Association Between AIRE Polymorphisms rs870881(C>T), rs1003854(T>C) and Rheumatoid Arthritis Risk: A Hungarian Case-control Study.

BACKGROUND/AIM: Autoimmune regulator (AIRE) is a transcription factor that plays pivotal role in controlling autoimmunity. In the thymus, it supports the presentation of peripheral tissue antigens to developing T cells, where recognition of these self-antigens negatively selects the autoimmune naïve T-cells by central tolerance. Studies demonstrated that single-nucleotide polymorphisms (SNPs) in AIRE alter transcription and propagate clonal survival of autoimmune T cells, therefore increase susceptibility to autoimmune diseases. This study intended to identify SNPs in exon and intron sequences that determine AIRE transcription, where their genotypes are associated with rheumatoid arthritis (RA) risk and clinical parameters. PATIENTS AND METHODS: After a thorough in silico research, we enrolled 100 patients with RA and 100 healthy controls to analyze the association of SNP rs870881(C>T) and rs1003854(T>C) in AIRE coding sequence with RA risk by using five different genetic models and selected clinical parameters. Multiplex quantitative polymerase chain reaction was used to determine allelic discrimination of SNPs. RA risk was assessed by odds ratios (ORs) and confidence intervals (CIs). RESULTS: In a recessive model of rs878081, minor allele TT homozygotes were associated with RA (p=0.032, OR=5.44, 95%CI=1.16-25.52); in a recessive model of rs1003854, minor allele CC homozygotes were associated with RA (p=0.047, OR=4.84, 95%CI=1.02-23.02). Higher C-reactive protein (CRP) levels in patients with RA were significantly associated with minor allele homozygotes in recessive and codominant genetic models (p=0.029 and p=0.043, respectively) of rs1003854. CONCLUSION: Genotypes for minor alleles of rs878081 and rs1003854 might be involved in RA pathogenesis and risk prediction.

Is Balneotherapy Protective Against Oxidative Stress? A Pilot Study.

BACKGROUND/AIM: This study aimed to research the effects of Harkány healing water on oxidative stress. The study was performed in a randomized, placebo-controlled, double-blind setup. PATIENTS AND METHODS: Twenty patients with psoriasis who underwent a 3-week-long inward balneotherapy-based rehabilitation were enrolled. Psoriasis Area and Severity Index (PASI) score and Malondialdehyde (MDA) - a marker of oxidative stress - were determined, on admission and before discharge. Patients were treated with dithranol. RESULTS: The mean PASI score - determined on admission and before discharge - decreased significantly after the 3-week-long rehabilitation 8.17 vs. 3.51 (p<0.001). The baseline MDA value of patients with psoriasis was significantly higher compared to controls (3.0±3.5 vs. 8.4±7.4) (p=0.018). MDA levels of patients receiving placebo water increased significantly compared to MDA levels of patients receiving healing water (p=0.049). CONCLUSION: The effectiveness of dithranol resides in the formation of reactive oxygen species. No increased oxidative stress was found in the patients treated with healing water, thus healing water seems to be protective against oxidative stress. However, further research is needed to confirm these preliminary results.

Effect of single end-range and not end-range Maitland mobilization on pressure pain threshold and functional measures in knee osteoarthritis: randomised, controlled clinical trial.

BACKGROUND: Hyperalgesia is attributed to peripheral and central sensitization in knee osteoarthritis (OA). Pressure pain threshold (PPT) is a relevant method for evaluating pain sensitivity in knee OA. The effect of end-range and not end-range Maitland mobilization for certain time-period on pain sensitivity has not been investigated in knee OA. AIM: The aim of this study was to investigate the effect of end-range and not end-range Maitland mobilization compared to sham manual therapy technique on PPT and functional measures. DESIGN: Randomised, controlled clinical trial. SETTING: Outpatient setting. POPULATION: Sixty-six patients with mild-to-severe knee OA. METHODS: Twenty-one patients (N.=21) received end-range Maitland mobilization (EMGr), twenty patients (N.=20) received not end-range Maitland mobilization (nEMGr) and twenty-two patients (N.=22) received sham manual therapy technique (CG). All interventions were performed once. Evaluation was conducted pre-, postintervention and on the following consecutive second days within a 6-day period. Outcomes were local and distant PPT, Timed Up and Go Test (TUG) and strength of passive resistance of knee at onset of pain. RESULTS: Local and distant PPT increased, TUG time and strength of passive resistance decreased immediately, local and distant PPT remained decreased in 6-day and 4-day period, TUG time remained decreased in 6-day period in EMGr (all changes P≤0.017). Local PPT increased immediately compared to baseline in nEMGr. In between group comparison, increase of local, distant PPT and strength of passive resistance endures on 2nd day, 4th day and postintervention, respectively, in EMGr compared to CG. EMGr compared to nEMGr presented significant difference on 6th day and 4th day in local and distant PPT, respectively (all changes P≤0.021). NEMGr presented no significant difference compared to CG on either follow-up. CONCLUSIONS: Single end-range Maitland mobilization is effective immediately and in 4-day period on pain sensitization and immediately on physical function compared to not end-range Maitland mobilization and sham manual therapy technique in knee OA. CLINICAL REHABILITATION IMPACT: Based on the present results, applying end-range Maitland mobilization is suggested on every second day to maintain alleviation of pain sensitization and increasing passive knee joint mobility effectively in knee OA.

Effect of HEAT therapy in patiEnts with type 2 Diabetes mellitus (HEATED): protocol for a randomised controlled trial.

INTRODUCTION: The burden of type 2 diabetes mellitus (T2DM) is increasing worldwide. Heat therapy has been found effective in improving glycaemic control. However, to date, there is a lack of randomised controlled studies investigating the efficacy of heat therapy in T2DM. Therefore, we aim to investigate whether heat therapy with natural thermal mineral water can improve glycaemic control in patients with T2DM. METHODS AND ANALYSIS: The HEAT therapy in patiEnts with type 2 Diabetes mellitus (HEATED) Study is a single-centre, two-arm randomised controlled trial being conducted at Harkány Thermal Rehabilitation Centre in Hungary. Patients with T2DM will be randomly assigned to group A (bath sessions in 38°C natural thermal mineral water) and group B (baths in thermoneutral water (30°C-32°C)). Both groups will complete a maximum of 5 weekly visits, averaging 50-60 visits over the 12-week study. Each session will last 30 min, with a physical check-up before the bath. At baseline, patients' T2DM status will be investigated thoroughly. Possible microvascular and macrovascular complications of T2DM will be assessed with physical and laboratory examinations. The short form-36 questionnaire will assess the quality of life. Patients will also be evaluated at weeks 4, 8 and 12. The primary endpoint will be the change of glycated haemoglobin from baseline to week 12. An estimated 65 patients will be enrolled per group, with a sample size re-estimation at the enrolment of 50% of the calculated sample size. ETHICS AND DISSEMINATION: The study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (818-2/2022/EÜIG). Written informed consent is required from all participants. We will disseminate our results to the medical community and will publish our results in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT05237219.

End-range Maitland mobilization decreasing pain sensitivity in knee osteoarthritis: randomized, controlled clinical trial.

BACKGROUND: Pressure pain threshold (PPT) is a widely applied method for measuring the magnitude of increased peripheral and central pain sensitivity causing hyperalgesia in knee osteoarthritis (OA). Although manual therapy techniques effects positively PPT, the effect of end-range Maitland mobilization has not been evaluated in knee OA. AIM: The aim of this study was to investigate the effect of end-range Maitland mobilization compared to sham manual therapy technique on PPT and function-related measures. DESIGN: The design of the study was of a randomized, controlled clinical trial. SETTING: Outpatient setting. POPULATION: Forty women with moderate-to-severe knee OA. METHODS: Twenty patients (N.=20) were randomly assigned to Maitland group (MG) and twenty patients (N.=20) to control group (CG). Patients in MG received single end-range Maitland mobilization while patients in CG received sham manual therapy technique. Assessment was performed at baseline, 30 minutes and after 1-week period. Outcome measures were PPT locally at knee and distant at ipsilateral extensor carpi radialis longus muscle, general pain during the previous week using the Visual Analogue Scale (VAS), Timed Up and Go Test (TUG) time associated with pain measured with Numerating Pain Rating Scale (NPRS) and strength of passive resistance of knee at onset of pain. RESULTS: Despite all outcome measures improved significantly postintervention, no changes were detected after 1-week period compared to postintervention in MG. No change of outcome measures was found also postintervention and after 1-week period compared to postintervention in CG. All postintervention results showed significant improvement in between-group comparison in favor of MG. However, after 1-week period, only strength of passive resistance revealed significant difference in between-group comparison in favor of MG (P<0.001). CONCLUSIONS: Although end-range Maitland mobilization has an immediate effect on decreasing peripheral and central pain sensitivity and improving function-related measures in knee OA, these changes may not cause clinically relevant effect based on data measured after 1-week period. CLINICAL REHABILITATION IMPACT: Investigating the time-course of end-range Maitland mobilization for determining the optimal treatment frequency during rehabilitation is suggested in knee OA.

A New and Validated, Randomised, Controlled Placebo Water Development Trial for Medicinal Water-based Research.

BACKGROUND/AIM: To develop and validate an easy-to-use and cheap method capable of producing placebo from tap water for medicinal water efficacy trials. PATIENTS AND METHODS: Patients were divided into two groups, medicinal water and tap water group. A single 20-minute-long treatment was performed in bathtubs. Patients were asked four times during the bath to tell if they were treated with medicinal water, tap water, or could not decide. Patients were scored, one point was given for each correct answer. RESULTS: A total of 174 patients were enrolled. No significant differences were found either between the average scores or the answers of the two groups. Being familiar with the Harkány medicinal water did not influence the rate of correct answers either. There was no statistically significant difference in the number of changes of opinions between the two groups. CONCLUSION: The used method is appropriate for producing a validated placebo from tap water.

Urinary orosomucoid: a new marker of cardiovascular risk in psoriatic patients?

PURPOSE: Psoriasis is one of the most common lifelong lasting dermatologic diseases. According to the latest studies, psoriatic patients have a higher risk of developing cardiovascular diseases. Psoriasis is considered as a systemic inflammatory disease. Several oxidative stress markers have been shown to be elevated in psoriasis. However, a panel of biomarkers has not been used yet. This study was aimed at exploring the connection between a panel of biomarkers (C-reactive protein, asymmetric dimethylarginine, uric acid, total antioxidant capacity, malondialdehyde, and orosomucoid [ORM]) and cardiovascular risk in psoriatic patients. PATIENTS AND METHODS: The inclusion criterion was the onset of psoriasis with skin lesions. Exclusion criteria were impaired renal function (eGFR<60 mL/min/1.73 m2), acute inflammations (urinary, respiratory, skin inflammation, etc), autoimmune disorders (rheumatoid arthritis, systemic lupus erythematosus, or inflammatory bowel disease), and any kind of biological antipsoriatic treatment. Patients with a medical history of myocardial infarction, coronary heart disease, stroke, transient ischemic attack, and carotid artery stenosis were also excluded. Biomarkers were measured by routine procedures, ELISA and HPLC. QRISK®2-2017 was used to assess 10-year risk of cardiovascular disease development. Psoriasis severity was measured by the Psoriasis Area and Severity Index. RESULTS: One hundred and fourteen psoriatic patients were enrolled. Only urinary orosomucoid and urinary orosomucoid/urinary creatinine (u-ORM/u-CREAT) ratio showed significant correlation with QRISK score (u-ORM, r=0.245; u-ORM/u-CREAT, r=0.309). When comparing mild psoriatic patients to moderate psoriatic patients, significant differences could only be found in u-ORM and u-ORM/u-CREAT ratio. CONCLUSION: There seems to be a connection between urinary ORM and cardiovascular risk. U-ORM and u-ORM/u-CREAT ratio could be used as an indicator of low-grade inflammation in mild and moderate psoriasis. However, it is the 10-year follow-up of cardiovascular events that will determine the usefulness of this biomarker panel.

[Utilization indicators of balneotherapy in Hungary]. / A gyógyfürdoellátások igénybevételi mutatói Magyarországon.

INTRODUCTION: The role of spa therapy is well defined and its importance has significantly increased in the healthcare but the utilization indicators of the implemented treatments are less known. AIM: The objective of our study was to analyze the utilization and the social insurance indicators of the healthcare publicly financed by health insurance in spa institutions. DATA AND METHODS: The data used for the analysis were derived from the funding database of the National Health Insurance Fund of Hungary. The period examined covered the years between 2009 and 2016. The spa treatment counts, social insurance expenses, the territorial inequalities in utilization, sex and age distribution of the treatments were examined. RESULTS: The treatment counts were the highest (7 349 587) in 2009 and they gradually decreased with 6 558  204 treatments by 2012. 'Spa pool of medicinal water' treatment was the most common care in each year which incidence showed a downward trend during the past years: 2 544  617 treatments were performed in 2009 but 2016 showed only 1 898  338 treatments. We found the highest health insurance expenditures in 2016: 4.261 billion HUF or 13.8 EUR. In the previous years, there was a lower health insurance expenditure: in 2010 3.928 billion HUF (14.3 million EUR), in 2011 3.921 billion HUF (14.0 million EUR) and in 2012 3.875 billion HUF (13.4 million EUR). The utilization made the highest incidence of treatments in Csongrád county with 13 174/10 000 inhabitants and 8160 thousand HUF/10 000 inhabitants of social security subsidy in 2016. The lowest utilization counts for treatments were found in Nógrád county with 3233/10 000 inhabitants and 2192 thousand HUF/10 000 inhabitants of social security subsidy. The highest utilization indicators were found in the age group between 60 and 69 in the distribution of population and genders. CONCLUSION: In the utilization of spa therapy funded by health insurance fund, no significant change has occurred during the past years but territorial discrepancies can be seen in sex, age, and county breakdown. Orv Hetil. 2019; 160(Suppl 1): 22-28.

Transcutaneous Carbon Dioxide Treatment Is Capable of Reducing Peripheral Vascular Resistance in Hypertensive Patients.

AIM: We aimed to investigate the effects of a single carbon dioxide (CO2) treatment on arterial stiffness by monitoring the changes of aortic pulse-wave velocity (PWV) and aortic augmentation index (AIXao), which are indicators of arterial stiffness. PATIENTS AND METHODS: PWV and AIXao were measured by an invasively validated oscillometric device. The measurements of stiffness parameters were performed before the CO2 treatment, and at 1, 4 and 8 h after the first treatment. RESULTS: Thirty-one patients were included. No significant changes were found in PWV. AIXao decreased significantly 1 h and 4 h after CO2 treatment compared to baseline values (p=0.034 and p<0.001). AIXao increased 8 h after the CO2 treatment, but remained significantly lower than baseline AIXao values (p=0.016). CONCLUSION: CO2 treatment is capable of reducing peripheral vascular resistance. We hypothesize that CO2 is not only a temporal vasodilator but is also capable of activating vasodilation pathways.

Urinary Orosomucoid A Potential Marker Of Inflammation In Psoriasis.

Background: Psoriasis is one of the most common chronic, life-long dermatologic diseases, which has considerable negative effects on quality of life. Psoriasis is considered as a systemic inflammatory disease, thus acute phase proteins such as C-reactive protein (CRP) and orosomucoid (ORM) have been shown to play a role in its pathophysiology. This study was aimed to compare CRP, serum ORM (se-ORM) and urinary ORM (u-ORM) levels of psoriatic patients to healthy individuals. Methods: 87 psoriatic patients and 41 healthy individuals were enrolled. Simultaneously obtained venous blood and spot urine samples were analysed. High sensitivity CRP and se-ORM levels were determined by routine procedures on automated analyzers. Urinary ORM was measured by a novel automated turbidimetric assay. U-ORM was referred to urinary creatinine (u-ORM/u-CREAT, mg/mmol). Results: Significantly higher hsCRP (p<0.001) and u-ORM/u-CREAT (p=0.001) levels were found among psoriatic patients compared to controls. No significant differences were found between the groups regarding se-ORM levels. HsCRP, se-ORM and u-ORM/u-CREAT levels were significantly higher in patients with severe psoriasis than in mild and moderate cases (p<0.05). Conclusion: As a highly sensitive, easily available biomarker u-ORM shows itself capable of becoming a new inflammatory marker in psoriasis providing clinically useful information on disease severity.

Transcutaneous Carbon Dioxide Treatment Affects Heart Rate Variability - A Pilot Study.

BACKGROUND: The aim of this study was to investigate the effects of carbon-dioxide treatment on heart rate variability (HRV) parameters: mean RR interval (RRI), standard deviation of RR intervals (SDNN), root mean square of successive RR differences (RMSSD); and Porta and Guzik indices, as measures of heart rate asymmetry. MATERIALS AND METHODS: Twenty patients were enrolled (mean±SD, age=59±7.8 years). Measurements were performed before CO2 treatment, at the beginning of treatment, at 15 min of treatment, immediately after and 1 h after the treatment. RESULTS: Significant increase in SDNN was found 1 h after the treatment when compared to that before it (p=0.011). There were no significant changes in other parameters. CONCLUSION: CO2 treatment can influence the autonomic nervous system identified by SDNN changes. However, larger studies are required to confirm these results.

Balneotherapy in Psoriasis Rehabilitation.

BACKGROUND/AIM: This study aimed to report a balneotherapy-based psoriasis rehabilitation protocol and assess its effectivity. PATIENTS AND METHODS: Eighty psoriatic patients who underwent a 3-week-long inward balneotherapy-based rehabilitation were enrolled. Psoriasis Area and Severity Index (PASI) score and high sensitivity C-reactive protein (CRP) were determined on admission and before discharge. RESULTS: The mean PASI score and CRP level -determined on admission and before discharge-decreased significantly after the 3-week-long rehabilitation 7.15±7.3 vs. 2.62±3.05 (p<0.001) and 4.1±3.8 vs. 3.5±3.1 (p=0.026). A negative correlation was found between PASI delta and the number of spa therapies received (r=-0.228). CONCLUSION: After completing the 3-week-long spa therapy based rehabilitation, both PASI score and CRP levels showed improvement of psoriasis. The complex spa therapy used during the rehabilitation is an effective tool to reduce the symptoms of psoriasis and improve the patient's well-being.

Angiotensin-converting Enzyme Inhibition Improves the Effectiveness of Transcutaneous Carbon Dioxide Treatment.

AIM: To study the effect of carbon dioxide (CO2) therapy on the nitric oxide (NO) pathway by monitoring plasma asymmetric dimethylarginine (ADMA) concentrations. PATIENTS AND METHODS: Forty-seven hypertensive patients who underwent transcutaneous CO2 therapy were enrolled. Thirty healthy individuals were recruited for the control group. Blood samples were taken one hour before, as well as one hour, 24 hours and 3 weeks after the first CO2 treatment. Controls did not undergo CO2 treatment. Plasma ADMA levels were measured by ELISA. RESULTS: ADMA levels decreased significantly one hour after the first CO2 treatment compared to the baseline concentrations (p=0.003). Significantly greater reduction was found among patients in whom angiotensin converting enzyme inhibitors (ACEIs) were administered (p=0.019). CONCLUSION: The short- and long-term decrease of ADMA levels suggests that CO2 is not only a vasodilator, but also has a beneficial effect on the NO pathway. ACE inhibition seems to enhance the effect of CO2 treatment.

[Psoriasis and oxidative stress]. / A psoriasis és az oxidatív stressz.

Psoriasis is among the most common dermatological diseases worldwide. Its significance is emphasized by adverse effects on quality of life, caused by chronic pain, physical and psychical disability due to psoriatic plaques. Besides the development of psoriatic arthritis, which often causes permanent joint damage, former studies revealed an increased risk of inflammatory bowel disease, cardiovascular disease and certain types of cancer. Genetic predisposition and oxidative stress caused by exogenous and endogenous factors can contribute to abnormal differentiation and hyperproliferation of keratinocytes, accordingly the development and maintenance of psoriasis. Moreover, excessive oxidative stress can be responsible for the onset of psoriasis complications. After a brief pathophysiological summary the authors discuss the role of oxidative stress in the development of psoriasis and its complications through several well studied biomarkers (asymmetric dimethylarginine, malondialdehyde, superoxide dismutase, catalase). Orv. Hetil., 2016, 157(45), 1781-1785.

New Validated Signal-averaging-based Electrocardiography Method to Determine His-ventricle Interval.

BACKGROUND/AIM: The signal-averaging (SA) technique is used to record high-resolution electrocardiograms (HRECGs) showing cardiac micropotentials. We aimed to develop a non-invasive signal-averaging-based portable bedside device to determine His-ventricle interval. PATIENTS AND METHODS: After amplifying the HRECG recordings, signal duration and voltage can be measured up to four decimal precision. To validate our system, comparison of the invasively and non-invasively determined HV intervals has been performed in 20 patients. RESULTS: Our workgroup has developed a system capable of displaying and measuring cardiac micropotentials on storable ECG. Neither related paired-sample T-test (p=0.263) nor Wilcoxon's non-parametric signed ranks test (p=0.245) showed significant deviations of the HV intervals. Furthermore, related paired-sample T-test showed strong correlation (corr=0.910, p<0.001) between HV intervals determined by electrophysiology (EP) and non-invasive measurements. CONCLUSION: Our research group managed to assemble and validate an easy to use device capable of determining HV intervals even under ambulatory conditions.

Monitoring of L-Arginine and Endogenous Dimethylarginines in Survivor Septic Patients - A Pilot Study.

BACKGROUND/AIM: Nitric oxide (NO) pathway plays a major role in the development and advancement of inflammation. We aimed to design a study and investigate its feasibility to show the changes of L-arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), which are important regulators of the NO pathway. PATIENTS AND METHODS: Concentrations of L-arginine, ADMA and SDMA were measured by liquid chromatography-tandem mass spectrometry. Seventeen septic survival patients were enrolled and blood samples were obtained on the first, third and fifth day after the diagnosis of sepsis. Sixteen non-septic matched controls were recruited. RESULTS: ADMA levels on admission correlated well with sequential organ failure assessment (SOFA) score. During the follow-up, L-arginine/ADMA ratio increased significantly from day 1 to day 3 (p=0.005), then decreased from day 3 to day 5 (p=0.023). CONCLUSION: This study design seems feasible to investigate changes of L-Arginine, ADMA and SDMA in sepsis survival patients.

Visualising differences in professionals' perspectives on quality and safety.

BACKGROUND: The safety-and-quality movement is now two decades old. Errors persist despite best efforts, indicating that there are entrenched overt and perhaps less explicit barriers limiting the success of improvement efforts. OBJECTIVES AND HYPOTHESES: To examine the perspectives of five groups of healthcare workers (administrative staff, nurses, medical practitioners, allied health and managers) and to compare and contrast their descriptions of quality-and-safety activities within their organisation. Differences in perspectives can be an indicator of divergence in the conceptualisation of, and impetus for, quality-improvement strategies which are intended to engage healthcare professions and staff. DESIGN, SETTING AND PARTICIPANTS: Study data were collected in a defined geographical healthcare jurisdiction in Australia, via individual and group interviews held across four service streams (aged care and rehabilitation; mental health; community health; and cancer services). Data were collected in 2008 and analysed, using data-mining software, in 2009. RESULTS: Clear differences in the perspectives of professional groups were evident, suggesting variations in the perceptions of, and priorities for, quality and safety. CONCLUSIONS: The visual representation of quality and safety perspectives provides insights into the conceptual maps currently utilised by healthcare workers. Understanding the similarity and differences in these maps may enable more effective targeting of interprofessional improvement strategies.