ICPC-2--international classification of primary health care and its application in Croatian health care

A consensus reached by the medical profession, Croatian Institute of Health Insurance, Croatian Institute of Public Health, and Ministry of Health constitutes a solution to the problem of a data standard required in building an information system for primary health care. This consists of accepting ICPC-2 as a data standard for our Family Medicine, Pediatrics and Women's Health. The classification structure of the International Classification of Primary Care allows, recommends and urges that special codes be established by individual states or local authorities when registering patients' reasons for seeking medical aid or medical procedures. Namely, it urges the authorities to set the codes for such reasons about which a state or local agreement or determination has been made. This is the first public presentation of the proposal Croatia's Additions to the International Classification of Primary Care. They are essential to its implementation in our health insurance, health statistics and medical informatics.     

The MCP-1 -2518 (A to G) single nucleotide polymorphism is not associated with myocardial infarction in the Czech population

Monocyte chemoattractant protein (MCP)-1 is the key chemokine in the process of atheroslerotic vascular inflammation. Examining already reported association between coronary artery disease (CAD) and the SNP A/G in the MCP-1 gene (position -2518), 139 Czech patients with CAD manifested as myocardial infarction (MI) and 359 unrelated healthy control (C) subjects were genotyped by PCR-SSP. Genotype and allele frequencies were not different in MI and C groups (allele G: MI, 20.5%; C, 23.8%, OR = 0.8, P > 0.05). No differences were detected when the patients were subdivided based on sex or the age of MI first occurrence. Further, no relationship was observed between circulating MCP-1 levels and carriage of the G allele. The data do not support a role for the MCP-1 -2518 single nucleotide polymorphism in susceptibility to CAD manifested by myocardial infarction.     

Cardiac Rhythm and Conduction Disturbances: What is the Role of Autoimmune Mechanisms?

The immunopathogenesis of cardiac rhythm and conduction disorders has been underestimated. Therefore, the aim of this review is to analyze the current data and controversial issues in this area. The incidence of autoantibodies to human conducting tissue has been analyzed in sick sinus syndrome, bradyarrhythmia, and hypersensitive carotid sinus syndrome. Patients with anti-sinus node antibodies (ASNab) have a 10-fold higher risk of developing sick sinus syndrome, compared to age-matched controls. The risk of acquiring an atrioventricular block was up to 3-fold in patients with anti-atrioventricular node antibodies (AAVNab) in comparison to controls. The incidence of anti His antibodies (AHISab) was low both in patients and controls. Anti-cardiac Purkinje cell antibodies (ACPCab) seemed to be an epiphenomenon and not a pathogenetic marker of conduction disorders. In congenital heart block association with HLA-B27 and HLA-DR3 is a possible prerequisite in the pathophysiology of the disease, although transplacental passage of various antibodies and immune complexes is widely recognized. The main autoantibodies detected both in children with congenital heart block and their mothers are anti-Ro/SS-A and anti-La/SS-B antibodies. The cross-reactivity of laminin with anti-La antibodies could be important in the initiation of the autoimmune process. Autoantibodies against adrenoceptors and muscarinic cholinergic receptors of neonatal heart and human endogenous retrovirus-3 expressed in fetal cardiac tissue could also play a role in the pathogenesis of the congenital heart block. Of note, apoptosis could be one of the possible mechanisms of the progression of the congenital conduction disturbances to the complete heart block. In addition, evidence is compiling that cellular activation and cellular cytotoxicity specific for a given target tissue appears to be at least equally important in the pathogenesis of the disease as the humoral response. In conclusion, the immunopathogenesis of certain cardiac rhythm and conduction disorders is well established in sick sinus syndrome, congenital heart block, and connective tissue diseases. ASNab, AAVNab, anti-Ro/SS-A, and anti-La/SS-B antibodies can be regarded as diagnostic and prognostic markers.     

Linking non‐invasive parametric MRI with invasive physiological measurements (MR‐PHYSIOL): towards a hybrid and integrated approach for investigation of acute kidney injury in rats

Acute kidney injury of various origins shares a common link in the pathophysiological chain of events: imbalance between renal medullary oxygen delivery and oxygen demand. For in vivo assessment of kidney haemodynamics and oxygenation in animals, quantitative but invasive physiological methods are established. A very limited number of studies attempted to link these invasive methods with parametric Magnetic Resonance Imaging (MRI) of the kidney. Moreover, the validity of parametric MRI (pMRI) as a surrogate marker for renal tissue perfusion and renal oxygenation has not been systematically examined yet. For this reason, we set out to combine invasive techniques and non‐invasive MRI in an integrated hybrid setup (MR‐PHYSIOL) with the ultimate goal to calibrate, monitor and interpret parametric MR and physiological parameters by means of standardized interventions. Here we present a first report on the current status of this multi‐modality approach. For this purpose, we first highlight key characteristics of renal perfusion and oxygenation. Second, concepts for in vivo characterization of renal perfusion and oxygenation are surveyed together with the capabilities of MRI for probing blood oxygenation‐dependent tissue stages. Practical concerns evoked by the use of strong magnetic fields in MRI and interferences between MRI and invasive physiological probes are discussed. Technical solutions that balance the needs of in vivo physiological measurements together with the constraints dictated by small bore MR scanners are presented. An early implementation of the integrated MR‐PHYSIOL approach is demonstrated including brief interventions of hypoxia and hyperoxia.     

Inhibition of focal adhesion kinase enhances antitumor response of radiation therapy in pancreatic cancer through CD8+ T cells

Objective:Pancreatic ductal adenocarcinoma(PDAC)is a deadly malignancy,due in large part to its resistance to conventional therapies,including radiotherapy(RT).Despite RT exerting a modest antitumor response,it has also been shown to promote an immunosuppressive tumor microenvironment.Previous studies demonstrated that focal adhesion kinase inhibitors(FAKi)in clinical development inhibit the infiltration of suppressive myeloid cells and T regulatory(T regs)cells,and subsequently enhance effector T cell infiltration.FAK inhibitors in clinical development have not been investigated in combination with RT in preclinical murine models or clinical studies.Thus,we investigated the impact of FAK inhibition on RT,its potential as an RT sensitizer and immunomodulator in a murine model of PDAC.Methods:We used a syngeneic orthotopic murine model to study the effect of FAKi on hypofractionated RT.Results:In this study we showed that IN10018,a small molecular FAKi,enhanced antitumor response to RT.Antitumor activity of the combination of FAKi and RT is T cell dependent.FAKi in combination with RT enhanced CD8+T cell infiltration significantly in comparison to the radiation or FAKi treatment alone(P<0.05).FAKi in combination with radiation inhibited the infiltration of granulocytes but enhanced the infiltration of macrophages and T regs in comparison with the radiation or FAKi treatment alone(P<0.01).Conclusions:These results support the clinical development of FAKi as a radiosensitizer for PDAC and combining FAKi with RT to prime the tumor microenvironment of PDAC for immunotherapy.     

The Armenian healthcare system: recent changes and challenges

Background  Armenian healthcare reforms have been carried out since independence in 1991, but achieved their full scale starting in 1995–1996. Although the healthcare system has already been modified and changed for 10 years, there is a lack of research in this regard. Objectives  This paper aims to present the organization of the healthcare system in Armenia, its changes and challenges throughout the reform process. Methods  This paper is mainly based on a review of the relevant professional literature, a review and interpretation of legal acts in the healthcare field, and a review of research and assessment works done by several international and local organizations. Results  There are still large numbers of elements typical for the Soviet Semashko model in Armenian healthcare structures. Implemented reforms have separated the institutions of the public payer and the providers, but did not manage to change the model of financing to be based on compulsory insurance. The level of financing is similar to the average in Central and Eastern Europe, but is based mainly on out-of-pocket payments contributing to about 80% of all system resources. The informal payments reach even 45% of expenditures. The structure of hospital beds remains ineffective, and there are still no mechanisms of increasing the quality of services. Privatization has been applied, but the role of private providers is still limited. Conclusions  The reforms have not caused satisfactory improvement in healthcare performance, although the health indicators are better than at the beginning of the transformation period. The stability of the reforming processes in previous years as well as the engagement of international institutions is a chance for positive changes in the near future.