Iron Status and Short-Term Recovery after Non-Severe Acute Myocarditis: A Prospective Observational Study.

Pathomechanisms responsible for recovery from acute myocarditis (MCD) or progression to non-ischemic cardiomyopathy have not been comprehensively investigated. Iron, positioned at the crossroads of inflammation and the energy metabolism of cardiomyocytes, may contribute to the pathophysiology of inflammatory myocardial disease. The aim of this study was to evaluate whether systemic iron parameters are related to myocardial dysfunction in MCD patients. We prospectively enrolled 42 consecutive patients hospitalized for MCD. Their iron status and their clinical, laboratory, and echocardiographic indices were assessed during hospitalization and during ambulatory visits six weeks after discharge. A control group comprising healthy volunteers was recruited. The MCD patients had higher serum ferritin and hepcidin and lower serum iron concentration and transferrin saturation (TSAT) than the healthy controls (all p < 0.01). Six weeks after discharge, the iron status of the MCD patients was already comparable to that of the control group. During hospitalization, lower serum iron and TSAT correlated with higher NT-proBNP (both p < 0.05). In-hospital lower serum iron and TSAT correlated with both a lower left ventricular ejection fraction (LVEF) and worse left ventricular global longitudinal strain at follow-up visits (all p < 0.05). In conclusion, in patients with acute MCD, iron status is altered and normalizes within six weeks. Low serum iron and TSAT are related to greater in-hospital neurohormonal activation and subtle persistent left ventricular dysfunction.

Primary Human Cardiomyocytes and Cardiofibroblasts Treated with Sera from Myocarditis Patients Exhibit an Increased Iron Demand and Complex Changes in the Gene Expression.

Cardiac fibroblasts and cardiomyocytes are the main cells involved in the pathophysiology of myocarditis (MCD). These cells are especially sensitive to changes in iron homeostasis, which is extremely important for the optimal maintenance of crucial cellular processes. However, the exact role of iron status in the pathophysiology of MCD remains unknown. We cultured primary human cardiomyocytes (hCM) and cardiofibroblasts (hCF) with sera from acute MCD patients and healthy controls to mimic the effects of systemic inflammation on these cells. Next, we performed an initial small-scale (n = 3 per group) RNA sequencing experiment to investigate the global cellular response to the exposure on sera. In both cell lines, transcriptomic data analysis revealed many alterations in gene expression, which are related to disturbed canonical pathways and the progression of cardiac diseases. Moreover, hCM exhibited changes in the iron homeostasis pathway. To further investigate these alterations in sera-treated cells, we performed a larger-scale (n = 10 for controls, n = 18 for MCD) follow-up study and evaluated the expression of genes involved in iron metabolism. In both cell lines, we demonstrated an increased expression of transferrin receptor 1 (TFR1) and ferritin in MCD serum-treated cells as compared to controls, suggesting increased iron demand. Furthermore, we related TFR1 expression with the clinical profile of patients and showed that greater iron demand in sera-treated cells was associated with higher inflammation score (interleukin 6 (IL-6), C-reactive protein (CRP)) and advanced neurohormonal activation (NT-proBNP) in patients. Collectively, our data suggest that the malfunctioning of cardiomyocytes and cardiofibroblasts in the course of MCD might be related to alterations in the iron homeostasis.

Could an analysis of mean corpuscular volume help to improve risk stratification in non-anemic patients with acute myocardial infarction?

BACKGROUND: Nowadays, when the majority of patients with acute myocardial infarction (AMI) are treated with primary percutaneous coronary intervention and modern pharmacotherapy, risk stratification becomes a challenge. Simple and easily accessible parameters that would help in a better determination of prognosis are needed. The aim of the study was to estimate the prevalence of high mean corpuscular volume (MCV, defined as MCV > 92 fL) and to establish its prognostic value in non-anemic patients with AMI. METHODS: We retrospectively analyzed the data of 248 consecutive non-anemic patients hospitalized due to AMI (median age: 65 [59-76] years, men: 63%, ST segment elevation myocardial infarction: 31%, and median left ventricular ejection fraction [LVEF]: 50%). RESULTS: The prevalence of high MCV was 39 ± 6% (± 95% confidence interval) in the entire AMI population. High MCV was more prevalent in males, patients with low body mass index, non-diabetics and cigarette smokers (all p < 0.05). During the 180-day follow-up, there were 38 (15%) events, defined as another AMI or death. In a multivariable Cox proportional hazard model, female gender (p < 0.01), low LVEF (p < 0.001), previous AMI (p < 0.05), arterial hypertension (p < 0.05), and high MCV (p < 0.001) were prognosticators of pre-defined events. CONCLUSIONS: In non-anemic patients with AMI, high MCV is an independent prognostic factor of poor outcome defined as another AMI or death.

Stratifying risk for progression in IgA nephropathy: how to predict the future?

INTRODUCTION:  IgA nephropathy (IgAN) is characterized by a highly heterogeneous clinical course, which results in controversies regarding the assessment of individual prognosis and establishing the optimal treatment approach. OBJECTIVES:  The aim of the present study was to define risk factors for IgAN progression. We evaluated histopathological features derived from the Oxford classification of IgAN and additional, non­Oxford biopsy findings, as well as baseline and follow­up clinical data. PATIENTS AND METHODS:  We conducted a single­center retrospective study on 52 patients with biopsy­proven IgAN. The endpoint was an increase in serum creatinine levels of 50% from baseline. RESULTS:  Eight subjects (12%) reached the endpoint. Poor renal outcome was independently related to time­average proteinuria (TA­P) exceeding 2.0 g/d (P = 0.047), estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73 m2 (P = 0.01), history of tonsillectomy (P = 0.01), and crescent lesions in renal biopsy (P = 0.03). High global sclerosis index (GSI) (P = 0.009), TA­P (P = 0.03), and the presence of microscopic hematuria (P = 0.03) were independent predictors of a more rapid rate of renal function loss, assessed by the velocity of eGFR decline. Of the variables included in the Oxford classification, only interstitial fibrosis and tubular atrophy proved to have prognostic value, as revealed by a univariate, but not multivariate Cox regression analysis. CONCLUSIONS:  The extent of proteinuria during follow­up and impaired renal function at the time of diagnosis remain the most significant clinical prognostic factors in IgAN. We also report additional, non­Oxford histopathological features that can be used for risk stratification in IgAN, including the GSI and the presence of crescents.  

[Analysis of severe and threefold atypical and serious course of catatonic-paranoid psychosis]. / Analiza ciezkiego i potrójnie nietypowego przebiegu psychozy katatoniczno-paranoidalnej.

The paper describes the difficult course of catatonic-paranoid psychosis which began with symptoms similar to the myasthenia. The growing symptoms of catatonia (in this oral mechanisms with the compulsion of mastication, injuring with teeth of the mouth, tongue biting and damage, such as lockjaw) brought about choking which was followed by aspiration pneumonia. The patient had to have pharmacological coma induced, along with muscle relaxation and artificial ventilation in the conditions of the intensive care department. Despite treatment with high doses of neuroleptics, the repeated trials of bringing the patient out from the coma caused recurrence of the catatonic symptoms. A decision was made to go along with electroconvulsive therapy. During one of the ECT treatments there were complications in the form of circulation cessation which required defibrillation. The paper contains basic information about the serious complications of the electroconvulsive therapy. It moreover carries out the critical analysis of the whole treatment period.