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The document is an interview with Professor Sabine Werner, a renowned figure in the field of dermatology and venereology. Professor Werner's career trajectory, research interests, mentors, achievements, and advice for young colleagues are discussed. She highlights her work in molecular dermatology, wound healing, and interdisciplinary collaborations. Professor Werner also shares her concerns about the challenges facing dermatology in the future and predicts breakthroughs in gene therapies and personalized medicine. [Extracted from the article]

Assessing the risk of cancer among people living with HIV (PLHIV) in the current era of antiretroviral therapy (ART) is crucial, given their increased susceptibility to many types of cancer and prolonged survival due to ART exposure. Our study aims to compare the association between HIV infection and specific cancer sites in Rwanda. Population‐based cancer registry data were used to identify cancer cases in both PLHIV and HIV‐negative persons. A probabilistic record linkage approach between the HIV and cancer registries was used to supplement HIV status ascertainment in the cancer registry. Associations between HIV infection and different cancer types were evaluated using unconditional logistic regression models. We performed several sensitivity analyses to assess the robustness of our findings and to evaluate the potential impact of different assumptions on our results. From 2007 to 2018, the cancer registry recorded 17,679 cases, of which 7% were diagnosed among PLHIV. We found significant associations between HIV infection and Kaposi's Sarcoma (KS) (adjusted odds ratio [OR]: 29.1, 95% CI: 23.2–36.6), non‐Hodgkin lymphoma (NHL) (1.6, 1.3–2.0), Hodgkin lymphoma (HL) (1.6, 1.1–2.4), cervical (2.3, 2.0–2.7), vulvar (4.0, 2.5–6.5), penile (3.0, 2.0–4.5), and eye cancers (2.2, 1.6–3.0). Men living with HIV had a higher risk of anal cancer (3.1, 1.0–9.5) than men without HIV, but women living with HIV did not have higher risk than women without HIV (1.0, 0.2–4.3). Our study found that in an era of expanded ART coverage in Rwanda, HIV is associated with a broad range of cancers, particularly those linked to viral infections. [ABSTRACT FROM AUTHOR]

"When you can measure what you are speaking about, and express it in numbers, you know something about it." is a famous quote attributed to Lord Kelvin. This sentiment puts viral load measurements at the center of virology. Viral load, or more precisely, DNA copy number measurements, are also used to follow infections with human herpesviruses, such as Kaposi sarcoma herpesvirus (KSHV) and Epstein–Barr Virus (EBV). EBV and KSHV are associated with human cancers, and determining their DNA copy numbers in the context of cancer prediction and progression on therapy is of fundamental scientific and translational interest. Yet, there is no generally accepted assay for KSHV DNA quantitation, and KSHV viral load is not used in clinical decision‐making. Here, we review the history of KSHV DNA detection assays, explore factors that affect sensitivity and specificity, and describe an automated, high‐throughput, real‐time quantitative polymerase chain reaction (PCR) assay for KSHV and EBV. In conjunction with a digital PCR assay using the same primer/probe combination, we describe how to determine the absolute KSHV genome copy numbers in plasma, peripheral blood mononuclear cells, saliva, and other easily accessible body fluids. [ABSTRACT FROM AUTHOR]

De novo or viral reactivation cancers are a major cause of morbidity and mortality in the solid organ transplant (SOT) population. Primary sclerosing cholangitis (PSC) is an aggressive disease which can lead to cholestatic liver damage and cirrhosis. PSC often cooccurs with inflammatory bowel disease (IBD). Here, we describe the case of a 28‐year‐old male with PSC along with poorly controlled IBD who underwent a liver transplant and developed colonic Kaposi sarcoma (KS). Our case highlights the importance of adequate pretransplant screening for endemic viruses, high clinical suspicion for KS in the setting of difficult‐to‐control colitis, and early multidisciplinary involvement. [ABSTRACT FROM AUTHOR]

ABSTRACT Kaposi sarcoma is a human herpesvirus 8–associated angio‐proliferative tumor arising from lymphatic endothelial cells. Four clinical subtypes are known: classic, epidemic, endemic, and iatrogenic. The development of Kaposi sarcoma and lymphedema may be interlinked, where each condition could potentially support the progression of the other. Post‐mastectomy lymphedema is a commonly recognized complication following radical mastectomy. Angiosarcoma is the most frequently reported neoplasm in such a situation. We present a 72‐year‐old female who developed Kaposi sarcoma on the same side of mastectomy 9 years following her initial diagnosis and treatment for cancer breast. The diagnosis of Kaposi sarcoma was based on the histopathologic findings and was confirmed with immunohistochemical staining for human herpes virus 8 and D2‐40. Lymphedema may be associated with local immune suppression manifested in the form of defective cell–mediated immunity and antigen‐presenting cell migration defect which may facilitate development of neoplasms. It is important to differentiate Kaposi sarcoma from other vascular tumors which may have a much worse prognosis. Patients with lymphedema should receive appropriate management and undergo long‐term follow‐up for early detection of any potential malignancies. [ABSTRACT FROM AUTHOR]

Background: Human herpes virus 8 (HHV‐8) or Kaposi sarcoma herpesvirus (KSHV) is an opportunistic oncovirus that causes multiple pathologic entities. Methods: We present a case of fatal HHV‐8‐associated multisystem illness with disseminated Kaposi sarcoma and HHV8‐associated lymphoproliferative disorder with systemic inflammation. We conducted a narrative review of the literature on HHV‐8 in transplantation with a goal of illuminating the spectrum of HHV‐8‐associated diseases in this vulnerable population, modes of disease transmission, and the potential role for donor and recipient screening. Results: HHV‐8‐associated KS, primary effusion lymphoma (PEL), multicentric Castleman disease (MCD), and KSHV inflammatory cytokine disorder (KICS) may affect transplant recipients; with the exception of KS, these conditions are rare but carry high morbidity and mortality. Conclusion: HHV‐8‐associated diseases have diverse and protean manifestations in transplant recipients, with potentially fatal outcomes. HHV‐8 seroprevalence among organ donors and the magnitude of risk for donor‐derived HHV‐8 infection or clinically significant disease remain unknown and require further study. [ABSTRACT FROM AUTHOR]

Background: Preferentially expressed antigen in melanoma (PRAME) has been extensively studied in cutaneous melanocytic tumors and has proven valuable as a diagnostic adjunct in routine dermatopathology practice. However, its expression in cutaneous vascular neoplasms, particularly angiosarcomas (AS), remains largely unexplored. Methods: To further explore PRAME expression in cutaneous AS, 18 cases of post‐irradiation and 13 cases of primary cutaneous AS were evaluated for PRAME. For comparison, sections from 11 deep soft tissue/visceral AS, 10 Kaposi sarcomas, 8 microvenular hemangiomas, 7 infantile hemangiomas, 8 atypical vascular lesions, 6 epithelioid hemangioendotheliomas, 6 pyogenic granulomas, 6 papillary endothelial hyperplasias, 6 epithelioid hemangiomas, 3 capillovenous malformations, 3 hobnail hemangiomas, 2 spindle cell hemangiomas, 2 pseudomyogenic hemangioendotheliomas, and 2 composite hemangioendotheliomas were also retrieved. Results: Overall, 22 of 31 (70.9%; 12 post‐irradiation and 10 primary) cutaneous AS were positive for PRAME. In contrast, only 1 of 11 (9.1%) deep soft tissue/visceral AS showed diffuse and strong PRAME nuclear staining. All other tumor types were negative for PRAME, except for 5 of 7 (71.4%) infantile hemangiomas, which demonstrated rare (<5%; four cases) and 1+ (5–25%; one case) nuclear staining. Conclusions: In this study, we have demonstrated frequent nuclear PRAME expression in cutaneous AS. PRAME immunohistochemistry may serve as a valuable additional marker in selected clinical settings. [ABSTRACT FROM AUTHOR]

The article discusses a case of iatrogenic Kaposi sarcoma (KS) in a Hispanic patient with rheumatoid arthritis (RA) due to treatment with Janus kinase (JAK) and tumor necrosis factor (TNF) α inhibitors. The patient developed disseminated lesions after starting methotrexate, baricitinib, and deflazacort, which worsened with golimumab. Treatment involved discontinuing immunosuppressive medications and using doxorubicin, peginterferon alfa‐2a, and valganciclovir, resulting in lesion regression. The study also reviews similar cases of RA patients developing iatrogenic KS from JAK and TNF‐α inhibitors, emphasizing the importance of considering this condition in autoimmune disease treatment. [Extracted from the article]

Objective: This study aims to examine the expression of androgen receptor (AR) and estrogen receptor (ER) in patients with classic Kaposi's sarcoma (CKS) in Xinjiang, as well as to assess the serum levels of sex hormones in these patients. The objective is to explore potential new directions and targets for diagnosing and treating CKS in Xinjiang. Methods: The case group comprised 35 patients diagnosed with CKS who presented at our hospital from 2014 to 2021. The control group consisted of 35 patients with pyogenic granuloma (PG) who visited the hospital during the same period, selected using propensity score matching (PSM). Immunohistochemistry was used to detect AR, human herpesvirus type 8 (HHV‐8), and ER in paraffin‐embedded tissue samples from patients diagnosed with CKS and PG. Additionally, enzyme‐linked immunosorbent assay (ELISA) was used to quantitatively measure serum sex hormone levels in the 35 patients with CKS and 35 patients with PG. Results: AR expression was relatively weak in both the CKS and PG groups, with the PG group exhibiting a slightly stronger expression than the CKS group. Conversely, the expression of ER was significantly higher in the CKS group compared to the PG group (p < 0.05). Additionally, serum testosterone (T) levels were elevated in the CKS group, while serum estradiol (E2) levels were higher in the PG group (p < 0.05). Conclusion: Sex hormones and their receptors are implicated in the pathogenesis of CKS in Xinjiang. The use of ER antagonists may represent a novel avenue for research and treatment of CKS. [ABSTRACT FROM AUTHOR]

This study aimed to describe the prevalence of high‐risk human papillomavirus (HR‐HPV) types in the anal canal in a cohort of people living with HIV (PLWHIV) with a history of malignancy. Setting: Referral tertiary care hospital for adult patients with cancer. Methods: We reviewed data of patients from the AIDS Cancer Clinic on antiretroviral therapy in chronic control who were consecutively referred for high‐resolution anoscopy (HRA), where they underwent anal evaluation, collection of specimens for anal cytology and anal human papillomavirus (HPV) followed by HRA with directed biopsy if needed. Results: A total of 155 patients were included; 149 (96.1%) were men, all of them men who have sex with men (MSM); the median age was 39 (IQR 32‐47) years; 105 (67.7%) with Kaposi sarcoma, 40 (25.8%) with non‐Hodgkin lymphoma and 10 (6.4%) with other neoplasms; only 7 (4.5%) had active cancer. The prevalence of HR‐HPV infection was 89% (n=138) (95% CI 83–93) with at least one HR‐HPV infection, and 62% (96) had coinfection with at least two types; the median HR‐HPV types of coinfection were 3 (IQR 2–4). The number of patients infected with HPV 16 was 64 (41.3%, 95% CI 33.8–49.3), HPV 18 was 74 (47.7%, 95% CI 39.9–55.7) and with both 35 (22.6%). Some 59 patients (38%) had high‐grade squamous intraepithelial lesions (HSIL) and 49 (31.6%) had low‐grade squamous intraepithelial lesions (LSIL). The prevalence of HR‐HPV and HSIL among patients aged ≤35 and >35 years was the same. Conclusions: In this cohort of PLWHIV with a history of malignancy we found a high prevalence of HR‐HPV 16 and 18 and anal HSIL, even in persons aged ≤35 years. These data highlight the importance of anal cancer screening in PLWHIV and history of malignancy. [ABSTRACT FROM AUTHOR]

Kaposi's Sarcoma Herpesvirus (KSHV) is the causative agent of several human diseases. There are no cures for KSHV infection. KSHV establishes biphasic lifelong infections. During the lytic phase, new genomes are replicated by seven viral DNA replication proteins. The processivity factor's (PF‐8) functions to tether DNA polymerase to DNA, so new viral genomes are efficiently synthesized. PF‐8 self‐associates, interacts with KSHV DNA replication proteins and the viral DNA. Inhibition of viral DNA replication would diminish the infection within a host and reduce transmission to new individuals. In this review we summarize PF‐8 molecular and structural studies, detail the essential protein‐protein and nucleic acid interactions needed for efficient lytic DNA replication, identify future areas for investigation and propose PF‐8 as a promising antiviral target. Additionally, we discuss similarities that the processivity factor from Epstein‐Barr virus shares with PF‐8, which could promote a pan‐herpesvirus antiviral therapeutic targeting strategy. [ABSTRACT FROM AUTHOR]

Background: Kaposi sarcoma (KS) is a multicentric vascular and lymphatic neoplasm caused by human herpesvirus 8 (HHV‐8). It generally concerns the elderly and immunosuppressed population. Four major clinical types of KS have been described. The most common subtype is Classical KS (CKS). Objectives: Our retrospective study aimed to better define prognostic subgroups among patients with CKS, which is the most common in our country. Method: Between 2014 and 2020, 43 patients with CKS were treated with local excision, radiotherapy and chemotherapy. Reviewed information included demographics, clinical features, laboratory findings, treatment responses and overall survival. Results: During the follow‐up, eight patients (18.6%) died of CKS. The complete response rate was 46.5%, partial response and stable disease 51.2%, and progressive disease 2.3% of all patients. Gender, haemoglobin level at diagnosis, and disseminated involvement were prognostic factors affecting survival in all patients. Conclusion: We confirmed that male gender, low haemoglobin levels, and disseminated involvement are associated with poor prognosis in CKS patients. It is the only Turkish study in which prognostic analysis was performed for this rare cancer. [ABSTRACT FROM AUTHOR]

Background: Renal transplant recipients (RTRs) are prone to skin cancer due to the immunosuppression required to maintain graft function. Existing studies of skin cancer in RTRs focus on patients with Fitzpatrick skin types I‐II, with limited documentation of incidence in skin types III‐VI. This study seeks to better characterize skin cancers in RTRs with skin types III‐VI. Primary aims: Compare the incidence of skin cancer in RTRs of skin types I‐II with skin types III‐VI. Secondary aims: Explore the association between the development of skin cancer and other contributing factors in RTRs of skin types I‐VI. Methods: Retrospective chart review of RTRs at a single institution between January 1, 2000 and December 31, 2022. Patients were followed from the date of transplant to the last clinical follow‐up or death. 777 RTRs were included in the study, including 245 patients with Fitzpatrick skin types I‐II and 532 with skin types III‐VI. A total of 48 patients developed NMSCs, 2 patients developed melanoma, and 3 patients developed Kaposi sarcoma. Results and conclusions: There is a higher incidence of skin cancer in RTRs with Fitzpatrick skin types III‐VI compared to the reported incidence among non‐transplant recipients of the same skin types, but the incidence remains considerably lower compared to RTR of skin types I‐II. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma (KS) is an angio‐proliferative disease with a viral etiology and a multifactorial pathogenesis that results from immune dysfunction. In patients affected by latent viral infections such as herpesviruses, SARS‐CoV‐2 infection may result in lytic cycle reactivation in host cells. A robust immune system response is crucial for eliminating pathogens and resolving both latent and non‐latent viral infections. We report a case series of KS characterized by tumor progression after SARS‐CoV‐2 infection. We performed a systematic literature review of the PubMed/MEDLINE and EMBASE databases. The keyword terms included "SARS‐CoV‐2," "HHV‐8," "Kaposi's sarcoma," "IL‐6," and "COVID‐19." English language restriction was applied. Items not covered by our study were excluded. KS is a complex disease linked to an impaired immune system. Conditions that result in temporary or permanent immunodeficiency can trigger viral reactivation or exacerbate an existing disease. It is feasible that the increase in cytokine levels in COVID‐19 patients, coupled with lymphocyte downregulation and treatment that induces herpesvirus lytic reactivation, may contribute to the progression of KS after SARS‐CoV‐2 infection. These observations suggest that patients with KS should be clinically monitored both during and after SARS‐CoV‐2 infection. Nevertheless, prospective data should be collected to validate this hypothesis and enhance our understanding of the mechanisms implicated in the onset or progression of KS. [ABSTRACT FROM AUTHOR]

Kaposi sarcoma (KS) is a neoplasm of vascular origin that promotes angiogenesis and the growth of endothelial cells triggered by the Kaposi Sarcoma‐associated Herpes Virus (KSHV). When associated with HIV, KSHV becomes more aggressive and rapidly evolves. The HIV‐1 TAT protein can be essential in developing AIDS‐associated KS by promoting angiogenesis and increasing KSHV replication. Therefore, we evaluated the genetic profile of the first exon of tat gene among groups of people living with HIV (PLHIV) with (case group, n = 36) or without KS, this later with (positive control group, n = 46) and without KSHV infection (negative control group, n = 24); all individuals under antiretroviral therapy. The genetic diversity, the DN/DS ratio, and the genetic entropy of the first exon of tat were higher in the case group, followed by the positive control group, which was higher than the negative control group. The number of tat codons under positive selection was seven in the case group, six in the positive control group, and one in the negative control group. The prevalence of HIV viral loads below the detection limit was equal in the case and positive control groups, which were lower than in the negative control group. The mean CD4+ T cell counts were higher in the negative control group, followed by the positive control group, and followed by the case group. These results emphasize the negative influence of KSHV in antiretroviral treatment, as well as the HIV‐specific TAT profile among PLHIV who developed KS. [ABSTRACT FROM AUTHOR]

The article explores the expression of programmed cell death proteins in patients with atypical fibroxanthoma and pleomorphic dermal sarcoma, indicating their potential for anti-PD-1/PD-L1 therapy. The study analyzed tissue samples from patients and found higher PD-L1 expression in pleomorphic dermal sarcoma compared to atypical fibroxanthoma. The research suggests that immunotherapeutic interventions may be more relevant for pleomorphic dermal sarcoma due to its higher rate of metastases. The findings also highlight the association of tumor thickness with disease relapse and survival in these types of skin cancers. [Extracted from the article]

This article, published in the Veterinary Record Case Reports, describes a case of cutaneous haemangiosarcoma with ovarian metastases in an aquarium-managed mirror carp. The study highlights the limited scientific literature on neoplasia in common carp and mirror carp, with only a few reported cases of different types of tumors. The case presented in this article is significant because cutaneous haemangiosarcoma has not been previously reported in carp. The study emphasizes the potential for metastasis in fish neoplasia and the importance of local invasion as a determinant feature of malignancy. The authors conclude that further research is needed to understand the behavior and predilections of haemangiosarcoma in carp species. [Extracted from the article]

This article discusses two cases of Kaposi sarcoma (KS) in Russian patients who had undergone kidney transplantation and were receiving immunosuppressive therapy. KS is a vascular disease that affects various parts of the body, including the skin. The article highlights the importance of human herpesvirus-8 (HHV-8) as a potential trigger for KS, particularly in transplant recipients. The patients presented with characteristic skin lesions and were found to be HHV-8 positive. The article suggests that testing donors and recipients for HHV-8 before transplantation could help predict the risk and prognosis of KS. [Extracted from the article]

Kaposi's sarcoma (KS) may derive from Kaposi's sarcoma herpesvirus (KSHV)‐infected human mesenchymal stem cells (hMSCs) that migrate to sites characterized by inflammation and angiogenesis, promoting the initiation of KS. By analyzing the RNA sequences of KSHV‐infected primary hMSCs, we have identified specific cell subpopulations, mechanisms, and conditions involved in the initial stages of KSHV‐induced transformation and reprogramming of hMSCs into KS progenitor cells. Under proangiogenic environmental conditions, KSHV can reprogram hMSCs to exhibit gene expression profiles more similar to KS tumors, activating cell cycle progression, cytokine signaling pathways, endothelial differentiation, and upregulating KSHV oncogenes indicating the involvement of KSHV infection in inducing the mesenchymal‐to‐endothelial (MEndT) transition of hMSCs. This finding underscores the significance of this condition in facilitating KSHV‐induced proliferation and reprogramming of hMSCs towards MEndT and closer to KS gene expression profiles, providing further evidence of these cell subpopulations as precursors of KS cells that thrive in a proangiogenic environment. [ABSTRACT FROM AUTHOR]

Human Herpesvirus 8 (HHV‐8) has been classified by sequence analysis of open reading frame (ORF) K1, ORF K15, and variable sequence loci within the central constant region. The purpose of this study was to examine the molecular epidemiology of HHV‐8 in an Irish population. This retrospective study included 30 patients who had HHV‐8 DNA detected in plasma. Nested end‐point PCR was used to characterise four regions of the HHV‐8 genome, K1, T0.7 (K12), ORF 75, and K15. Sequencing data were obtained for 23 specimens from 19 patients. Phylogenetic analysis of ORF K1 demonstrated that subtypes A, B, C and F were present in 37%, 11%, 47% and 5%, respectively. For T0.7 and ORF 75, sequencing data were obtained for 12 patients. For T0.7, subtypes A/C, J, B, R and Q were present in 58%, 17%, 8%, 8%, and 8%, respectively. For ORF 75, subtypes A, B, C and D were present in 58%, 8%, 25%, and 8%, respectively. K15 sequences were determined for 13 patients. 69% had the P allele and 31% had the M allele. The data generated by this study demonstrate that a broad variety of HHV‐8 subtypes are represented in patients exhibiting HHV‐8‐related disease in Ireland, a low prevalence country. The predominance of C and A K1 subtypes was as expected for a Western European population. The 31% prevalence for K15 subtype M was higher than expected for a Western European population. This may represent the changing and evolving epidemiology in Ireland due to altered migration patterns. [ABSTRACT FROM AUTHOR]

This article, published in the journal Pediatric Dermatology, presents a case study of an 8-year-old boy with a raised lesion on his scalp. The lesion rapidly grew in size over three months and was characterized by an erythematous to yellowish-white, dome-shaped exophytic nodule. The diagnosis was determined to be angiolymphoid hyperplasia with eosinophilia (ALHE) based on histopathological examination. ALHE is a rare vasoproliferative disorder with an unclear etiology, and treatment options include corticosteroids, surgery, cryotherapy, and lasers. The patient in this case study did not experience recurrence after surgical excision. [Extracted from the article]

Human herpesviruses (HHVs) cause a wide variety of central nervous system (CNS) infections including meningitis and encephalitis. While HHV‐8 is not typically associated with neurological diseases, several studies have indicated a relationship, such as secondary central nervous system (CNS) metastases and a few isolated cases of HHV‐8 encephalitis in acquired immunodeficiency syndrome (HIV). However, it has not been previously linked to encephalitis in solid organ transplantation (SOT). This case presents the first‐ever instance of HHV‐8 encephalitis in a SOT recipient. Our case highlights the association of HHV‐8‐related diseases, such as post‐transplant Kaposi's Sarcoma (KS), with encephalitis. The patient was diagnosed with KS before developing neurological symptoms and received a prompt clinical response through intravenous foscarnet and ganciclovir treatment for 14 days. It is important to note that HHV‐8 is a rare cause of encephalitis, and diagnosis requires a high index of suspicion in the appropriate clinical context, allowing for the use of antiviral therapy. This case also underscores the importance of considering the possibility of HHV‐8‐related diseases in SOT recipients, as they are at risk of developing such infections. [ABSTRACT FROM AUTHOR]

This article discusses a rare case of disseminated Kaposi sarcoma (KS) in a kidney transplant recipient without primary cutaneous involvement. The patient, a 69-year-old male, had a history of end-stage renal disease and had undergone a kidney transplant. The KS was complicated by KSHV-inflammatory cytokine syndrome (KICS), which presented as multi-system inflammation. The patient's case was atypical because it occurred in the United States without known geographic or sexual risk factors. The article provides information on the prevalence, diagnosis, and treatment of KS in transplant recipients. [Extracted from the article]

Aims: Follicular helper T‐cell (TFH) lymphoma of the angioimmunoblastic‐type (AITL), one of the most prevalent T‐cell lymphomas, typically encompasses proliferation of high endothelial venules and Epstein–Barr virus‐positive immunoblasts, but neither infection with HHV8 nor association with Kaposi's sarcoma (KS) have been described. The aims of this study are to characterise the association between AITL and HHV8 infection or KS. Methods and results: Three male patients aged 49–76 years, HIV‐negative, with concurrent nodal involvement by AITL and KS, were identified from our files and carefully studied. Two patients originated from countries where endemic KS occurs, including one with cutaneous KS. The lymphomas featured abundant vessels, expanded follicular dendritic cells and neoplastic TFH cells [PD1+ (three of three), ICOS+ (three of three), CXCL13+ (three of three), CD10+ (two of three), BCL6 (two of three)] but lacked EBV+ immunoblasts. The foci of KS consisted of subcapsular proliferations of ERG+, CD31+ and/or CD34+, HHV8+ spindle cells. High‐throughput sequencing showed AITL‐associated mutations in TET2 (three of three), RHOA (G17V) (three of three) and IDH2 (R172) (two of three), which were absent in the microdissected KS component in two cases. Relapses in two patients consisted of AITL, without evidence of KS. No evidence of HHV8 infection was found in a control group of 23 AITL cases. Conclusion: Concurrent nodal involvement by AITL and KS is rare and identification of both neoplastic components may pose diagnostic challenges. The question of whether the association between AITL and KS may be fortuitous or could reflect the underlying immune dysfunction in AITL remains open. [ABSTRACT FROM AUTHOR]

This article discusses a study conducted at a dermatology center to determine the relationship between the cutaneous CD4:CD8 ratio in skin biopsies and the serum CD4:CD8 ratio in patients with Kaposi sarcoma (KS) and HIV infection. The study found that an inverted cutaneous CD4:CD8 ratio correlated with an inversion in the serum CD4:CD8 ratio. The researchers also observed that a perivascular-peritumoral pattern of CD8+ TL distribution was the most frequent in KS patients. The study suggests that the role of CD8+ TL in KS is poorly understood and further research is needed to understand its implications. [Extracted from the article]

This article discusses the risk of developing Kaposi sarcoma (KS) as a second primary cancer in individuals who have already had a malignancy. The study analyzed data from over 6 million individuals and found that males, particularly those under 40, had the highest risk of developing KS within a year of their initial cancer. Patients who received chemotherapy had the highest increased risk of KS compared to other treatments. The study also found that patients of all genders had an increased risk of developing cancers of the anorectum, lymphoma, and leukemia. The study suggests that immune dysregulation and viral infections may contribute to the development of KS. Providers are advised to be vigilant for KS in male patients who have had certain types of cancers. [Extracted from the article]

This document is an interview with Professor Michel Janier, a prominent figure in the field of dermatology and venereology. Professor Janier discusses his background, education, and professional achievements, including his role in keeping venereology within the field of dermatology. He also mentions his disappointment that young doctors are not familiar with the pioneers of dermatology. Professor Janier shares his favorite writer, composer, and painter, and expresses his belief that venereology needs dermatology experts. He predicts that the greatest problem in dermatology in the next 10 years will be the overwhelming importance of aesthetics, and he believes that artificial intelligence will be the next breakthrough in the field. [Extracted from the article]

Objectives: Despite the improved survival of patients with AIDS and Kaposi's sarcoma (KS), competing events are a non‐negligible issue affecting the survival of such patients. In this study, we explored the prognostic factors of KS‐specific and non‐KS‐specific mortality in patients with AIDS‐related KS (AIDS‐KS), accounting for competing risk. Methods: We identified 17 103 patients with AIDS‐KS aged 18–65 years between 1980 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) 18 registry database. Prognostic factors for KS‐specific and non‐KS‐specific mortality were determined by the Fine and Grey proportional subdistribution hazard model. We built competing risk nomograms and assessed their predictive performance based on the identified prognostic factors. Results: In total, 12 943 (75.68%) patients died, 1965 (15.50%) of whom died from competing events. The KS‐specific mortality rate was 14 835 per 100 000 person‐years, and the non‐KS specific mortality rate was 2719 per 100 000 person‐years. Specifically, age >44 years was associated with an 11% decrease in the subdistribution hazard of KS‐specific mortality compared with age <43 years but a 50% increase in the subdistribution hazard of non‐KS‐specific mortality. Being male was associated with a 26% increase in the subdistribution hazard of KS‐specific mortality compared with being female but a 32% decrease in the subdistribution hazard of non‐KS‐specific mortality. Notably, being in the antiretroviral therapy (ART) era consistently showed a decrease in the subdistribution hazard of both KS‐specific and non‐KS‐specific mortality than being in the pre‐ART era. Conclusions: Competing events commonly occurred among patients with AIDS‐KS, which deserves further attention to improve the prognosis of these patients. [ABSTRACT FROM AUTHOR]

Kaposi sarcoma (KS) is the most common cancer in people living with HIV (PLWH) in many countries where KS‐associated herpesvirus is endemic. Treatment has changed little in 20 years, but the disease presentation has. This prospective cohort study enrolled 122 human immunodeficiency virus (HIV) positive KS patients between 2017 and 2019 in Malawi. Participants were treated with bleomycin, vincristine and combination antiretroviral therapy, the local standard of care. One‐year overall survival was 61%, and progression‐free survival was 58%. The 48‐week complete response rate was 35%. RNAseq (n = 78) differentiated two types of KS lesions, those with marked endothelial characteristics and those enriched in inflammatory transcripts. This suggests that different KS lesions are in different disease states consistent with the known heterogeneous clinical response to treatment. In contrast to earlier cohorts, the plasma HIV viral load of KS patients in our study was highly variable. A total of 25% of participants had no detectable HIV; all had detectable KSHV viral load. Our study affirms that many KS cases today develop in PLWH with well‐controlled HIV infection and that different KS lesions have differing molecular compositions. Further studies are needed to develop predictive biomarkers for this disease. [ABSTRACT FROM AUTHOR]

Human herpesvirus‐8 (HHV‐8) viremia is associated with refractory conditions in patients infected with HIV‐1. Therefore, we evaluated the factors related to plasma HHV‐8‐DNA. Participants included patients infected with HIV‐1 who visited our hospital. Plasma HHV‐8‐DNA levels were measured using real‐time polymerase chain reaction, and anti‐HHV‐8 antibodies were assessed through enzyme immunoassays using multiple antigens (K8.1, ORF59, ORF65, and LANA). Factors related to plasma HHV‐8‐DNA were examined using Fisher's exact test or Mann–Whitney U test. The study involved 36 patients infected with HIV‐1, of whom 19 were histologically diagnosed with Kaposi's sarcoma (KS), two had multicentric Castleman's disease (MCD), and 15 did not exhibit HHV‐8‐related disease. Before the introduction of antiretroviral therapy (ART), plasma HHV‐8‐DNA was detected in 44% (7/16) of patients with KS and in 9% (1/11) of patients without HHV‐8‐related disease. Among patients with KS, elevated plasma HHV‐8‐DNA levels (≥0.05 copies/µL) correlated with the presence of CDC category C diseases other than KS (p = 0.0337), anti‐HHV‐8 antibody negativity (p = 0.0337), anemia (p = 0.0474), and thrombocytopenia (p = 0.0146). Following ART initiation, the percentage of patients positive for plasma HHV‐8‐DNA decreased from 44% (7/16) to 6% (1/17), and the percentage of patients positive for anti‐HHV‐8 antibodies increased from 44% (7/16) to 88% (15/17). Finally, plasma HHV‐8‐DNA positivity and anti‐HHV‐8 antibody negativity were observed in two patients with MCD. Our findings suggest that insufficient production of anti‐HHV‐8 antibodies was associated with HHV‐8 viremia, and that anti‐HHV‐8 antibody production was recovered with ART; thus, indicating the possibility of involvement of humoral immunity in suppressing HHV‐8 viremia. [ABSTRACT FROM AUTHOR]

The article discusses a case report of a patient with angiolymphoid hyperplasia with eosinophilia (ALHE) on the palm, a rare vascular proliferative disease. Traditional treatments like surgical excision often lead to recurrence, so the patient underwent a combination therapy of propranolol and vascular laser, resulting in significant improvement without recurrence during an 8-month follow-up. The study highlights the effectiveness of this combined treatment approach and suggests that it should be considered a first-line therapy for ALHE, emphasizing the need for long-term follow-up to confirm its benefits. [Extracted from the article]

The article discusses a case of retiform hemangioendothelioma (RH), a rare vascular tumor that is locally aggressive. The patient, a 20-year-old female, presented with a red plaque on her lower leg, which was successfully treated with Mohs micrographic surgery (MMS). The article highlights the challenges in diagnosing RH, the importance of clear margins in surgical excision, and the potential benefits of MMS in treating this rare tumor. The authors suggest further research to establish broader clinical guidelines for the treatment of RH. [Extracted from the article]

Kaposi sarcoma‐associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma and several other tumors and hyperproliferative diseases seen predominantly in human immunodeficiency virus‐infected and other immunocompromised persons. There is an increasing body of evidence showing that hypoxia and hypoxia‐inducible factors (HIFs) play important roles in the biology of KSHV and in the pathogenesis of KSHV‐induced diseases. Hypoxia and HIFs can induce lytic activation of KSHV and KSHV can in turn lead to a hypoxic‐like state in infected cells. In this review, we describe the complex interactions between KSHV biology, the cellular responses to hypoxia, and the pathogenesis of KSHV‐induced diseases. We also describe how interference with HIFs can lead to decreased tumor growth and/or death of infected cells and KSHV‐induced tumors. Finally, we show how these observations may lead to novel strategies for the treatment of KSHV‐induced diseases. [ABSTRACT FROM AUTHOR]

Background: Cutaneous vascular lesions (VLs) are benign or malignant processes involving blood and/or lymphatic vessels, usually readily diagnosed with dermoscopy. However, cases showing unclear clinical/dermoscopic findings may require further investigations. Line‐field confocal optical coherence tomography (LC‐OCT) is a new, non‐invasive imaging technique displaying high resolution and deep penetration. The aim of this study was to describe the LC‐OCT features of the most common benign and malignant VLs and to correlate them with histopathological substrates. Methods: Clinical, dermoscopic, LC‐OCT and histopathological images of VLs were retrospectively collected. Detailed LC‐OCT description and histopathological correlations were produced for different types of VLs. Results: The study included 71 VLs belonging to 50 caucasian patients [31 (62%) females; median age 56.8 (30–83) years] study lesions included 25 cherry haemangiomas, 15 angiokeratomas, 10 thrombosed haemangiomas, six pyogenic granulomas, five venous lakes, four targetoid haemosiderotic haemangiomas, four Kaposi's sarcomas and two extraungual glomus tumours. LC‐OCT detected increased dermal vascularity, assuming different size and shape according to the particular type of VLs. LC‐OCT criteria correlated well to established histopathologic findings. Conclusion: The results of our preliminary observations indicate that in vivo evaluation with LC‐OCT may provide practical clues for the identification of the vascular nature of a lesion and its differential diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: The Kaposi sarcoma (KS) T0 versus T1 staging classification does not address the unique clinical features of paediatric KS in human gammaherpesvirus 8 (HHV‐8) endemic regions of Africa. This study seeks to define patterns of childhood KS using a paediatric‐specific approach. Methods: The Lilongwe paediatric KS staging classification categorizes disease based on clinical phenotype: stage 1 = mild/moderate KS limited to cutaneous/oral involvement, stage 2 = primarily lymphadenopathic disease, stage 3 = woody edema KS, stage 4 = visceral and/or severe/disseminated mucocutaneous disease. Characteristics and outcomes were evaluated from paediatric referral centres in Lilongwe, Malawi, and Mbeya, Tanzania. Results: Among 171 patients, the median age was 9.3 years, 37% (n = 63) were female, and 87% (n = 149) had HIV. Breakdown by stage was as follows: 18% (n = 31) stage 1, 33% (n = 56) stage 2, 19% (n = 33) stage 3, and 30% (n = 51) stage 4. Age (younger stage 2 and older stage 3), severe CD4 count suppression (lower CD4 for stages 1 and 4), and presence of severe anaemia and thrombocytopenia (worse for stages 2 and 4) differed across stages. Estimated 2‐year event‐free survival/progression‐free survival/overall survival by stage was as follows: stage 1, 81%/81%/87%; stage 2, 50%/50%/63%; stage 3, 24%/49%/81%; and stage 4, 29%/34%/54%. Sub‐analysis of stage 2 lymphadenopathic KS demonstrated superior long‐term 6‐year event‐free survival of 70% (95% confidence interval [CI] 49–83) for younger children (aged <7 years) versus 27% (95% CI 8–51) for older children. Conclusions: This paediatric‐specific staging classification categorizes patients with distinct characteristics and patterns of treatment response. This platform may guide clinicians to provide risk‐stratified treatment with the hope of improving survival among children with KS. [ABSTRACT FROM AUTHOR]

Kaposi sarcoma‐associated herpesvirus (KSHV) causes Kaposi sarcoma (KS). The risk of KS is amplified in HIV‐immunosuppressed individuals and antiretroviral therapy (ART) reduces KS incidence. Reliable data on the relationship between these factors are lacking in Africa. We used questionnaires and serum from 7886 black South Africans (18‐74 years) with incident cancer, recruited between 1995 and 2016. ART rollout started in 2004. We measured associations between KS, HIV‐1 and KSHV before and after ART rollout. We measured seropositivity to HIV‐1, KSHV latency‐associated nuclear antigen (LANA) and glycoprotein (K8.1) and calculated case‐control‐adjusted odds ratios (ORadj) and 95% confidence intervals (CI) in relation to KS and KSHV infection, before (1995‐2004), early (2005‐2009) and late (2010‐2016) ART rollout periods. KSHV seropositivity among 1237 KS cases was 98%. Among 6649 controls, KSHV seropositivity was higher in males (ORadj = 1.4 [95%CI 1.23‐1.52]), in persons with HIV, (ORadj = 4.2 [95%CI 3.74‐4.73]) and lower in high school leavers (ORadj = 0.7 [95%CI 0.59‐0.83]). KSHV seropositivity declined over the three ART rollout periods (37%, 28% and 28%, Ptrend <.001) coinciding with increases in high school leavers over the same periods (46%, 58% and 67%, Ptrend <.001). HIV‐1 seroprevalence increased from 10% in the pre‐ART period to 22% in the late ART period (Ptrend <.001). Compared to HIV‐1 and KSHV seronegatives, KSHV seropositives yielded an OR for KS of 26 (95%CI 11‐62) in HIV‐1 seronegative participants and an OR of 2501 (95%CI 1083‐5776) in HIV‐1 seropositive participants. HIV‐1 increases the risk of KS in those infected with KSHV by 100‐fold. Declines in KSHV seroprevalence coincide with ART rollout and with improvements in educational standards and general hygiene. [ABSTRACT FROM AUTHOR]

Background: Kaposi sarcoma (KS) is an endothelial cell tumor, rare in children. It is 200 times more frequent after solid organ transplantation than in the general population. Methods: We report three cases of pediatric patients who developed KS after liver transplantation (LT). Results: Case 1, a 4‐year‐old boy undergoing LT due to familial intrahepatic cholestasis. Five months after LT, he presented with fever, dyspnea, and cough with enlarged lymph nodes and splenomegaly, anemia, thrombocytopenia, elevated liver enzymes, and positive EBV viral load. Lymph node biopsy diagnosed KS with an elevated HHV8 viral load. Case 2, a 4‐year‐old boy who underwent LT due to secondary biliary cirrhosis resulting from extrahepatic biliary atresia. Two years later, graft dysfunction was noticed with positive EBV viral load, thrombocytopenia, massive cervical lymph node enlargement, and splenomegaly. Lymph node biopsy diagnosed KS, Castleman's disease, and plasmablastic lymphoma related to HHV8 infection. Case 3, a 15‐month‐old girl, who received two LT due to biliary cirrhosis. Six months later, she presented with diarrhea, abdominal distension, anemia, thrombocytopenia, enlarged lymph nodes, splenomegaly, and positive CMV viral load. Axillary lymph node biopsy diagnosed KS and HHV8 infection was confirmed. In all three cases, tacrolimus was discontinued and, after diagnosis, sirolimus was started. All recovered without relapse and have a good graft function. Conclusions: Kaposi sarcoma is a rare disease post‐LT in children. Recognizing keywords and early diagnosis is crucial for timely treatment and survival. [ABSTRACT FROM AUTHOR]

This review will provide an overview of the notion that Kaposi sarcoma (KS) is a disease that manifests under diverse and divergent circumstances. We begin with a historical introduction of KS and KS‐associated herpesvirus (KSHV), highlight the diversity of clinical presentations of KS, summarize what we know about the cell of origin for this tumor, explore KSHV viral load as a potential biomarker for acute KSHV infections and KS‐associated complications, and discuss immune modulators that impact KSHV infection, KSHV persistence, and KS disease. [ABSTRACT FROM AUTHOR]

This article discusses a rare case of classic Kaposi sarcoma (KS) in a middle-aged Asian man. The patient initially presented with multiple hyperpigmented plaques on his lower legs, which were misdiagnosed as cellulitis and treated with antibiotics. However, further examination and testing revealed the presence of classic KS. The patient was treated with paclitaxel and later received additional chemotherapy due to an incomplete response. The article emphasizes the importance of clinical suspicion and histopathology for accurate diagnosis of classic KS. [Extracted from the article]

The article discusses the emerging use of hyaluronidase in dermatology, particularly in the treatment of complications caused by cosmetic procedures involving hyaluronic acid (HA) fillers. These complications, known as vascular adverse events (VAEs), can result in severe complications and tissue loss. The article highlights two protocols for managing VAEs: hyaluronidase "flooding" and ultrasound-guided targeted intravascular injection. In addition to treating VAEs, hyaluronidase injections have potential applications in treating other dermatological conditions such as scars, keloids, and fibrosis in hidradenitis suppurativa. The article emphasizes the importance of dermatologists being prepared to manage potential side effects of esthetic procedures and suggests that further research into the pharmacology of hyaluronidase in the skin could lead to innovative applications in dermatology. [Extracted from the article]

OP in HIV patients Patients with HIV have risk factors for decreased bone mineral density (BMD) from both HIV infection itself and from ART medications. Chief symptoms A 56-year-old African American man with a history of well-controlled HIV presented to the rheumatology clinic with longstanding bilateral foot pain. FINAL DIAGNOSIS Multifocal skeletal hemangiomatosis of both feet, with severe regional OP contributed to by prolonged immobilization and vitamin D deficiency, with incidental cutaneous Kaposi's sarcoma in an HIV patient with controlled disease. Studies have documented imaging patterns found in OP resulting from immobilization, often after casting in orthopedic patients, similar to the boot immobilization in our patient. [Extracted from the article]

Kaposi sarcoma‐associated herpesvirus (KSHV) is the etiological agent of several human diseases, including Kaposi sarcoma, primary effusion lymphoma, and a subset of multicentric Castleman's disease. KSHV uses its gene products to manipulate many aspects of the host responses during its life cycles. Among KSHV‐encoded proteins, ORF45 is unique in both temporal and spatial expression: it is expressed as an immediate‐early gene product and is an abundant tegument protein contained in the virion. ORF45 is specific to the gammaherpesvirinae subfamily but the homologs share only very limited homology and differ dramatically in protein length. In the past two decades, we and others have shown that ORF45 plays critical roles in immune evasion, viral replication, and virion assembly by targeting various host and viral factors. Herein, we summarize our current knowledge of ORF45 throughout the KSHV life cycle. We discuss the cellular processes targeted by ORF45 with emphasis on the modulation of host innate immune responses and rewiring the host signaling through impacting three major posttranslational modifications: phosphorylation, SUMOylation, and ubiquitination. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate HIV testing of patients aged ≥50 years presenting to secondary care with clinical indicator conditions (CICs) for HIV. Methods: Retrospective audit of electronic records for patients aged ≥50 years discharged from hospital between January 1st and July 31st 2019 who had at least one documented CIC. Patient demographics and HIV testing data were collected from clinical systems (excluding sexual health databases). Results: 2478 patients with a CIC were identified. 222 (9.0%) received an HIV test within 31 days of discharge. Patients receiving a test were significantly younger (mean 68.6 versus 75.3 years; P < 0.001) and significantly more men underwent testing than women (60.4% versus 39.6%; P = 0.001). 32 CICs were identified across nine disease systems. By system, those with a haematological CIC were significantly more likely to undergo testing compared with all other CICs combined (P < 0.001). Of individual CICs, patients with Kaposi's sarcoma, hepatitis C, neutropenia, lymphadenopathy, pyrexia of unknown origin and thrombocytopenia (P < 0.001), and seborrhoeic dermatitis, hepatitis B, other unexplained blood dyscrasia, and non‐Hodgkin's lymphoma (P < 0.05) were more likely to undergo testing than those presenting with other CICs. Patients with dementia and lung cancer were less likely to undergo testing (P < 0.001). Patients presenting with a greater number of CICs were significantly more likely to undergo testing (P = 0.002). Conclusions: HIV testing among patients aged ≥50 years presenting to secondary care with a CIC is low. Work is needed to improve HIV testing practice in this patient group. [ABSTRACT FROM AUTHOR]

Background: Survivors of non‐Hodgkin lymphoma (NHL) have increased secondary malignancy (SM) risk. We quantified this risk by patient and treatment factors. Methods: Standardized incidence ratios (SIR, observed‐to‐expected [O/E] ratio) were assessed in 142,637 NHL patients diagnosed from 1975 to 2016 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Comparisons were made between subgroups in terms of their SIRs relative to respective endemic populations. Results: In total, 15,979 patients developed SM, more than the endemic rate (O/E 1.29; p < 0.05). Compared with white patients, relative to respective endemic populations, ethnic minorities had a higher risk of SM (white O/E 1.27, 95% CI 1.25–1.29; black O/E 1.40, 95% CI 1.31–1.48; other O/E 1.59, 95% CI 1.49–1.70). Relative to respective endemic populations, patients who received radiotherapy had similar SM rates to those who did not (O/E 1.29 each), but irradiated patients had increased breast cancer (p < 0.05). Patients who received chemotherapy had higher SM rates than those who did not (O/E 1.33 vs. 1.24, p < 0.05) including more leukemia, Kaposi sarcoma, kidney, pancreas, rectal, head and neck, and colon cancers (p < 0.05). Conclusions: This is the largest study to examine SM risk in NHL patients with the longest follow‐up. Treatment with radiotherapy did not increase overall SM risk, while chemotherapy was associated with a higher overall risk. However, certain subsites were associated with a higher risk of SM, and they varied by treatment, age group, race and time since treatment. These findings are helpful for informing screening and long‐term follow‐up in NHL survivors. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma (KS) is a malignancy caused by the reactivation of human herpes virus 8 (HHV8) infecting lymphatic endothelial cells.[1] Clinical manifestations of KS include angiomatous patches, plaques and nodules on the skin and can rarely involve visceral organs. In the same session, 15 KS nodules on the arm and 12 nodules on the right hand were treated with intralesional chemotherapy, injecting a total of 2.9 mL of vincristine at 1 mg/mL. [Extracted from the article]

South Africa's HIV epidemic has evolved over time in terms of numbers of people living with HIV, access to antiretroviral treatment (ART) and age. These changes have profoundly influenced local cancer patterns. The Johannesburg Cancer Study has, over a period of 22 years (1995‐2016), recruited over 20 000 incident black cancer patients who consented to provide answers to a questionnaire and blood samples (serum, DNA). This has presented a unique opportunity to examine the evolving association of HIV with cancer in Africa. We used logistic regression models to explore case‐control associations between specific cancers and HIV, using participants with non‐infection related cancers as controls. Using data of 20 835 cancer patients with confirmed HIV status, we found the following cancers to be associated with HIV: Kaposi's sarcoma (ORadj; 95%CI): (99.1;72.6‐135.1), non‐Hodgkin lymphoma (11.3;9.3‐13.6), cervical cancer (2.7;2.4‐3.0), Hodgkin lymphoma (3.1;2.4‐4.2), cancer of the eye/conjunctiva (18.7;10.1‐34.7), anogenital cancers (anus [2.1;1.4‐3.2], penis [5.4;2.7‐10.5], vulva [4.8;3.5‐6.4], vagina [5.5;3.0‐10.2]), oropharyngeal cancer (1.6;1.3‐1.9), squamous cell carcinoma of the skin (3.5;2.4‐4.9), melanoma (2.0;1.2‐3.5) and cancer of the larynx (1.7;1.3‐2.4). Kaposi's sarcoma odds ratios increased from the pre‐ART (1995‐2004) to the early ART (2005‐2009) period but declined in the late ART (2010‐2016) period. Odds ratios for cancers of the eye/conjunctiva, cervix, penis and vulva continued to increase in recent ART periods. Our study confirms the spectrum of HIV‐associated cancers found in other African settings. The odds ratios of conjunctival and HPV‐related cancers continue to rise in the ART era as the HIV positive population ages. [ABSTRACT FROM AUTHOR]

Background and Objectives: Kaposi's sarcoma (KS) is a locally aggressive mesenchymal tumor that involves the lymphovascular system, with a tendency to become multifocal. Electrochemotherapy (ECT) is considered a valuable treatment option in selected patients with cutaneous and subcutaneous KS lesions. Methods: We report a retrospective study that included 14 classic and endemic KS patients that underwent ECT sessions for the treatment of KS cutaneous and subcutaneous lesions at our institution. Results: According to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, our patients had an overall response rate (ORR) of 100% to the ECT treatment. A complete response (CR) was obtained in 92.8% of patients after one or more ECT sessions. Only one patient had a progressive disease (PD). The treatment was well tolerated with a low complication rate, mainly transitory local pain or skin ulceration. Conclusions: ECT represents a locoregional therapy for containment and symptomatic control of classic and endemic KS cutaneous and subcutaneous lesions. Further studies including different subtypes of KS patients should also be performed. [ABSTRACT FROM AUTHOR]

Multiple treatment modalities for Kaposi sarcoma (KS) have been reported, including chemotherapy, radiation therapy, surgical excision, electrochemotherapy, and cryotherapy. Common topical treatments include timolol, imiquimod, and alitretinoin. We searched our institutional database for patients with ICD‐9 or 10 codes for KS seen by a dermatologist with experience in KS management from July 1, 2004 to January 1, 2022. We screened patient charts to include patients who received combination therapy of cryotherapy followed by topical imiquimod three times a week for 2 months (n = 9). Patients were followed in the clinic every 3 months. Time to resolution was assessed by photographic evidence of resolution as determined by a dermatologist and corroborated with clinical documentation in patient charts. Median age (IQR) at KS diagnosis was 58 (27.5) years. All patients were male (n = 9, 100%). Majority were white (n = 7, 78%) and non‐Hispanic (n = 8, 89%). Five (56%) had classic KS, one (11%) had HIV‐associated KS, and three (33%) were HIV‐negative men who have sex with men. Median time to resolution was 30.5 weeks, with a median of two treatments. In our study, 93% (n = 42/45) of lesions and 89% (n = 8/9) of patients experienced complete resolution during a median (range) duration of follow‐up of 58 (13–209) weeks. Side effects were limited to pain during cryotherapy, occasional blister formation after cryotherapy, and mild inflammation due to imiquimod. No infections were observed. Combination therapy of cryotherapy and topical imiquimod may be an efficacious and comparatively low‐risk treatment for limited, cutaneous KS. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma‐associated herpesvirus (KSHV) is the etiological agent for Kaposi's sarcoma (KS), an HIV/AIDS‐associated malignancy. Effective treatments against KS remain to be developed. The sugar analog 2‐deoxy‐ d‐glucose (2‐DG) is an anticancer agent that is well‐tolerated and safe in patients and was recently demonstrated to be a potent antiviral, including KSHV and severe acute respiratory syndrome coronavirus 2. Because 2‐DG inhibits glycolysis and N‐glycosylation, identifying its molecular targets is challenging. Here we compare the antiviral effect of 2‐DG with 2‐fluoro‐deoxy‐ d‐glucose, a glycolysis inhibitor, and 2‐deoxy‐fluoro‐ d‐mannose (2‐DFM), a specific N‐glycosylation inhibitor. At doses similar to those clinically achievable with 2‐DG, the three drugs impair KSHV replication and virion production in iSLK.219 cells via downregulation of viral structural glycoprotein expression (K8.1 and gB), being 2‐DFM the most potent KSHV inhibitor. Consistently with the higher potency of 2‐DFM, we found that d‐mannose rescues KSHV glycoprotein synthesis and virus production, indicating that inhibition of N‐glycosylation is the main antiviral target using d‐mannose competition experiments. Suppression of N‐glycosylation by the sugar drugs triggers ER stress. It activates the host unfolded protein response (UPR), counteracting KSHV‐induced inhibition of the protein kinase R‐like endoplasmic reticulum kinase branch, particularly activating transcription factor 4 and C/EBP homologous protein expression. Finally, we demonstrate that sugar analogs induce autophagy (a prosurvival mechanism) and, thus, inhibit viral replication playing a protective role against KSHV‐induced cell death, further supporting their direct antiviral effect and potential therapeutic use. Our work identifies inhibition of N‐glycosylation leading to ER stress and UPR as an antienveloped virus target and sugar analogs such as 2‐DG and the newly identified 2‐DFM as antiviral drugs. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma (KS) is the second most common tumor in people infected with human immunodeficiency virus worldwide, but its pathogenesis is still unclear. In this study, we discovered that the expression of GATA‐binding protein 3 (GATA3) was lowly expressed in KS tissues and KSHV‐infected cells, while microRNA‐155 (miR‐155) was highly expressed in KS serum and KSHV‐infected cells. miR‐155 promoted the proliferation, migration and invasion of KSHV infection by targeting GATA3. Further, The KSHV‐encoded protein, the Latency associated nuclear antigen (LANA), promotes the proliferation, migration and invasion of KSHV‐infected cells by regulating the miR‐155/GATA3 axis. Regarding the molecular mechanism, c‐Jun and c‐Fos interact to form a complex. LANA upregulates the expression of c‐Jun and c‐Fos and enhances the formation of c‐Jun/c‐Fos complex. The complex binds to the −95∼−100 bp site of miR‐155 promoter and transcriptionally activates miR‐155. All in all, LANA enhances the c‐Jun/c‐Fos interaction, resulting in enhanced transcriptional regulation of miR‐155 by the c‐Jun/c‐Fos complex, thereby downregulating GATA3 and promoting the proliferation, migration and invasion of KSHV‐infected cells. The discovery of LANA/c‐Jun/c‐Fos/miR‐155/GATA3 further refines the pathogenesis of KS, potentially opening a new avenue for developing effective drugs against KS. [ABSTRACT FROM AUTHOR]