Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Objectives The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. Methods Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized. Results On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P = 0.0455) and T215Y (P = 0.0455). Conclusions In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performe

Existence of a lens-shaped cluster of surfaces self-shrinking by mean curvature

We rigorously show the existence of a rotationally and centrally symmetric "lens-shaped" cluster of three surfaces, meeting at a smooth common circle, forming equal angles of 120 degrees, self-shrinking under the motion by mean curvature.Comment: 22 pages, 2 figure

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Ann Epidemiol

PURPOSE: Prognostic studies derived from samples of patients managed in tertiary hospitals are subject to referral bias. We aimed to characterise this bias using the example of infective endocarditis (IE). METHODS: We analysed data from a French population-based cohort which included 497 patients with IE in 2008. Patients were admitted directly to a tertiary hospital (group T), or admitted to a non-tertiary hospital and referred to a tertiary hospital (group NTT) or not (group NT). We compared patients' characteristics and survival rates and prognostic factors between groups. RESULTS: Compared to group T (N=291), NTT patients (N=144) were more often males (81.3% vs 72.5%, p=0.046), injection drug users (9.7% vs 4.5%, p=0.033), had more frequent surgical indications (78.5% vs 64.3%, p=0.003). Compared to group NT (N=62), NTT patients were more often males (81.3% vs 67.7%, p=0.034) and had surgical indications more often (78.5% vs 19.4%, p<0.001). One-year survival was higher in (NTT+T) patients than in NT patients (73.0% vs 56.1%, p=0.01). Prognostic factors as well as HR estimates varied across groups. CONCLUSION: When derived from samples mixing patients admitted directly and those referred to tertiary hospitals, validity of characteristics description, survival estimates, and HRs is threatened by referral bias

Data Brief

This article describes supplementary tables and figures associated with the research paper entitled "Impact of referral bias on prognostic studies outcomes: insights from a population-based cohort study on infective endocarditis". The aforementioned paper is a secondary analysis of data from the EI 2008 cohort on infective endocarditis and aimed at characterising referral bias. A total of 497 patients diagnosed with definite infective endocarditis between January 1(st) and December 31(st) 2008 were included in EI 2008. Data were collected from hospital medical records by trained clinical research assistants. Patients were divided into three groups: admitted to a tertiary hospital (group T), admitted to a non-tertiary hospital and referred secondarily to a tertiary hospital (group NTT) or admitted to a non-tertiary hospital and not referred (group NT). The pooled (NTT+T) group mimicked studies recruiting patients in tertiary hospitals only. Two different starting points were considered for follow up: date of first hospital admission and date of first admission to a tertiary hospital if any (hereinafter referred to as "referral time"). Referral bias is a type of selection bias which can occur due to recruitment of patients in tertiary hospitals only (excluding those who are admitted to non-tertiary hospitals and not referred to tertiary hospitals). This bias may impact the description of patients' characteristics, survival estimates as well as prognostic factors identification. The six tables presented in this paper illustrate how patients' selection (population-based sample [pooled (NT+NTT+T) group] versus recruitment in tertiary hospitals only [pooled (NTT+T) group]) might impact Hazards Ratios values for prognostic factors. Crude and adjusted Cox regression analyses were first performed to identify prognostic factors associated with 3-month and 1-year mortality in the whole sample using inclusion as the starting point. Analyses were then performed in the pooled (NTT+T) group first using inclusion as the starting point and finally using referral time as the starting point. Figures 1 to 3 illustrate how HR increase with time for covariates that were considered as time-varying covariates (covariate*time interaction)

Amylose AA secondaire à une tuberculose pulmonaire multi-résistante : implications thérapeutiques

International audienceMultidrug resistant pulmonary tuberculosis was diagnosed to a 32-year-old man. An AA-amyloidosis was subsequently diagnosed on the renal biopsy performed for nephrotic syndrome and macroscopic hematuria. A 6-drug antibiotic treatment was delivered quickly after first results of genotypic antibiogram given the renal failure, and was secondarily adapted to the phenotypic antibiogram. Multidrug therapy was fairly well tolerated. Clinical and biological improving were slow. Although tuberculosis is a classic cause of amyloidosis, this is the first case reporting an association between a multidrug resistant case and an amyloidosis in adults. This case also raises the question of MDR probabilistic treatments in situations whether a vital organ prognosis is engaged.Une tuberculose pulmonaire, qui s’avèrera multi-résistante et associée à une amylose rénale secondaire, est diagnostiquée chez un homme de 32 ans d’origine arménienne. Une hexa-antibiothérapie probabiliste basée sur les résultats bactériologiques préliminaires de l’antibiogramme génotypique est débutée en urgence, sans attendre l’antibiogramme phénotypique définitif. L’évolution clinique et biologique sera lentement favorable et la tolérance du traitement sera acceptable. Cette observation illustre le premier cas d’association entre amylose secondaire et tuberculose multi-résistante, qui pose le problème de la nécessité de traiter en urgence un patient chez qui les risques de résistance et d’échec thérapeutique sont élevés