Long-term Oral Suppressive Antimicrobial Therapy in Infective Endocarditis (SATIE Study): An Observational Study.

Background: The role of suppressive antimicrobial therapy (SAT) in infective endocarditis (IE) management has yet to be defined. The objective of this study was to describe the use of SAT in an IE referral center and the patients' outcomes. Methods: We conducted a retrospective observational study in a French IE referral center (Paris). All patients with IE who received SAT between 2016 and 2022 were included. Results: Forty-two patients were included (36 male [86%]; median age [interquartile range {IQR}], 73 [61-82] years). The median Charlson Comorbidity Index score (IQR) was 3 (1-4). Forty patients (95%) had an intracardiac device. The most frequent microorganisms were Enterococcus faecalis (15/42, 36%) and Staphylococcus aureus (12/42, 29%). SAT indications were absence of surgery despite clinical indication (28/42, 67%), incomplete removal of prosthetic material (6/42, 14%), uncontrolled infection source (4/42, 10%), persistent abnormal uptake on nuclear imaging (1/42, 2%), or a combination of the previous indications (3/42, 7%). Antimicrobials were mainly doxycycline (19/42, 45%) and amoxicillin (19/42, 45%). The median follow-up time (IQR) was 398 (194-663) days. Five patients (12%) experienced drug adverse events. Five patients (12%) presented with a second IE episode during follow-up, including 2 reinfections (different bacterial species) and 3 possible relapses (same bacterial species). Fourteen patients (33%) in our cohort died during follow-up. Overall, the 1-year survival rate was 84.3% (73.5%-96.7%), and the 1-year survival rate without recurrence was 74.1% (61.4%-89.4%). Conclusions: SAT was mainly prescribed to patients with cardiac devices because of the absence of surgery despite clinical indication. Five (12%) breakthrough second IE episodes were reported. Prospective comparative studies are required to guide this empirical practice.

Aberrant DNA repair reveals a vulnerability in histone H3.3-mutant brain tumors.

Pediatric high-grade gliomas (pHGG) are devastating and incurable brain tumors with recurrent mutations in histone H3.3. These mutations promote oncogenesis by dysregulating gene expression through alterations of histone modifications. We identify aberrant DNA repair as an independent mechanism, which fosters genome instability in H3.3 mutant pHGG, and opens new therapeutic options. The two most frequent H3.3 mutations in pHGG, K27M and G34R, drive aberrant repair of replication-associated damage by non-homologous end joining (NHEJ). Aberrant NHEJ is mediated by the DNA repair enzyme polynucleotide kinase 3'-phosphatase (PNKP), which shows increased association with mutant H3.3 at damaged replication forks. PNKP sustains the proliferation of cells bearing H3.3 mutations, thus conferring a molecular vulnerability, specific to mutant cells, with potential for therapeutic targeting.

Deep cutaneous mycoses in kidney transplant recipients: Diagnostic and therapeutic challenges.

Deep cutaneous mycoses (DCMs) are rare infections that extend throughout the dermis and subcutis, often occurring after inoculation with pathogenic fungi. Trends toward a growing incidence have been observed that may be partially related to an increasing population of solid organ transplant patients. The aim of this study is to describe the diagnostics and the outcomes of DCM among kidney transplant recipients so as to optimize their management. We performed a retrospective review of cases of DCM occurring among kidney transplant recipients in our institution over 12 years. Twenty cases were included. Lesions were only located on the limbs and presented mainly as single (10/20, 50%) nodular lesions (15/20, 75%), with a mean size of 3 cm. Direct mycological examination was positive for 17 patients (17/20, 85%) and the cultures were consistently positive. Thirteen different fungal species were observed, including phaehyphomycetes (n = 8), hyalohyphomycetes (n = 3), dermatophytes (n = 1), and mucorale (n = 1). The (1-3) beta-D-glucan antigen (BDG) was also consistently detected in the serum (20/20, 100%). Systematic imaging did not reveal any distant infectious lesions, but locoregional extension was present in 11 patients (11/14, 79%). Nineteen patients received antifungal treatment (19/20, 95%) for a median duration of 3 months, with surgery for 10 (10/20, 50%). There is a great diversity of fungal species responsible for DCMs in kidney transplant recipients. The mycological documentation is necessary to adapt the antifungal treatment according to the sensitivity of the species. Serum BDG positivity is a potentially reliable and useful tool for diagnosis and follow-up.

Clinical characteristics of ambulatory and hospitalized patients with monkeypox virus infection: an observational cohort study.

OBJECTIVES: A global outbreak of monkeypox virus infections in human beings has been described since April 2022. The objectives of this study were to describe the clinical characteristics and complications of patients with a monkeypox infection. METHODS: All consecutive patients with a polymerase chain reaction (PCR)-confirmed monkeypox infection seen in a French referral centre were included. RESULTS: Between 21 May and 5 July 2022, 264 patients had a PCR-confirmed monkeypox infection. Among them, 262 (262/264, 99%) were men, 245 (245/259, 95%) were men who have sex with men, and 90 (90/216, 42%) practiced chemsex in the last 3 months. Seventy-three (73/256, 29%) patients were living with human immunodeficiency virus infection, and 120 (120/169, 71%) patients were taking pre-exposure prophylaxis against human immunodeficiency virus infection. Overall, 112 (112/236, 47%) patients had contact with a confirmed monkeypox case; it was of sexual nature for 95% of the contacts (86/91). Monkeypox virus PCR was positive on the skin in 252 patients, on the oropharyngeal sample in 150 patients, and on blood in eight patients. The majority of patients presented with fever (171/253, 68%) and adenopathy (174/251, 69%). Skin lesions mostly affected the genital (135/252, 54%) and perianal (100/251, 40%) areas. Overall, 17 (17/264, 6%) patients were hospitalized; none of them were immunocompromised. Complications requiring hospitalization included cellulitis (n = 4), paronychia (n = 3), severe anal and digestive involvement (n = 4), non-cardia angina with dysphagia (n = 4), blepharitis (n = 1), and keratitis (n = 1). Surgical management was required in four patients. CONCLUSION: The current outbreak of monkeypox infections has specific characteristics: it occurs in the men who have sex with men community; known contact is mostly sexual; perineal and anal areas are frequently affected; and severe complications include superinfected skin lesions, paronychia, cellulitis, anal and digestive involvement, angina with dysphagia, and ocular involvement.

Illicit massive silicone injections always induce chronic and definitive silicone blood diffusion with dermatologic complications.

Male-to-female transgender (MtF TG) individuals often report using illegal subcutaneous silicone injections for body feminisation. It leads to silicone dissemination and various dermatologic complications.We report the long-term complications of these feminisation procedures with blood smear examination and dermatologic examination.Between July 2015 and December 2015, 77 MtF TG consulting at Bichat Hospital (Paris, France) were included in this cross-sectional study. Blood smear examinations were performed by a trained haematologist to quantify the presence of silicone vacuoles in monocytes.All patients reported a history of massive amounts of silicone injections (mean 4 L, range 0.5-15 L). Most patients were South American (75/77, 97%). Fifty-nine (59/75, 79%) were HIV-seropositive, mostly with undetectable HIV RNA plasma levels (46/58, 80%). Clinical examinations reported dermatologic complications for all patients: lymphatic or subcutaneous migration of silicone (59%), inflammation (50%), varicose veins (39%), post-inflammatory pigmentation (20%), infection (14%) and abscesses (4%). Blood smear examination showed intracytoplasmic vacuoles containing silicone in monocytes in all patients.We did not chemically prove the silicone nature of the vacuoles. The design of this study does not allow evaluation of short-term complications that should not be minimized.Illicit massive silicone injections always induced chronic and definitive silicone blood diffusion with dermatologic complications. This study highlights the dangers and the inefficiency of clandestine esthetic surgery. There is a need for targeted information campaigns with transgender populations about silicone injections. Otherwise, these practices may persist.