A large-scale genome-wide gene expression analysis in peripheral blood identifies very few differentially expressed genes related to antidepressant treatment and response in patients with major depressive disorder

A better understanding of the biological factors underlying antidepressant treatment in patients with major depressive disorder (MDD) is needed. We perform gene expression analyses and explore sources of variability in peripheral blood related to antidepressant treatment and treatment response in patients suffering from recurrent MDD at baseline and after 8 weeks of treatment. The study includes 281 patients, which were randomized to 8 weeks of treatment with vortioxetine (N = 184) or placebo (N = 97). To our knowledge, this is the largest dataset including both gene expression in blood and placebo-controlled treatment response measured by a clinical scale in a randomized clinical trial. We identified three novel genes whose RNA expression levels at baseline and week 8 are significantly (FDR < 0.05) associated with treatment response after 8 weeks of treatment. Among these genes were SOCS3 (FDR = 0.0039) and PROK2 (FDR = 0.0028), which have previously both been linked to depression. Downregulation of these genes was associated with poorer treatment response. We did not identify any genes that were differentially expressed between placebo and vortioxetine groups at week 8 or between baseline and week 8 of treatment. Nor did we replicate any genes identified in previous peripheral blood gene expression studies examining treatment response. Analysis of genome-wide expression variability showed that type of treatment and treatment response explains very little of the variance, a median of <0.0001% and 0.05% in gene expression across all genes, respectively. Given the relatively large size of the study, the limited findings suggest that peripheral blood gene expression might not be the best approach to explore the biological factors underlying antidepressant treatment.Subject terms: Predictive markers, Depression     

Seroepidemiology of hepatitis E in patients on haemodialysis in Croatia

International Urology and Nephrology - Data on the seroprevalence of hepatitis E virus (HEV) in heamodialysis (HD) patients are conflicting, ranging from 0 to 44%. The aim of this study was to...     

Contrast agents in abdominal imaging: current and future directions

Magnetic resonance imaging is an established imaging method for the evaluation of the abdomen. Accurate assessment of the liver, spleen, pancreas, bile ducts, vascular structures, and retroperitoneal organs (eg, the kidneys, the collecting system, and the adrenals) are possible on MR imaging. The intravenous administration of MR contrast agents can frequently improve the examination and provide more specific diagnoses. The advent of more specific, "hepatobiliary" contrast agents has further improved the differential diagnostic process, particularly for MR imaging of the liver. The availability of orally administered MR contrast agents has further extended the range of abdominal applications, making MR imaging of the small bowel and the colon established imaging procedures.     

Anosmia induced with alpha interferon in a patient with chronic hepatitis C

This is a report of the alpha interferon-induced acute anosmia in a 37-year old patient with chronic hepatitis C. This exceptionally rare side-effect started in our patient as a smelling problem 2 weeks after the initiation of the therapy, and anosmia is still present 13 months after the discontinuation of the alpha interferon. We presume that neurotoxic mechanism could be responsible for this side-effect.     

A prospective controlled trial on effect of percutaneous transluminal angioplasty on functioning arteriovenous fistulae survival

Balloon angioplasty (PTA) is an established treatment modality for stenosis in dysfunctional arteriovenous fistulae (AVF), although most studies showing efficacy have been retrospective, uncontrolled, and nonrandomized. In addition, it is unknown whether correction of stenosis not associated with significant hemodynamic, functional, and clinical abnormality may improve survival in AVF. This study was a prospective controlled open trial to evaluate whether prophylactic PTA of stenosis not associated with access dysfunction improves survival in native, virgin, radiocephalic forearm AVF. Sixty-two stenotic, functioning AVF, i.e., able to provide adequate dialysis, were enrolled in the study: 30 were allocated to control and 32 to PTA. End points of the study were either AVF thrombosis or surgical revision due to reduction in delivered dialysis dose. Kaplan-Meier analysis showed that PTA improved AVF functional failure-free survival rates (P = 0.012) with a fourfold increase in median survival and a 2.87-fold decrease in risk of failure. Cox proportional hazard model identified PTA as the only variable associated with outcome (P = 0.012). PTA induced an increase in access blood flow rate (Qa) by 323 (236 to 445) ml/min (P < 0.001), suggesting that improved AVF survival is the result of increased Qa. PTA was also associated with a significant decrease in access-related morbidity by approximately halving the risk of hospitalization, central venous catheterization, and thrombectomy (P < 0.05). This study shows that prophylactic PTA of stenosis in functioning forearm AVF improves access survival and decreases access-related morbidity, supporting the usefulness of preventive correction of stenosis before the development of access dysfunction. It also strongly supports surveillance program for early detection of stenosis.     

Gentamicin-induced hair cell death is not dependent on the apoptosis receptor Fas

OBJECTIVES/HYPOTHESIS: The hair cells are the most vulnerable elements in the cochlea, and damage to them is the most common cause of sensorineural hearing loss. Understanding the intracellular events that lead to the death of hair cells is a key to developing protective strategies. The Fas death receptor-mediated apoptotic pathway is well studied and plays an important role in the elimination of damaged cells in a number of different cellular systems. We have studied the role of the Fas receptor in aminoglycoside-mediated toxicity in vitro. We employed the MRL/MpJ-Fas mouse, which does not express a functional Fas receptor. STUDY DESIGN: Response of Fas-deficient hair cells to gentamicin was compared with the response of normal hair cells in vitro. METHODS: Basal turn organ of Corti explants from p3-5 mice were maintained in tissue culture and treated with gentamicin for 72 hours. The explants were fixed and were stained with phalloidin, and counting was performed. RESULTS: There was no difference in hair cell loss between Fas mutant mice and control MRL/MpJ mice with a functional Fas receptor. CONCLUSION: The gentamicin-mediated hair cell death is not dependent on a functional Fas receptor.     

Lithium treatments: single and multiple daily dosing

OBJECTIVE: To review the feasibility and effectiveness of single daily dosing of lithium in patients with affective disorder and to discuss advantages and disadvantages of this schedule of administration. METHOD: A comprehensive search of the literature was conducted using a combination of electronic databases and a search of reference lists and relevant journals. English-language articles were selected for the review if they discussed the issues comparing multiple and single daily dosing schedules of lithium. RESULTS: We found 9 comparative studies. Single daily dosing of lithium causes transient higher peak lithium concentrations; however, no comparative study revealed a significant difference in side effects between multiple and single daily dosing groups. Numerous reports concluded that taking lithium in a single dose prevents, or at least limits, the increase in urine output (and the reduction of osmolality) and subsequent thirst. There is no evidence that a single lithium dosing schedule preserves glomerular function. CONCLUSION: According to the presented data, it could be reasonable to use lithium as a single evening dose in patients who can tolerate this schedule because no studies have suggested any benefit from administration of multiple daily doses. Possible advantages of single daily dosing, especially in improved compliance, could not be veiled by disadvantages of transient and mild postabsorptive side effects.     

Is there a reason for concern or is it just hype? – A systematic literature review of the clinical consequences of switching from originator biologics to biosimilars

Introduction: While prescribing biosimilars to patients naive to a biologic treatment is a well-accepted practice, switching clinically stable patients from an originator to a biosimilar is an issue for clinicians. Well-designed clinical trials and real-world data which study the consequences of switching from an originator biologic treatment to its biosimilar alternative are limited, especially for monoclonal antibodies.

Areas covered: A systematic literature review was conducted on PubMed to identify evidence of the consequences of switching from original biologics to biosimilars. References of included papers were also scrutinized. After a title-, abstract- and full text screening, out of the 153 original hits and 77 additional ones from screening the references, 58 papers (12 empirical papers, 5 systematic reviews and 41 non-empirical papers) were included.

Expert opinion: Preventing patients on biologic medicines from switching to biosimilars due to anticipated risks seems to be disproportional compared to the expected cost savings and/or improved patient access. Indeed, it is the opinion of the authors that the concern of switching to biosimilars is overhyped.