MRI and spondyloarthropathy: diagnostic performance compared to long-term clinical follow-up with evaluation of gadolinium chelates injection.

OBJECTIVES: To evaluate MRI performance on both initial and long-term rheumatologic diagnosis of spondyloarthritis (SpA), taking into account clinical evolution and treatment response, and the impact of gadolinium injection. METHODS: In this single-center study, patients who underwent both spinal and sacroiliac (SI) joint MRI were prospectively recruited between May 2013 and January 2014 and followed for 7 years until 2020. Clinical, biological, and radiologic parameters were collected. At 7-year follow-up (2020), two independent readers reevaluated the initial MRI datasets for specific radiological features of SpA with a 5-point Likert scale to record the estimation of confidence. The centralized MRI interpretations were compared to the established rheumatologic diagnoses in 2013 and 2020. RESULTS: In total, 145 patients (52 men and 93 women) were included. During the 7-year follow-up, the number of patients with positive SpA diagnosis decreased from 93 to 58. Mean sensitivity, specificity, and accuracy of non-contrast MRI were 18, 97, and 49% and 27, 97, and 69% considering 2013 and 2020 rheumatologic diagnoses, respectively. Mean sensitivity, specificity, and accuracy values of gadolinium-enhanced MRI were 26, 97, and 54% and 38, 97, and 73% considering 2013 and 2020 diagnoses, respectively. Post-contrast MRI enabled identification of a subgroup of enthesis-only lesions, without any bone lesions, corresponding to 14% of the pathological cohort. It confirmed uncertain diagnoses in an additional 8.5% of pathological cases. CONCLUSIONS: MRI performance for SpA diagnosis is higher when long-term clinical follow-up is considered than when compared to initial diagnosis. Gadolinium injection increases MRI diagnostic performance and may demonstrate a pure enthesic form of the disease, without bone abnormality. KEY POINTS: • Compared to the rheumatologist's diagnosis over long-term clinical follow-up, MRI performance for SpA is higher than usually estimated. • Gadolinium injection increases diagnostic performance of MRI as it may identify a purely enthesis form of the disease. • Gadolinium injection should be discussed in patients for whom the diagnostic suspicion is strong and whose initial non-injected examination is normal or doubtful.

A real-world experience of SARS-CoV-2 infection in a tertiary referral centre of Montréal: Unexpected low prevalence and low mortality.

BACKGROUND: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with chronic liver disease (CLD) and liver transplant (LT) recipients remains a concern. The aim of this study was to report the impact of coronavirus disease 2019 (COVID-19) infection among patients at the tertiary health care centre Centre hospitalier de l'Université de Montréal (CHUM) during the first wave of the SARS-CoV-2 pandemic. METHODS: This real-world, retrospective cohort included all patients admitted to our liver unit and/or seen as an outpatient with CLD with or without cirrhosis and/or LT recipients who tested positive to SARS-CoV-2 infection. Cases were considered positive as defined by the detection of SARS-CoV-2 by reverse-transcription polymerase chain reaction (RT-PCR) on nasopharyngeal swabs. RESULTS: Between April 1 and July 31, 2020, 5,637 were admitted to our liver unit and/or seen as outpatient. Among them, 42 were positive for SARS-CoV-2. Twenty-two patients had CLD without cirrhosis while 16 patients had cirrhosis at the time of the infection (13, 2, and 1 with Child-Pugh A, B, and C scores, respectively). Four were LT recipients. Overall, 15 of 42 patients (35.7%) were hospitalized; among them, 7 of 42 (16.7%) required respiratory support and 4 of 42 (9.5%) were transferred to the intensive care unit. Only 4 of 42 (9.5%) patients died: 2 with CLD without cirrhosis and 2 with CLD with cirrhosis. Overall survival was 90.5%. CONCLUSION: This real-world study demonstrates an unexpectedly low prevalence and low mortality in the context of SARS-CoV-2 infection among patients with CLD with or without cirrhosis and LT recipients.

Safety and immunogenicity of the therapeutic vaccine TG1050 in chronic hepatitis B patients: a phase 1b placebo-controlled trial.

Treatment of chronic hepatitis B (CHB) typically requires life-long administration of drugs. Cohort and pre-clinical studies have established the link between a functional T-cell-mounted immunity and resolution of infection. TG1050 is an adenovirus 5-based vaccine that expresses HBV polymerase and domains of core and surface antigen and has shown immunogenicity and antiviral effects in mice. We performed a phase 1 clinical trial to assess safety and explore immunogenicity and early efficacy of TG1050 in CHB patients. This randomized, double blind, placebo-controlled study included two sequential phases: one single dose cohort (SD, n = 12) and one multiple (3) doses cohort (MD, n = 36). Patients, virally suppressed under nucleoside(d)tide analog NUC therapy, were randomized 1:1:1 across 3 dose levels (DL) and assigned to receive 109, 1010, 1011 virus particles (vp) of TG1050 and then randomized within each DL to placebo (3:1 and 9:3 vaccines/placebo in each DL, respectively, for the SD and MD cohorts). Cellular (ELISPOT) and antibody responses (anti-Adenovirus), as well as evolution of circulating HBsAg and HBcrAg, were monitored. All doses were well tolerated in both cohorts, without severe adverse event. TG1050 was capable to induce IFN-γ producing T-cells targeting 1 to 3 encoded antigens, in particular at the 1010vp dose. Overall, minor decreases of HBsAg were observed while a number of vaccinees reached unquantifiable HBcrAg by end of the study. In CHB patients under NUC, TG1050 exhibited a good safety profile and was capable to induce HBV-specific cellular immune response. These data support further clinical evaluation, especially in combination studies.

Management of Hepatitis B Virus Infection: 2018 Guidelines from the Canadian Association for the Study of Liver Disease and Association of Medical Microbiology and Infectious Disease Canada.

Hepatitis B virus (HBV) infection is an important public health problem in Canada. In keeping with evolving evidence and understanding of HBV pathogenesis, the Canadian Association for the Study of Liver Disease periodically publishes HBV management guidelines. The goals of the 2018 guidelines are to (1) highlight the public health impact of HBV infection in Canada and the need to improve diagnosis and linkage to care, (2) recommend current best-practice guidelines for treatment of HBV, (3) summarize the key HBV laboratory diagnostic tests, and (4) review evidence on HBV management in special patient populations and include more detail on management of HBV in pediatric populations. An overview of novel HBV tests and therapies for HBV in development is provided to highlight the recent advances in HBV clinical research. The aim and scope of these guidelines are to serve as an up-to-date, comprehensive resource for Canadian health care providers in the management of HBV infection.

Assessment of MS/MS search algorithms with parent-protein profiling.

Peptide mass spectrometry relies crucially on algorithms that match peptides to spectra. We describe a method to evaluate the accuracy of these algorithms based on the masses of parent proteins before trypsin endoprotease digestion. Measurement of conformance to parent proteins provides a score for comparison of the performances of different algorithms as well as alternative parameter settings for a given algorithm. Tracking of conformance scores for spectrum matches to proteins with progressively lower expression levels revealed that conformance scores are not uniform within data sets but are significantly lower for less abundant proteins. Similarly peptides with lower algorithm peptide-spectrum match scores have lower conformance. Although peptide mass spectrometry data is typically filtered through decoy analysis to ensure a low false discovery rate, this analysis confirms that the filtered data should not be considered as having a uniform confidence. The analysis suggests that use of different algorithms and multiple standardized parameter settings of these algorithms can increase significantly the numbers of peptides identified. This data set can be used as a resource for future algorithm assessment.

Palladium-silver mesowires for the extended detection of H2.

Palladium-silver mesowires are prepared by electrochemical decoration of graphite step-edges with a good control of the alloy composition and wire diameter. As-prepared arrays are used for hydrogen sensing and demonstrate extended detection capabilities up to the whole concentration range of H(2) depending on the alloy composition. At low silver content, low hydrogen concentration is detected but the sensing window is narrow because of sensor saturation. The sensing window is advantageously extended to higher hydrogen concentrations for quantitative measurements up to pure H(2) flows with Ag-rich alloys. The mechanism responsible for these behaviors implies the statistical distribution in surface composition rather than the structural characteristics and stability domains of the corresponding hydride phases.

Amino termini of many yeast proteins map to downstream start codons.

Comprehensive knowledge of proteome complexity is crucial to understanding cell function. Amino termini of yeast proteins were identified through peptide mass spectrometry on glutaraldehyde-treated cell lysates as well as a parallel assessment of publicly deposited spectra. An unexpectedly large fraction of detected amino-terminal peptides (35%) mapped to translation initiation at AUG codons downstream of the annotated start codon. Many of the implicated genes have suboptimal sequence contexts for translation initiation near their annotated AUG, and their ribosome profiles show elevated tag densities consistent with translation initiation at downstream AUGs as well as their annotated AUGs. These data suggest that a significant fraction of the yeast proteome derives from initiation at downstream AUGs, increasing significantly the repertoire of encoded proteins and their potential functions and cellular localizations.

Association between brain-derived neurotrophic factor gene and a severe form of bipolar disorder, but no interaction with the serotonin transporter gene.

BACKGROUND: Recent data suggest that brain-derived neurotrophic factor (BDNF) and the serotonergic system are involved and interact in major depressive disorder and suicidal behavior (SB). Several family and population-based studies have reported associations between the BDNF gene and serotonin-related genes, specifically the serotonin transporter (5HTT) gene, with bipolar disorder (BD) and SB. However, despite the fact that gene-by-gene interaction between BDNF and 5HTT has been demonstrated in monoamine deficiencies in animals, this kind of interaction has never been tested in humans. Our hypothesis is that some BDNF and 5HTT polymorphisms might confer increased risk for BD and SB and that both genes may interact with each other. METHODS: To test this hypothesis, we genotyped the most common BDNF polymorphisms, G196A (Val66Met), A-633T and BDNF-LCPR, as well as 5HTT (5HTT-LPR), in 447 BD patients and 370 controls. RESULTS: We replicated the association previously reported between BDNF G196A (Val66Met) polymorphism and BD. We also observed a correlation between the number of G196 alleles and short alleles of 5HTT-LPR and the severity of SB in BD. However, we found no significant interaction between these two markers. CONCLUSIONS: These results suggest that BDNF G196A as well as 5HTT-LPR polymorphisms confer risk for SB in BD, but we did not observe any evidence for an interaction between them.

Antiviral therapy of chronic hepatitis B: prevention of drug resistance.

The emergence of viral resistance during treatment is becoming an important clinical issue for hepatitis B virus (HBV) antiviral therapy. Considerable progress has been achieved in the efficacy of treatment, with the development of new drugs that allow a sustained suppression of HBV replication, or at least maintain the viral load below a clinically relevant threshold. Although most drugs currently registered for the treatment of chronic hepatitis B are effective in suppressing viral load, long-term therapy is required to avoid viral reactivation and progression of liver disease. Because of the variability of the HBV genome, such long-term treatments are associated with the emergence of resistant viral strains, which may compromise the initial clinical benefit of the treatment.