Diagnostic of acute hepatitis A virus (HAV) infection is based on the detection of anti‐HAV IgM without testing for the pathogen itself. We evaluated the usefulness of HAV RNA testing for confirmation of acute hepatitis A and to provide indications about the level of HAV replication in HIV‐positive and HIV‐negative subjects during an unprecedented outbreak of HAV observed in France in 2017. HAV RNA was detected in 38 out of 41 (92.6%) subjects with a clinical diagnosis of acute hepatitis A, whereas nine cases tested positive for anti‐HAV IgM in whom the diagnosis of acute hepatitis A was not retained were found negative for HAV RNA. All subjects in the control group were also tested negative for HAV RNA. HAV viremia was correlated to ALT peak (r = .64; P < .0001). HIV‐infected patients have similar HAV RNA levels but were less likely to have prolonged international normalized ratio of prothrombin time when compared to the HIV‐uninfected group (P = .016), suggesting a less severe course of acute hepatitis. HAV RNA was detected in the serum of most of the patients with acute hepatitis A, indicating that the direct detection of HAV can be used to confirm hepatitis A in patients tested positive for anti‐HAV IgM antibodies. Nucleic acid tests should serve more broadly during the diagnosis workup of acute hepatitis A to improve the predictive values of HAV in vitro diagnostic tests and to confirm acute hepatitis A in patients tested positive with IgM with moderate or low S/CO values.
Eukaryotic cells employ a broad range of mechanisms to regulate gene expression. Among others, mRNA alternative splicing is a key process. It consists of introns removal from an immature mRNA (pre-mRNA) via a transesterification reaction to create a mature mRNA molecule. Large-scale genomic studies have shown that in the human genome, almost 95% of protein-encoding genes go through alternative splicing and produce transcripts with different exons combinations (and sometimes retained introns), thus increasing the proteome diversity. Considering the importance of RNA regulation in cellular proliferation, survival, and differentiation, alterations in the alternative splicing pathway have been linked to several human cancers, including adult T-cell leukemia/lymphoma (ATL). ATL is an aggressive and fatal malignancy caused by the Human T-cell leukemia virus type 1 (HTLV-1). HTLV-1 genome encodes for two oncoproteins: Tax and HBZ, both playing significant roles in the transformation of infected cells and ATL onset. Here, we review current knowledge on alternative splicing and its link to cancers and reflect on how dysregulation of this pathway could participate in HTLV-1-induced cellular transformation and adult T-cell leukemia/lymphoma development.
Introduction: There has been continued debate and limited research on the efficacy of ventricular assist devices such as intra-aortic balloon pumps and Impella devices on improving survival outcomes in post cardiac arrest patients. Objective: The primary objective of this study is to assess whether the use of ventricular assist devices is associated with improved survival outcome in patients resuscitated from out-of-hospital cardiac arrest in Michigan. Methods: We matched cardiac arrest cases from 2014-2017 in the Michigan CARES Registry (CARES) and the Michigan Inpatient Database (MIDB) using probabilistic linkage. Ventricular assist devices (VAD) are defined as either Intra-aortic balloon pump (IABP) or Impella device identified using ICD-9 or 10 procedure codes. Multilevel, multivariable regression analyses were employed to evaluate the impact of device use on survival to hospital discharge, adjusting for variables normally predictive of cardiac arrest survival (age, location, witnessed, shockable rhythm). Results: A total of 3,790 CARES cases were matched with the MIDB of which 183 (4.8%) received IABP, 50 (1.3%) received impella devices, and 1,131 (29.8%) survived to hospital discharge. VAD use was associated with improved survival to discharge (OR=2.07, 95% CI 1.55, 2.77). IABP were used more frequently and associated with an improved outcome (OR=2.16, 95%CI 1.59, 2.93) compared to the Impella device (OR=1.72, 95% CI 0.96, 3.06). In a multivariable model, however, VAD use was no longer associated with an improved outcome (aOR =0.95, 95% CI 0.69, 1.31). In the subset of patients with a diagnosis of cardiogenic shock (n=725) we identified an improved survival to discharge with VAD use (OR= 1.84 95% CI 1.24, 2.73). IABP use was more frequent and associated with an improved outcome (OR=1.98, 95% CI 1.32, 2.98). After adjusting for patient characteristics, VAD use increased the odds of an improved outcome by 14% but was not statistically significant (aOR = 1.14, 95% CI 0.74, 1.77 ). Conclusion: Although limited by a low frequency of use, VAD or IABP alone was associated with improved outcome for post arrest care. However, in a multivariable analysis, VAD use was not associated with an independent improvement in post arrest survival.
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