Antiphospholipid Antibodies and Vascular Thrombosis in Patients with Severe Forms of COVID-19.

Antiphospholipid antibodies (aPLA) are a laboratory criterion for the classification of antiphospholipid syndrome (APS) and are known to cause clinical symptoms such as vascular thrombosis or obstetric complications. It is suggested that aPLA may be associated with thromboembolism in severe COVID-19 cases. Therefore, we aimed to combine clinical data with laboratory findings of aPLA at four time points (admission, worsening, discharge, and 3-month follow-up) in patients hospitalized with COVID-19 pneumonia. In 111 patients with COVID-19 pneumonia, current and past history of thrombosis and pregnancy complications were recorded. Nine types of aPLA were determined at four time points: anticardiolipin (aCL), anti-ß2-glycoprotein I (anti- ß2GPI), and antiphosphatidylserine/prothrombin (aPS/PT) of the IgM, IgG, or IgA isotypes. During hospitalization, seven patients died, three of them due to pulmonary artery thromboembolism (none were aPLA positive). Only one of the five who developed pulmonary artery thrombosis was aPLA positive. Out of 9/101 patients with a history of thrombosis, five had arterial thrombosis and none were aPLA positive at admission and follow-up; four had venous thrombosis, and one was aPLA positive at all time points (newly diagnosed APS). Of these 9/101 patients, 55.6% were transiently aPLA positive at discharge only, compared to 26.1% without a history of thrombosis (p = 0.041). Patients with severe forms of COVID-19 and positive aPLA should receive the same dose and anticoagulant medication regimen as those with negative aPLA because those antibodies are mostly transiently positive and not linked to thrombosis and fatal outcomes.

2021 EULAR recommendations regarding lifestyle behaviours and work participation to prevent progression of rheumatic and musculoskeletal diseases.

OBJECTIVES: A European League Against Rheumatism taskforce was convened to review the literature and develop recommendations on lifestyle behaviours for rheumatic and musculoskeletal diseases (RMDs). METHODS: Six lifestyle exposures (exercise, diet, weight, alcohol, smoking, work participation) and seven RMDs (osteoarthritis, rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, systemic lupus erythematosus, systemic sclerosis, gout) were considered. The taskforce included health professionals in rheumatology, geriatricians, epidemiologists, public health experts, people with RMDs and exposure domain experts. Systematic reviews were conducted to gather available evidence, from which recommendations were developed. RESULTS: Five overarching principles and 18 specific recommendations were defined based on available evidence. The overarching principles define the importance of a healthy lifestyle, how lifestyle modifications should be implemented, and their role in relation to medical treatments. Exercise recommendations highlight the safety and benefits of exercise on pain and disability, particularly among people with osteoarthritis and axial spondyloarthritis. The diet recommendations emphasise the importance of a healthy, balanced diet for people with RMDs. People with RMDs and health professionals should work together to achieve and maintain a healthy weight. Small amounts of alcohol are unlikely to negatively affect the outcomes of people with RMDs, although people with rheumatoid arthritis and gout may be at risk of flares after moderate alcohol consumption. Smokers should be supported to quit. Work participation may have benefits on RMD outcomes and should be discussed in consultations. CONCLUSIONS: These recommendations cover a range of lifestyle behaviours and can guide shared decision making between people with RMDs and health professionals when developing and monitoring treatment plans.

Association of vocational interventions and work-related factors with disease and work outcomes in people with RMDs: A systematic review.

OBJECTIVE: A EULAR taskforce was convened to develop recommendations for lifestyle behaviours amongst people with rheumatic and musculoskeletal diseases (RMDs). This paper reviews the literature on work-related factors and disease-specific outcomes for people with osteoarthritis, rheumatoid arthritis (RA), systemic lupus erythematosus, axial spondyloarthritis (axSpA), psoriatic arthritis, systemic sclerosis (SSc) and gout. METHODS: Two separate systematic literature reviews (SLRs) were conducted. The first identified SLRs, published between 01/2013 and 09/2018. The second identified original observational and intervention studies published before 05/2019. Manuscripts were included if they assessed the effects of vocational interventions on disease-specific outcomes (i.e. clinical outcomes, patient-reported outcomes, and work outcomes) or if they assessed the association between work-related factors and these outcomes. Medline, Embase, Cochrane Library of systematic reviews and CENTRAL databases were searched. RESULTS: Two SLRs were identified including individuals with SSc and inflammatory arthritis. Subsequently, 23 original manuscripts were identified, with most of them (43.5%) including people with RA and no manuscripts on gout. Most observational studies evaluated the association between work-related factors and work outcomes while limited information was available on the impact of work on clinical outcomes. A few studies suggested that physically demanding jobs have a small detrimental effect on radiographic progression in axSpA and PsA. Intervention studies showed beneficial effects of vocational interventions for disease-specific outcomes, but with small effect sizes. CONCLUSION: Many studies indicated that work participation is not likely to be detrimental and, in some cases, may be beneficial for RMD-specific outcomes and should therefore receive attention within healthcare consultations.

Effects of diet on the outcomes of rheumatic and musculoskeletal diseases (RMDs): systematic review and meta-analyses informing the 2021 EULAR recommendations for lifestyle improvements in people with RMDs.

BACKGROUND: A EULAR taskforce was convened to develop recommendations for lifestyle behaviours in rheumatic and musculoskeletal diseases (RMDs). In this paper, the literature on the effect of diet on the progression of RMDs is reviewed. METHODS: Systematic reviews and meta-analyses were performed of studies related to diet and disease outcomes in seven RMDs: osteoarthritis (OA), rheumatoid arthritis (RA), systemic lupus erythematosus, axial spondyloarthritis, psoriatic arthritis, systemic sclerosis and gout. In the first phase, existing relevant systematic reviews and meta-analyses, published from 2013 to 2018, were identified. In the second phase, the review was expanded to include published original studies on diet in RMDs, with no restriction on publication date. Systematic reviews or original studies were included if they assessed a dietary exposure in one of the above RMDs, and reported results regarding progression of disease (eg, pain, function, joint damage). RESULTS: In total, 24 systematic reviews and 150 original articles were included. Many dietary exposures have been studied (n=83), although the majority of studies addressed people with OA and RA. Most dietary exposures were assessed by relatively few studies. Exposures that have been assessed by multiple, well conducted studies (eg, OA: vitamin D, chondroitin, glucosamine; RA: omega-3) were classified as moderate evidence of small effects on disease progression. CONCLUSION: The current literature suggests that there is moderate evidence for a small benefit for certain dietary components. High-level evidence of clinically meaningful effect sizes from individual dietary exposures on outcomes in RMDs is missing.

Effects of physical exercise and body weight on disease-specific outcomes of people with rheumatic and musculoskeletal diseases (RMDs): systematic reviews and meta-analyses informing the 2021 EULAR recommendations for lifestyle improvements in people with RMDs.

BACKGROUND: A European League Against Rheumatism (EULAR) taskforce was convened to develop recommendations for lifestyle behaviours in rheumatic and musculoskeletal diseases (RMDs). This paper reviews the literature on the effects of physical exercise and body weight on disease-specific outcomes of people with RMDs. METHODS: Three systematic reviews were conducted to summarise evidence related to exercise and weight in seven RMDs: osteoarthritis, rheumatoid arthritis, systemic lupus erythematosus, axial spondyloarthritis (axSpA), psoriatic arthritis, systemic sclerosis and gout. Systematic reviews and original studies were included if they assessed exercise or weight in one of the above RMDs, and reported results regarding disease-specific outcomes (eg, pain, function, joint damage). Systematic reviews were only included if published between 2013-2018. Search strategies were implemented in the Medline, Embase, Cochrane Library of systematic reviews and CENTRAL databases. RESULTS: 236 articles on exercise and 181 articles on weight were included. Exercise interventions resulted in improvements in outcomes such as pain and function across all the RMDs, although the size of the effect varied by RMD and intervention. Disease activity was not influenced by exercise, other than in axSpA. Increased body weight was associated with worse outcomes for the majority of RMDs and outcomes assessed. In general, study quality was moderate for the literature on exercise and body weight in RMDs, although there was large heterogeneity between studies. CONCLUSION: The current literature supports recommending exercise and the maintenance of a healthy body weight for people with RMDs.

Smoking, alcohol consumption and disease-specific outcomes in rheumatic and musculoskeletal diseases (RMDs): systematic reviews informing the 2021 EULAR recommendations for lifestyle improvements in people with RMDs.

BACKGROUND: A EULAR taskforce was convened to develop recommendations for lifestyle behaviours in rheumatic and musculoskeletal diseases (RMDs). The aim of this paper was to review the literature on the relationship between smoking and alcohol consumption with regard to RMD-specific outcomes. METHODS: Two systematic reviews were conducted to identify systematic reviews and meta-analyses, published between 2013 and 2018, related to smoking and alcohol consumption in seven RMDs: osteoarthritis (OA), rheumatoid arthritis (RA), systemic lupus erythematosus, axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), systemic sclerosis (SSc) and gout. Two additional systematic reviews were performed to identify original longitudinal studies on smoking and alcohol consumption and disease-specific outcomes. RESULTS: Nine reviews and 65 original studies on smoking as well as two reviews and 14 original studies on alcohol consumption met the inclusion criteria. While most studies were moderate/poor quality, smoking was significantly associated with poorer outcomes: cardiovascular comorbidity; poorer response to RA treatment; higher disease activity and severity in early RA; axSpA radiographic progression. Results were heterogeneous for OA while there was limited evidence for PsA, SSc and gout. Available studies on alcohol mainly focused on RA, reporting a positive association between alcohol intake and radiographic progression. Five studies assessed alcohol consumption in gout, reporting a significant association between the number and type of alcoholic beverages and the occurrence of flares. CONCLUSION: Current literature supports that smoking has a negative impact on several RMD-specific outcomes and that moderate or high alcohol consumption is associated with increased risk of flares in RA and gout.

Longitudinal Analysis of Antiphospholipid Antibody Dynamics after Infection with SARS-CoV-2 or Vaccination with BNT162b2.

Antiphospholipid antibodies (aPL) comprise a group of autoantibodies that reflect prothrombotic risk in antiphospholipid syndrome (APS) but may also be present in a small proportion of healthy individuals. They are often transiently elevated in infections, including SARS-CoV-2, and may also be associated with vaccine-induced autoimmunity. Therefore, we aimed to investigate the dynamics of aPL in COVID-19 patients and in individuals (healthcare professionals-HCPs) after receiving BNT162b2 vaccine and to compare aPL levels and positivity with those found in APS patients. We measured solid-phase identifiable aPL, including anticardiolipin (aCL), anti-ß2 glycoprotein I (anti-ß2GPI), and anti-prothrombin/phosphatidylserine (aPS/PT) antibodies in 58 HCPs before and after vaccination (at 3 weeks, 3, 6, and 9 months after the second dose, and 3 weeks after the third booster dose), in 45 COVID-19 patients hospitalized in the ICU, in 89 COVID-19 patients hospitalized in the non-ICU (at admission, at hospital discharge, and at follow-up), and in 52 patients with APS. The most frequently induced aPL in COVID-19 patients (hospitalized in non-ICU) were aCL (50.6% of patients had positive levels at at least one time point), followed by anti-ß2GPI (21.3% of patients had positive levels at at least one time point). In 9/89 COVID-19 patients, positive aPL levels persisted for three months. One HCP developed aCL IgG after vaccination but the persistence could not be confirmed, and two HCPs developed persistent anti-ß2GPI IgG after vaccination with no increase during a 1-year follow-up period. Solid-phase aPL were detected in 84.6% of APS patients, in 49.4% of COVID-19 patients hospitalized in the non-ICU, in 33.3% of COVID-19 patients hospitalized in the ICU, and in only 17.2% of vaccinated HCPs. aPL levels and multiple positivity were significantly lower in both infected groups and in vaccinated individuals compared with APS patients. In conclusion, BNT162b2 mRNA vaccine may have induced aPL in a few individuals, whereas SARS-CoV-2 infection itself results in a higher percentage of aPL induction, but the levels, persistence, and multiple positivity of aPL do not follow the pattern observed in APS.

Strawberry (Fragaria ananassa duch.) Alba extract attenuates DNA damage in lymphocytes of patients with Alzheimer's disease.

Increased levels of oxidative stress and oxidative DNA damage are common features in the pathology of Alzheimer's disease (AD) found in neurons and peripheral cells like peripheral blood lymphocytes (PBL). Natural products such as strawberry cultivar Alba are an important source of bioactive nutrients that could help in lowering both the oxidative stress and DNA damage levels. The objective was to estimate the effects of Alba extract on DNA damage in peripheral blood lymphocytes of sporadic AD (aged 60-84 years) patients, and healthy elderly (aged 69-83 years) and young (aged 21-30 years) individuals in in vitro conditions. Comet assay was used as a sensitive technique for the evaluation of PBL DNA damage levels. Reduction of basal DNA damage level in PBL was shown in the young group after the incubation with Alba extract ranging from 25 to 200 µg/ml, with 100 µg/ml being the most effective concentration. Selected Alba extract of 100 µg/ml was further used for PBL treatment of AD and healthy elderly age matched group, displaying potential to significantly attenuate DNA damage levels in both groups (p < .05). Alba extract displayed biological activity against oxidative DNA damage, suggesting that its functional ingredients may have beneficial health effects. PRACTICAL APPLICATIONS: The data obtained in this preliminary study displayed that strawberry Alba extract is efficient against DNA damage induced by endogenous and exogenous oxidative stress in peripheral blood lymphocytes of Alzheimer`s disease in vitro. An active area of future research of Alba cultivar should be to determine the trials in in vivo systems. Our findings also suggest that Alba cultivar's functional ingredients potentially may have beneficial health effects in AD.

Complex Regional Pain Syndrome (Sudeck Atrophy) Prevention Possibility and Accelerated Recovery in Patients with Distal Radius at the Typical Site Fracture Using Polarized, Polychromatic Light Therapy.

Objective: Distal radius fracture (DRF) is one of the most frequent population fracture mostly affecting women, and frequently leading to complex regional pain syndrome (CRPS). Management of DRF and CRPS in gerontology is complex. The aim was to evaluate the use of polarized, polychromatic, low-energy light therapy combined with conventional treatment after DRF in gerontology and to follow up patients for CRPS emergence. Materials and methods: After plaster removal, female patients (n = 52) were divided into two groups. Group 1 (n = 26) was treated with exercises and cryotherapy on the wrist and dorsal hand (control). Group 2 (n = 26) was additionally treated with light therapy (Bioptron). Results: While pain decreased and supination and pronation improved in all patients after 15 days of therapy, pain reduction was accelerated and supination enhanced in the light therapy-treated group (p < 0.05). None of the patients in the light therapy-treated group developed CRPS during the 6-month follow-up, compared with four patients (15.4%) in the control group (p < 0.05). Complete hand fist-forming capacity was achieved in 19 patients (73.1%) in the light therapy-treated group compared with 16 patients (61.5%) in the control group (p > 0.05). Conclusions: Bioptron light therapy combined with conventional therapy improves patient outcome after DRF in gerontology, compared with conventional treatment alone.

Systemic Lupus Erythematosus Presenting as Acute Lupus Pneumonitis / Lupus eritematoso sistémico manifestado como neumonitis lúpica aguda

No disponible

The training type influence on male elite athletes' ventilatory function.

BACKGROUND/AIM: To assess and compare measured ventilatory volumes (forced expiratory volume in 1 s (FEV1), peak expirium flow (PEF) and maximal voluntary ventilation (MVV)), ventilatory function capacities (forced vital capacity (FVC) and vital capacity (VC)) and FEV1/VC ratio in a sample of power and endurance elite athletes and their age-matched and sex-matched sedentary control group. METHODS: A cross-sectional study was applied on male elite athletes (n=470) who were classified according to the type of the predominantly performed exercise in the following way: group 1: endurance group (EG=270), group 2: power athletes group (SG=200) and group 3: sedentary control group (CG=100). The lung VC, FVC, FEV1, FEV1/FVC ratio, PEF and MVV were measured in all of the observed subjects, who were also classified with regard to body mass index (BMI) and the percentage of the body fat (BF%). RESULTS: The CG had the highest BF% value, while the endurance group had the lowest BMI and BF% value, which is significantly different from the other two groups (p<0.05). The observed values of VC, FVC and FEV1 in the EG were significantly higher than those from the other two groups (p<0.05). There were no differences concerning the observed FEV1/FVC ratio. CONCLUSIONS: A continued endurance physical activity leads to adaptive changes in spirometric parameters (VC, FVC and FEV1), highlighting the fact that there is a need for specific consideration of different respiratory 'pattern' development in different types of sport, which also has to be further evaluated.

Adaptation and validation of the Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire for use in Serbia.

Rheumatoid arthritis (RA) is one of the most prevalent inflammatory rheumatic diseases. As it is a chronic and a lifelong destructive disease, the aim of the treatment is to reduce disability and improve quality of life. The Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire is a patient-reported outcome measure, specific to RA. To adapt and validate the RAQoL for use in Serbia, two translation panels were involved to produce the Serbian RAQoL. After successful translation, face and content validity was determined via cognitive debriefing interviews. The psychometric properties of the questionnaire were examined, including reliability and construct validity, by using the Nottingham Health Profile (NHP) as a comparator scale. The RAQoL was translated successfully and rated as applicable, relevant and comprehensive by respondents. The questionnaire had high internal consistency (alpha = 0.94 at both time points) and test-retest reliability (r = 0.92). Moderately high correlations were found between the RAQoL and physical mobility, pain and energy level sections of the NHP, providing evidence of convergent validity. The RAQoL was able to distinguish between patients grouped by perceived general health, incidence of flare-up and disease severity. The Serbian language version of the RAQoL showed strong evidence of reliability and validity and is recommended for use in clinical trials and routine general practice in RA.

Dry Olive Leaf Extract in Combination with Methotrexate Reduces Cell Damage in Early Rheumatoid Arthritis Patients-A Pilot Study.

The effects of co-administration of dry olive leaf extract (DOLE) with standard methotrexate (MTX) therapy on the parameters of cell damage and inflammation in patients with early and long-term rheumatoid arthritis (RA) were evaluated at baseline, 3 and 6 weeks. Patients were assigned to groups: the early phase RA group on MTX monotherapy (E MTX), and the two RA groups that received co-treatment with DOLE and MTX: early (E MTX + DOLE) and long-term phase patients (L-t MTX+ DOLE). Baseline values indicated increased parameters of cell damage and disruption of redox balance in all groups. After three weeks the E MTX + DOLE group maintained high catalase activity, exhibited decrease of lipid peroxidation and protein damage indicators-thiols and nitrites, while levels of DNA damage and pro-inflammatory interleukin-6 were significantly reduced. In E MTX group catalase activity remained unaltered while significant lipid peroxidation and DNA damage reductions were seen only after six weeks. L-t MTX + DOLE group showed only modest alterations of cell damage parameters during six weeks. Combined administration of DOLE with MTX contributes to faster reduction of cell damage, restores oxidative balance and improves interleukin-6 suppression during high disease activity in early phase RA, but not in long term patients. Copyright © 2016 John Wiley & Sons, Ltd.

THE REGULATION ROLE OF CAROTID BODY PERIPHERAL CHEMORECEPTORS IN PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL CONDITIONS.

INTRODUCTION: The major oxygen sensors in the human body are peripheral chemoreceptors. also known as interoreceptors- as connected with internal organs, located in the aortic arch and in the body of the common carotid artery. Chemoreceptor function under physiological conditions. Stimulation of peripheral chemoreceptors during enviromental hypoxia causes a reflex-mediated increased ventilation, followed by the increase of the muscle sympatic activity, aiming to maintain tissue oxygen homeostatis, as well as glucosae, homeostatis. Besides that, peripheral chemoreceptors interact with central chemoreceptors. responsible for carbon dioxide changes . and they are able to modulate each other. Chemoreceptor function in pathophysiological conditions. Investigations of respiratory function in many pathological processes, such as hypertension, obstructive sleep apnea, congestive heart failure and many other diseases that are presented with enhanced peripheral chemosensitivity and impaired functional sy mpatholysis ultimately determine the peripheral chemorcceptor role and significance of peripheral chemoreceptors in the process of those pathological conditions development. Considering this, the presumed influence of peripheral chemoreceptors is important in patients having the above mentioned pathology. CONCLUSION: The importance and the role of peripheral chemoreceptors in the course of the breathing control is still controversial, despite many scientific attempts to solve this problem. The main objective of this review is to give the latest data on the peripheral chemoreceptor role and to highlight the importance of peripheral chemoreceptors for maintaining of oxygen homeostasis in pateints with hypoxia caused by either physiological or pathological conditions.

Prevalence of rheumatoid arthritis in Serbia.

The aim of this study was to estimate the prevalence of rheumatoid arthritis (RA) in Serbia, using the European EULAR project methodology. In a detection phase, a previously translated and validated telephone Questionnaire was used by lay interviewers on 6,213 randomly selected telephone numbers representing urban population from four Serbian towns: Belgrade (north), Cacak, Uzice and Krusevac (south). Patients with suspected RA were called again by a rheumatologist. For patients with self-reported diagnosis and positive symptoms, patient's rheumatologist was contacted to confirm diagnosis; a complete rheumatologist examination was scheduled for those with positive symptoms only. Prevalence estimates were standardised for age and sex in relation to Serbian population (census 2002) and further to French population, according to EULAR project methodology. The response rate was 63.6 % (3,950 respondents). The rheumatologist called 571 people, among whom 23 RA cases were confirmed (21 diagnosed previously and 2 newly diagnosed during the examination). The prevalence was 0.16 % (95 % confidence interval CI 0.01-0.32) for men and 0.51 % (95 % CI 0.26-0.76) for women; a female-to-male ratio 3.18. The overall Serbian standardised prevalence was 0.35 % (95 % CI 0.18-0.52); when standardised on French population 0.34 % (95 % CI 0.17-0.51). The highest age-specific rate was in the 65-74-year age band. The EULAR prevalence study, conducted with similar methodology and design, showed that RA prevalence estimates in Serbia (0.34 %) were in accordance with France (0.31 %), but lower than in Lithuania (0.55 %).

Psoriatic arthritis classification criteria: Moll and Wright, ESSG and CASPAR -- a comparative study.

OBJECTIVES: to evaluate and compare Moll and Wright, ESSG and CASPAR criteria for psoriatic arthritis (PsA) classification. PATIENTS AND METHODS: Study comprised 356 patients (pts): 120 PsA pts in the investigated group, 123 pts with rheumatoid arthritis (RA) and 113 pts with non-inflammatory musculoskeletal symptoms (NIMS) in two control groups. Clinical diagnosis was the gold standard. Moll and Wright, ESSG and CASPAR criteria were applied to all pts. Sensitivity was calculated for each of the classification criteria sets; specificity was assessed in relation to RA and to NIMS groups, separately. Concordance between the investigated criteria sets was determined. RESULTS: Sensitivity was 91.7% for CASPAR, 85.8% for Moll and Wright and 63.3% for ESSG criteria. Specificity for Moll and Wright criteria was 100%, with relation to both RA and to NIMS group. Specificity of CASPAR criteria was 99.2% and 99.1%; specificity of ESSG criteria was 94.3% and 67%, with regard to RA and to NIMS groups, respectively. Significant fair concordance was found only between CASPAR and Moll and Wright criteria (k=0.379 p<0.001). CONCLUSIONS: The highest sensitivity had the CASPAR criteria, followed by Moll and Wright and ESSG. The highest specificity showed Moll and Wright criteria, followed by CASPAR and ESSG. CASPAR criteria demonstrated high specificity when applied to both NIMS and RA group. The lowest specificity was found for the ESSG criteria in relation to NIMS group. The only significant concordance was shown between CASPAR and Moll and Wright criteria.

United in prevention-electrocardiographic screening for chronic obstructive pulmonary disease.

CONFLICT OF INTEREST: NONE DECLARED. INTRODUCTION: P-wave abnormalities on the resting electrocardiogram have been associated with cardiovascular or pulmonary disease. So far, "Gothic" P wave and verticalization of the frontal plane axis is related to lung disease, particularly obstructive lung disease. AIM: We tested if inverted P wave in AVl as a lone criteria of P wave axis >70° could be screening tool for emphysema. MATERIAL AND METHOD: 1095 routine electrocardiograms (ECGs) were reviewed which yielded 478 (82,1%) ECGs with vertical P-axis in sinus rhythm. Charts were reviewed for the diagnosis of COPD and emphysema based on medical history and pulmonary function tests. CONCLUSION: Electrocardiogram is very effective screening tool not only in cardiovascular field but in chronic obstructive pulmonary disease. The verticality of the P axis is usually immediately apparent, making electrocardiogram rapid screening test for emphysema.

[The efficacy and tolerability of allopurinol dose escalation in patients with gout].

INTRODUCTION: Allopurinol is still the drug of choice for the long-term control of hyperuricemia in patients with gout. Objective The aim of the study was to investigate the efficacy and tolerability of different allopurinol doses used in order to attain a target serum uric acid concentration (SUc) of <6 mg/dl (360 micromol/L). METHODS: Prospective trial was carried out in patients with primary gout and normal renal function, no relevant liver disease, and SUc-lowering treatment indications involving 1-2 gout episodes per year, presence oftophus and/or chronic urate arthropathy or X-ray finding of erosions. The patients were administered allopurinol in a step-up dose scheme (beginning with 100 mg/ day then raised for 100 mg every four weeks) until therapeutic goal was achieved or development of adverse effects. RESULTS: Forty-one patients were enrolled in the study; 27 ended it so far.The treatment target was reached in 19/27 patients using allopurinol 300 mg/day (70.4%). After the increased dose up to 600 mg/day, the overall treatment success was reached in 25/27 patients (92.5%). Adverse drug reactions (ADRs) were evidenced in 12/27 patients; the most frequent ADRs were gouty flares. The mean SUc reduction from baseline 533.9+/-83.4 micromol/L to 346.9+/-87.9 micromol/L was obtained with allopurinol at a dose of 300 mg/day (p=0.000) as well as at a dose up to 600 mg/day (274.9+/-92.7 micromol/L) (p=0.000). CONCLUSIONS: Most of the investigated gouty patients attained target SUc <360 mmol/L at a 300 mg/day allopurinol dose. However, in 30% of patients further dose escalation up to 600 mg/day was needed but the increased dose was well tolerated, and the therapeutic goal was achieved even in 92.5% of patients. Such doses are in general well tolerated under the conditions of well preserved renal function.