Search

Patients with primary aldosteronism (PA) have increased morbidity and mortality compared to those with essential hypertension. Accurate detection of lateralized PA is important so that affected patients can receive potentially curative adrenalectomy. However, around 40% of patients with lateralized PA have "normal" adrenal glands on computed tomography (CT). Additional independent review of imaging has been shown to improve diagnostic accuracy in many areas of imaging. Therefore, the authors sought to establish if multi-reader re-assessment of previously reported normal CT scans would result in increased detection of surgically remediable disease. The authors found that re-assessment of CT imaging by one, two, or three additional radiologists (or a combination thereof) slightly increased the detection of lateralized disease, but these differences were not statistically significant (p > .05). Readers had low inter-observer agreement (kappa = 0.17). If detection of a discrete nodule on CT was made a prerequisite for adrenal vein sampling (AVS), a second read by another reviewer would still result in an excess of missed cases (84.2%, 36.8%, and 65.8%, respectively, for each of the three independent reviewers). Therefore, a "normal" CT does not preclude the possibility of lateralized PA. Adrenal vein sampling should still be strongly considered wherever available and whenever surgery is considered for treatment of PA, irrespective of CT findings., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Mouse mammary tumor virus (MMTV) is a betaretrovirus that plays a causal role in the development of breast cancer and lymphoma in mice. Closely related sequences that share 91-99% nucleotide identity with MMTV have been repeatedly found in humans with neoplastic and inflammatory diseases. Evidence for infection with a betaretrovirus has been found in patients with breast cancer and primary biliary cholangitis and referred to as the human mammary tumor virus and the human betaretrovirus (HBRV), respectively. Using the gold standard technique of demonstrating retroviral infection, HBRV proviral integrations have been detected in cholangiocytes, lymph nodes, and liver of patients with primary biliary cholangitis. However, the scientific biomedical community has not embraced the hypothesis that MMTV like betaretroviruses may infect humans because reports of viral detection have been inconsistent and robust diagnostic assays are lacking. Specifically, prior serological assays using MMTV proteins have produced divergent results in human disease. Accordingly, a partial HBRV surface (Su) construct was transfected into HEK293 to create an ELISA. The secreted HBRV gp52 Su protein was then used to screen for serological responses in patients with breast cancer and liver disease. A greater proportion of breast cancer patients ( n  = 98) were found to have serological reactivity to HBRV Su as compared to age- and sex-matched control subjects (10.2% versus 2.0%, P =0.017, OR = 5.6 [1.25-26.3]). Similarly, the frequency of HBRV Su reactivity was higher in patients with primary biliary cholangitis ( n   =  156) as compared to blood donors (11.5% vs. 3.1%, P =0.0024, OR = 4.09 [1.66-10.1]). While the sensitivity of the HBRV Su ELISA was limited, the assay was highly specific for serologic detection in patients with breast cancer or primary biliary cholangitis, respectively (98.0% [93.1%-99.7%] and 97.0% [93.4%-98.6%]). Additional assays will be required to link immune response to betaretrovirus infection and either breast cancer or primary biliary cholangitis., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Guangzhi Zhang et al.)

Background: Central pontine and extrapontine myelinolysis (CPEPM) is a rare but potentially fatal complication after orthotopic liver transplantation (OLT). The aim of this study was to identify risk factors for development of CPEPM after OLT and to assess patient outcome., Methods: We reviewed the clinical data of 1,378 patients who underwent OLT between 1987 and 2009 in Geneva, Switzerland and Edmonton, Canada. Nineteen patients (1.4 %) developed CPEPM. We compared their characteristics with control patients, matched by age, gender, date of OLT, and MELD score., Results: The 19 patients with CPEPM (7F, mean age 52.1 ± 2 years) had a mean MELD score of 26 ± 2.2. Before OLT, patients who develop CPEPM presented more frequently low (<130 mmol/l; p < 0.04) and very low (<125 mmol/l; p < 0.009) sodium than controls. In patients developing CPEPM, the number of platelet units and fresh frozen plasma transfused during surgery was higher (p = 0.05 and 0.047), hemorrhagic complications were more frequent after OLT (p = 0.049), and variations of sodium before and after OLT were higher (p = 0.023). The association of >2 of these conditions were strongly associated with CPEPM (p = 0.00015). Mortality at 1 year of patients developing CPEPM was higher (63 vs. 13 %, p < 0.0001)., Conclusions: High MELD score patients undergoing OLT, receiving massive perfusions of Na-rich products, experiencing surgery-related hemorrhagic complication and important fluctuations of Na are at risk of developing CPEPM. Therefore careful monitoring of natremia in the perioperative period and use of water-free perfusion in case of massive blood-products transfusion are critical points of this patient management.

Background & Aims: A human betaretrovirus resembling the mouse mammary tumor virus (MMTV) has been characterized in primary biliary cirrhosis (PBC) and associated with aberrant pyruvate dehydrogenase complex (PDC)-E2-like expression. As MMTV is prevalent in mice as either an exogenous or endogenous infection, we tested the hypothesis that MMTV is linked with anti-mitochondrial antibody (AMA) production in models with severe immune dysfunction., Methods: Evidence for MMTV was assessed in the liver and spleen of mice by PCR and immunochemistry and PDC-E2-like protein by immunochemistry. ELISA and Western blot were used to investigate AMA and anti-MMTV antibody production., Results: Increased MMTV gag or env expression was detected in the livers of AMA producing mice including NOD.c3c4, CD4 directed dominant negative TGF-β receptor II and IL-2 receptor α knockout mice as well as the NOD parental strain when compared to healthy strains and biliary disease control mice. The NOD.c3c4 mice expressed MMTV surface and capsid proteins and aberrant PDC-E2-like protein in the bile ducts, whereas IL-2 receptor α knockout mice, NOD.c3c4 and the NOD mice expressed MMTV proteins and aberrant PDC-E2-like protein in the spleen. A significant correlation between anti-MMTV antibody production and AMA production was observed in the sera of NOD and NOD.c3c4 mice (p<0.0001)., Conclusions: The association of betaretroviral protein production and aberrant PDC-E2-like protein expression in the NOD.c3c4, NOD, and the IL-2 receptor α knockout mice is comparable to observations in patients with PBC. The correlation of AMA and anti-MMTV suggests the hypothesis that MMTV infection may trigger the production of AMA., (Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.)