CCR5 receptor expression is down-regulated in HIV type 2 infection: implication for viral control and protection

HIV-2 is known to display an attenuated phenotype in vivo with prolonged time to disease and decreased rate of transmission. Observational studies in Senegal have demonstrated protection from HIV-1 infection, although the putative mechanism for immunoprotection remains undefined. We evaluated HIV-2-seropositive women from a cohort of commercial sex workers in Dakar, Senegal and identified individuals with very low surface CCR5 receptor expression on CD4+ T cells. In vitro up-regulation of the CCR5 receptor was readily achieved. Down-regulation of the CCR5 was not correlated with activation markers (HLA-DR), beta-chemokine levels, or plasma viral loads. A correlation was observed with HIV-2-specific CD8+ T cell activity as measured by intracellular cytokine production. We postulate that down-regulation of the CCR5 receptor in HIV-2 infection contributes to slower disease course and to the protective mechanism against HIV-1 superinfection, mediated in part by HIV-2-specific cellular immune responses.     

Online Quantitative Aortographic Assessment of Aortic Regurgitation After TAVR: Results of the OVAL Study

ObjectivesThe aim of this study was to investigate the online assessment feasibility of aortography using videodensitometry in the catheterization laboratory during transcatheter aortic valve replacement (TAVR).BackgroundQuantitative assessment of regurgitation after TAVR through aortography using videodensitometry is simple, reproducible, and validated in vitro, in vivo, in clinical trials, and in “real-world” patients. However, thus far the assessment has been done offline.MethodsThis was a single center, prospective, proof-of-principle, feasibility study. One hundred consecutive patients with aortic stenosis and indications to undergo TAVR were enrolled. All final aortograms were analyzed immediately after acquisition in the catheterization laboratory and were also sent to an independent core laboratory for blinded offline assessment. The primary endpoint of the study was the feasibility of the online assessment of regurgitation (percentage of analyzable cases). The secondary endpoint was the reproducibility of results between the online assessment and the offline analysis by the core laboratory.ResultsPatients’ mean age was 81 ± 7 years, and 56% were men. The implanted valves were either SAPIEN 3 (97%) or SAPIEN 3 Ultra (3%). The primary endpoint of online feasibility of analysis was 92% (95% confidence interval [CI]: 86% to 97%) which was the same feasibility encountered by the core laboratory (92%; 95% CI: 86% to 97%). Reproducibility assessment showed a high correlation between online and core laboratory evaluations (R² = 0.87, p < 0.001), with an intraclass correlation coefficient of 0.962 (95% CI: 0.942 to 0.975; p < 0.001).ConclusionsThis study showed high feasibility of online quantitative assessment of regurgitation and high agreement between the online examiner and core laboratory. These results may pave the way for the application of videodensitometry in the catheterization laboratory after TAVR. (Online Videodensitometric Assessment of Aortic Regurgitation in the Cath-Lab [OVAL]; NCT04047082)     

Interference of tobacco smoke with immunochromatography assay for urinary drug detection

BackgroundThis study aimed to evaluate the interference of tobacco smoke on immunochromatography assay of urinary drug detection.MethodsOur study included 256 voluntary subjects (143 passive smokers and 113 current smokers). Cotinine was measured by immunoenzymatic method and thiocyanates (SCN^?) by selective electrode. Urinary drug was detected by immunochromatography assay. A positive result is completed by an analytical method with an immunometric assay.ResultsFalse positive results for benzodiazepines are significantly more frequent in smokers compared with passive smokers (90.2% Vs 22.4%; χ² = 116.62, p < 10^?3). For smokers, the number of cigarettes was significantly higher in subjects with falsely positive results for benzodiazepines compared with subjects with negative results (32 ± 11 Vs 20 ± 10; p = 0.04). Between these two groups, we established a significant difference for urinary cotinine (345 ± 211 Vs 117 ± 54 μg/μmol; p < 10^?3) and for plasma SCN^? (101.6 ± 3.4 Vs 98.8 ± 2.1 μmol/L; p = 10^?3). Urinary cotinine and consumption duration present the highest values of areas under curves (AUC) of the receiver-operating-characteristic (ROC) curves. The cut-off of 167.6 μg/μmol and 10.5 years were found as predictive factors of false positive results.ConclusionTobacco smoke interferes with immunochromatography assay of urinary drug detection; therefore, all subjects must be questioned about their smoking status to avoid such false results during results interpretation.     

Arachnoiditis ossificans of the cauda equina

A case of post-traumatic arachnoiditis ossificans of the cauda equina is reported. The lesion is a rare pathological entity usually confined to the thoracic and high lumbar regions that can cause progressive spinal cord and cauda equine compression. The pathophysiology and therapeutic strategy of this rare entity are still controversial.     

Thrombose très tardive d’un stent nu dix ans après son implantation : à propos d’une observation

Very late thrombosis occurring after bare-metal stent (BMS) implantation is a rare complication. It differs from very late thrombosis of drug-eluting stents in terms of both frequency and pathophysiological mechanism. We report a case of very late stent thrombosis of a bare-metal stent 10 years after his implantation for treatment of a myocardial infarction. The patient had a new acute coronary syndrome without persistent ST-segment elevation related to bare-metal stent thrombosis. He was treated by thrombo-aspiration and implantation of a new bare-metal stent.     

Etiology and prevention of pulmonary complications following beta-mimetic mediated tocolysis

Objectives: This study documents biological (haematocrit variations) and therapeutic parameters (salbutamol doses, volumes perfused) in two groups tocolysed with salbutamol, one with and the other without APO in order to define the risk factors linked to APO and to establish a standard protocol of management. Study design: This retrospective study includes data from 68 intravenous salbutamol tocolysis with four resulting APOs, carried out between January 1st, 1993 and December 31st, 1995. Results: There was an excessive level of salbutamol administered over 48 h in the complicated APO-group (122.5±52 mg) opposed to the non-APO group (44.9±21 mg) as well as an overload of perfused solute (3.1±1.1 l) versus (1.9±1.1 l). Blood hemodilution was demonstrated in the APO group with a decrease of haematocrit by over 10% between the admission and the control value. No other risk factor was found. Conclusion: Tocolysis should be administered at the lowest possible perfusion rate with incremental doses as long as the heart rate stays under 120 beats/min and stopped after 48 h. Administration of maximal 1 l of solute perfused/day is recommended. For the patient's follow-up we estimate daily input and output fluid to avoid hydric overload, and a daily control of haematocrit whose variation must be less than 10%.     

Somatic mutations of the β-catenin gene are frequent in mouse and human hepatocellular carcinomas

Hepatocellular carcinoma (HCC) is the major primary malignant tumor in the human liver, but the molecular changes leading to liver cell transformation remain largely unknown. The Wnt-β-catenin pathway is activated in colon cancers and some melanoma cell lines, but has not yet been investigated in HCC. We have examined the status of the β-catenin gene in different transgenic mouse lines of HCC obtained with the oncogenes c-myc or H-ras. Fifty percent of the hepatic tumors in these transgenic mice had activating somatic mutations within the β-catenin gene similar to those found in colon cancers and melanomas. These alterations in the β-catenin gene (point mutations or deletions) lead to a disregulation of the signaling function of β-catenin and thus to carcinogenesis. We then analyzed human HCCs and found similar mutations in eight of 31 (26%) human liver tumors tested and in HepG2 and HuH6 hepatoma cells. The mutations led to the accumulation of β-catenin in the nucleus. Thus alterations in the β-catenin gene frequently are selected for during liver tumorigenesis and suggest that disregulation of the Wnt-β-catenin pathway is a major event in the development of HCC in humans and mice.