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ObjectivesTo disseminate and assess the level of acceptability and applicability of the European Alliance of Associations for Rheumatology (EULAR) recommendations for patient education among professionals in rheumatology across Europe and three Asian countries and identify potential barriers and facilitators to their application.MethodsA parallel convergent mixed-methods design with an inductive approach was used. A web-based survey, available in 20 different languages, was distributed to health professionals by non-probability sampling. The level of agreement and applicability of each recommendation was assessed by (0–10) rating scales. Barriers and facilitators to implementation were assessed using free-text responses. Quantitative data were analysed descriptively and qualitative data by content analysis and presented in 16 categories supported by quotes.ResultsA total of 1159 completed the survey; 852 (73.5%) were women. Most of the professionals were nurses (n=487), rheumatologists (n=320), physiotherapists (n=158). For all recommendations, the level of agreement was high but applicability was lower. The four most common barriers to application were lack of time, lack of training in how to provide patient education, not having enough staff to perform this task and lack of evaluation tools. The most common facilitators were tailoring patient education to individual patients, using group education, linking patient education with diagnosis and treatment and inviting patients to provide feedback on patient education delivery.ConclusionsThis project has disseminated the EULAR recommendations for patient education to health professionals across 23 countries. Potential barriers to their application were identified and some are amenable to change, namely training patient education providers and developing evaluation tools.

Cardiovascular (CV) morbidity, mortality and metabolic syndrome are associated with rheumatoid arthritis (RA). A recent trial has suggested increased risk of major CV events (MACE) upon the Janus kinase (JAK) inhibitor tofacitinib compared with anti-tumor necrosis factor α (TNF-α) therapy. In our study, we evaluated lipids and other metabolic markers in relation to vascular function and clinical markers in RA patients undergoing one-year tofacitinib therapy.Thirty RA patients treated with either 5 mg or 10 mg bid tofacitinib were included in a 12-month follow-up study. Various lipids, paraoxonase (PON1), myeloperoxidase (MPO), thrombospondin-1 (TSP-1) and adipokine levels, such as adiponectin, leptin, resistin, adipsin and chemerin were determined. In order to assess flow-mediated vasodilation (FMD), common carotid intima-media thickness (IMT) and arterial pulse-wave velocity (PWV) ultrasonography were performed. Assessments were carried out at baseline, and 6 and 12 months after initiating treatment.One-year tofacitinib therapy significantly increased TC, HDL, LDL, APOA, APOB, leptin, adipsin and TSP-1, while significantly decreasing Lp(a), chemerin, PON1 and MPO levels. TG, lipid indices (TC/HDL and LDL/HDL), adiponectin and resistin showed no significant changes. Numerous associations were found between lipids, adipokines, clinical markers and IMT, FMD and PWV (JAK inhibition by tofacitinib exerts balanced effects on lipids and other metabolic markers in RA. Various correlations may exist between metabolic, clinical parameters and vascular pathophysiology during tofacitinib treatment. Complex assessment of lipids, metabolic factors together with clinical parameters and vascular pathophysiology may be utilized in clinical practice to determine and monitor the CV status of patients in relation with clinical response to JAK inhibition.

Background The outcome of rheumatoid arthritis (RA) should be determined early. Rapid radiological progression (RRP) is > or = 5 units increase according to the van der Heijde-Sharp score within a year. The risk of RRP can be estimated by a matrix model using non-radiographic indicators, such as C-reactive protein (CRP), rheumatoid factor (RF) and swollen joint count (SJC). Patients and methods A non-interventional, cross-sectional, retrospective study was conducted in eleven Hungarian arthritis centres. We assessed RRP risk in biologic-naïve RA patients with the prevalence of high RRP risk as primary endpoint. RRP was calculated according to this matrix model. As a secondary endpoint, we compared RRP in methotrexate (MTX) responders vs non-responders. Results We analyzed data from 1356 patients. Mean CRP was 17.7 mg/l, RF was 139.3 IU/ml, mean 28-joint disease activity score (DAS28) was 5.00 and mean SJC was 6.56. Altogether 18.2% of patients had high risk (≥40%) of RRP. RA patients with high RRP risk of RRP (n = 247) had significantly lower age compared to those with RRP

Summary Janus kinase (JAK) inhibitors are used to treat rheumatoid arthritis (RA). We assessed the effects of tofacitinib on bone density and bone markers in association with clinical and laboratory parameters in RA. Tofacitinib stabilized bone density and resulted in a positive balance of bone turnover. Introduction Janus kinase (JAK) inhibitors emerged as new therapeutic options in rheumatoid arthritis (RA). We have little information on how it affects areal and volumetric bone mineral density (BMD) and bone turnover markers. The aim of this study was to assess the effects of 1-year tofacitinib therapy on bone metabolism in RA. Methods Thirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib for 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF), and anti-cyclic citrullinated peptide (CCP) levels, as well as serum levels of sclerostin, osteocalcin (OC), P1NP, DKK-1, OPG, RANKL, and 25-hydroxy-vitamin D3. Areal and volumetric BMD were assessed by DXA and peripheral quantitative CT (QCT), respectively. Results Twenty-six patients (13 on each arm) completed the study. Tofacitinib was clinically effective by suppressing DAS28, CRP, and HAQ. This was accompanied by the attenuation of further bone loss. Tofacitinib therapy significantly increased OC, OPG, and vitamin D3, while decreased CTX levels (p < 0.05). Age and multiple bone markers (OC, CTX, P1NP, RANKL) inversely correlated with L2–4 and femoral neck BMD by DXA. CRP, DAS28, and RANKL inversely determined volumetric BMD by QCT. Age, CRP, anti-CCP, and DKK-1 influenced the effects of tofacitinib therapy on BMD changes. Conclusions One-year tofacitinib treatment stabilized BMD in RA patients and resulted in a positive balance of bone turnover as indicated by bone biomarkers. Further studies are needed to evaluate the potential beneficial effects of JAK inhibitors on inflammatory bone loss. Supplementary Information The online version contains supplementary material available at 10.1007/s00198-021-05871-0.

Objective.Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with cardiovascular disease. The treatment of arthritis by tumor necrosis factor-α (TNF-α) inhibitors may decrease the serum concentrations of vascular biomarkers. We determined circulating levels of oxidized low-density lipoprotein (oxLDL)/β2 glycoprotein I (β2-GPI) complexes, antibodies to 60 kDa heat shock protein (anti-Hsp60), soluble urokinase plasminogen activator receptor (suPAR), and B-type natriuretic peptide (BNP) fragment in sera of RA and AS patients undergoing anti-TNF treatment.Methods.Fifty-three patients with RA/AS were treated with etanercept or certolizumab pegol for 1 year. Circulating oxLDL/β2-GPI complex (AtherOx), anti-Hsp60 IgG, and BNP8-29 fragment levels were assessed by ELISA. suPAR levels were determined by suPARnostic Quick Triage test. Flow-mediated vasodilation (FMD), carotid intima-media thickness (CIMT), and arterial pulse wave velocity (PWV) were determined by ultrasound.Results.One-year anti-TNF treatment significantly decreased oxLDL/β2-GPI levels, as well as suPAR levels in patients with critically high suPAR levels at baseline. In RA, BNP levels were higher in seropositive vs seronegative patients. Serum levels of these vascular biomarkers variably correlated with lipids, anticitrullinated protein antibodies, rheumatoid factor, and C-reactive protein. CIMT positively correlated with BNP, and PWV with suPAR and anti-Hsp60, whereas FMD inversely associated with anti-Hsp60. In repeated measures ANOVA analysis, disease activity supported the effects of anti-TNF treatment on 12-month changes in oxLDL/β2-GPI. CIMT supported the effects of therapy on changes in anti-Hsp60 and suPAR.Conclusion.These biomarkers may be involved in the pathogenesis of atherosclerosis underlying RA/AS. TNF inhibition variably affects the serum levels of oxLDL/β2-GPI, suPAR, and BNP.

The distinction between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related and community-acquired pneumonias poses significant difficulties, as both frequently involve the elderly. This study aimed to predict the risk of SARS-CoV-2-related pneumonia based on clinical characteristics at hospital presentation. Case-control study of all patients admitted for pneumonia at Semmelweis University Emergency Department. Cases (n = 30) were patients diagnosed with SARS-CoV-2-related pneumonia (based on polymerase chain reaction test) between 26 March 2020 and 30 April 2020; controls (n = 82) were historical pneumonia cases between 1 January 2019 and 30 April 2019. Logistic models were built with SARS-CoV-2 infection as outcome using clinical characteristics at presentation. Patients with SARS-CoV-2-related pneumonia were younger (mean difference, 95% CI: 9.3, 3.2–15.5 years) and had a higher lymphocyte count, lower C-reactive protein, presented more frequently with bilateral infiltrate, less frequently with abdominal pain, diarrhoea, and nausea in age- and sex-adjusted models. A logistic model using age, sex, abdominal pain, C-reactive protein, and the presence of bilateral infiltrate as predictors had an excellent discrimination (AUC 0.88, 95% CI: 0.81–0.96) and calibration (p = 0.27–Hosmer-Lemeshow test). The clinical use of our screening prediction model could improve the discrimination of SARS-CoV-2 related from other community-acquired pneumonias and thus help patient triage based on commonly used diagnostic approaches. However, external validation in independent datasets is required before its clinical use.

Over the past decades, a number of complementary treatments for schizophrenia have emerged. One of these is metacognitive training (MCT), which combines the principles of cognitive-behavioral therapies, cognitive remediation, and psychoeducation into a hybrid approach placing emphasis on increasing metacognitive awareness. The aim of our study was to investigate the efficacy of MCT on symptom severity, and neurocognitive and social cognitive functioning in schizophrenia; also, attention was paid to the assessment of subjective acceptability. Forty-six patients diagnosed with schizophrenia were included in our single-blind randomized controlled trial, who were assigned to the intervention or control group. The intervention group was provided standard MCT, while the control group received treatment as usual. We assessed symptom severity and cognitive functions before and after the training, as well as after a 6-month follow-up period. Compared to the control group, the intervention group showed improvement in overall symptom severity, and positive and disorganized symptoms. Training participans showed further improvement at the follow-up assessment. Regarding neurocognitive functions, improvement in visuospatial functions was observed between pre- and post-intervention assessments compared to the control group. Patients showed excellent adherence, and evaluated the training as useful and interesting. In line with the results of previous studies, our results demonstrate the efficacy of MCT on symptom severity in schizophrenia. Improvements in cognitive functions that are closely related to the onset and prevalence of symptoms of schizophrenia were also found.

Anemia is a common finding in the elderly. Approximately 10 percent of the elderly suffers from anemia. Anemia per se is an independent factor of mortality in older patients regardless its cause. Frailty is also frequent in geriatric patients. That means that there is a decreased reserve capacity to react to different stress factors including anemia. The frequent presence of heart failure and also impaired cerebrovascular circulation makes more difficult to tolerate anemia in older age. Anemia is a symptom, finding and treating the underlying cause is also important. Treatment always depends on clinical findings: the more severe the symptoms, the more important to treat them. Severity of anemia depends not only the underlying cause, degree of anemia, co-morbidities and frailty of the patients, but also the speed of its development. Sudden blood loss due to an accident is less well tolerated than the same degree of anemia due to B12 deficiency. Main causes of anemia in the elderly include nutritional deficiencies, chronic diseases, tumors, and certain hematological malignancies such as chronic lymphocytic leukemia, multiple myeloma, myelodysplastic syndrome.

Background: Cardiovascular (CV) morbidity, mortality, and metabolic syndrome are associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Here, lipids and other metabolic markers in relation to vascular function and clinical markers were evaluated in RA and AS patients undergoing one-year anti-TNF therapy. Patients and methods: Fifty-three patients including 36 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 17 AS patients treated with ETN were included in a 12-month follow-up study. Various lipids, paraoxonase (PON) and arylesterase (ARE) activities, myeloperoxidase (MPO) and adipokine levels were determined overtime. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT), and arterial pulse-wave velocity (PWV) in all patients. All assessments were performed at baseline and 6 and 12 months after treatment initiation. Results: Anti-TNF therapy decreased ARE activity, MPO, adiponectin, and chemerin levels after 12 months (p &lt, 0.05). Lipids, PON activity, and leptin remained unchanged. Regression analyses suggested variable associations of IMT, PWV, and FMD with ARE, MPO, leptin, and lipids (p &lt, 0.05). On the other hand, these metabolic parameters were significantly associated with disease duration, CV history, CRP, obesity, PWV, and IMT (p &lt, 0.05). One-year anti-TNF treatment together with baseline leptin (p = 0.039) or CRP (p = 0.016) levels determined 12 months of lipid changes overtime. TNF inhibition together with baseline disease activity determined ARE activity changes (p = 0.046). Anti-TNF therapy and baseline chemerin levels determined IMT changes overtime (p = 0.003). Conclusions: Assessment of various metabolic parameters together with disease activity, CRP, and ultrasound-based techniques may exert additional value in determining CV burden and in monitoring the effects of biologics on preclinical vascular pathophysiology.

Theory of mind is one of the most intensively studied phenomena in the development of schizophrenic symptoms and impairments in social adjustment. Complex theory of mind processing requires both visual and verbal aspects of the social-perceptual and social-cognitive components of mind reading. Reliable assessment methods are considered essential for the proper conduct of research. The current study aims at investigating the psychometric properties of the Theory of Mind Picture Stories Task (ToM PST). Forty-seven patients with schizophrenia were enrolled in the study from three sites. Data from ToM PST were used for computing the consistency, reliability, and internal and construct validity of the test.Our preliminary findings showed less appropriate consistency. Therefore, we attempted to carry out structural changes on the task while preserving its scales and subscales, which measure crucial factors of ToM. The newly structured task has four scales. They show proper consistency (Sequencing: Cronbach's α = 0.70, Theory of a Single Person's Mind: α = 0.74, Switching Between Minds: α = 0.70, Comprehension of Misleading Behaviour: α = 0.67, Total: α = 0.80) with appropriate internal and construct validity, a moderate test-retest reliability over a four-month-course, and a proper inter-rater reliability.

Introduction: The aim of the study was to determine the effects of the pelvic floor muscle (PFM) training (PFM-T) in combination with transverse abdominal (TRA) muscle activation (cPFM-T) in female urinary incontinence. Methods: We enrolled nulliparous women in supine (SUG) (n = 22), sitting (SIG) (n = 19), and control (COG) (n = 14) groups. We conducted an 8-week cPFM-T programme. We examined the effect of training on the parameters with the Kruskal-Wallis test, the pairwise comparisons with the Mann-Whitney U test, and the Wilcoxon rank test with the Bonferroni correction. Results: Before training, 15 participants reported occasional urinary leakage. After cPFM-T, 7 participants reported that urinary leakage had disappeared. Maximal isometric contraction of the PFMs until fatigue improved significantly in the SUG (p < 0.001) and SIG (p = 0.015) groups but not significantly in the COG group (p = 0.499). Holding time increased in the SUG (p = 0.972) and the SIG (p = 0.717) groups and decreased in the COG group (p = 0.132). The dynamic endurance of the PFM improved significantly in the SUG group (p < 0.001) but not in the SIG (p = 0.798) and the COG (p = 0.153) groups. The number of maximal fast contractions within 1 min increased in both the SUG (p < 0.001) and SIG (p = 0.813) groups and decreased in the COG group (p = 0.257). Relaxation improved significantly in the SIG group (p = 0.011). TRA mucle thickness increased in both training groups. Conclusion: Slow-twitch fibres of the PFM can be trained effectively with PFM-T in both the body positions.

Cardiovascular (CV) disease and osteoporosis (OP) have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Bone and vascular biomarkers and parameters along with the effect of 1-year anti-TNF therapy on these markers were assessed in order to determine correlations between vascular pathophysiology and bone metabolism in RA and AS. Thirty-six patients treated with etanercept or certolizumab pegol and 17 AS patients treated with ETN were included in a 12-month follow-up study. Bone and vascular markers were previously assessed by ELISA. Bone density was measured by DXA and quantitative CT (QCT). Flow-mediated vasodilation (FMD), common carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) were assessed by ultrasound. Multiple correlation analyses indicated associations between bone and vascular markers. Osteoprotegerin, sclerostin and cathepsin K were significantly associated with FMD, IMT and PWV, respectively (p

Background. People with diabetic cardiovascular autonomic neuropathy (CAN) have increased cardiovascular mortality. However, the association between distal symmetric polyneuropathy (DSPN) or CAN with all-cause mortality is much less investigated. Thus, we set out to examine the effect of CAN and DSPN on all-cause mortality in a well-phenotyped cohort. Methods. All diabetes cases ( n = 1,347 ) from the catchment area of a secondary diabetes care centre who had medical examination including neuropathy assessment between 1997 and 2016 were followed up for all-cause mortality in the NHS Hungary reimbursement database until 2018. We investigated the association of CAN (Ewing tests) and DSPN (Neurometer) with all-cause mortality using Cox models stratified by diabetes type. Results. Altogether, n = 131 / 1,011 persons with type 1/type 2 diabetes were included. Of the participants, 53%/43% were male, mean age was 46 ± 12 / 64 ± 10 years, diabetes duration was 13 ± 10 / 7 ± 8 years, 42%/29% had CAN, and 39%/37% had DSPN. During the 9 ± 5 / 8 ± 5 -year follow-up, n = 28 / 494 participants died. In fully adjusted models, participants with type 1 diabetes patients with versus without DSPN had an increased mortality (HR 2.99, 95% CI 1.4-8.63), while no association with CAN was observed. In type 2 diabetes, both DSPN and CAN independently increased mortality (HR 1.32, 95% CI: 1.07-1.64, and HR 1.44, 95% CI: 1.17-1.76). Conclusions. Our results are compatible with an increased risk of mortality in people with type 1 diabetes and DSPN. Furthermore, we report a similarly strong association between DSPN and CAN and all-cause mortality in type 2 diabetes mellitus.

Abstract Introduction Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are associated with osteoporosis. There have not been many peripheral quantitative computed tomography (QCT) studies in patients receiving biologics. We assessed volumetric and areal bone mineral density (BMD) by forearm QCT and dual-energy X-ray absorptiometry (DXA), respectively in addition to laboratory biomarkers in these arthritides. Methods Forty RA and AS patients treated with either etanercept (ETN) or certolizumab pegol (CZP) were undergoing follow-ups for one year. Volumetric and areal BMD, as well as parathyroid hormone (PTH), osteocalcin, RANKL, 25-hydroxyvitamin D (VITD), P1NP, CTX, sclerostin (SOST), Dickkopf 1 (DKK-1) and cathepsin K (CATHK) were determined. Results We did not observe any further bone loss during the 12-month treatment period. Volumetric and areal BMD showed significant correlations with each other (p Conclusions BMD as determined by QCT did not change over one year of anti-TNF treatment. Disease activity, CATHK, RANKL and VITD may be associated with the effects of anti-TNF treatment on QCT BMD changes. RA and AS may differ in this respect.

A model anaerobic bacterium strain from the gut microbiome (Clostridium butyricum) producing anti-inflammatory molecules was incorporated into polymer-free fibers of a water-soluble cyclodextrin matrix (HP-β-CD) using a promising scaled-up nanotechnology, high-speed electrospinning. A long-term stability study was also carried out on the bacteria in the fibers. Effect of storage conditions (temperature, presence of oxygen) and growth conditions on the bacterial viability in the fibers was investigated. The viability of the sporulated anaerobic bacteria in the fibers was maintained during 12 months of room temperature storage in the presence of oxygen. Direct compression was used to prepare tablets from the produced bacteria-containing fibers after milling (using an oscillating mill) and mixing with tableting excipients, making easy oral administration of the bacteria possible. No significant decrease was observed in bacterial viability following the processing of the fibers (milling and tableting).

Objective. Monophasic glucose response (MGR) during an oral glucose tolerance test (OGTT) and gestational diabetes mellitus (GDM) are predictors of type 2 diabetes mellitus (T2DM). We investigated the association between current MGR and (1) glucose tolerance during a pregnancy 3 years before and (2) current glucose tolerance status. We also sought (3) other determinants of MGR. Research Design and Methods. We conducted a nested case-control study of GDM (n=47 early GDM, diagnosed between 16 and 20 weeks of gestation; n=40 late GDM, diagnosed between 24 and 28 weeks of gestation) and matched healthy controls (n=37, normal glucose tolerance during pregnancy) all free from diabetes at follow-up 3.4±0.6 years after delivery. Glucose tolerance was determined by 2-hour 75 g OGTT. Monophasic and biphasic groups were defined based on serum glucose measurements during OGTT. Results. The biphasic group was younger, had lower triglyceride levels and area under the OGTT glucose curve, and was less frequently diagnosed with early GDM (25 vs. 45%, all p<0.05). Women with a biphasic response also tended to have lower systolic blood pressure (p<0.1). No differences were found in fasting and 2-hour glucose and insulin levels, or BMI. According to multiple logistic regression, MGR was associated with prior early GDM (OR 2.14, 95% CI 0.92-4.99) and elevated triglyceride levels (OR 2.28, 95% CI 1.03-5.03/log (mmol/l)). Conclusions. We found that more severe, early-onset GDM was an independent predictor of monophasic glucose response suggesting that monophasic response may represent an intermediate state between GDM and manifest type 2 diabetes.

Weight-bearing (WB) on the lower extremities is an important outcome parameter in the rehabilitation of poststroke hemiparesis. However, the patients often regain this ability by compensatory movement patterns.Our goal was to characterize with a simple method the trunk alignment of healthy subjects and stroke patients (n = 17 for both groups) during standing and following lateral weight shift (WS). To describe trunk alignment, five markers were placed on the subjects' back, and the angles of the trunk at both sides were defined by the lines drawn from the posterior angle of the acromion and the iliac crest on the same body side to the seventh thoracic spinal process. Weight distributions on the lower extremities during standing and lateral WS were determined with a force platform.The patients had significantly limited WB capacity on their paretic limb, which was accompanied with significant asymmetry in the trunk alignment during standing and following WS to the paretic side.Our results show that this patient population tends to use abnormal compensatory movement patterns to optimize weight shifting, and changes of trunk alignment play a key role in this. This should be taken into consideration during rehabilitation.

Objective We wished to determine bone alterations in systemic sclerosis (SSc) patients by conventional densitometry (DXA), peripheral quantitative computed tomography (pQCT), and bone biomarkers. Methods We included 44 SSc patients and 33 age-matched healthy controls. Lumbar spine and femoral neck bone mineral density (BMD) was assessed by DXA. Volumetric BMD was measured by pQCT at the radius. FRAX, 25-hydroxyvitamin-D3 (25-OH-D3), parathyroid hormone, osteocalcin, C-terminal collagen telopeptide, and procollagen type I amino-terminal propeptide were also assessed. Results SSc patients had lower L2–4 BMD (0.880 ± 0.108 vs. 0.996 ± 0.181 g/cm2; p = 0.019) and femoral neck (FN) BMD (0.786 ± 0.134 vs. 0.910 ± 0.090 g/cm2; p = 0.007) by DXA. In SSc vs. controls, pQCT indicated lower mean cortical (328.03 ± 103.32 vs. 487.06 ± 42.45 mg/cm3; p 3; p = 0.037). Vitamin D3 deficiency was more common in SSc vs. controls (60.0% vs. 39.3%; p = 0.003). L2–4 (p = 0.002) and FN BMD (p = 0.015) positively correlated with BMI. pQCT assessments confirmed an inverse correlation between pulmonary manifestation and total (p = 0.024), trabecular (p = 0.035), and cortical density (p = 0.015). Anti-Scl70 positivity inversely correlated with pQCT total density (p = 0.015) and the presence of digital ulcers with cortical density (p = 0.001). We also found that vertebral and FN BMD as determined by DXA significantly correlated with pQCT total, trabecular, and cortical density (p Conclusion The results of our study suggest that bone loss in SSc patients may be associated with lower BMI, anti-Scl70 positivity, and the presence of pulmonary manifestations and digital ulcers. Both DXA and pQCT are appropriate tools to evaluate the bone alterations in SSc patients.

Objectives There is a direct correlation between 25-hydroxyvitamin D (25[OH]D) levels and insulin sensitivity. Furthermore, women with gestational diabetes (GDM) may have lower levels of 25(OH)D compared to controls. The present study intended to investigate 25(OH)D levels and their association with insulin sensitivity and insulin secretion in women with prior GDM and in controls 3.2 years after delivery. Methods A total of 87 patients with prior GDM and 45 randomly selected controls (age range, 22 to 44 years) with normal glucose tolerance during pregnancy nested within a cohort of all deliveries at Saint Margit Hospital, Budapest, between January 1 2005, and December 31 2006, were examined. Their 25(OH) D levels were measured by radioimmunoassay. Insulin sensitivity and fasting insulin secretion were estimated using the homeostasis model asssessment (HOMA) calculator and early insulin secretion by the insulinogenic index based on a 75 g oral glucose tolerance test. Results There was no significant difference in 25(OH)D levels between cases and controls (27.2±13.1 [±SD] vs. 26.9±9.8 ng/L). There was a positive association between HOMA insulin sensitivity and 25(OH)D levels (beta = 0.017; 95% CI 0.001 to 0.034/1 ng/mL) that was robust to adjustment for age and body mass index. There was a nonsignificant association between HOMA insulin secretion and 25(OH)D (p=0.099), while no association was found with the insulinogenic index. Conclusions Prior GDM status was not associated with 25(OH)D levels; however, 25(OH) D levels were associated with HOMA insulin sensitivity. It is hypothesized that the association between HOMA insulin secretion and 25(OH)D levels is related to the autoregulation of fasting glucose levels because no association between 25(OH)D and insulinogenic index was found.

Accelerated atherosclerosis, increased cardiovascular morbidity and mortality have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Vascular function, clinical and laboratory markers and the effects of anti-TNF therapy were assessed in arthritides. Fifty-three 53 patients including 36 RA patients treated with either etanercept (ETN) or certolizumab pegol and 17 AS patients treated with ETN were included in a 12-month follow-up study. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and arterial pulse-wave velocity (PWV) in all patients. All assessments were performed at baseline and 6 and 12 months after treatment initiation. A significant improvement of brachial artery FMD was observed after 6 months (p = 0.004). A tendency of FMD improvement was also observed after 12 months (p = 0.065). ccIMT did not change throughout the year. PWV significantly improved after 12 months (p = 0.034). Higher baseline ccIMT (p = 0.009) and PWV (p = 0.038) were associated with clinical non-response (cNR) versus response (cR) to biologics. Multiple analysis confirmed the association of baseline ccIMT with age (p = 0.003) and cNR (p = 0.009), as well as that of baseline PWV with age at diagnosis (p = 0.022) and current chest pain (p = 0.004). Treatment itself determined the 12-month changes in FMD (p = 0.020) and PWV (p = 0.007). In a mixed cohort of RA and AS patients, TNF inhibition improved or stabilized vascular pathophysiology. Inflammation may be associated with FMD, while, among others, cNR may influence vascular function.

We assessed cognitive function of female rheumatoid arthritis (RA) patients and analyze the determinants, with special focus on cerebrovascular morphology. Sixty methotrexate (MTX-) or biologic-treated RA patients and 39 healthy controls were included in a cross-sectional study. Smoking habits, alcohol intake and time spent in education were recorded. Standard measures were performed to assess cognitive function (Montreal Cognitive Assessment, MOCA; Trail Making Test, TMT; Victoria Stroop Test, VST; Wechsler Adult Intelligence Scale, WAIS; Benton Visual Retention test, BVRT), depression (Beck Depression Inventory, BDI), anxiety (State-Trait Anxiety Inventory, STAIT/S) and general health status (Short Form 36, SF-36). Mean disease activity (28-joint Disease Activity Score, mDAS28; erythrocyte sedimentation rate, mESR; C-reactive protein, mCRP) of the past 12 months was calculated; anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) were assessed. Cerebral vascular lesions and atrophy, carotid intima-media thickness (cIMT) and plaques, as well as median cerebral artery (MCA) circulatory reserve capacity (CRC) were assessed by brain magnetic resonance imaging (MRI), carotid ultrasound and transcranial Doppler, respectively. Cognitive function tests showed impairment in RA vs controls. Biologic- vs MTX-treated subgroups differed in TMT-A. Correlations were identified between cognitive function and depression/anxiety tests. WAIS, STAIS, STAIT and BDI correlated with most SF-36 domains. Numerous cognitive tests correlated with age and lower education. Some also correlated with disease duration, mESR and mDAS28. Regarding vascular pathophysiology, cerebral vascular lesions were associated with VST-A, carotid plaques with multiple cognitive parameters, while MCA and CRC with MOCA, BVRT and BDI. RA patients have significant cognitive impairment. Cognitive dysfunction may occur together with or independently of depression/anxiety. Older patients and those with lower education are at higher risk to develop cognitive impairment. Cognitive screening might be a useful tool to identify subgroups to be further investigated for cerebrovascular pathologies.

To investigate the effects of balance training to improve postural control in adults older than 60. Our aim was to find out if Kinect training is superior to the conventional balance training in aspects of functional balance tests and posturography measurements testing postural stability through visual feedback.Thirty subjects participated in the Kinect training group (29 women and 1 man), practiced Kinect Adventures and Sports, 23 volunteers (22 women and 1 man) attended the conventional balance training, and 22 participants (18 women and 4 men) were allocated to the no-intervention control group. Both interventions lasted for 6 weeks, three times a week, and 30 minutes per session. The Four-Square Step Test, Functional Reach Test, Timed Up and Go test, Timed Up and Go cognitive dual-task test were measured, and for the assessment of the limit of stability (LOS), we used computerized posturography. Measurements were taken before the training at baseline and 6 weeks after (follow-up) the interventions. Statistical analysis was done through two-factor mixed analysis of variance and Newman-Keuls post hoc test.Both training groups showed progress in the follow-up measurements; however, more statistically significant improvements were found in favor of the Kinect balance training group (Timed Up and Go test [P 0.05], Timed Up and Go cognitive dual-task test [P 0.05], Four-Square Step Test [P 0.05], Functional Reach Test [P 0.05], LOS movement velocity [P 0.05]).Our results suggest that Kinect balance training may be a preferable and safe method for the healthy older adults to improve postural control and reduce the possibility of falling.

Introduction Genetic and autoimmune risk factors contribute to the development of thrombotic thrombocytopenic purpura (TTP) but triggers are needed to bring about acute disease. The aim of the study was to investigate the association of neutrophil activation with acute TTP, to assess whether neutrophil activation changes during plasma exchange therapy and to show if complement- and neutrophil activation are parallel, characteristic processes in acute TTP. Materials and Methods Altogether 49 EDTA-plasma samples of 21 TTP patients with acute disease and 17 in remission were investigated along with 20 healthy controls. A stable complex of PMNE-proteinase-inhibitor was measured by ELISA (Calbiochem, Merck-Millipore, Darmstadt, Germany). Results Acute disease was associated with significantly increased PMNE levels, the group medians were similarly low in TTP patients in remission and in healthy controls. Increased PMNE levels were characteristic for hematologically active and ADAMTS13 deficient form of TTP. PMNE concentration inversely correlated to disease activity markers platelet count (r = − 0.349, p = 0.032) and hemoglobin levels (p = − 0.382 p = 0.018). Achievement of remission was associated with significant reduction of plasma PMNE levels (p = 0.031, Wilcoxon test). There was positive correlation between PMNE levels and complement activation markers C3a and Bb. Conclusions We report increased PMNE levels in acute TTP and showed its association to activity markers of acute TTP and complement activation. Effective treatment of an acute TTP episode resulted in marked decrease in PMNE levels. Our data support and extend previous observations that neutrophil extracellular traps may be released in acute TTP and potentially contribute to the pathophysiology of this disease.

Parkinson's disease affects more than 6,3 million people worldwide. Most patients and relatives are left alone to struggle with the symptoms associated with fluctuations in drug levels and the psychotic side effects of the anti-Parkinson's medications. Moreover, quite often even health providers may find difficult to interpret and manage the problems that have been encountered.The aims of the authors were to analyze systematically the biopsychosocial needs of Parkinson's patients, and to develop a complex, evidence-based Parkinson's-nursing-care model.Patients' needs were assessed based on an observational study involving an old patient with Parkinson's disease for more than 28 years. The model has been specified as a multidisciplinary care framework adapted to the special characteristics of Parkinson's disease which transcends the limitations of different standard nursing models.The elaborated model contains a detailed description of cooperative problem solving, which is organized around individual patients along with recommendations for addressing various potential problems that might be encountered.Implementation of the presented model can improve the life quality of Parkinson's patients and can facilitate the life of affected families provided that these families are well aware about the potential benefits of the novel care delivery system.

To estimate and compare the prevalence of self-reported diabetes based on nationally representative surveys of the Hungarian adult population in 2002 (published data - Hungarostudy) and a survey in 2012.A cross-sectional computer-assisted telephone interview survey on a stratified representative sample of community-dwelling adults (n=1000) in 2012. To describe self-reported diabetes prevalence and its temporal changes generalized linear models were used and results were compared to figures from Hungarostudy.Age standardized prevalence of self-reported type 2 diabetes was 11.7% (95%CI 10.0-13.8%) without gender or rural-urban differences in 2012. People with self-reported diabetes were older than controls (mean [SE]: 63.9 [0.9] vs. 45.9 [0.3] years, p0.0001). The prevalence of diabetes sharply increased after 40 years of age and peaked at age 70 (27.7% [2.5], pWe reported an alarming increase in the prevalence of self-reported type 2 diabetes in the last decade that mostly affects working age people. If this trend continues, a major public health crisis in Hungary can be envisaged.

There is a bidirectional connection between tumors and thrombosis. On one hand, thromboembolic events are more frequent in cases of malignancies, on the other hand, proliferation of tumor cells, progression of the malignant process and metastasis formation are facilitated by the activation of the hemostatic system. Thromboembolic events are associated with a worse prognosis in case of patients with malignant diseases. Thromboembolism is the second most frequent cause of death in patients with malignant tumors. Mortality is twice as high in patients with thromboembolism compared to those without it. The incidence of thromboembolism shows an increasing tendency. There has been a 28% increase among hospitalized cancer patients between 1995 and 2003. One reason is that the new anti-tumor agents have more pronounced prothrombotic activity than those of traditional chemotherapeutic drugs. Assessment of the thrombotic risk of cancer patients becomes more important. Several guidelines have been published concerning the prevention and treatment of thromboembolism in patients with malignancy. The risk of thrombosis is influenced not only by the type of malignancy but there are also large individual differences. Furthermore, the risk of thrombosis changes during the disease process in the same patient. Perioperative thromboprophylaxis is a very important issue considering oncologic surgery. Thromboprophylaxis of oncologic patients has a high significance in respect of morbidity and mortality. However, thromboprophylaxis may also cause serious complications thus the correct risk assessment of cancer patients is very important. Orv. Hetil., 2012, 153, 934–947.

Summary. Background: Ultra-large von Willebrand factor and deficiency of its cleaving protease are important factors in the events leading to thrombotic microangiopathy; however, the mechanisms involved are only partly understood. Whereas pathological activation of the alternative complement pathway is linked to atypical hemolytic uremic syndrome, the role of complement activation in thrombotic thrombocytopenic purpura (TTP) is unknown. The aim of this study was to investigate whether signs of complement activation are characteristic of TTP. Patients and methods: Twenty-three patients with TTP (18 women, median age 38 years) and 17 healthy controls (13 women, median age 38 years) were included. Complement parameters (C3, Factors H, I, B and total alternative pathway activity) together with complement activation fragments (C3a) or complexes (C1rs-INH, C3bBbP, sC5b9) were measured by ELISA or RID. ADAMTS13 activity and anti-ADAMTS13 inhibitory antibodies were measured by the VWF-FRET73 assay. Results: Increased levels of C3a, and SC5b9 were observed in TTP during acute episodes, as compared with healthy controls. Decreased complement C3 levels indicative of complement consumption occurred in 15% of acute TTP patients. Significant decrease of complement activation products C3a and SC5b9 was observed during plasma exchange (PEX). The sustained presence of anti-ADAMTS13 inhibitory antibodies in complete remission was associated with increased complement activation. Conclusion: These data document in an observational study the presence of complement activation in TTP. Further investigation is needed to determine its potential pathogenetic significance.

AL amyloidosis is a systemic disease characterised by pathogenetic proteins produced by malignant plasma cells and the deposition of them in different organs of the body. Amyloidogenic protein is the light chain of the monoclonal immunoglobulin, which becomes water insoluble, precipitates and deposites in the extracellular space resulting damage of organ function. AL amyloidosis belongs to plasma cell dyscrasias or it can associate to other monoclonal B-cell diseases. Diagnosis – such as in case of other types of amyloidosis – is based on histology. Identification of the amyloidogenic protein often needs special examinations. The goal of the therapy is the eradication of the malignant cell clone. Therapeutical armamentarium has been largely flared in the past few decades, several drugs with new mechanisms of action are available (thalidomide, lenalidomide, bortezomib). The standard treatment is high dose chemotherapy followed by autologous stem cell transplantation in case of eligible patients. Transplantation uneligible patients can be treated with a low dose alkylating agent with or without dexamethasone, or with the new agents. The therapeutical decision must be preceded by very thorough risk assessment. Early diagnosis and the prompt beginning of the treatment has great significance because the evolving functional abnormalities of parenchymal organs (mainly cardiac failure) prevents the effectivity of the treatment. Amyloidosis is an orphan disease, special centers play a significant role in the field of clinical trials. Orv. Hetil., 2012, 153, 563–573.

An effective control of healthcare-associated infections is not realized without an intensive participation of microbiologic activities. Authors present the model of a centre for healthcare-associated infection control established in 2008 at Semmelweis University. The new model of the surveillance system is based on diagnostic and experimental microbiologic data. Clinical and epidemiological microbiologic examinations are performed in the same laboratory using identical methods, and the results are continually compared. Reports consist of two functional parts; namely list of pathogens isolated and antibiotic sensitivity patterns for clinicians and messages especially for epidemiologists including abbreviated information on bacteria of nosocomial importance. Rapid detection of the most important pathogens both from clinical samples and from those obtained for detecting nasal carriage is carried out by a sensitive and specific method of an automated real time PCR. Biotyping of isolates by detailed biochemical substrate spectrum, genotyping by ready-to-use kits depending on polymorphism of repetitive DNA sequences, and cluster analysis of data are used for up-to-date survey of nosocomial situation. Statistical analysis of reports is performed by the multifactorial software OSIRIS Epidemiology. Orv. Hetil., 2011, 152, 437–442.

The changes in postural control in elderly people after an 8-week training course were characterized. Static postural stability was measured during standing on a single force platform first with the eyes open and then with the eyes closed. Body sway was analysed on a force plate in groups of elderly and of young subjects. Half of the elderly subjects then took part in the training course. The posturographic measurements were repeated after the course. The sway in anteroposterior (AP) and mediolateral (ML) directions was subjected to spectral analysis. The frequency spectrum of the platform oscillations was calculated by fast Fourier transformation in the intervals 0.1-0.3, 0.3-1 and 1-3 Hz. It was found that the sway path was longer and the frequency power was higher in the elderly group. The training caused a significant improvement in functional performance, but a significantly longer sway path was observed after the training in the ML direction. The frequency analysis revealed a significantly higher power after 8 weeks without visual control in the ML direction in the training group in the low and the middle frequency bands. The results suggest that the participants' balance confidence and the control of ML balance improved in response to the training. The higher ML frequency power exhibited after the training may be indicative of a better balance performance. Thus, the increase in the sway path in this age group did not mean a further impairment of the postural control.

Many multi-resistant patogens appear continuously resulting in a permanent need for the development of novel antibiotics. A large number of antibiotics introduced in clinical and veterinary practices are not effective. Antibacterial peptides with unusual mode of action may represent a promising option against multi-resistant pathogens. The entomopathogenic Xenorhabdus budapestensis bacteria produce several different antimicrobial peptides compounds such as bicornutin-A and fabclavin.The aim of the authors was to evaluate the in vitro antibacterial effect of Xenorhabdus budapestensis using zoonotic patogen bacteria.Cell-free conditioned media and purified peptide fractions of Xenorhabdus budapestensis were tested on Gram-positive (Rhodococcus equi, Erysipelothrix rhusiopathia, Staphylococcus aureus, Streptococcus equi, Corynebacterium pseudotuberculosis, Listeria monocytagenes) and Gram-negative bacteria (Salmonella gallinarum, Salmonella derbi, Bordatella bronchoseptica, Escherichia coli, Pasteurella multocida, Aeromonas hydrophila) using agar diffusion test on blood agar plates.It was found that Xenorhabdus budapestensis bacteria produced compounds with strong and dose-dependent effects on the tested organisms. Purified peptid fraction exerted a more marked effect than cell free conditioned media. Gram-positive bacteria were more sensitive to this antibacterial effect than Gram-negative bacteria.Antibacterial peptide compound from Xenorhabdus budapestensis exert marked antibacterial effect on zoonotic patogen bacteria and they should be further evaluated in future for their potential use in the control or prevention of zoonoses.

Mental disorders with psychotic features are overlapping in many ways and there are a growing number of comparative studies in the last decades regarding this. Cognitive deficit is well underpinned in schizophrenia, but fewer studies are conducted in this area including patients with bipolar affective disorder. Therefore the aim of the present study was to investigate the cognitive performance of these two patient groups and healthy controls. The Wisconsin Card Sorting Task is a very sensitive measure of the shifting function. Schizophrenic patients perform consistently poorer on this task than healthy controls, while there are not much data about individuals with bipolar affective disorder.The Wisconsin Card Sorting Task and clinical symptom rating scales were administered to 26 patients with schizophrenia, 24 with bipolar affective disorder and 21 healthy controls.Significant differences were found among the performance of the three groups using four different dimensions of the Wisconsin Card Sorting Task. The schizophrenic group made more perseverative errors and achieved less conceptual level responses and completed fewer categories compared to healthy controls. Patients with schizophrenia were able to complete fewer categories and had fewer conceptual level responses than the bipolar group. No significant differences were observed between patients with bipolar disorder and healthy controls.According to these results, patients with schizophrenia and bipolar affective disorder showed no similarities on the Wisconsin Card Sorting Task. Bipolar patients performed the task on the same level as healthy individuals did. The two mental disorders influence cognitive performance differently.

Insulin therapy is the most effective treatment of diabetes. It is proven to prevent microvascular disease and likely to decrease the risk of cardiovascular complications. However, these benefits are associated with a 2-3 times increased risk of hypoglycaemia and a faster weight gain compared to other antidiabetic medications. In addition, one study found elevated all-cause mortality among patients on intensive therapy (requiring more frequent insulinisation). Insulin has growth factor properties that may translate to increased mitogenicity. These factors could prevent the medical team or the patient from initiation or intensification of insulin therapy. The authors describe evidence on long-term remission related to transient intensified insulin therapy at diabetes diagnosis. The currently recommended method of insulin initiation is once daily basal insulin treatment that offers different schedules for intensification. The authors review the pharmacokinetics of analogue insulins that translate to similar efficacy to human insulins with a 20-30% lower risk of hypoglycaemia.

Despite several therapeutic possibilities the morbidity and mortality of thromboembolic disorders remain high. Improving drug compliance - i. e. keeping up the doctor's prescriptions - may be an effective tool to reach better results. To improve patients' compliance, the risk factors of non-compliance should be recognized. Among these patients' fear of adverse effects of drugs, their lack of knowledge about their illness and medication, forgetfulness, and other social, economic factors may be the most important. Furthermore, adherence may be worsened when the patient feels that the decision has been made over his/her head. Sustained medical adherence is important because anticoagulation may be a life-long treatment. The new oral anticoagulants make the matter of compliance to be current. These new type of drugs do not need regular laboratory monitoring and, therefore, compliance cannot be strictly followed. There are several studies concerning drug compliance to anticoagulant medications. Improvement of adherence is based on regular patient education after reviewing the factors of non-compliance, which needs teamwork with important roles of doctors, pharmacists, dietetics and nurses. Careful and accurate work of the participants of primary care might be complemented by the activity of anticoagulant clinics.

This article reports a case of bilateral simultaneous central retinal vein occlusion (CRVO) and protein S deficiency. The 27-year-old male patient presented with a sudden decrease in vision in both eyes. The patient's medical history documented the death of his father at the age of 33 years due to pulmonary embolism. Thrombophilia screening revealed protein S deficiency.We report this case to emphasize that in any case of young onset retinal vein occlusion, protein S deficiency should be suspected.Thrombophilia assays and taking a thorough medical history should be performed.

Multiple myeloma (MM) is a B-cell neoplasm characterized by infiltration of the bone marrow with malignant plasma cells, synthesizing and secreting monoclonal immunoglobulin fragments. The malignant transformation of this terminally differentiated plasma cell is the result of a multistep transformation process. In spite of recent advances in this field, the cause and the exact molecular genetic basis of MM remain obscure. In this review, an attempt has been made to summarize the genetic alterations having functional significance in the generation and progression of MM, and also the existing relationship between genetic abnormalities and chemosensitivity, as well as the typical genetic alterations in various MM subgroups. Factors known to have a role in the conversion of monoclonal gammopathy of unknown significance (MGUS) to MM are also reviewed.

Thrombocytopenia means low platelet count. This is the most frequent cause of bleeding abnormalities. Petechias, purpuras, mucosal bleeding are typical clinical findings. Severe, even life threatening gastrointestinal or intracranial bleeding may also occur. Diagnostic laboratory finding is the prolonged bleeding time. There are several causes of thrombocytopenia. The major mechanisms for a reduced platelet count are decreased production and increased destruction of platelets, or both. The major task is to reveal the underlying cause. Examination of the bone marrow and the peripheral blood smear can be helpful as well as special diagnostics of the assumed disease. Therapy targets the underlying disease, and also involves platelet transfusion. However, in case of diseases with increased platelet activation and consumption, platelet transfusion is contraindicated because it may lead to aggravation of the pathologic process.Thrombocytopenia alatt a vérlemezkék számbeli csökkenését értjük. Ez a vérzékenység leggyakoribb oka. Klinikailag petechiák, purpurák megjelenése, nyálkahártyavérzés jellemzi. Előfordulhat azonban akár életet fenyegető, emésztőrendszert vagy központi idegrendszert érintő vérzés is. A haemostaseologiai laboratóriumi vizsgálatok közül a megnyúlt vérzési idő utal thrombocytaeredetű vérzékenységre. Kialakulásában vagy a csontvelői csökkent megakaryopoesis, vagy a fokozott thrombocytapusztulás, illetve a kettő kombinációja játszik szerepet. Thrombocytopenia észlelésekor a teendő az ok tisztázása. Ebben a csontvelő és a perifériás vérkenet vizsgálata mellett a háttérben álló feltételezett alapbetegség célzott diagnosztikája lehet segítségünkre. A kezelés részint az alapbetegséget célozza, részint a hiányzó komponens – a thrombocyta – pótlását jelenti. Utóbbi a thrombocyták aktiválódása és felhasználódása által előidézett kórképek esetén azonban szigorúan tilos, mivel a kórfolyamat progresszióját idézheti elő. Orv. Hetil., 2014, 155(8), 291–303.

The aim of this study was to evaluate a Chemiluminescence Enzyme Immunoassay (CLIA) developed for the detection of E. coli O157:H7, using different E. coli O157 serotypes. The sensitivity and specificity of the kit were determined from the tenfold dilutions of the 24-hour broth cultures of the test strains. According to the results obtained in this trial, the sensitivity of the kit is 103–104 cells ml−1, and it is specific for E. coli O157. Twenty-five g ground raw beef samples were prepared and inoculated with E. coli O157:H7 at different CFU g−1. The samples were incubated in 225 ml of modified E. coli broth with novobiocin (mEC + n) at 42 °C for 4 h and the immunoassays were performed following the instructions of the manufacturer. According to the results obtained by the CLIA test 101–102E. coli O157 g−1 can be detected from the sample. So this kit seems to be suitable for screening the samples before selective cultivation of E. coli O157:H7.

Multiple myeloma (MM) is a currently incurable disease caused by the proliferation of malignant plasma cells. Although the pathogenesis of the disease still remains unclear, recent research in the biology of MM has produced new insights into the factors that control the growth and survival of myeloma cells. Among the growth factors, interleukin-6 (IL-6) has an essential role. Evidence suggests that IL-6 is not only a growth factor, but also a survival factor in MM, inhibiting apoptosis in myeloma cells. IL-6 interacts with several factors which are involved in the pathogenesis of MM, such as adhesion molecules, tumour suppressor genes and oncogenes. Considering the essential role of IL-6, it could serve as a target for new therapeutic interventions. Neutralizing the effect of IL-6 may result in a regression of tumour progression.

Human herpesvirus type 8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus (KSHV) is a new member of the γ-herpesvirus family. It is an unusual herpesvirus in that it carries a large number of genes that encode oncoproteins or cell signaling proteins. In addition to being the causative agent of both HIV-associated and non-HIV-associated Kaposi’s sarcoma this DNA tumor virus has been implicated in the pathogenesis of several diseases. These include multiple myeloma (MM), Waldenstrom’s macroglobulinemia (WM), multicentric Castleman’s disease (MCD), body cavity-based lymphoma (BCBL), and various other conditions such as sarcoidosis and pemphigus. While the causative role of the viral infection is fairly certain in the development of BCBL and multicentric Castleman’s disease, HHV-8 may act through a different mechanism to induce plasma cell malignancies. It has been suggested - though the finding is still controversial -that infection of bone marrow stromal dendritic cells by HHV-8 might be a key factor in the etiology and pathogenesis of monoclonal gammopathies. The aim of this review is to provide a short introduction into the tumorigenic potential of HHV-8 as well as to detail the available data and possible mechanisms on the involvement of this virus in different hematologic diseases.

Amyloidosis is still enigmatic. The etiology and mechanism of storage and organ impairment are still unknown. Not all amyloidogen molecules are definitely pathogenic; some precursors of tissue amyloid are structurally analogous to normal substances produced in the organism. This paper reviews the currently accepted categories, aspects of etiology and pathogenesis, and therapeutic trends of amyloidosis with a special emphasis on plasmapheresis.—

Seventy-two whole blood samples were investigated to determine the relationship between their spectral data measured in the near infrared (NIR) wavelength region and haemoglobin content based on laboratory data determined by a routine standard method as reference. Blood samples were obtained from the 1st Department of Medicine, Imre Haynal University of Health Sciences. Donors were selected randomly without respect to age, sex, state of health or medical treatment, from apparently healthy volunteers as well as from ambulatory and hospitalized patients. NIR spectra were measured with a SPECTRALYZER 1025 (PMC) computerized spectrophotometer in the 1000-2500 nm wavelength region. The relationship between laboratory data and values of the second derivative (i.e. second order finite difference) of the log(1/TF) spectra measured at different wavelengths was determined by multiple linear regression (MLR) using three- and four-term linear summation equations. The cross-validated standard error of performance (SEP) for haemoglobin was 1.348 g dL-1 with a three term model and 1.251 g dL-1 with a four term model over the range from 5.9 to 20 g dL-1. This preliminary study indicates that NIR measurements can be directly related to haemoglobin content and can be used to determine haemoglobin content in human whole blood.

Antiphospholipid syndrome is characterized by arterial and venous thromboembolic events and persistent laboratory evidence of antiphospholipid antibodies. Obstetric complications such as recurrent miscarriage, early delivery, oligohydramnios, prematurity, intrauterine growth restriction, fetal distress, fetal or neonatal thrombosis, pre-eclampsia/eclampsia, and HELLP syndrome are also hallmarks of antiphospholipid syndrome. This syndrome is one of the diseases associated with the most severe thrombotic risk. Changes in the hemostatic system during normal pregnancy also result in a hypercoagulable state resulting in elevated thrombotic risk. Thromboembolic events are responsible of the vast majority of maternal and fetal deaths. Administration of appropriate thromboprophylaxis helps prevent thromboembolic complications during pregnancy in women with antiphospholipid syndrome and also give birth to healthy children. It is important to centralize the medication and management of these patients. It helps in the thoughtful care of these pregnant women encountering serious problems. Orv. Hetil., 2012, 153, 1207–1218.

Both chromophobe carcinoma and sarcomatoid carcinoma of the kidney are rare. The former is characterized by a relatively good prognosis, while the latter is a highly aggressive tumor. Coexistence of the two components in one renal tumor, which has been reported only rarely, is therefore paradoxical. Both sarcomatoid and chromophobe renal carcinoma were diagnosed in a 52-year-old woman following nephrectomy and resection of metastases in the right lobe of the liver. She died of the disease two months after the first operation; only the sarcomatoid component of her tumor was seen in the liver metastasis and the recurrent carcinoma. Differences in phenotype, immunophenotype and DNA-ploidy patterns of the two components are reported. The intensive p53 staining observed only in the sarcomatoid area supports the role of the TP53 gene in the transformation of chromophobe renal carcinoma to sarcomatoid carcinoma.

Purpose To report late ocular (primary endpoint) and other toxicity, disease control, and survival (secondary endpoints) after intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials Between 1998 and 2009, 130 patients with nonmetastatic sinonasal tumors were treated with IMRT at Ghent University Hospital. Prescription doses were 70 Gy ( n = 117) and 60–66 Gy ( n = 13) at 2 Gy per fraction over 6–7 weeks. Most patients had adenocarcinoma ( n = 82) and squamous cell carcinoma ( n = 23). One hundred and one (101) patients were treated postoperatively. Of 17 patients with recurrent tumors, 9 were reirradiated. T-stages were T1–2 ( n = 39), T3 ( n = 21), T4a ( n = 38), and T4b ( n = 22). Esthesioneuroblastoma was staged as Kadish A, B, and C in 1, 3, and 6 cases, respectively. Results Median follow-up was 52, range 15–121 months. There was no radiation-induced blindness in 86 patients available for late toxicity assessment (≥6 month follow-up). We observed late Grade 3 tearing in 10 patients, which reduced to Grade 1–2 in 5 patients and Grade 3 visual impairment because of radiation-induced ipsilateral retinopathy and neovascular glaucoma in 1 patient. There was no severe dry eye syndrome. The worst grade of late ocular toxicity was Grade 3 ( n = 11), Grade 2 ( n = 31), Grade 1 ( n = 33), and Grade 0 ( n = 11). Brain necrosis and osteoradionecrosis occurred in 6 and 1 patients, respectively. Actuarial 5-year local control and overall survival were 59% and 52%, respectively. On multivariate analysis local control was negatively affected by cribriform plate and brain invasion ( p = 0.044 and 0.029, respectively) and absence of surgery ( p = 0.009); overall survival was negatively affected by cribriform plate and orbit invasion ( p = 0.04 and p = 0.001). Conclusions IMRT for sinonasal tumors allowed delivering high doses to targets at minimized ocular toxicity, while maintaining disease control and survival. Avoidance of severe dry eye syndrome and radiation-induced blindness suggests IMRT as a standard treatment for sinonasal tumors.

Introduction While adjuvant immunotherapy with Bacille Calmette Guérin (BCG) is effective in non-muscle-invasive bladder cancer (BC), adverse events (AEs) are considerable. Monocyte-derived activated killer cells (MAK) are discussed as essential in antitumoural immunoresponse, but their application may imply risks. The present trial compared autologous intravesical macrophage cell therapy (BEXIDEM®) to BCG in patients after transurethral resection (TURB) of BC. Materials and methods This open-label trial included 137 eligible patients with TaG1-3, T1G1-2 plurifocal or unifocal tumours and ≥ 2 occurrences within 24 months and was conducted from June 2004 to March 2007. Median follow-up for patients without recurrence was 12 months. Patients were randomized to BCG or mononuclear cells collected by apheresis after ex vivo cell processing and activation (BEXIDEM). Either arm treatment consisted of 6 weekly instillations and 2 cycles of 3 weekly instillations at months 3 and 6. Toxicity profile (primary endpoint) and prophylactic effects (secondary endpoint) were assessed. Results Patient characteristics were evenly distributed. Of 73 treated with BCG and 64 with BEXIDEM, 85% vs. 45% experienced AEs and 26% vs. 14% serious AEs (SAE), respectively (p < 0.001). Recurrence occurred significantly less frequent with BCG than with BEXIDEM (12% vs. 38%; p < 0.001). Discussion This initial report of autologous intravesical macrophage cell therapy in BC demonstrates BEXIDEM treatment to be safe. Recurrence rates were significantly lower with BCG however. As the efficacy of BEXIDEM remains uncertain, further data, e.g. marker lesions studies, are warranted. Trial registration The trial has been registered in the ISRCTN registry http://isrctn.org under the registration number ISRCTN35881130.

There are conflicting results regarding the role of tau (MAPT) haplotypes in neurodegenerative disorders. Recent reports suggest that ethnicity factors and gene-gene interactions may influence the risk of developing Alzheimer's disease (AD). The present study investigates possible synergism between MAPT haplotype and ApoE state in Hungarian Caucasian AD cases (n=91) and control (n=83) population. The difference in MAPT H1 allele frequency did not reach significant level in AD (78%), and control individuals (73.5%), however ApoE4 carriers were significantly overrepresented in AD (34.1% vs. 20%) compared to the control population. Though a specific combination of ApoE4 and H1 alleles were found to be associated to AD (14.5% vs. 30.8%), synergistic genetic interaction could not be inferred. Our findings support the notion that while ApoE4 might be involved in AD pathology the MAPT H1 allele neither associates nor interacts through an epistasis with ApoE4 in the development of the disease.

It has been suggested that human herpesvirus 8 (HHV-8), also known as KSHV (Kaposi's sarcoma-associated human herpesvirus), might possess a promoting effect in the development and progression of monoclonal gammopathies. In this study, the presence of Epstein-Barr virus (EBV), human cytomegalovirus (CMV), human herpesvirus 6 (HHV-6) and human herpesvirus 8 (HHV-8) were tested in patients with multiple myeloma (MM) using both serologic and nucleic acid amplification techniques. The transient reactivation or continuous presence of EBV, CMV, HHV-6 and HHV-8 could be detected in, respectively, 36, eight, 13 and 29 of 69 MM patients; nine, one, four and six of 16 monoclonal gammopathy of unknown significance patients; and seven, four, zero and five of 10 Waldenstrom's macroglobulinemia patients. The total number of MM patients was 95. HHV-8 PCR-positivity was significantly more frequent in the MM group than in the control group of patients with non-Hodgkin's lymphoma (NHL). However, serologic testing did not reveal significant differences between the two patient groups. The number of MM patients with concomitant herpesvirus infections as detected by PCR was as follows: 15 double, seven triple and two quadruple virus nucleic acid positive. In 13/95 MM patients, the simultaneous presence of acute EBV infection and HHV-8 PCR-positivity was detected compared with none of the control group (P=0.009). These results indicate that in addition to HHV-8, the transitional reactivation of EBV may also play a role in the pathogenesis of MM.