Genetic landscape of indolent and aggressive Kaposi sarcomas.

BACKGROUND: Kaposi sarcoma (KS) is a rare skin tumour caused by herpesvirus 8 infection and characterized by either indolence or an aggressive course necessitating systemic therapies. The genetic basis of this difference remains unknown. OBJECTIVES: To explore the tumour mutational burden in indolent and aggressive KS. METHODS: We performed whole-exome sequencing on a cohort of 21 KS patients. We compared genetic landscape including tumor mutational burden between the two forms of indolent and agressive KS. RESULTS: Aggressive KS tumours had a significantly higher TMB and a larger cumulative number of deleterious mutations than indolent KS tumours. In addition, all aggressive tumours had at least three deleterious mutations, whereas most indolent tumours harboured only one or no predicted deleterious mutations. Deleterious mutations listed in the Cancer Gene Census were detected exclusively in patients with aggressive disease. An analysis of somatic copy-number alterations (SCNA) revealed a tendency towards higher number of alterations in aggressive KS. CONCLUSIONS: These data suggest that SCNA alterations and an increase in mutational burden promote aggressive KS and that it might be more appropriate to consider indolent KS as an opportunistic skin disease rather than a cancer.

High prevalence of syphilis in women, minors and precarious patients: a cross-sectional study in a Reunion Island sexually transmitted infection clinic, 2017-2020.

BACKGROUND: Syphilis is a sexually transmitted infection (STI) with a global prevalence estimated at 0.5% in 2012. Syphilis has been on the rise among men who have sex with men (MSM) in high-income countries and remains at endemic levels in low- and middle-income countries. This trend, however, has not been observed in Reunion Island. OBJECTIVES: To determine the prevalence, clinical characteristics and risk factors of syphilis in at-risk patients visiting the South Reunion STI clinic in Reunion Island. METHODS: This monocentric cross-sectional study included all patients who visited our STI clinic between 2017 and 2020. Syphilis serology was performed on all included patients, and data were collected using a standardized self-administered questionnaire. RESULTS: Over the 3-year study period, 2593 patients were enrolled. The prevalence of syphilis was 7.52% (n = 195, 95% CI, 6.50-8.65%) in the overall study population, 11.76% (n = 18, 95% CI, 6.97-18.59%) in minors (aged under 18 years) and 36.36% (n = 16, 95% CI, 21-59%) in pregnant women. The risk factors identified in multivariate analysis were being female [adjusted Prevalence Ratio (aPR) 1.85, 95% CI, 1.10-3.11], being MSM (aPR 2.87, 95% CI, 1.71-4.80), being aged under 18 years (aPR 3.54, 95% CI, 1.90-6.57), living in precarious conditions [aPR 3.12, 95% CI, 2.11-4.62] and being born in Reunion Island (aPR 2.43, 95% CI, 1.42-4.13). The clinical presentation was heterogeneous (plaques and papules, chancre, atypical ulcerations, multiple ulcerations, condyloma lata, etc.). CONCLUSIONS: These findings suggest a high prevalence of syphilis in at-risk patients visiting our STI clinic. Unlike the situation in other high-income countries, the people most at risk of syphilis in Reunion Island are local-born residents, minors, women and precarious patients. This is a source of concern, especially given the risk of resurgence of congenital syphilis on the island.

Azithromycin resistance in Treponema pallidum in Reunion Island: A cross-sectional study.

OBJECTIVE: Since the beginning of the 21st century, Reunion Island has experienced a syphilis epidemic. Infected patients are mostly heterosexual, with a high proportion of women, suggesting that congenital syphilis is present on the island. To determine whether azithromycin can be used for mass treatment of syphilis on Reunion Island, we assessed the prevalence of macrolide resistance in Treponema pallidum (TP). METHODS: This monocentric cross-sectional study was conducted at the Reunion Island University Hospital. Samples were collected from lesions suggestive of primary or secondary syphilis. Samples positive for TP by multiplex polymerase chain reaction (PCR) were sent to the French National Reference Centre (NRC) for further analysis. Nested PCR-tpp47 was performed on these samples for detection of TP-DNA; 23s rRNA was amplified by PCR in confirmed positive samples. The Restriction Fragment Length Polymorphism (RFLP) technique was performed on samples with amplified 23s rRNA for detection of the A2058G mutation. RESULTS: A total of 129 samples were collected from 119 patients. Of these, 18 tested positive for TP using multiplex PCR and were sent to the NRC. Fifteen (83.3%) of the 18 samples were confirmed positive by nested PCR-tpp47, and 23s rRNA was amplified in only 7 (38.9%) samples. Azithromycin resistance was detected in all TP strains with amplified 23s rRNA. CONCLUSION: Amplification of 23s rRNA was successful in only 7 TP strains, all of which displayed resistance to macrolides. Keeping in mind the small sample size of our study, this suggests that azithromycin should not be used for mass treatment of syphilis in Reunion Island.

Benefits of simulation using standardized patients for training dermatology residents in breaking bad news.

INTRODUCTION: Simulation in healthcare is a rapidly developing teaching method in the training of technical procedures. It is also used to enable caregivers to learn how to inform patients of serious illness and complex health status. However, its use is not widespread in the field of dermatology. This study investigated the utility of simulation as regards disclosing melanoma diagnosis, taking resident physician satisfaction as a primary endpoint. MATERIALS AND METHODS: Fifteen dermatology residents were recruited as trainees. Four scenarios were allocated based on length of residency. An introductory briefing was held prior to the training sessions. Debriefing took place on completion of the diagnosis disclosure consultation. The participants completed questionnaires after the simulation session, after debriefing, and 3 months after the simulation session. The primary endpoint was usefulness of the session felt by trainees several months after the simulation. RESULTS: The majority of participants (93.3%) thought the session helped with stress management, improved their attitude and control over their reaction (86.6%), and improved their communication skills (100%). They rated the usefulness of the simulation at 7.79/10 on average (range: 5-10). DISCUSSION: According to our findings the resident physicians involved, particularly those with the least experience, were satisfied with this type of learning technique. Any difficulties encountered by these residents were brought to light and addressed during debriefing. CONCLUSION: There would appear to be real benefits to be reaped from simulation, whatever the stage of medical training at which it takes place. Simulation should become an increasingly important part of contemporary pregraduate specialty programs.

2020 European guideline on the management of syphilis.

The 2020 edition of the European guideline on the management of syphilis is an update of the 2014 edition. Main modifications and updates include: -The ongoing epidemics of early syphilis in Europe, particularly in men who have sex with men (MSM) -The development of dual treponemal and non-treponemal point-of-care (POC) tests -The progress in non-treponemal test (NTT) automatization -The regular episodic shortage of benzathine penicillin G (BPG) in some European countries -The exclusion of azithromycin as an alternative treatment at any stage of syphilis -The pre-exposure or immediate post-exposure prophylaxis with doxycycline in populations at high risk of acquiring syphilis.

Use of a Multiplex PCR Assay To Assess the Presence of Treponema pallidum in Mucocutaneous Ulcerations in Patients with Suspected Syphilis.

We evaluated the utility of the commercial Allplex genital ulcer real-time PCR multiplex assay for detecting Treponema pallidum, herpes simplex virus 1 (HSV-1) and 2 (HSV-2), and Chlamydia trachomatis serovar L (lymphogranuloma venereum [LGV]) DNA in mucosal and genital ulcers in the context of suspected syphilis. In total, 374 documented genital and mucosal ulcers from patients with and without syphilis presenting at several sexually transmitted infection (STI) centers in France from October 2010 to December 2016 were analyzed at the National Reference Center (CNR) for Bacterial STIs at Cochin Hospital in Paris. T. pallidum subsp. pallidum detection results were compared with the final diagnosis based on a combination of clinical examination, serological results, and in-house nested PCR (nPCR). Detections of HSV and LGV were validated against reference methods. We found that 44.6% of the 374 samples tested were positive for T. pallidum subsp. pallidum, 21% for HSV, and 0.8% for LGV. No positive results were obtained for 30.7% of samples, and 4.8% presented coinfections. For T. pallidum subsp. pallidum detection, the overall sensitivity was 80% (95% confidence interval [CI], 76.1 to 84.1%), specificity was 98.8% (95% CI, 97.7 to 99.9%), positive predictive value was 98.8% (95% CI, 97.7 to 99.9%) and negative predictive value was 80.2% (95% CI, 76.2 to 84.2%), with a rate of concordance with the reference method of 92.5% (k = 0.85). This PCR multiplex assay is suitable for T. pallidum subsp. pallidum detection in routine use and facilitates the simultaneous rapid detection of a broad panel of pathogens relevant in a context of suspected syphilis lesions.

[A case of "early" syphilis]. / Une syphilis « précoce ¼.

INTRODUCTION: Syphilis mainly affects men who have sex with men (MSM) between the ages of 20 and 49. Herein we report a case in a teenager illustrating extension of the epidemic to other populations. PATIENTS AND METHODS: A 15-year-old boy consulted in May 2018 for an anal fissure and painful oral erosions. He reported having had unprotected anal sex with another male teenager of the same age three months earlier. Syphilis serology was positive, with a positive treponemal test (TT) and non-treponemal test (VDRL) at 1/128. A treponemal bacterial DNA PCR assay was also positive for swabs obtained from the oral erosions and anal fissure. Due to a history of allergy to penicillin the patient was treated with doxycycline 200mg daily for 14 days. One month later, the mucosal lesions had subsided, and 3 months later the VDRL titer had decreased by 2 dilutions. CONCLUSION: This case of "early" syphilis illustrates a change in the French epidemiology of sexually transmitted diseases (STIs). STIs currently affect very young and previously unexposed metropolitan French populations. These infections are increasing in teenagers due to an increase in high-risk sexual behavior associated with a lack of knowledge of STIs. This case is a reminder of the current decline in the level of knowledge about STIs among teenagers as compared to young people of the same age in the 1990s.