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MAPK/ERK kinase (MEK) 1/2 are central signaling proteins that serve as specificity determinants of the MAPK/ERK cascade. More than twenty activating mutations have been reported for MEK1/2, and many of them are known to cause diseases such as cancers, arteriovenous malformation and RASopathies. Changes in their intrinsic activity do not seem to correlate with the severity of the diseases. Here we studied four MEK1/2 mutations using biochemical and molecular dynamic methods. Although the studied mutants elevated the activating phosphorylation of MEK they had no effect on the stimulated ERK1/2 phosphorylation. Studying the regulatory mechanism that may explain this lack of effect, we found that one type of mutation affects MEK stability and two types of mutations demonstrate a reduced sensitivity to PP2A. Together, our results indicate that some MEK mutations exert their function not only by their elevated intrinsic activity, but also by modulation of regulatory elements such as protein stability or dephosphorylation. [ABSTRACT FROM AUTHOR]

Introduction Peu de données sont disponibles sur le portage asymptomatique des IST en Nouvelle-Calédonie (NC). Nous avons réalisé une étude afin d’évaluer la fréquence du portage asymptomatique de Chlamydia trachomatis (CT) et Neisseria gonorrhoeae (NG) et les facteurs de risque associés dans un centre de dépistage des IST en NC. Matériels et méthodes Les données ont été recueillies de façon anonyme et prospective de fin avril à fin décembre 2017. Les critères d’inclusion étaient un âge de 15 ans ou plus, d’être cliniquement asymptomatique et d’avoir eu un dépistage de CT (hommes et femmes) et NG (femmes), par PCR (Multiplex diagenode-CT/NG-050) sur 1 er jet urinaire chez les hommes ou auto-prélèvement vaginal chez les femmes. Les données ont été saisies sur Excel, les variables quantitatives ont été comparées par un test de Fisher et les variables quantitatives par un test de Wilcoxon (seuil à 5 %) avant régression logistique. Résultats Quatre cent cinquante patients ont été inclus : 225 femmes (50 %), 220 hommes (48,9 %) et 5 transsexuelles (1,1 %) L Les patients étaient majoritairement hétérosexuels (418/450 ; 92,9 %). L’âge médian était de 25 ans (IQR : 20–31). En excluant les HSH, 47 sur 423 patients (11,1 %) étaient positifs pour CT : 20/198 hommes (10,1 %) et 27/225 femmes (12 %). Après ajustement pour toutes les autres variables par régression logistique, l’ odd ratio (OR) associé à l’infection asymptomatique par CT était de 3,8 [1,8–7,7 ; p < 0,001] pour l’origine ethnique mélanésienne et de 0,95 [0,90–0,99], p = 0,04] pour la catégorie d’âge. Parmi les 215 femmes testées pour NG, 9 (4,2 %) étaient positives. Après ajustement pour les autres variables, l’origine mélanésienne (OR = 17,8 [1,9–162,9] ; p = 0,01), et le nombre de partenaires (OR = 1,66 [1,1–2,4] ; p = 0,01) étaient significativement associés à l’infection génitale asymptomatique par NG. Conclusion Les prévalences des infections asymptomatiques génitales à CT et NG sont élevées dans notre population et comparables à une enquête menée en 2012 par l’Agence sanitaire et sociale de NC en population générale. Le principal facteur associé est l’origine ethnique mélanésienne qui n’est qu’un reflet d’un ensemble particulier de risques. Une stratégie spécifique de dépistage des IST est nécessaire en NC. [ABSTRACT FROM AUTHOR]

Introduction La syphilis est un problème de santé publique dans notre région. L’estimation de sa prévalence en population générale en 2012 était de 0,4 % [0,0–0,9] pour la syphilis active et 3 % [1,7–4,3] pour la syphilis cicatricielle. Matériels et méthodes Il s’agit d’une étude rétrospective des dossiers des patients ayant été diagnostiqués et/ou traités pour la syphilis entre 2015 et 2017 dans un centre référent pour les IST. L’objectif de cette étude est de connaître le profil des patients infectés afin de mieux cibler le dépistage et ainsi aider à lutter contre cette IST. Résultats Cent soixante-dix neufs personnes ont été prises en charge pour syphilis dans notre centre entre 2015 et 2017. La moyenne d’âge était de 28,16 ans (16–67) pour les 86 femmes (dont 30 enceintes), 88 hommes et 5 personnes transsexuelles (H–F) investigués. Ils étaient principalement d’origine ethnique mélanésienne (145/179, 81 %) ou européenne (15/179, 8,4 %). Ils étaient en couple pour 77,65 % (139/179) d’entre eux mais seulement 55,9 % (100/179) ont consulté ensemble. Les modes de découverte principaux étaient un chancre syphilitique (42/179, 23,5 %), une autre IST (38/179, 21,2 %), un signe cutané (13/179, 7,3 %), une syphilis diagnostiquée chez le/la partenaire (35/179, 19,5 %), ou fortuite (47/179, 26,2 %) : bilan de grossesse (25/179, 13,9 %), dépistage (18/179, 10 %), ou un dong de sang (3/179, 1,7 %), un décès fœtal et une demande d’IVG (1/179). Le stade au moment de la découverte était primaire ( n = 47, 26,25 %), secondaire ( n = 13, 7,26 %), tertiaire ( n = 2, 1,12 %), latent précoce ( n = 27, 15,08 %) ou latent tardif ( n = 90, 50,28 %). Le mode de contamination avéré ou supposé était pour 86,6 % hétérosexuel ( n = 155), 10,6 % homosexuel ( n = 19), 2,8 % indéterminé ( n = 5). La co-infection principale était Chlamydia trachomatis . Six patients étaient connus séropositifs pour le VIH. Les traitements ont été complets pour 85,47 % des patients ( n = 153), incomplets pour 8,94 % d’entre eux ( n = 16) et non réalisés ou réalisés ailleurs pour 5,56 % ( n = 10). Le traitement du(des) partenaire(s) n’a été réalisé de façon certaine seulement dans 45,81 % des cas (partenaires de 82 patients). Le suivi sérologique est bien effectué pour uniquement 36,88 % des patients ( n = 66), et on ne peut conclure pour 13,41 % ( n = 24) d’entre eux qui ont été traités depuis moins de 3 mois. Conclusion Le dépistage de la syphilis doit être renforcé et adapté à notre territoire car le profil des patients diffère de celui généralement retrouvé en France, touchant de nombreux couples hétérosexuels et femmes enceintes. Ces résultats soulignent l’importance de développer des campagnes d’information destinées au grand public pour sensibiliser la population à cette IST afin de promouvoir son dépistage puis son traitement. La prise en charge des partenaires doit être améliorée, ainsi que le suivi sérologique après traitement. [ABSTRACT FROM AUTHOR]

Background: Although GqPCR activation often leads to cell survival by activating the PI3K/AKT pathway, it was previously shown that in several cell types AKT activity is reduced and leads to JNK activation and apoptosis. The mechanism of AKT inactivation in these cells involves an IGBP1-coupled PP2Ac switch that induces the dephosphorylation and inactivation of both PI3K and AKT. However, the machinery involved in the initiation of PP2A switch is not known. Methods: We used phospho-mass spectrometry to identify the phosphorylation site of PP2Ac, and raised specific antibodies to follow the regulation of this phosphorylation. Other phosphorylations were monitored by commercial antibodies. In addition, we used coimmunoprecipitation and proximity ligation assays to follow protein–protein interactions. Apoptosis was detected by a TUNEL assay as well as PARP1 cleavage using SDS-PAGE and Western blotting. Results: We identified Ser24 as a phosphorylation site in PP2Ac. The phosphorylation is mediated mainly by classical PKCs (PKCα and PKCβ) but not by novel PKCs (PKCδ and PKCε). By replacing the phosphorylated residue with either unphosphorylatable or phosphomimetic residues (S24A and S24E), we found that this phosphorylation event is necessary and sufficient to mediate the PP2A switch, which ultimately induces AKT inactivation, and a robust JNK-dependent apoptosis. Conclusion: Our results show that the PP2A switch is induced by PKC-mediated phosphorylation of Ser24-PP2Ac and that this phosphorylation leads to apoptosis upon GqPCR induction of various cells. We propose that this mechanism may provide an unexpected way to treat some cancer types or problems in the endocrine machinery. [ABSTRACT FROM AUTHOR]

Genetic alterations in BRAF, NRAS and NF1 that activate the ERK cascade, account for over 80% of metastatic melanomas. However, ERK cascade inhibitors have been proven beneficial almost exclusively for BRAF mutant melanomas. One of the hallmarks of the ERK cascade is the nuclear translocation of ERK1/2, which is important mainly for the induction of proliferation. This translocation can be inhibited by the NTS-derived peptide (EPE) that blocks the ERK1/2-importin7 interaction, inhibits the nuclear translocation of ERK1/2, and arrests active ERK1/2 in the cytoplasm. In this study, we found that the EPE peptide significantly reduced the viability of not only BRAF, but also several NRAS and NF1 mutant melanomas. Importantly, combination of the EPE peptide and trametinib showed synergy in reducing the viability of some NRAS mutant melanomas, an effect driven by the partial preservation of negative feedback loops. The same combination significantly reduced the viability of other melanoma cells, including those resistant to mono-treatment with EPE peptide and ERK cascade inhibitors. Our study indicates that targeting the nuclear translocation of ERK1/2, in combination with MEK inhibitors can be used for the treatment of different mutant melanomas. [ABSTRACT FROM AUTHOR]

The recommended treatment duration of chronic hepatitis C virus (HCV) in patients infected with human immunodeficiency virus (HIV) is 48 weeks. This report describes a patient co-infected with HCV genotype 2 and HIV who discontinued HCV therapy after 6 weeks because of adverse events and had a sustained virologic response. J. Med. Virol. 82:1150-1151, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background/Aims: Results from recent studies suggest that extremely low frequency magnetic fields (ELF-MF) interfere with intracellular signaling pathways related to proliferative control. The mitogen-activated protein kinases (MAPKs), central signaling components that regulate essentially all stimulated cellular processes, include the extracellular signal-regulated kinases 1/2 (ERK1/2) that are extremely sensitive to extracellular cues. Anti-phospho-ERK antibodies serve as a readout for ERK1/2 activation and are able to detect minute changes in ERK stimulation. The objective of this study was to explore whether activation of ERK1/2 and other signaling cascades can be used as a readout for responses of a variety of cell types, both transformed and non-transformed, to ELF-MF. Methods: We applied ELF-MF at various field strengths and time periods to eight different cell types with an exposure system housed in a tissue culture incubator and followed the phosphorylation of MAPKs and Akt by western blotting. Results: We found that the phosphorylation of ERK1/2 is increased in response to ELF-MF. However, the phosphorylation of ERK1/2 is likely too low to induce ELFMF- dependent proliferation or oncogenic transformation. The p38 MAPK was very slightly phosphorylated, but JNK or Akt were not. The effect on ERK1/2 was detected for exposures to ELF-MF strengths as low as 0.15 ìT and was maximal at ~10 ìT. We also show that ERK1/2 phosphorylation is blocked by the flavoprotein inhibitor diphenyleneiodonium, indicating that the response to ELF-MF may be exerted via NADP oxidase similar to the phosphorylation of ERK1/2 in response to microwave radiation. Conclusions: Our results further indicate that cells are responsive to ELF-MF at field strengths much lower than previously suspected and that the effect may be mediated by NADP oxidase. However, the small increase in ERK1/2 phosphorylation is probably insufficient to affect proliferation and oncogenic transformation. Therefore, the results cannot be regarded as proof of the involvement of ELF-MF in cancer in general or childhood leukemia in particular. [ABSTRACT FROM AUTHOR]

Background: G protein-coupled receptors (GPCRs) usually regulate cellular processes via activation of intracellular signaling pathways. However, we have previously shown that in several cell lines, GqPCRs induce immediate inactivation of the AKT pathway, which leads to JNK-dependent apoptosis. This apoptosis-inducing AKT inactivation is essential for physiological functions of several GqPCRs, including those for PGF2α and GnRH. Methods: Here we used kinase activity assays of PI3K and followed phosphorylation state of proteins using specific antibodies. In addition, we used coimmunoprecipitation and proximity ligation assays to follow protein–protein interactions. Apoptosis was detected by TUNEL assay and PARP1 cleavage. Results: We identified the mechanism that allows the unique stimulated inactivation of AKT and show that the main regulator of this process is the phosphatase PP2A, operating with the non-canonical regulatory subunit IGBP1. In resting cells, an IGBP1-PP2Ac dimer binds to PI3K, dephosphorylates the inhibitory pSer608-p85 of PI3K and thus maintains its high basal activity. Upon GqPCR activation, the PP2Ac-IGBP1 dimer detaches from PI3K and thus allows the inhibitory dephosphorylation. At this stage, the free PP2Ac together with IGBP1 and PP2Aa binds to AKT, causing its dephosphorylation and inactivation. Conclusion: Our results show a stimulated shift of PP2Ac from PI3K to AKT termed "PP2A switch" that represses the PI3K/AKT pathway, providing a unique mechanism of GPCR-stimulated dephosphorylation. 9Vm-TQNungMKvUWU45aeyU Video Abstract [ABSTRACT FROM AUTHOR]

L'angiœdème héréditaire (AOH) est une maladie génétique rare, caractérisée par la survenue imprévisible d'œdèmes sous-cutanés/sous-muqueux transitoires, impactant la qualité de vie. Le lanadelumab (LNB) est un anticorps monoclonal humain ciblant la kallicréine plasmatique. La posologie recommandée est de 300 mg toutes les 2 semaines par voie sous-cutanée. Depuis son autorisation de mise sur le marché en novembre 2018 en France, LNB est indiqué dans la prévention des crises récurrentes d'AOH chez les patients (pts) âgés de ≥ 12 ans. LNB a reçu une autorisation temporaire d'utilisation de cohorte (ATUc) en France, entre septembre 2018 et mars 2019. Ce résumé présente les résultats d'une analyse intermédiaire de l'étude observationnelle SERENITI. SERENITI est une étude observationnelle, multicentrique, ambispective, mise en place à partir de décembre 2019, ayant inclus consécutivement les pts atteints d'AOH, âgés de ≥ 12 ans, ayant reçu ≥ 1 dose de LNB depuis le début de l'ATUc. La date d'initiation au LNB (T0) était la date de référence. Les patients pouvaient avoir initié LNB avant (rétrospectifs) ou au moment de l'inclusion (prospectifs). L'objectif principal était d'évaluer l'efficacité de LNB par l'évolution du taux mensuel de crises d'AOH confirmées par le médecin au cours des 6 mois (6 M) et 12 mois (12 M) depuis T0 (Test de Wilcoxon). Les critères secondaires incluaient la description de 1) l'utilisation de LNB, 2) l'efficacité de LNB évaluée par le questionnaire patient « angioedema activity score 28 » (AAS28) (Test de McNemar), 3) la qualité de vie (AE-QoL, Test de Wilcoxon) et 4) la tolérance de LNB. Les données étaient recueillies à l'inclusion, puis au suivi tous les 6 mois pour total de 18 mois. L'étude se terminera en décembre 2022. Les données présentées couvrent le suivi jusqu'au 29/07/2022. Les données recueillies à l'inclusion comprenaient le profil sociodémographique, les antécédents médicaux, les données rétrospectives sur le taux mensuel de crises, les traitements antérieurs d'AOH dans les 6 M avant T0, l'AE-QoL et l'AAS28 (pts prospectifs seulement). La survenue des crises d'AOH, les modalités de traitement par LNB, les événements indésirables (EI) ont été collectés de T0 à l'inclusion pour les pts rétrospectifs. Les données recueillies lors du suivi étaient la survenue des crises d'AOH, les modalités de traitement par LNB, les EIs, l'AE-QoL et l'AAS28 (pts prospectifs). Du 12/12/2019 au 31/05/2021, 163 pts ont été inclus par 18 centres français ; 155 pts, dont 65 prospectifs, avec des données complètes à l'inclusion ont été analysés (âge moyen de 44,1 ± 16,5 ans ; 64,5 % de femmes). Sept patients étaient âgés de 12 à 17 ans au moment d'inclusion. 89 % et 7,1 % des pts avaient respectivement un AOH de type I et II, et 3,9 % avaient un AOH avec C1-INH normal. 86,5 % des pts recevaient une prophylaxie à long terme avant T0. Le taux mensuel de crises moyen a diminué, de 2,01 ± 1,9 à T0 à 0,13 ± 0,4 à 6 M (p < 0,01, n = 122) et de 2,06 ± 1,9 à T0 à 0,10 ± 0,2 à 12 M (p < 0,01, n = 102). Le score AE-QoL total médian était de 27,2 à T0 et de 19,9 au suivi 1 (p < 0,01, n = 78) ; de 23,5 à T0 et de 14,7 au suivi 2 (p < 0,01, n = 47), indiquant une amélioration de la qualité de vie. Pour l'AAS28 : 60,5 % à T0 et 79,1 % au suivi 1(p < 0,01, n = 86), et 63,3 % à T0 et 81,6 % au suivi 2 (p < 0,01, n = 49) avaient un score de 0, indiquant une amélioration des symptômes. 193 modifications de la fréquence d'administration (FA) ont été rapportées chez 111 pts : 54 pts ont 1 modification, dont 51 liées à une réduction des taux de crises (diminution de FA à toutes les ≥ 3 semaines) ; 41 pts ont 2 modifications : la FA a été réaugmentée à toutes les 2 semaines pour 10 pts en raison d'une augmentation des taux de crises. Dix pts ont 3 modifications, dont 5 pour une réduction des taux de crises. Quatre pts ont 4 modifications : 3 pour une réduction des crises et 1 due à un EI. 12/155 pts ont arrêté LNB dans les 30 mois suivant T0. 121 EIs ont été rapportés chez 52 pts (dont 17 graves tous non-liés à LNB). 28 réactions au site d'injection ont été rapportées chez 21 pts et 4 cas d'hypersensibilité chez 2 pts. Un décès a été reporté, non-lié à LNB. Les résultats intermédiaires de SERENITI suggèrent l'efficacité du LNB avec une réduction significative et durable du taux mensuel de crises, et une amélioration de la qualité de vie. Le profil de tolérance de LNB ne semble pas différent de celui précédemment rapporté. Une réduction de la FA en raison de la stabilité de la maladie sous traitement a été observée chez près de la moitié des pts (dont 1/6 a dû augmenter de nouveau la FA du fait d'une aggravation), reflétant l'efficacité du LNB en vie réelle comme traitement prophylactique de l'AOH. [ABSTRACT FROM AUTHOR]

Immunocompromised patients have an increased risk of a severe form of COVID-19. The clinical efficacy of the tixagevimab/cilgavimab monoclonal antibody combination as pre-exposure prophylaxis against BA.1 and BA.2 SARS-CoV-2 Omicron sublineages is unknown. We aimed to describe the incidence and outcomes of COVID-19 among immunocompromised patients receiving tixagevimab/cilgavimab as preexposure prophylaxis during the Omicron wave in France. This was an observational multicentre cohort study of immunocompromised patients receiving tixagevimab/cilgavimab as preexposure prophylaxis between December 28, 2021 and March 31, 2022. Patients received tixagevimab/cilgavimab 150/150 mg intramuscularly if they had impaired vaccine response and a high risk of severe form of COVID-19. Tixagevimab/cilgavimab was administered to 1112 immunocompromised patients. After a median (range) follow-up of 63 (49–73) days, COVID-19 was confirmed in 49/1112 (4.4%) ≥5 days after treatment. During the study period, mean weekly incidence rate was 1669 in 100 000 inhabitants in Ile-de-France and 530 in 100 000 among patients who received tixagevimab/cilgavimab prophylaxis. Among infected patients, 43/49 (88%) had a mild-to-moderate form and 6/49 (12%) had a moderate-to-severe form of COVID-19. Patients with moderate-to-severe illnesses were less likely to have received early therapies than patients with mild forms (53.5% vs. 16.7% respectively) and 2/49 (4%) patients died from COVID-19. Our study reported a low rate of infections and severe illnesses among immunocompromised patients treated with tixagevimab/cilgavimab. A global preventive strategy including vaccines, preexposure prophylaxis with monoclonal antibodies, and early therapies might be effective to prevent severe forms of COVID-19 among severely immunocompromised patients. [ABSTRACT FROM AUTHOR]

Introduction: In Cambodia, we implemented a pilot surveillance of superficial surgical site infections (SSSI) following caesarean deliveries (CD) in a provincial hospital, to estimate their incidence, describe their clinical management, and determine their causative pathogens. Methodology: Between October 2010 and February 2011, all women admitted for CD were included in the surveillance. Their clinical condition was monitored for a post-operative period of 30 days, including two assessments performed by surgeons. Cases were clinically diagnosed by surgeons, with bacterial cultures performed. Results: Of the 222 patients admitted for CD, 176 (79.3%) were monitored for 30 days. Of these, 11 were diagnosed with a SSSI, giving an incidence rate of 6.25% (95% CI 3.2-10.9). Four of the cases (36.4%) were detected after hospital discharge. Length of hospitalization was significantly longer for the SSSI cases. All 222 patients were prescribed antibiotics. Ampicillin was administered intravenously to 98.6% of them, with subsequent oral amoxicillin given to 82.9%. Three of six pus samples collected were positive on culture: two with Staphylococcus aureus and one with Staphylococcus lugdunensis. One S.aureus was methicillin resistant (MRSA). The other was clindamycin and erythromycin resistant. Conclusion: Surveillance of health-care associated infections in a setting with limited resources is challenging but feasible. Effective post-discharge surveillance was essential for the estimation of the incidence rate of SSSI following caesarean deliveries. This surveillance led to a peer-review of medical practices. [ABSTRACT FROM AUTHOR]

Objectives The aim of the study was to investigate the frequency and severity of adverse events ( AEs) and laboratory abnormalities of interest over 96 weeks of treatment with etravirine or placebo in the pooled TMC125 DUET (Demonstrate Undetectable viral load in patients Experienced with ARV Therapy) trials. Methods Treatment-experienced, HIV-1-infected patients randomly received etravirine 200 mg twice a day (bid) or placebo, plus a background regimen. The frequency and severity of neuropsychiatric, rash, hepatic and lipid AEs were analysed; frequencies were also adjusted for total patient-years of exposure ( PYE). Results A total of 599 and 604 patients received etravirine and placebo, respectively (median treatment duration 96.0 and 69.6 weeks, respectively). There was no significant difference between the treatment groups in the frequency of neuropsychiatric AEs. However, a significant difference in the frequency of rash was observed (20.5% vs. 11.8%, respectively; P < 0.0001); rash was generally mild to moderate in severity; the rate of discontinuation because of rash was low (2.2% vs. 0% in the etravirine and placebo groups, respectively). The frequency of hepatic AEs was low and similar between the treatment groups (8.7% vs. 7.1%, respectively; P = 0.3370); hepatic enzyme levels did not increase over time. Lipid-related laboratory abnormalities and changes over time in lipid levels were generally comparable between treatment groups. Adjusting for treatment exposure, the frequency of AEs remained similar between treatment groups, with the exception of rash [13.7 vs. 9.3 per 100 PYE; relative risk (95% confidence interval) 1.48 (1.02-1.95)]. Conclusions The frequency of AEs of interest was generally similar between the treatment groups, both overall and when adjusted for treatment exposure, with the exception of rash which was more frequent in the etravirine group. [ABSTRACT FROM AUTHOR]

Background. The number of international trips undertaken by French citizens is rising and we wished to assess the appropriateness of advices given to travelers in a vaccine and travel medicine center in France. Methods. We conducted a 3-month prospective study in one center in Paris where prescriptions and advice to travelers are given by trained physicians in travel medicine who have access to a computerized decision support system (Edisan). A questionnaire was used to record trip characteristics, patients' demographics, and prescriptions. Main outcome measure was the adequacy of prescriptions for malaria prophylaxis, yellow fever, and hepatitis A vaccines to French guidelines. Results. A total of 730 subjects were enrolled in this study, with a median age of 28 years. Travel destinations were sub-Saharan Africa (58%), Asia (21%), and South America (18%). Among the 608 patients (83%) traveling to malaria-endemic areas, malaria prophylaxis was in accordance with guidelines in 578/608 patients (95.1%, 95% CI: 93-96.5), and doxycycline was the regimen of choice (48%). Inappropriate malaria prophylaxis was given to eight patients, one of whom developed plasmodium falciparum malaria. All 413 patients (100%, 95% CI: 99-100) traveling to yellow fever-endemic areas who needed vaccination were correctly vaccinated. However, three patients received yellow fever vaccination without indication. Also, 442 of 454 patients (97.4%, 95% CI: 95.4-98.5) eligible to receive hepatitis A vaccination were immunized. Conclusion. Appropriate advice for malaria prophylaxis, yellow fever, and hepatitis A vaccinations was provided in a travel medicine and vaccine center where trained physicians used a computerized decision support system. Even in this setting, however, errors can occur and professional practices should be regularly assessed to improve health care. [ABSTRACT FROM AUTHOR]

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. [ABSTRACT FROM AUTHOR]

Only one study to date has focused on people living with HIV (PLWH) who refused to participate in a HIV cure/remission-related clinical trial (HCCT)-"decliners" hereafter-that included analytical treatment interruption (ATI). Exploring why these persons refuse may provide valuable information to ensure more ethical recruitment and support in HCCTs within the bigger picture of improving HIV cure research. The qualitative component of the AMEP-EHVA-T02/ANRS-95052 study, called AMEP-Decliners, documented the experiences of French PLWH who refused to participate in EHVA-T02/ANRS-VRI07, a phase II randomized, placebo-controlled HCCT with ATI. AMEP-Decliners comprised semi-structured individual interviews with six decliners in two HIV care sites in France between September 2022 and March 2023. The interviews documented their expectations regarding HCCTs, reasons for refusal, and perceived factors that might have led them to participate. Audio files were transcribed, and an inductive thematic analysis was performed. Surprisingly, the main reason for refusal was not ATI but the trial monitoring. Besides the frequency of appointments, respondents emphasized the incompatibility with their active life. One underlying reason for refusal was that participating would have meant "break[ing] the carefree attitude about the disease," reflecting the substantial psychological burden associated with participation. Finally, respondents perceived that the trial's clinical team did not sufficiently recognize their "normal life" and the level of commitment required to participate, leading them to call for greater involvement by the team: "they have to make an effort too." Results from decliners' discourses highlighted that two levels of commitment to participation must be considered when developing HCCTs: psychological burden and logistical constraints. We suggest allowing home examinations and flexible appointment times, prioritizing face-to-face invitations in order to address the psychological burden associated with HCCT participation, and explaining the reasons for monitoring constraints when they cannot be alleviated. Further studies are necessary to confirm our results.

Background: The prevalence of sexually transmitted infections (STIs) is high in New Caledonia (NC), but there are no data on Mycoplasma genitalium (MG). However, the syndromic treatment of urethritis used in the territory includes a single dose of azithromycin, which could generate resistance in MG., Methods: We recruited 217 men referred to the Noumea public medical centre (CMP) with signs of urethritis and meeting the inclusion criteria from May 2016 to March 2018. Each was tested for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV) and for the first time in NC for MG by polymerase chain reaction (PCR)., Results: The prevalence of MG was 10.1% (22/217). Azithromycin resistance of MG (mutation in the 23S rRNA gene) could only be assessed for 10 of the 22 strains. Only one (1/10; 10%) was resistant. The prevalence of other STIs tested was high, as CT, NG and/or TV were associated in 77.3% (17/22) of MG-positive cases., Conclusions: Although co-infections further justify syndromic management, the presence of MG in NC urethritis cases could call treatment guidelines into question.

Objectives: To evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hospitalization and fatality rates in residents of homeless shelters run by Samusocial of Paris., Methods: We conducted a retrospective serological study between July and August 2020 on all residents and staff members of three homeless shelters run by Samusocial of Paris: two centres providing healthcare accommodation (HCA) and one a women's dormitory. We included all adults present in the shelters or who died of a proven SARS-CoV-2 infection during the first wave (March-May). SARS-CoV-2 antibodies were detected in serum samples using the SARS-CoV-2 IgG Architect (Abbott) test. Any participant with a positive PCR or serology was defined as a confirmed SARS-CoV-2 case., Results: We included 100 residents and 83 staff members. The confirmed SARS-CoV-2 rate by PCR or serology was 72/100 (72.0%) for residents and 17/83 (20.5%) for staff members. Women accommodated in the dormitory had the highest infection rate (90.6%). The hospitalization rate in residents was 17/72 (23.6%) and the death rate 4/72 (5.6%). All hospitalizations and deaths occurred among HCA residents. Among the residents of HCA shelters, 34/68 (50%) presented at least two comorbidity factors associated with being at high risk for severe SARS-CoV-2 infection., Conclusion: The SARS-CoV-2 infection rate was high in residents of these homeless shelters (10.6% seroprevalence in the Île-de-France region during the first wave). Severe SARS-CoV-2 infection was highly associated with the prevalence of comorbidities. This population should be considered as a priority in vaccination campaigns and in access to individual housing units when at risk., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives and Methods: Retrospective study of all patients who started antiretroviral therapy (ART) in 2007 in a single center in Paris, with baseline characteristics and 1-year outcome, to assess adherence to national guidelines., Results: We analyzed 118 patients. Time of ART initiation was in agreement with the guidelines for only 64 (54.2%) patients. Fifty patients (42%) started ART with AIDS or a CD4 count <200 cells/mm(3). In all, 62 (52%) and 47 patients (40%) received a combination of 2 nucleoside analogues with efavirenz (EFV) and 1 ritonavir-boosted protease inhibitor (PI/r), respectively. Treatment regimens were in accordance with the guidelines for 114 patients (97%). At 1 year, 16 patients (13.5%) were lost to follow-up, only 5 (4.9%) experienced HIV disease progression or death, but 19 (18.6%) required hospitalization. Antiretroviral therapy was changed in 21 patients (21%). Ten patients (8.4%) experienced virologic failure., Conclusion: Antiretroviral therapy was in agreement with guidelines for the choice of combination but was often initiated too late.

Hospital staff and all other human or veterinary health care workers, including laboratory, research, emergency service, or cleaning personnel are exposed to the risk of occupational infection following accidental exposure to blood or body fluids (BBF) contaminated with a virus, a bacteria, a parasite, or a yeast. The human immunodeficiency virus (HIV) or those of hepatitis B (HBV) or C (HCV) account for most of this risk in France and worldwide. Many other pathogens, however, have been responsible for occupational infections in health care workers following exposure to BBF, some with unfavorable prognosis. In developed countries, a growing number of workers are referred to clinicians responsible for the evaluation of occupational infection risks following accidental exposure. Although their principal task remains the evaluation of the risks of HIV, HBV, or HCV transmission and the possible usefulness of postexposure prophylaxis, these experts are also responsible for evaluating risks of occupational infection with other emergent or more rare pathogens and their possible timely prevention. The determinants of the risks of infection and the characteristics of described cases are discussed in this article.

We conducted a multi-centre study in West African hospital wards to document accidental blood exposure (ABE) risks in these settings, and assessed the incidence of ABE in participating healthcare workers (HCWs) retrospectively. In total, 1241 HCWs participated in the survey from 43 hospital wards. Among them, 567 (45.7%) had sustained at least one ABE with an estimated incidence of 0.33 percutaneous injuries (PCIs) and 0.04 mucocutaneous contacts (MCCs)/HCW/year in medical or intensive care personnel and 1.8 PCIs/HCW/year in surgeons. The ABE was a needlestick in 454 (80.1%) of 567 cases, a cut in 19 cases (3.4%), a splash or contact with non-intact skin in 87 cases (15.3%), and was undocumented in seven cases (1.2%). The source patient's human immunodeficiency virus (HIV) serostatus was positive in 74 cases (13.1%), negative in 65 cases (11.5%), and unknown in 416 cases (73.4%). The ABE was not notified in the ward in 392 cases (69.1%). Healthcare structures can improve HCWs' safety and reduce the stigma against HIV-infected patients by improving access to training, information, primary prevention (ABE prevention equipment) and secondary prevention (postexposure prophylaxis) of occupational infection risks.

A French nurse presented Plasmodium falciparum malaria 10 d after a needlestick while sampling blood in a source patient with malaria. As did the source patient, the nurse recovered fully although diagnosis was delayed and her malaria severe. We proceeded to a thorough description of the transmission profile of P. falciparum following occupational needlestick. A review of the literature found 21 published reports of occupational malaria including our own, documenting 22 P. falciparum infections. One of these was lethal. The mean incubation time to fever onset was documented in 21 reports including our own and is 11.60 +/- 3.38 d (median 12.0, range 4-17 d). The incubation period was compatible to that found in experimental anopheline bites or transfusion malaria. The transmission profile cites a pathogen which may be more easily transmissible by occupational exposure to blood than human immunodeficiency virus (HIV) or hepatitis C virus (HCV). Undiagnosed malaria in non-immune health care workers can be lethal. Presumptive treatment of malaria is widely available and well tolerated. Clinicians should consider P. falciparum malaria when faced with a febrile patient who has or may have been exposed to biological fluids. Further research is needed in the field of P. falciparum prophylaxis following accidental exposure to a malaria patient's blood.

Background: Our aim was to identify factors predisposing HIV-infected patients on long-term antiretroviral therapy (ART) to major hypertriglyceridemia (HTG)., Patients and Methods: We conducted a retrospective, case-control study involving 76 HIV-infected patients with HTG, defined by 12-hour fasting plasma triglyceride (TG) > 4.5 mmol/l on at least one occasion, and 150 HIV-infected matched control patients with TG consistently below 1.8 mmol/l., Results: Patients coinfected by the hepatitis C virus appeared to be protected from HTG. In addition to known predisposing factors for HTG in HIV-infected patients (ART and immune/viral status), patients with a history of excess body weight were twice as likely to have HTG (odds ratio [OR] 2.8, 95% confidence interval [CI]: 1.1-6.9); HTG was also more frequent in patients who had a first-degree relative with cardiovascular disease (CVD) or a major risk factor for CVD (OR = 3.6, CI: 1.3-9.9)., Conclusion: By identifying subgroups of highly predisposed patients, appropriate lifestyle and dietary measures could be recommended on ART initiation.

Objective: To investigate factors related to early virological response among a cohort of 224 patients who started a protease inhibitor (PI) for the first time. To determine which factors are associated with persistent response among patients with early response., Patients and Methods: Early complete response was defined as an undetectable plasma viral load 2 to 3 months after treatment onset (< 400 copies/ml, Quantiplex HIV 2.0 Chiron diagnostics), incomplete response as at least 1 log reduction of viral load. In patients with an undetectable plasma viral load at 2 or 3 months, we also assessed the persistence of the response on the same regimen. Virology failure was defined by two consecutive viral load levels above the detection limit., Results: In the total cohort, 66% of the patients had an early complete response, 11% a partial response and 23% no response. Complete virological response was significantly more frequent in naive (89%) than in pretreated (59%) patients (p < 0.001). Multivariate analysis of factors predictive of early response in pretreated patients (n = 169) showed that viral load (p = 0.001), the number of nucleoside analogs previously received (p = 0.06) and a full or partial treatment switch (p = 0.10) were associated with complete response. Analysis of later response in the 45 naive patients with prolonged follow-up showed that 22% had treatment failure after 3 to 16 months. None of the baseline variables (viral load, CD4+ cell count or nature of the PI) were associated with duration of response. The only factor associated with persistent response in pretreated patients was a low number of antiretroviral drugs previously received (log-rank test, p = 0.04)., Conclusions: The absence of previous antiretroviral treatment as the main factor associated with an early complete virological response. In patients pretreated with nucleoside analogs who presented early virological success, the number of drugs previously received, often associated with full or partial switch of nucleoside analog, significantly influence the persistence of response to a given triple-drug regimen.