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ObjectivesTo determine how the load of rilpivirine-resistant variants (mutational load) influences the virological response (VR) of HIV-1-infected patients to a rilpivirine-based first-line regimen.Patients and methodsFour hundred and eighty-nine patients infected with HIV-1 whose reverse transcriptase gene had been successfully resistance genotyped using next-generation sequencing were given a first-line regimen containing rilpivirine. Variables associated with the VR at 12 months were identified using a logistic model. The results were used to build a multivariate model for each mutational load threshold and the R2 variations were analysed to identify the mutational load threshold that best predicted the VR.ResultsThe mutational load at baseline was the only variable linked to the VR at 12 months (P  1700 copies/mL and to 50% when the mutational load was > 9000 copies/mL. The threshold of 9000 copies/mL was associated with the VR at 12 months with an OR of 36.7 (95% CI 4.7-285.1). The threshold of 1700 copies/mL was associated with the VR at 12 months with an OR of 7.2 (95% CI 1.4-36.8).ConclusionsThere is quantifiable evidence that determining a mutational load threshold can be used to identify those patients on a first-line regimen containing rilpivirine who are at risk of virological failure. The clinical management of HIV-infected patients can be improved by evaluating the frequency of mutant variants at a threshold of

Summary: The nucleotide substitution G1896A on the precore (pc) region has been implicated in virological and serological responses during treatment in hepatitis B virus (HBV)‐infected patients. Whether this mutation affects the therapeutic course of HIV‐HBV co‐infected patients, especially from Western Africa, is unknown. In this prospective cohort study, 86 antiretroviral (ARV)‐naïve HIV‐HBV co‐infected patients from Côte d'Ivoire, initiating ARV‐treatment containing lamivudine (n = 53) or tenofovir (n = 33), had available baseline pc sequences. Association of the pcG1896A mutation with time to undetectable HBV‐DNA, hepatitis B "e" antigen (HBeAg) seroclearance (in HBeAg‐positive patients), and hepatitis B surface antigen (HBsAg) seroclearance was evaluated using Cox proportional hazards regression. At ARV‐initiation, median HBV‐DNA was 6.04 log10 copies/mL (IQR = 3.70‐7.93) with 97.7% harbouring HBV genotype E. Baseline pcG1896A mutation was identified in 51 (59.3%) patients, who were more commonly HBeAg‐negative (P < .001) and had basal core promotor A1762T/G1764A mutations (P < .001). Patients were followed for a median 36 months (IQR = 24‐36). Cumulative proportion of undetectable HBV‐DNA was significantly higher in patients with baseline mutation (pcG1896A = 86.6% vs no pcG1896A = 66.9%, P = .04), but not after adjusting for baseline HBV‐DNA levels and anti‐HBV agent (P = .2). No difference in cumulative proportion of HBeAg seroclearance was observed between mutation groups (pcG1896A = 57.1% vs no pcG1896A = 54.3%, P = .7). Significantly higher cumulative proportion of HBsAg seroclearance was observed in patients without this mutation (pcG1896A = 0% vs no pcG1896A = 36.9%, P < .001), even after adjusting for baseline HBsAg quantification and anti‐HBV agent (P < .001). In conclusion, lacking the pcG1896A mutation before ARV initiation appeared to increase HBsAg seroclearance rates during treatment. The therapeutic implications of this mutation need further exploration in this setting. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) induces multi-organ pathogenesis in hematopoietic stem cell transplant (HSCT) and kidney transplant (KT) recipients. Effective management involves systematic monitoring for CMV reactivation by quantitative real-time PCR, allowing timely preemptive intervention. However, the optimal blood compartment for CMV surveillance remains undetermined., Objective: The aim of the study was to compare the quantification of CMV DNA in paired plasma and whole blood samples., Study Design: From June and October 2022, we conducted a prospective study with 390 sets of paired plasma and whole blood specimens collected from 60 HSCT and 24 KT recipients. CMV DNA levels were compared between the cobas® CMV assay on the automated cobas® 6800 system for plasma and the reference assay, Abbott RealTime CMV assay on the m2000 RealTime platform for whole blood., Results: The sensitivity and specificity of CMV quantification in plasma using the cobas® CMV assay were 90.0 % (95 %CI: 81.5 to 95.9) and 94.8 % (95 %CI: 91.8 to 96.8), respectively, compared to whole blood quantification with the Abbott assay. The overall agreement between these two strategies was 0.89 (95 %CI: 0.86-0.91). In samples with quantifiable results, a correlation was observed between the two methods (R 2 = 0.62, 95 %CI: 0.65-0.87, p < 0.0001). CMV loads were significantly higher in whole blood, with a mean bias of 0.42 log 10 IU/mL (95 %CI: -0.32-1.15)., Conclusion: The cobas® CMV assay in plasma showed significant concordance with the Abbott RealTime CMV assay in whole blood, confirming the relevance of plasma samples for CMV monitoring in HSCT and KT recipients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Linda Feghoul reports grants from Roche Diagnostics France. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Axillary lymph node involvement (ALNI) is associated with an increased risk of local recurrence and poor prognosis in early breast cancer. The determination of the risk of positive axillary lymph node contributes to therapeutic decisions., Objectives: The aim of this study was to identify clinicopathological predictive factors of axillary lymph node metastases in patients with early breast cancer., Methods: We included patients with clinical T0, T1 andT2 invasive breast carcinoma who underwent resection of the primary tumor and axillary staging by sentinel lymph node biopsy and/or axillar lymph node dissection between 2012 and 2018., Results: Of the 135patients included, 41.5% had ALNI. Regarding univariate analysis, clinical factors correlated with positive ALNM were clinical tumour size>30mm, clinical tumour stage, clinical number of tumours, clinical axillary nodal status and nodal status on ultrasound. Pathologic factors associated with nodal involvement were pathologic tumour stage, tumour grade SBR, number of foci, lymphovascular invasion, perineural invasion and Ki67>20%.In multivariate logistic regression, clinical axillary nodal status, pathologic tumour stage and lymphovascular invasion (LVI) remained as independent predictors of ALNI., Conclusions: Based on these results, we suggest that clinical axillary nodal status, pathologic tumour stage and LVI are predictive factors for ALNM in Tunisian women with early breast cancer., (© 2023 Leila A et al.)

The genome of the Omicron variant of concern (VOC) contains more than 50 mutations, many of which have been associated with increased transmissibility, differing disease severity, and the potential to elute immune responses acquired after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination or infection with previous VOCs. Due to a better tropism for the upper respiratory tract, it was suggested that the detection of the Omicron variant could be preferred in saliva, compared to nasopharyngeal swabs (NPS). Our objective was to compare the SARS-CoV-2 levels in saliva fluid and NPS to estimated Ct values, according to the main SARS-CoV-2 variants circulating in France since the beginning of 2021. We analyzed 1,289 positive reverse transcription-polymerase chain reaction (RT-PCR) results during the three major waves: Alpha, Delta, and Omicron. NPS and saliva sampling were performed for 909 (71%) and 380 (29%) cases, respectively. The Ct values were significantly lower in the NPS samples than in the saliva samples for the three main VOCs. Still, the difference was less pronounced with the Omicron variant than for the Alpha and Delta variants. In contrast, in the saliva samples, Ct values were significantly lower for the Omicron variant than for the Delta (difference of -2.7 Ct) and the Alpha (difference of -3.0 Ct) variants, confirming a higher viral load in saliva. To conclude, the higher viral load in saliva was evidenced for the Omicron variant, compared to the Alpha and Delta variants, suggesting that established diagnostic methods might require revalidation with the emergence of novel variants. IMPORTANCE Established methods for SARS-CoV-2 diagnostics might require revalidation with the emergence of novel variants. This is important for screening strategy programs and for the investigation of the characteristics of new variants in terms of tropism modification and increased viral burden leading to its spread. SARS-CoV-2 RT-PCR screening on saliva samples reported lower but acceptable performance, compared to nasopharyngeal samples. Due to a better tropism for the upper respiratory tract, it was suggested that the detection of the Omicron variant could be preferred in saliva, compared to nasopharyngeal swabs. Our study analyzed 1,289 positive RT-PCR results during the three major waves in France: Alpha, Delta, and Omicron. Our findings also showed a higher viral load in saliva for the Omicron variant, compared to the Alpha and Delta variants.

Background: Ectopic breast tissue is present in 2-6% of women. Ectopic mammary tissue can experience physiological changes and the same pathological processes as the eutopic breast. Ectopic breast cancer represents an uncommon condition accounting for 0.3% of all breast neoplasms, and it is most frequently located in the axilla., Case Report: We report a rare case of a 57-year-old Tunisian woman who presented with a left-sided axillary mass evolving for about 1 month. The axillary ectopic breast tissue containing the mass was excised with axillary dissection. Pathology revealed a medullary multifocal carcinoma and metastasis was detected in two lymph nodes. She had local radiotherapy after six cycles of chemotherapy. She received herceptin therapy and hormonotherapy. After a 2-year follow-up, no evidence of local recurrence or distant metastases have been identified., Conclusion: Ectopic breast carcinoma is a rare entity that should be the first diagnosis to be considered if an axillary lump is present in ectopic breast tissue. No particular guidelines on diagnosis and treatment are available. Therefore, physicians should be aware of this condition to avoid treatment delays. Once diagnosed, careful patient follow-up is essential because of the ambiguous natural history of this rare entity., (© 2022. The Author(s).)

The ID NOW COVID-19 system (IDNOW) is a point-of-care test (POCT) providing results within 15 min. We evaluated the impact of IDNOW use on patient length of stay (LOS) in an emergency department (ED). In the ED of Saint-Louis Hospital, Paris, France, adult patients requiring a rapid diagnosis of SARS-CoV-2 were tested with Cepheid Xpert Xpress SARS-CoV-2 or FilmArray respiratory panel RP2 in the virology laboratory between 18 October and 3 November 2020 (period 1) and with IDNOW between 4 November and 30 November 2020 (period 2). A total of 676 patients participated in the study, 337 during period 1 and 339 during period 2. The median LOS in ED was significantly higher in period 1 than in period 2 (276 versus 208 min, P  < 0.0001). More patients spent less than 4 h in the ED in period 2 (61.3%) than in period 1 (38.3%) ( P  < 0.0001). By univariate analysis, factors associated with ED LOS were hypertension, anosmia/ageusia, number of patients per day, and ID NOW implementation in period 2. By multivariate analysis, the period of testing remained significantly associated with ED LOS. Rapid molecular SARS-CoV-2 POCT was associated with a reduced LOS for patients admitted to an ED. IMPORTANCE During COVID-19 pandemic upsurges, emergency departments had to deal with a massive flow of incoming patients. The need for COVID-19 infection status determination before medical ward admission worsened ED overcrowding. The development of molecular point-of-care testing gave new opportunities for getting faster results of SARS-CoV-2 genome detection 24 h a day. In our study, we show, with a multivariate analysis, that the use of the POCT COVID-19 IDNOW reduced the ED length of stay by 1 h. The rate of patients who waited less than 4 h in the ED increased significantly. Our study highlights the benefit of COVID-19 molecular POCT for preventing ED overcrowding and facilitating bed allocation and SARS-CoV-2-infected patient isolation.

Objective: The purpose of this study was to examine the effectiveness and mechanism of clear aligner therapy for the correction of anterior open bite in adult nonextraction cases., Methods: Sixty-nine adult patients with anterior open bite were enrolled and classified into Angle's Class I, II, and III groups. Fifty patients presented with skeletal open bite (mandibular plane angle [MPA] ≥ 38°), whereas 19 presented with dental open bite. Fifteen cephalometric landmarks were identified before (T1) and after (T2) treatment. The magnitudes of planned and actual movements of the incisors and molars were calculated., Results: Positive overbite was achieved in 94% patients, with a mean final overbite of 1.1 ± 0.8 mm. The mean change in overbite was 3.3 ± 1.4 mm. With clear aligners alone, 0.36 ± 0.58 mm of maxillary molar intrusion was achieved. Compared with the Class I group, the Class II group showed greater maxillary molar intrusion and MPA reduction. The Class III group showed greater mandibular incisor extrusion with no significant vertical skeletal changes., Conclusions: Clear aligners can be effective in controlling the vertical dimension and correcting mild to moderate anterior open bite in adult nonextraction cases. The treatment mechanism for Class III patients significantly differed from that for Class I and Class II patients. Maxillary incisor extrusion in patients with dental open bite and MPA reduction with mandibular incisor extrusion in patients with skeletal open bite are the most significant contributing factors for open bite closure.

VIROLOGICAL ASPECTS, DIAGNOSTIC TOOLS AND VARIANTS OF SARS-COV-2 SARS-CoV-2 is an enveloped non-segmented linear single-stranded positive RNA virus. The envelope carries the protein spike (S) which recognizes the ACE2 receptor on the target cell and allows entry of the virus. The numerous mutations on the S protein are at the origin of a great genetic diversity, involved in the species barrier and the escape from neutralizing antibodies. The main mode of transmission is respiratory. The virus replicates 24 hours after infection and the viral RNA is detected by direct diagnostic techniques as the reference technique is RT-PCR on a nasopharyngeal sample. To expand screening, RT-PCR on saliva samples and antigenic tests have been developed. The majority of patients develop specific antibodies within 10-15 days which are detectable by serological methods. It is recommended to combine the search for anti-N and anti-S antibodies. The viral genome has great plasticity and variants emerged from the summer of 2020. There are several classifications, including that of the WHO, which assigns each variant a Greek letter. Finally, Santé publique France has deployed an epidemiological surveillance system of variants using PCR screening and sequencing., Competing Interests: M. Helary, M. Salmona, E.-M. Walle, L. Feghoul, N. Mahjoub, N. Schnepf, S. Maylin, M.-L. Chaix et J. Le Goff déclarent n’avoir aucun lien d’intérêts. - C. Delaugerre déclare des liens d’intérêts avec ViiV, MSD, Gilead.

Objective: To describe lymphoma in HIV-2-infected patients and compare their characteristics with lymphoma in HIV-1-infected patients., Design: Ancillary analysis from a single center prospective cohort of HIV-lymphoma., Methods: We report on 16 patients with HIV-2-lymphoma diagnosed after 1996 and included in a prospective cohort of HIV lymphoma. Five additional HIV-2-infected patients coinfected with HIV-1 or/and HTLV-I (6 lymphomas) are separately reported. The incidence of lymphoma in HIV-2-infected patients was evaluated in the French multicentric HIV-2 cohort., Results: Incidence of lymphoma in the French HIV-2 cohort was estimated as 0.6/1000 patient-years. In our series, the median CD4+ cell count was 166 × 106/l at the time of lymphoma diagnosis and 50% of patients had undetectable plasma HIV-2-RNA. Lymphomas were non-Hodgkin lymphoma (n = 12) and classical Hodgkin lymphoma (n = 4). Similarly to HIV-1-lymphoma, clinical presentation was aggressive in most cases. All but one patient received intensive chemotherapy. Complete remission was achieved in 13 cases and 1 patient relapsed. The overall survival was not statistically different from that observed in patients with HIV-1 lymphoma. The six additional lymphomas observed in five HIV-2-infected patients coinfected with HIV-1 or/and HTLV-I presented with similar clinical presentation but worse prognosis., Conclusion: Despite the lower pathogenicity of HIV-2, the risk of developing lymphoma seems to be close to that observed in HIV-1 population with similar lymphoma characteristics. Compared with HIV-1, HIV-2-infected patients developed lymphoma later in their life but at a similar CD4+ cell count level., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Mechanisms of blood pressure (BP) regulation by endothelin (ET)-1 produced by endothelial cells are complex and remain unclear. Long-term exposure to human ET-1 (hET-1) in mice inducibly overexpressing hET-1 in the endothelium (ieET-1) caused sustained BP elevation. ET-1 has been shown to stimulate the release of aldosterone. Whether aldosterone plays a role in hET-1 overexpression-induced BP elevation and vessel injury is unknown., Method: Nine- to 12-week-old male ieET-1 mice and control mice expressing a tamoxifen-inducible Cre recombinase (CreERT2) in the endothelial cells (ieCre) were treated with tamoxifen for 5 days and studied 3 months later., Results: Endothelial hET-1 overexpression increased plasma aldosterone levels, which was reversed by 2-week treatment with atrasentan, an endothelin type A receptors blocker. Aldosterone synthase and cryptochrome 2 adrenal cortex mRNA expression was decreased in ieET-1 mice. Two-week treatment with eplerenone, a mineralocorticoid receptor antagonist, reduced systolic BP by 10 mmHg in ieET-1 mice during rest time. Saline challenge-induced sodium excretion and renal cortex thiazide-sensitive sodium-chloride cotransporter mRNA expression were decreased in ieET-1 mice. The sensitivity of mesenteric arteries to contraction by norepinephrine was increased in ieET-1 mice, and was abrogated by eplerenone treatment, whereas sensitivity of endothelium-independent relaxation responses to sodium nitroprusside was enhanced. Resistance artery remodeling was reduced in eplerenone-treated ieET-1 vs. ieET-1 and ieCre mice., Conclusion: These results demonstrate that aldosterone contributes to BP elevation and vascular norepinephrine sensitivity and remodeling caused by hET-1 overexpression in endothelium in mice., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged and is responsible for coronavirus disease 19 (COVID-19). Diagnostic tests have been developed, mainly based on reverse-transcriptase PCR (RT-PCR). Most RT-PCR assays target at least two SARS-CoV-2 genes. In some cases, only one target gene is detected; the interpretation of such cases remains unclear., Objectives: Our objective was to analyse one target positive (OPT) RT-PCR results, using two RT-PCR assays: the Xpert® Xpress SARS-CoV-2 (Cepheid diagnosis, "Cepheid") and the Cobas® 6800 SARS-CoV-2 Test (Roche Molecular Diagnostics, "Roche")., Methods: All SARS-CoV-2 RT-PCR results performed on respiratory samples with the Roche or the Cepheid tests, from 23rd March to 6th August 2020 were collected. A patient with an OPT result was classified as "probable COVID-19" if they met at least one of the three following criteria: (i) history of a two gene-positive SARS-CoV-2 RT-PCR result, (ii) anti-SARS-CoV-2 antibody (IgG) detection or (iii) compatible chest computed tomography scan (CT-scan)., Results: A total of 18,630 and 1189 SARS-CoV-2 RT-PCR tests were performed with the Roche and Cepheid tests, respectively. Among the positive SARS-CoV-2 RT-PCR, 293 samples - corresponding to 264 patients - were OPT (11% of the positive samples). Of these patients, 180 (68%) had at least one of the three criteria listed above and were classified as probable COVID-19., Conclusions: Sixty-eight percent of the patients with an OPT result were classified as probable COVID-19 and are probably at a late stage of infection. Serology and imaging can be helpful to confirm diagnosis., Competing Interests: None., (© 2021 The Author(s).)

Introduction: Postthrombotic syndrome (PTS) is a form of secondary chronic venous insufficiency (CVI) that occurs after deep vein thrombosis (DVT). Effective treatments for PTS are lacking. Micronized purified flavonoid fraction (MPFF) is a venoactive drug used in the treatment of CVI., Objective: To determine whether MPFF is a good candidate to explore as a therapeutic agent for PTS., Methods: We performed a narrative review in which we identified 14 systematic reviews, 33 randomized controlled trials, and 19 observational studies that discussed the use of MPFF in CVI, as well as studies that reported on the mechanistic action of MPFF in relation to the pathophysiology of PTS., Results: MPFF targets a number of pathophysiologic components of PTS. Based on animal models and human studies investigating objective vascular and lymphatic measures, MPFF promotes venous recanalization after DVT, decreases venous remodeling and reflux, inhibits inflammatory processes, improves venous tone and stasis, improves lymphatic circulation, improves capillary hyperpermeability, and decreases tissue hypoxia. Furthermore, MPFF shows promise in improving clinical manifestations, quality of life, and objective venous parameters of CVI. Studies suggest good patient acceptability and tolerability with the use of MPFF in CVI., Conclusion: MPFF is a good candidate to explore as a potential therapy for PTS. Confirmatory high-quality studies are still needed to reinforce the evidence supporting the use of MPFF in CVI. Double-blind randomized controlled trials with clinical endpoints are needed to assess the clinical efficacy of MPFF in the treatment of PTS., (© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Background: The management of gastric adenocarcinoma is essentially based on surgery followed by adjuvant treatment. Adjuvant chemotherapy (CT) as well as chemoradiotherapy (CTRT) have proven their effectiveness in survival outcomes compared to surgery alone. However, there is little data comparing the two adjuvant approaches. This study aimed to compare the prognosis and survival outcomes of patients with gastric adenocarcinoma operated and treated by adjuvant radio-chemotherapy or chemotherapy., Materials and Methods: We retrospectively evaluated 80 patients with locally advanced gastric cancer (LGC) who received adjuvant treatment. We compared survival outcomes and patterns of recurrence of 53 patients treated by CTRT and those of 27 patients treated by CT., Results: After a median follow-up of 38.48 months, CTRT resulted in a significant improvement of the 5-year PFS (60.9% vs. 36%, p = 0.03) and the 5-year OS (55.9% vs. 33%, p = 0.015) compared to adjuvant CT. The 5-year OS was significantly increased by adjuvant CTRT (p = 0.046) in patients with lymph node metastasis, and particularly those with advanced pN stage (p = 0.0078) and high lymph node ratio (LNR) exceeding 25% (p = 0.012). Also, there was a significant improvement of the PFS of patients classified pN2-N3 (p = 0.022) with a high LNR (p = 0.018). CTRT was also associated with improved OS and PFS in patients with lymphovascular and perineural invasion (LVI and PNI) compared to chemotherapy., Conclusion: There is a particular survival benefit of adding radiotherapy to chemotherapy in patients with selected criteria such as lymph node involvement, high LNR LVI, and PNI., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© 2021 Greater Poland Cancer Centre.)

Introduction: Breast cancer is a common and serious disease. It represents the first cause of mortality and morbidity from cancer of Tunisian women and worldwide., Aim: To analyze the clinico-pathological and evolutionary characteristics of the patients followed at the carcinology's pole in the region of the North-West of Tunisia., Methods: We conducted a retrospective descriptive study of 114 patients, who were diagnosed with non metastatic breast cancers over a 6-year period, from January 2011 to December 2016., Results: Among the 289 patients treated in the medical carcinology department of the Jendouba regional hospital for invasive breast carcinoma over a period of 6 years, 114 patients had localized breast carcinoma, they were the subject of our study. The average age was 51 years. Nonspecific invasive cancer was the most frequent histological type (95.6%). The mean histological size was 29.3 mm. SBR grade II was most prevalent. Histological lymph node involvement was observed in 50.9%. Lymphovascular invasion was detected in 23.9% of cases and perineural sheaths was detected in 21.9% of cases. The most common molecular subtype was Luminal B. After discussion in a multidisciplinary concertation meeting, the patients received locoregional treatment: surgery, radiotherapy and systemic treatment: chemotherapy, endocrine hormone therapy. After a median follow-up of 45 months, OS and PFS at 5 years were 85.6% and 79.2% respectively., Conclusion: In the region of the North-West of Tunisia, breast cancer is characterized by its occurrence at a young age, the importance of tumor size, the importance of lymph node involvement, the frequency of inflammatory breast carcinoma and especially by the predominance of the molecular groups Luminal B and HER2 neu.

The aim of this study was to assess the analytical performances, sensitivity and specificity, of two rapid tests (Covid- Presto® test rapid Covid-19 IgG/IgM and NG-Test® IgM-IgG COVID-19) and one automated immunoassay (Abbott SARS-CoV-2 IgG) for detecting anti- SARS-CoV-2 antibodies. This study was performed with: (i) a positive panel constituted of 88 SARS-CoV-2 specimens collected from patients with a positive SARS-CoV-2 RT-PCR, and (ii) a negative panel of 120 serum samples, all collected before November 2019, including 64 samples with a cross-reactivity panel. Sensitivity of Covid-Presto® test for IgM and IgG was 78.4% and 92.0%, respectively. Sensitivity of NG-Test® for IgM and IgG was 96.6% and 94.9%, respectively. Sensitivity of Abbott IgG assay was 96.5% showing an excellent agreement with the two rapid tests (κ = 0.947 and κ = 0.936 for NGTest ® and Covid-Presto® test, respectively). An excellent agreement was also observed between the two rapid tests (κ = 0.937). Specificity for IgM was 100% and 86.5% for Covid-Presto® test and NG-Test®, respectively. Specificity for IgG was 92.0%, 94.9% and 96.5% for Covid-Presto®, NGTest ®, and Abbott, respectively. Most of the false positive results observed with NG-Test® resulted from samples containing malarial antibodies. In conclusion, performances of these 2 rapid tests are very good and comparable to those obtained with automated immunoassay, except for IgM specificity with the NG-Test®. Thus, isolated IgM should be cautiously interpreted due to the possible false-positive reactions with this test. Finally, before their large use, the rapid tests must be reliably evaluated with adequate and large panel including early seroconversion and possible cross-reactive samples., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: Environmental contamination by patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through respiratory droplets suggests that surfaces and equipment could be a medium of transmission. We aimed to assess the surface and equipment contamination by SARS-COV-2 of an emergency department (ED) during the coronavirus infectious disease-2019 (COVID-19) outbreak., Methods: We performed multiple samples from different sites in ED patients care and non-patient care areas with sterile premoistened swabs and used real-time reverse transcriptase polymerase chain reaction (RT-PCR) to detect the presence of SARS-CoV-2 ribonucleic acid (RNA). We also sampled the personal protective equipment (PPE) from health care workers (HCWs)., Results: Among the 192 total samples, 10 (5.2%) were positive. In patient care areas, 5/46 (10.9%) of the surfaces directly in contact with COVID-19 patients revealed the presence of SARS-CoV-2 RNA, and 4/56 (7.1%) of the surfaces that were not directly in contact with COVID-19 patients were positive. SARS-CoV-2 RNA was present only in the patients' examination and monitoring rooms. Before decontamination SARS-CoV-2 RNA was present on the saturation clip, the scuff for blood pressure measurement, the stretcher, the plastic screens between patients and the floor. After decontamination, SARS-CoV-2 RNA remained on the scuff, the stretcher and the trolleys. All samples from non-patient care areas or staff working rooms were negative. Only one sample from the PPE of the HCWs was positive., Conclusions: Our findings suggest that surfaces and equipment contamination by SARS-CoV-2 RNA in an ED during the COVID-19 outbreak is low and concerns exclusively patients' examination and monitoring rooms, preserving non-patient care areas., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Background: Identification of HIV infection at the early stage is valuable for patient management, for prevention, and for research purposes. In practice, identification of a recent HIV infection at diagnosis proves challenging after HIV antibody seroconversion but can be suspected using Western blots (WBs) or immunoblots (IBs) as confirmatory assays., Methods: Five commercially available confirmatory assays were compared using 43 samples from recently infected individuals. This included 2 WBs (New LAV Blot I, Biorad, and HIV Blot 2.2, MP Biomedicals), 2 IBs (INNO-LIA HIV I/II, Fujirebio, and RecomLine HIV-1 & HIV-2, Mikrogen Diagnostik), and 1 immunochromatographic single-use assay (Geenius HIV1/2 supplemental assay, Biorad)., Results: Following the manufacturer's recommendations for interpretation, the 2 WBs led to indeterminate results for 30% and 42% of the samples, suggesting recent infection, compared with 2%-7% for the 3 other assays. When interpreted based on the Fiebig classification, concordant stages were observed in 42% of samples, and only 49% were classified as early seroconversion by all 5 assays. For the remaining specimens, the distinction with chronic infection was highly variable depending on the assay (5%-100%)., Conclusions: Clinical laboratories must consider this variability, which must be kept in mind both for initial diagnosis and for multicenter studies for which inclusion criteria refer to serological profiles by confirmatory assays., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

We used next-generation sequencing to evaluate the quantity and genetic diversity of the HIV envelope gene in various compartments in eight patients with acute infection. Plasma (PL) and seminal fluid (SF) were available for all patients, whole blood (WB) for seven, non-spermatozoid cells (NSC) for four, and saliva (SAL) for three. Median HIV-1 RNA was 6.2 log 10 copies/mL [IQR: 5.5-6.95] in PL, 4.9 log 10 copies/mL [IQR: 4.25-5.29] in SF, and 4.9 log 10 copies/mL [IQR: 4.46-5.09] in SAL. Median HIV-1 DNA was 4.1 log 10 copies/10 6 PBMCs [IQR: 3.15-4.15] in WB and 2.6 log 10 copies /10 6 Cells [IQR: 2.23-2.75] in NSC. The median overall diversity per patient varied from 0.0005 to 0.0232, suggesting very low diversity, confirmed by the clonal aspect of most of the phylogenetic trees. One single haplotype was present in all compartments for five patients in the earliest stage of infection. Evidence of higher diversity was established for two patients in PL and WB, suggesting compartmentalization. Our study shows low diversity of the env gene in the first stages of infection followed by the rapid establishment of cellular reservoirs of the virus. Such clonality could be exploited in the search for early patient-specific therapeutic solutions.

Background: Standardized and sensitive assays for Epstein Barr Virus (EBV) are needed to define universal cutoff for treatment initiation in allogeneic hematopoietic stem cells transplant recipients. In a context of accreditation and the availability of EBV international standard, we evaluated the Abbott RealTime EBV (RT) assay for EBV quantification in whole blood., Methods: The RT assay was compared on 282 prospective clinical samples with the Artus EBV PCR Kit V1 assay (V1) and we analyzed the kinetics of EBV load in 11 patients receiving rituximab treatment., Results: The estimated limit of detection was 88 IU/mL. The assay was linear (r 2  = 0.9974) in the range of all samples tested (100 to 1,000,000 IU/mL). Intra-assay coefficients of variation (CV) ranged between 0.35 and 1.35%, and inter-assay CV between 3.40 and 4.5%. On samples above the limit of quantification, the two assays were strongly correlated. EBV RT values were on average 0.30 log 10 IU/mL lower than those measured with the V1 assay. In patients treated with rituximab, the RT assay remained positive in 5 patients at the time it dropped below undetectable levels with the V1 assay., Conclusions: In conclusion, the RT assay is a reliable assay for EBV load in whole blood. Its sensitivity will enable to estimate the kinetics of EBV load and the impact of treatments to control EBV reactivations.

Background: A high incidence of acute hepatitis C virus (HCV) (AHCV) infection has been reported among at-risk HIV-negative MSM. The optimal strategy for early diagnosis of AHCV in this population is not clearly defined., Methods: In the ANRS IPERGAY PrEP trial, among high-risk HIV-negative MSM, HCV serology and serum alanine aminotransferase (ALT) were used for screening at enrollment and during follow-up. Behavioral risk factors were compared at baseline between participants who were diagnosed with AHCV during the study compared with those who did not. In participants with a positive HCV serology, we used stored sera to perform the following tests at diagnosis and on previous visits: HCV-antibodies rapid tests, plasma HCV viral load and HCV antigen immunoassay. We evaluated the sensitivity of each test for AHCV diagnosis., Results: Among 429 enrolled participants, 14 were diagnosed with AHCV infection, with a median follow-up of 2.1 (interquartile range, 1.5-2.8) years. AHCV incidence was 1.40 per 100 person-years (95% confidence interval, 0.74-2.39). Patients with AHCV reported a significantly higher number of sexual acts and/or partners, and more frequent recreational drug use at baseline. At the prior visit before AHCV diagnosis (median of 2 months earlier), sensitivities of HCV RNA and HCV antigen tests were, respectively, 100 and 89%, whereas none of the patients had a positive serology, and only 25% had elevated ALT., Conclusion: HCV antigen and RNA tests were positive within a median of 2 months before the detection of antibodies and ALT elevation. These tests could be considered for HCV screening in high-risk MSM.

Objectives: Patients with primary HIV-1 infection (PHI) are a particular population, giving important insight about ongoing evolution of transmitted drug resistance-associated mutation (TDRAM) prevalence, HIV diversity and clustering patterns. We describe these evolutions of PHI patients diagnosed in France from 2014 to 2016., Methods: A total of 1121 PHI patients were included. TDRAMs were characterized using the 2009 Stanford list and the French ANRS algorithm. Viral subtypes and recent transmission clusters (RTCs) were also determined., Results: Patients were mainly MSM (70%) living in the Paris area (42%). TDRAMs were identified among 10.8% of patients and rose to 18.6% when including etravirine and rilpivirine TDRAMs. Prevalences of PI-, NRTI-, first-generation NNRTI-, second-generation NNRTI- and integrase inhibitor-associated TDRAMs were 2.9%, 5.0%, 4.0%, 9.4% and 5.4%, respectively. In a multivariable analysis, age >40 years and non-R5 tropic viruses were associated with a >2-fold increased risk of TDRAMs. Regarding HIV diversity, subtype B and CRF02&#95;AG (where CRF stands for circulating recombinant form) were the two main lineages (56% and 20%, respectively). CRF02&#95;AG was associated with higher viral load than subtype B (5.83 versus 5.40 log10 copies/mL, P=0.004). We identified 138 RTCs ranging from 2 to 14 patients and including overall 41% from the global population. Patients in RTCs were younger, more frequently born in France and more frequently MSM., Conclusions: Since 2007, the proportion of TDRAMs has been stable among French PHI patients. Non-B lineages are increasing and may be associated with more virulent CRF02&#95;AG strains. The presence of large RTCs highlights the need for real-time cluster identification to trigger specific prevention action to achieve better control of the epidemic., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Vascular injury is an early manifestation in hypertension and a cause of end-organ damage. MicroRNAs play an important role in cardiovascular disease, but their implication in vascular injury in hypertension remains unclear. This study revealed using an unbiased approach, microRNA and mRNA sequencing with molecular interaction analysis, a microRNA-transcription factor coregulatory network involved in vascular injury in mice made hypertensive by 14-day Ang II (angiotensin II) infusion. A candidate gene approach identified upregulated miR-431-5p encoded in the conserved 12qF1 (14q32 in humans) microRNA cluster, whose expression correlated with blood pressure, and which has been shown to be upregulated in human atherosclerosis, as a potential key regulator in Ang II-induced vascular injury. Gain- and loss-of-function in human vascular smooth muscle cells demonstrated that miR-431-5p regulates in part gene expression by targeting ETS homologous factor. In vivo miR-431-5p knockdown delayed Ang II-induced blood pressure elevation and reduced vascular injury in mice, which demonstrated its potential as a target for treatment of hypertension and vascular injury.

Background & Aims: Replication markers exhibit substantial variation during chronic hepatitis B virus (HBV) infection, part of which can be explained by mutations on the surface (S) gene. We aimed to identify S-gene mutations possibly influencing the quantification of HBV replication markers (MUPIQH) in HBV genotype E infection, common to Western Africa., Methods: Seventy-three antiretroviral treatment (ART)-naïve human immunodeficiency virus (HIV)-HBV co-infected patients from Côte d'Ivoire, initiating anti-HBV-containing ART, had available HBV S-gene sequences. S-gene MUPIQHs were screened at ART initiation based on lower HBV-DNA or HBsAg quantification (qHBsAg) compared to wildtype. Their association with HBV virological response and qHBsAg slope during treatment was evaluated., Results: Genotype E was predominant (95.9%). At ART initiation, median HBV-DNA was 7.27 log 10 copies/mL (IQR = 5.26-8.33) and qHBsAg 4.08 log 10 IU/mL (IQR = 3.49-4.61). Twelve S-gene MUPIQHs were identified among 21 patients (28.8%): sS140L (n = 4), sD144A (n = 1), sS167L (n = 2), sS174N (n = 6), sP178Q (n = 2), sG185L (n = 2), sW191L (n = 2), sP203Q/R (n = 2), sS204N/I/R/K/T/G (n = 7), sN207T (n = 2), sF212C (n = 1) and sV224A/Y (n = 7). MUPIQHs at positions s185+s191+s224 and s178+s204 were within highly covarying networks of S-gene mutations. Older age (P = 0.02), elevated transaminases (P = 0.03) and anti-hepatitis B "e" antibody-positive serology (P = 0.009) were significantly associated with prevalent MUPIQHs at ART initiation. During treatment, baseline MUPIQHs were not associated with time-to-undetectable HBV-DNA (P = 0.7) and qHBsAg levels decreased at similar rates between those with vs without MUPIQHs (P = 0.5)., Conclusion: Several novel S-gene mutations were associated with reductions in replication markers among West African co-infected patients. These mutations, however, do not affect response during antiviral treatment. Their diagnostic and clinical consequences need clarification., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We evaluated the impact of on-demand oral tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) for pre-exposure prophylaxis (PrEP) on herpes simplex virus (HSV)-1/2 incidence among men who have sex with men (MSM) enrolled in the ANRS IPERGAY trial. Serum samples were tested at baseline and at the last visit for HSV-1/2 antibodies. Overall HSV-1 incidence was 11.7 per 100 person-years; 16.2 and 7.8 per 100 person-years in the TDF/FTC and placebo arm, respectively ( P = .19). Overall HSV-2 incidence was 7.6 per 100 person-years; 8.1 and 7.0 per 100 person-years in the TDF/FTC and placebo arm, respectively ( P = .75). On-demand oral PrEP with TDF/FTC failed to reduce HSV-1/2 incidence in this population.

Nephrotoxicity is a serious side effect for the immunosuppressant drug cyclosporine A(CSA). In this study, we tested the hypothesis that administration of calcium channel blockers such as verapamil or nifedipine ameliorates renal CSA-induced renal dysfunction. Furthermore, our study investigates the roles of inflammatory, oxidative, and fibrotic pathways in CSA-induced renal dysfunction. Six groups of male rats ( n = 6/group) were used and received one of the following treatments for seven consecutive days: vehicle (Cremophor EL ip), CSA (25 mg·kg -1 ·day -1 ip), verapamil (2 mg·kg -1 ·day -1 ip), nifedipine (3 mg·kg -1 ·day -1 ip), CSA in the presence or absence of either verapamil, or nifedipine. Biochemical and histomorphometric analyses showed that rats treated with CSA exhibited clear signs of nephrotoxicity that included 1) proteinuria and elevations in serum creatinine and blood urea nitrogen, 2) mesangial expansion, 3) increases in glomerular and tubular type IV collagen expression, and 4) increases in the glomerulosclerosis and tubulointerstitial fibrosis indices. Although the single administration of nifedipine or verapamil had no significant effect on renal pathology, or its biochemical and physiological function, the concurrent use of either calcium channel blockers significantly and equipotently ameliorated the biochemical, morphological, and functional derangements caused by CSA. More importantly, we report that the oxidative (reactive oxygen species production, NADPH-oxidase activity, and dual oxidase 1/2 levels), fibrotic (transforming growth factor-β1 expression), and inflammatory (NF-κB expression) manifestations of renal toxicity induced by CSA were significantly reversed upon administration of nifedipine or verapamil. Together, these results highlight the efficacy of calcium channel-blocking agents in attenuating CSA-induced nephrotoxicity and predisposing biochemical and molecular machineries.

We assessed the impact of early antiretroviral treatment (ART) on human immunodeficiency virus (HIV) antibody detection by rapid tests in 44 individuals after several years of successful ART. HIV self-tests and point-of-care tests were negative in 30% and 7%-9% of cases, respectively. These data reinforce the message that patients should never be retested after entering HIV care.