case Description: We describe EHE in a patient with weight loss and general weakness. The prognosis of EHE is variable, with few cases demonstrating an indolent clinical course, whereas others tend to metastasize. In our case, hepatic EHE had metastasized to the lungs and brain. Histopathological examination of the liver tissue revealed an epithelial hemangioendothelioma. On CK7 staining, hepatocytes were clearly reactive and arranged in the plates (CK7: negative), with positive immunohistochemical staining for CD34 (CD34: positive) alone. Surveillance was conducted and the clinical course was better than expected, probably due to her relatively good general condition, the lack of genetic factors associated with her familial medical history, and normal levels of tumor markers such as α-fetoprotein and carcinoembryonic antigen (CEA). During a follow-up examination, she was asymptomatic with a healthy general appearance. Conclusions: The prognosis of EHE is variable, with few cases demonstrating an indolent clinical course, whereas others tend to metastasize. The treatment method for EHE should be determined according to the patient's condition.

Training the Next Generation of the Human Immunodeficiency Virus Workforce: Needs, Challenges, and Opportunities.

Due to remarkable advancements in medications, more people are living longer with human immunodeficiency virus (HIV). The HIV workforce has been strained by a supply-demand mismatch, threatening the care of an aging population with multiple comorbidities. Solving the HIV workforce shortage requires multiple novel and creative solutions that recruit new trainees to the field, increase the workforce diversity, and improve disparities in access to care. New and expanded models of care that incorporate a wider array of clinicians and optimize the use of team-based care will also be crucial.

The patient perspective on sirolimus for epithelioid hemangioendothelioma (EHE): results of a community survey highlighting the importance of equitable access to treatments.

Background: Epithelioid hemangioendothelioma (EHE) is an ultra-rare, vascular sarcoma with clinical presentation ranging from an indolent to an aggressive form. Over 50% of patients present with metastatic disease, requiring systemic therapy, although no systemic therapies are specifically approved for EHE. Retrospective evidence supports the activity of mTOR inhibitors (e.g. sirolimus), although available only off-label. EHE patients and advocates are therefore working to support approval of effective treatments by collecting data on patient perspectives and experiences. Materials and methods: In February 2023, the EHE Rare Cancer Charity (UK) and The EHE Foundation (US), with other advocates, conducted a survey of perspectives and experiences of EHE patients regarding the use and accessibility of sirolimus. The survey consisted of 20 questions designed for individuals undergoing treatment, those who had been treated, or had never been treated with the drug. Widely promoted within the patient community, the online survey categorized patients into three cohorts for the analysis: liver transplant patients, non-transplant patients who had ever taken sirolimus and sirolimus-naïve non-transplant patients. Results: The survey evaluated data from 129 patient responses from 21 countries, mostly from USA, UK, Australia, and Canada (70%). The liver transplant, sirolimus and non-sirolimus cohorts were 16%, 25% and 59%, respectively. In the sirolimus group 66% reported treatment durations exceeding one year, with 16% exceeding five years, indicating the drug's efficacy. In the non-sirolimus group, the drug was not available for 42% and for 11% sirolimus was available but not selected for treatment because of its off-label status. Overall, 87% of all patients across all cohorts expressed the importance of the drug's availability as hugely or very important. Conclusion: The survey responses highlight the activity of sirolimus for EHE and the importance of securing a label extension for the drug delivering equitable access to this treatment for patients.

Development of a Machine Learning Modelling Tool for Predicting HIV Incidence Using Public Health Data from a County in the Southern United States.

BACKGROUND: Recent advancements in Machine Learning (ML) have significantly improved the accuracy of models predicting HIV incidence. These models typically utilize electronic medical records and patient registries. This study aims to broaden the application of these tools by utilizing de-identified public health datasets for notifiable sexually transmitted infections (STIs) from a southern U.S. County known for high HIV incidence rates. The goal is to assess the feasibility and accuracy of ML in predicting HIV incidence, which could potentially inform and enhance public health interventions. METHODS: We analyzed two de-identified public health datasets, spanning January 2010 to December 2021, focusing on notifiable STIs. Our process involved data processing and feature extraction, including sociodemographic factors, STI cases, and social vulnerability index (SVI) metrics. Various ML algorithms were trained and evaluated for predicting HIV incidence, using metrics such as accuracy, precision, recall, and F1 score. RESULTS: The study included 85,224 individuals, with 2,027 (2.37%) newly diagnosed with HIV during the study period. The ML models demonstrated high performance in predicting HIV incidence among males and females. Influential predictive features for males included age at STI diagnosis, previous STI information, provider type, and SVI. For females, they included age, ethnicity, previous STIs information, overall SVI, and race. CONCLUSIONS: The high accuracy of our ML models in predicting HIV incidence highlights the potential of using public health datasets for public health interventions such as tailored HIV testing and prevention. While these findings are promising, further research is needed to translate these models into practical public health applications.

Leveraging CD4 Cell Count at Entry Into Care to Monitor Success of Human Immunodeficiency Virus Prevention, Treatment, and Public Health Programming in the Greater St Louis Area Between 2017 and 2020.

CD4 cell count at entry into human immunodeficiency virus (HIV) care is a useful indicator of success of multiple steps in HIV public health programming. We demonstrate that CD4 cell count at care initiation was stable in St Louis between 2017 and 2019 but declined in 2020. Missouri efforts in the Ending the HIV Epidemic plan should focus on rapidly identifying individuals with undiagnosed HIV infection.

PrEP Persistence Support and Monitoring in Areas of High HIV Burden in the Midwestern United States.

Monitoring pre-exposure prophylaxis (PrEP) metrics can guide service delivery yet does not occur routinely. We developed a survey to understand current practices for monitoring PrEP at PrEP-providing organizations in Illinois and Missouri. The survey was distributed from September through November 2020; 26 organizations participated. Most respondents indicated ongoing efforts to screen for PrEP eligibility (66.7%), link to care (87.5%), and retain clients in care (70.8%); 70.8% reported collecting data on PrEP initiation, 41.7% on retention in care, and 37.5% on missed visits. Barriers to monitoring PrEP metrics included lack of IT support (69.6%), manual processes (69.6%), and lack of staff resources (65.2%). Most respondents offered clients support for PrEP retention and adherence and wanted to expand interventions for PrEP persistence, yet fewer monitored corresponding metrics. To enhance PrEP implementation, organizations should improve monitoring and evaluation of PrEP metrics along the entire continuum and respond with appropriate services to support clients.

An effectiveness-implementation trial protocol to evaluate PrEP initiation among U.S. cisgender women using eHealth tools vs. standard care.

Background: The United States' (U.S.) initiative to End the HIV Epidemic aims to reduce new HIV infections in areas of high HIV prevalence. Despite national efforts to reduce HIV incidence, cisgender women continue to represent approximately one out of every five new HIV diagnoses in the U.S. Taking pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy; however, PrEP initiation among cisgender women is suboptimal, with only 10% of eligible women receiving PrEP prescriptions in 2019. Methods: We designed a trial to test the effectiveness of interventions to increase PrEP initiation, while evaluating the implementation strategy (hybrid type II trial) in seven obstetrics and gynecology (OB/GYN) clinics (two federally qualified health centers, three community-based, and two academic) in Baltimore, Maryland. A total of 42 OB/GYN providers will be enrolled and randomized (1:1:1) into one of three clinical trial arms (standard of care, patient-level intervention, or multi-level intervention). Eligible patients of enrolled providers will receive a sexual health questionnaire before their appointment through the electronic health record's (EHR) patient portal. The questionnaire will be scored in three tiers (low, moderate, and high) to assess HIV risk. Patients at low risk will be offered an HIV test only, while those who score medium or high risk will be included in the clinical trial and assigned to the clinical trial arm associated with their provider. Differences in PrEP initiation, our primary outcome, across the three arms will be analyzed using generalized linear mixed-effect models with logistic regression. We will adjust results for demographic differences observed between arms and examine PrEP initiation stratified by patient's and provider's race and ethnicity.Additionally, a comprehensive economic analysis for each intervention will be conducted. Discussion: We hypothesize that gathering information on sensitive sexual behaviors electronically, communicating HIV risk in an understandable and relatable format to patients and OB/GYN providers, and deploying EHR alerts will increase PrEP initiation and HIV testing. Trial Registration: The trial is registered with ClinicalTrials.gov (NCT05412433) on 09 June 2022. https://clinicaltrials.gov/ct2/show/NCT05412433?term=NCT05412433&draw=2&rank=1.

Current Model Systems for Investigating Epithelioid Haemangioendothelioma.

Epithelioid haemangioendothelioma (EHE) is a rare sarcoma of the vascular endothelium with an unpredictable disease course. EHE tumours can remain indolent for long period of time but may suddenly evolve into an aggressive disease with widespread metastases and a poor prognosis. Two mutually exclusive chromosomal translocations define EHE tumours, each involving one of the transcription co-factors TAZ and YAP. The TAZ-CAMTA1 fusion protein results from a t(1;3) translocation and is present in 90% of EHE tumours. The remaining 10% of EHE cases harbour a t(X;11) translocation, resulting in the YAP1-TFE3 (YT) fusion protein. Until recently, the lack of representative EHE models made it challenging to study the mechanisms by which these fusion proteins promote tumorigenesis. Here, we describe and compare the recently developed experimental approaches that are currently available for studying this cancer. After summarising the key findings obtained with each experimental approach, we discuss the advantages and limitations of these different model systems. Our survey of the current literature shows how each experimental approach can be utilised in different ways to improve our understanding of EHE initiation and progression. Ultimately, this should lead to better treatment options for patients.

Incidence, demographics, and survival of malignant hemangioendothelioma in the United States.

BACKGROUND: Malignant hemangioendothelioma is an endothelial cancer with heterogeneous clinical behavior that can range from indolent to aggressive, of which the majority are epithelioid (EHE). Its incidence and demographics have not been previously well defined in a large cohort. METHODS: This retrospective analysis used the US Cancer Statistics National Program of Cancer Registries - Surveillance Epidemiology End Results (SEER) combined database to identify patients in the US newly diagnosed with hemangioendothelioma between the years of 2001 and 2017 (n = 1986). Survival analyses were performed on a subset of patients within the SEER-18 database with survival information available (n = 417). Outcomes included incidence, demographics of patients newly diagnosed with hemangioendothelioma, extent of disease at presentation, and overall survival. RESULTS: The incidence of hemangioendothelioma in the US is 0.4 cases per million person-years. Although cases rose to 122 newly diagnosed in the year 2017 (90 EHE, 32 other hemangioendothelioma), incidence rates were stable. Skin and connective tissues were the most common presenting sites (33.4%), followed by liver (24.5%), lung (17.6%), and bone (12.5%). Median age at diagnosis was 55 years; 27.2% of patients were pediatric, adolescent, or young adult (<40 years). At presentation, 36.4% of patients had localized disease; 21.6% presented with regional and 41.7% with distant metastases. Observed survival at 3 years was 79.7%, 70.7%, and 46.0% for patients presenting with local, regional, and distant disease and most deaths occurred within the first 2 years. CONCLUSIONS: Malignant hemangioendothelioma is ultra-rare but meaningfully impacts affected patients. These data may provide benchmarks for comparison of new approaches to hemangioendothelioma therapy and highlight poor survival outcomes.

Epithelioid hemangioendothelioma of the distal lower extremity and the role of radiotherapy: A report of two cases.

We report two cases of epithelioid hemangioendothelioma (EHE) in the distal lower extremity. Our first patient had unicentric EHE of the left os calcis initially treated with an intralesional procedure; however, later developed two recurrences which were managed with radiation therapy. Our second patient had multicentric EHE of the distal tibia and fibula managed with primary radiation therapy. Although EHE is typically treated with wide resection or an intralesional procedure, we present two cases of EHE in the distal lower extremity to discuss the therapeutic role of radiation therapy in the management of distal EHE.

Delayed metastatic pulmonary epithelioid hemangioendothelioma of the femoral vessels: case report and literature review.

Background: Epithelioid hemangioendothelioma (EHE) is a rare sarcoma of the blood vessels. We report a patient with vascular EHE with delayed pulmonary metastasis, of which there are no previously known case reports. Case Description: A 40-year-old female presents with a painful right groin mass and swelling in the lower extremity. A 3.8 cm soft tissue mass was identified in the femoral sheath with the abutment of the femoral artery on a computerized tomography (CT) scan. Surgical resection of the femoral vein was performed, and the final pathology confirmed a diagnosis of EHE. A second en-bloc resection of the femoral artery with bypass grafting was performed with clear surgical margins. The patient did well post-operatively with annual surveillance of the right groin as well as chest X-rays. However, the patient developed a metastatic Epithelioid hemangioendothelioma (EHE) to the right lower lobe, 12 years after the initial EHE treatment. She underwent a pulmonary resection with clear margins. The patient remains disease-free after one year. EHE is a rare soft tissue sarcoma with unpredictable clinical behavior. While most commonly presenting in the lung and liver they can also originate from any vascular system. Delayed pulmonary metastasis from vascular EHE has not been reported. Conclusions: Our case shows that indolent metastasis can occur in EHE, despite a prolonged disease-free interval. This case highlights the need for long-term surveillance with serial imaging of not only the primary site but pulmonary imaging beyond 5 years may be beneficial.

When left hands touch: shadow vows and Jung's quaternity.

Is there a connection between the exchange of vows and the fighting and suffering of couples that are unique to the institution of marriage? This essay introduces the concept of Shadow Vows, the unacknowledged assumptions, agreements, and obligations each partner brings to the relationship, which the authors believe are often responsible for longstanding marital discord and strife. The authors ground the existence of shadow vows in Jung's quaternity, alchemy, typology, archetypal theory, and depth approaches to couple therapy. The essay concludes with a list of themes indicative of shadow vow enactments in clinical work with couples.

Y a-t-il un lien entre l'échange des vœux et les conflits et souffrances des couples, un lien qui serait spécifique à l'institution du mariage ? Cet article introduit le concept de « vœux de l'ombre ¼ - les présomptions non-reconnues, les compromis, les obligations que chaque partenaire amène dans la relation. Les auteurs pensent que de tels vœux sont souvent responsables de discorde et querelles durables dans un couple marié. Les auteurs fondent l'existence de ces vœux de l'ombre dans la quaternité Jungienne, l'alchimie, la typologie, la théorie des archétypes et la thérapie de couple selon la psychologie des profondeurs. L'article se termine par une liste de thèmes révélateurs des mises en acte de ces vœux de l'ombre dans le travail clinique avec des couples.

Existe una conexión entre el intercambio de votos y el conflicto y sufrimiento de las parejas, que es única a la institución del matrimonio? El presente ensayo introduce el concepto de 'sombra de los votos' - las asunciones, acuerdos y obligaciones no reconocidas que cada integrante de la pareja trae a la relación, las cuales los autores creen que a menudo son responsables de largos conflictos y desavenencias en el matrimonio. Los autores basan la existencia de la sombra de los votos en la noción de cuaternidad de Jung, alquimia, tipología, teoría arquetipal, y los abordajes en psicología profunda a la terapia de pareja. El ensayo concluye con una lista de temas indicativos de actuaciones del lado sombrío de los votos en el trabajo clínico con parejas.

Associations Between Ambient Extreme Heat Exposure and Emergency Department Visits Related to Kidney Disease.

RATIONALE & OBJECTIVE: Extreme heat exposure is associated with multiple diseases. However, our current understanding of the specific impact of extreme heat exposure on kidney disease is limited. STUDY DESIGN: Case-crossover study. SETTING & PARTICIPANTS: 1,114,322 emergency department (ED) visits with a principal diagnosis of kidney disease were identified in New York state, 2005-2013. EXPOSURE: Extreme heat exposure was defined as when the daily temperature exceeded the 90th percentile temperature of that month during the study period in the county. OUTCOME: ED visits with a principal diagnosis of kidney disease and its subtypes (ICD-9 [International Classification of Diseases, Ninth Revision] codes 580-599, 788). ANALYTICAL APPROACH: Extreme heat exposure on the ED visit days was compared with extreme heat exposure on control days using a conditional logistic regression model, controlling for humidity, air pollutants, and holidays. The excess risk of kidney disease was calculated for a week (lag days 0-6) after extreme heat exposure during the warm season (May through September). We also stratified our estimates by sociodemographic characteristics. RESULTS: Extreme heat exposure was associated with a 1.7% (lag day 0) to 3.1% (lag day 2) higher risk of ED visits related to kidney disease; this association was stronger with a greater number of extreme heat exposure days in the previous week. The association with extreme heat exposure lasted for an entire week and was stronger in the transitional months (ie, May and September; excess rates ranged from 1.8% to 5.1%) rather than the summer months (June through August; excess rates ranged from 1.5% to 2.7%). The strength of association was greater among those with ED visits related to acute kidney injury, kidney stones, and urinary tract infections. Age and sex may modify the association between extreme heat exposure and ED visits. LIMITATIONS: Individual exposure to heat-how long people were outside or whether they had access to air conditioning-was unknown. CONCLUSIONS: Extreme heat exposure was significantly associated with a dose-dependent greater risk of ED visits for kidney disease.

Clinical Outcomes of Adults With Diagnosed HIV Living in Ending the HIV Epidemic Priority Areas, Medical Monitoring Project, 2018.

OBJECTIVES: The Ending the HIV Epidemic (EHE) initiative prioritizes treatment and prevention efforts in counties where most new HIV diagnoses occur and states with substantial incidence of new HIV diagnoses in rural areas. Understanding the characteristics of adults with HIV living in EHE priority areas, and how these characteristics compare with adults with HIV living in non-EHE priority areas, can inform EHE efforts. METHODS: We analyzed data from the 2018 Medical Monitoring Project (MMP) to understand the characteristics of adults with HIV living in 36 of 48 EHE priority counties; San Juan, Puerto Rico; and 1 of 7 EHE priority states. We calculated weighted percentages of sociodemographic characteristics, behaviors, and clinical outcomes of adults with diagnosed HIV living in MMP EHE priority areas and compared them with characteristics of adults who did not live in MMP EHE priority areas using prevalence ratios (PRs) with predicted marginal means. RESULTS: Living in an MMP EHE priority area was more common among adults who were non-Hispanic Black or Hispanic, experienced homelessness, or were food insecure compared with adults who were non-Hispanic White (59.3% and 58.4% vs 41.0%), not experiencing homelessness (60.9% vs 51.9%), or not food insecure (59.8% vs 51.0%). Adults who lived in MMP EHE priority areas were significantly less likely to be adherent to their HIV medications (PR = 0.95; 95% CI, 0.91-0.99) and durably virally suppressed (PR = 0.94; 95% CI, 0.91-0.97), and more likely to miss scheduled appointments for HIV care (PR = 1.31; 95% CI, 1.10-1.56) than adults who did not live in MMP EHE priority areas. CONCLUSION: To increase viral suppression and reduce HIV transmission, it is essential to strengthen public health efforts to improve medication and appointment adherence in this population.

Evaluating the sensitivity of jurisdictional heterogeneity and jurisdictional mixing in national level HIV prevention analyses: context of the U.S. ending the HIV epidemic plan.

BACKGROUND: The U.S. Ending the HIV epidemic (EHE) plan aims to reduce annual HIV incidence by 90% by 2030, by first focusing interventions on 57 regions (EHE jurisdictions) that contributed to more than 50% of annual HIV diagnoses. Mathematical models that project HIV incidence evaluate the impact of interventions and inform intervention decisions. However, current models are either national level, which do not consider jurisdictional heterogeneity, or independent jurisdiction-specific, which do not consider cross jurisdictional interactions. Data suggests that a significant proportion of persons have sexual partnerships outside their own jurisdiction. However, the sensitivity of these jurisdictional interactions on model outcomes and intervention decisions hasn't been studied. METHODS: We developed an ordinary differential equations based compartmental model to generate national-level projections of HIV in the U.S., through dynamic simulations of 96 epidemiological sub-models representing 54 EHE and 42 non-EHE jurisdictions. A Bernoulli equation modeled HIV-transmissions using a mixing matrix to simulate sexual partnerships within and outside jurisdictions. To evaluate sensitivity of jurisdictional interactions on model outputs, we analyzed 16 scenarios, combinations of a) proportion of sexual partnerships mixing outside jurisdiction: no-mixing, low-level-mixing-within-state, high-level-mixing-within-state, or high-level-mixing-within-and-outside-state; b) jurisdictional heterogeneity in care and demographics: homogenous or heterogeneous; and c) intervention assumptions for 2019-2030: baseline or EHE-plan (diagnose, treat, and prevent). RESULTS: Change in incidence in mixing compared to no-mixing scenarios varied by EHE and non-EHE jurisdictions and aggregation-level. When assuming jurisdictional heterogeneity and baseline-intervention, the change in aggregated incidence ranged from - 2 to 0% for EHE and 5 to 21% for non-EHE, but within each jurisdiction it ranged from - 31 to 46% for EHE and - 18 to 109% for non-EHE. Thus, incidence estimates were sensitive to jurisdictional mixing more at the jurisdictional level. As a result, jurisdiction-specific HIV-testing intervals inferred from the model to achieve the EHE-plan were also sensitive, e.g., when no-mixing scenarios suggested testing every 1 year (or 3 years), the three mixing-levels suggested testing every 0.8 to 1.2 years, 0.6 to 1.5 years, and 0.6 to 1.5 years, respectively (or 2.6 to 3.5 years, 2 to 4.8 years, and 2.2 to 4.1 years, respectively). Similar patterns were observed when assuming jurisdictional homogeneity, however, change in incidence in mixing compared to no-mixing scenarios were high even in aggregated incidence. CONCLUSIONS: Accounting jurisdictional mixing and heterogeneity could improve model-based analyses.

Successful surgical treatment of epithelioid hemangioendothelioma involving multiple liver lesions and bilateral lung nodules.

Epithelioid hemangioendothelioma (EHE) affects many organs, particularly lung and liver, and typically presents as multiple lesions. Treatment for EHE is not yet standardized, but surgery is appropriate when lesions are resectable. In our patient, radiography revealed multiple bilateral pulmonary nodules, and CT showed several liver tumors. The liver masses and those in the right lung were removed during the initial surgery; pathology of hepatic specimens confirmed the diagnosis of EHE. During the second operation, the left lung nodules were excised, and all were EHEs. Surgical removal of multiorgan multinodular EHE is a viable treatment option, especially for young patients.

"Everything Fell Apart Once COVID-19 Hit"-Leveraging the COVID-19 Response to Strengthen Public Health Activities toward Ending the HIV Epidemic: A Qualitative Study.

COVID-19 caused widespread disruption of activities for Ending the HIV Epidemic (EHE). In this study we assessed public health perspectives on leveraging the COVID-19 response to advance the goals of EHE. We conducted a qualitative study with 33 public health partners in the Midwestern and Southern United States from October 2020 to February 2022. Participants were asked how the strategies developed for COVID-19 could be applied to the HIV epidemic. Interviews were recorded, transcribed, and examined using rapid qualitative analysis. Four themes emerged: (1) Rebuilding teams and adapting culture for success in EHE activities; (2) Recognizing and modernizing the role of disease intervention specialists (DIS); (3) Enhanced community awareness of the public health role in disease response and prevention; and (4) Leveraging COVID-19 data systems and infrastructure for EHE activities. The COVID-19 pandemic called attention to the dearth of public health funding and outdated information technology (IT) infrastructure used for HIV activities. It also led to greater public health knowledge, including increased familiarity with partner services and molecular epidemiology of HIV, and opportunities to develop new data systems for surveillance that can be applied to efforts for EHE.

Molecular Epidemiology of HIV-1 Subtype B Infection across Florida Reveals Few Large Superclusters with Metropolitan Origin.

Florida is considered an epicenter of HIV in the United States. The U.S. federal plan for Ending the HIV Epidemic (EHE) within 10 years prioritizes seven of Florida's 67 counties for intervention. We applied molecular epidemiology methods to characterize the HIV infection networks in the state and infer whether the results support the EHE. HIV sequences (N = 34,446) and associated clinical/demographic metadata of diagnosed people with HIV (PWH), during 2007 to 2017, were retrieved from the Florida Department of Health. HIV genetic networks were investigated using MicrobeTrace. Associates of clustering were identified through boosted logistic regression. Assortative trait mixing was also assessed. Bayesian phylogeographic methods were applied to evaluate evidence of imported HIV-1 lineages and illustrate spatiotemporal flows within Florida. We identified nine large clusters spanning all seven EHE counties but little evidence of external introductions, suggesting-in the absence of undersampling-an epidemic that evolved independently from the rest of the country or other external influences. Clusters were highly assortative by geography. Most of the sampled infections (82%) did not cluster with others in the state using standard molecular surveillance methods despite satisfactory sequence sampling in the state. The odds of being unclustered were higher among PWH in rural regions, and depending on demographics. A significant number of unclustered sequences were observed in counties omitted from EHE. The large number of missing sequence links may impact timely detection of emerging transmission clusters and ultimately hinder the success of EHE in Florida. Molecular epidemiology may help better understand infection dynamics at the population level and underlying disparities in disease transmission among subpopulations; however, there is also a continuous need to conduct ethical discussions to avoid possible harm of advanced methodologies to vulnerable groups, especially in the context of HIV stigmatization. IMPORTANCE The large number of missing phylogenetic linkages in rural Florida counties and among women and Black persons with HIV may impact timely detection of ongoing and emerging transmission clusters and ultimately hinder the success of epidemic elimination goals in Florida.

Indications and Limitations of Sirolimus in the Treatment of Vascular Anomalies-Insights From a Retrospective Case Series.

Background: Despite recent developments, the role of sirolimus in the heterogeneous spectrum of vascular anomalies is yet to be defined, in terms of indication, dosage, and therapy duration, recognizing both its potential and limitations. Methods: We retrospectively analyzed 16 children with vascular anomalies treated with sirolimus in two pediatric centers between 2014 and 2020 [male: n = 7, the median age at diagnosis: 4.6 months (range, 0-281.4)]. In addition, repetitive volumetric analyses of the vascular anomalies were performed when possible (11 cases). Results: Ten patients were diagnosed with vascular malformations and 6 with vascular tumors. The mean therapy duration was 27.2 months (range, 3.5-65). The mean sirolimus level was 8.52 ng/ml (range, 5.38-12.88). All patients except one with central conducting lymphatic anomaly responded to sirolimus, with the most noticeable volume reduction in the first 4-6 months. Additional administration of vincristine was needed in five patients with kaposiform hemangioendothelioma and yielded a response, even in cases, refractory to sirolimus monotherapy. As a single agent, sirolimus led to impressive improvement in a patient with another vascular tumor-advanced epithelioid hemangioendothelioma. Complicated vascular malformations required long-term sirolimus therapy. Side effects of sirolimus included mucositis and laboratory abnormalities. No major infectious episodes were recorded. An infant with COVID-19, diagnosed while on sirolimus therapy, presented with a mild course. Conclusion: In the current series, we reported limitations of sirolimus as monotherapy, addressing the need to redefine its indications, and explore combination regimens and multimodal treatment strategies. Tools for objective evaluation of response trends over time could serve as a basis for the establishment of future therapeutic algorithms.

Hepatic Follicular Dendritic Cell Sarcoma with Epithelioid Morphology: Histopathologist's Perspective.

Follicular dendritic cell (FDC) sarcoma is an uncommon tumor of the liver with only 30 previous cases reported in the English literature. Histopathological examination is the gold standard for the diagnosis of FDC sarcoma although the diagnosis is often missed because of its rarity. It usually presents with spindle-cell morphology although epithelioid/biphasic morphology is also well-known. This morphological variation can also pose a diagnostic challenge. We discuss a case of unresectable hepatic FDC sarcoma in an adult male who was diagnosed in core biopsy. We highlight the relevant histomorphological differentials and diagnostic approaches to FDC sarcoma in this anecdote.