It is well known that smoking is the risk factor in the development and clinical course of Crohn´'s disease (CD), but on the other hand, smoking is a protective factor against ulcerative colitis (UC). The pathways that are influenced by smoking in CD and UC are poorly understood. The aim of our study was to analyse the influence of smoking on the mRNA expression of cytokines in mucosa in patients with CD and UC. We performed a cross-sectional study. The cohort consisted of 86 IBD patients (48 CD patients and 38 UC patients) and took place at the IBD Centre at the University Hospital Bratislava-Ružinov. We took the demographic and clinical data of each patient, including information about their smoking habits. We performed a colonoscopy on each patient and took biopsies from both inflamed and non-inflamed sigma (CD, UC) and terminal ileum (CD). mRNA was extracted from mucosal biopsy samples for each cytokine and was normalized to a housekeeping gene (GAPDH). Finally, we compared the mRNA expression of target cytokines in the mucosa of smokers and non-smokers in IBD patients. Smokers with Crohn's disease have a significantly higher mRNA expression of pro-inflammatory cytokine TNF α (p=0.003) in inflamed mucosa in sigma compared with non-smokers. In smokers with ulcerative colitis, we observed significantly higher mRNA expression of anti-inflammatory cytokine IL 10 (p=0.022) in non-inflamed mucosa of sigma. Similarly, smokers with UC have a significantly decreased mRNA expression of cytokine TLR 2 (p=0.024) and CCR1(p=0.049) in non-inflamed mucosa of sigma. Based on our results, smoking has a positive influence on cessation and the clinical course of UC due to the stimulation of anti-inflammatory cytokine IL 10 in mucosa. On the other hand, smokers with CD have a higher expression of pro-inflammatory cytokine TNF α, which could be associated with a worsening of the disease and response to therapy.

This article is focused on endocrine-mediated osteoporosis caused by growth hormone (GH) disorders; adult GH deficiency and acromegaly. GH and insulin like growth factor-1 (IGF-1) stimulate linear bone growth through complex hormonal interactions and activates epiphyseal prechondrocytes. GH, via receptor activator of nuclear factor-kappaB (RANK), its ligand (RANK-L), and the osteoprotegerin system, stimulates production of osteoprotegerin and its accumulation in bone matrix. Malfunction of this mechanism, could lead to specific bone impairment. However, the primary problem of bone disease in GH secretion disorders is the primary prevention of osteoporotic fractures, so it is important to determine bone quality that better reflects the patient's actual predisposition to fracture. A method estimating bone quality from lumbar spine dual X-ray absorptiometry (DXA) scans is trabecular bone score (TBS). TBS in addition to bone mineral density (BMD) is a promising predictor of the osteoporotic fracture risk in women with postmenopausal osteopenia. In acromegaly TBS better defines risk of fracture because BMD is normal or even increased. TBS helps to monitor the effect of growth hormone therapy. Despite these findings, TBS should not be used alone, but a comprehensive consideration of all fracture risk factors, BMD and bone turnover markers is necessary.

Drug-induced liver injury (DILI) is a common event in patients with rheumatic diseases (RD) on biological therapy (BT). We aimed at evaluating the prevalence and pattern of DILI. Consecutive RD patients treated with BT were followed for 6 months. ALT and ALP >the upper limit normal (ULN) and3xULN injury Grade 2. 582 liver function tests (LFTs) in 199 patients were evaluated, median age 53y, 59.3 % females, RA in 108, AS 49, and PsA 42 patients. ALT Grade 1 elevation was observed in 25.6 %, transient in 18.6 %, persisting in 7 %, Grade 2 in 1.5 %, ALP Grade 1 in 3.5 %, transient in 2 %, persisting in 1.5 %. We report no case of ALP Grade 2 or Hy´s law (ALT>3xULN, bilirubin>2xULN). Patients with persisting ALT elevation had higher BMI (28.23 vs. 25.74, p=0.016), lower DAS28 (2.22 vs. 5.28, p=0.046). ALT Grade 1 injury was more frequent with solo tocilizumab compared with other agents (27.5 % vs. 13.6 %, p=0.01). DILI was frequent, in 18.6 % transient, in 7 % persisting, Grade 2 in 1.5 %, led to treatment alteration in 0.5 %, with higher prevalence on solo tocilizumab therapy. We report no new safety signals for BT in RD.

Osteoporosis is an increasingly widespread disease, as well as diabetes mellitus. It is now accepted that osteoporotic fractures are a serious co-morbidity and complication of diabetes. Despite of good bone mineral density in Type 2 Diabetes (T2DM) patients is the fracture risk elevated. It is due to reduced bone quality. To determine the effect of glycemic compensation on bone density and trabecular bone score (TBS) in T2DM. We analyzed a cohort of 105 postmenopausal women with T2DM. For all patients, central bone density (spinal and lumbar spine) was tested by DXA methodology, glycemic control parameters were assessed, and anthropometric parameters were measured. Bone quality was analyzed using TBS software. The results were statistically processed. Good glycemic compensation with glycated hemoglobin (A1c) value <7.0 % DCCT did not lead to BMD changes in patients with T2DM. However, patients with HbA1c <7 % DCCT had significantly better TBS (1.254±0.148 vs. 1.166±0.094, p=0.01). There was a negative correlation between TBS and glycated hemoglobin (r= -0,112, p<0.05) with glycemic fasting (r= -0.117, p<0.05). The optimal effect on TBS is achieved when all three markers of glycemic compensation (glycated hemoglobin, fasting plasma glucose and postprandial glycemia) are in optimal range. By using ROC curves glycated hemoglobin has the most significant effect on TBS. Optimal glycemic compensation, evaluated by glycated hemoglobin, does not lead to changes in BMD but has a beneficial effect on TBS in T2DM. Good glycemic control is required also for reduction of the risk of osteoporosis and osteoporotic fractures.

The aim of this study was to analyze the influence of 25(OH)VD serum concentration on the expression of mRNA cytokines (IL-6, IL-8, IL-12, IL-17, IL-23, TNFα, CCR1, CCR2, CCR5, CCR9, CCL5, TLR2, TLR4, TLR5, CD207 ,CD206, FoxP3) in mucosa of IBD patients. The cohort consisted of 86 IBD patients (48 CD and 38 UC) followed at the IBD center of University Hospital Bratislava-Ruzinov. We performed colonoscopy in each patient and took biopsies from mucosa of sigma and terminal ileum. Serum concentration of 25(OH)VD was assessed at the time of colonoscopy. mRNA was extracted from mucosal biopsy samples for each cytokine. Then we analyzed the correlation between VD and the expression of mRNA of cytokines from biopsies samples.  In CD we observed a significant positive correlation of serum concentration 25(OH)VD and the expression mRNA level of IL-6. There was also trend towards significant positive correlation of the expression mRNA of TNFα, IL-10, IL-23, TLR 2 in inflamed mucosa of terminal ileum as well as the expression mRNA of CCR5 and CCR1 in non-inflamed mucosa from terminal ileum. We also found a trend towards positive correlation between 25(OH)VD and the expression mRNA of IL-23, TLR4, CD 207, CCR1, CCR5 and CD 206 in non-inflamed mucosa of sigma in UC.VD significantly correlated with the levels of expression of several inflammatory cytokines including TNFα in colonic mucosa of patients with IBD (Tab. 4, Fig. 3, Ref. 31).

SummaryTo assess the current practice patterns in the diagnosis and treatment of male osteoporosis based on questionnaires. Questionnaires were presented and filled out by osteoporosis experts from Austria, Bulgaria, the Czech Republic, Hungary, Poland, Romania, Slovakia, Slovenia and Russia. The questions included focused on the proportion of male referrals to DXA, the main reasons for referral, the preferred measurement sites and reference database, the definition of male osteoporosis, needed laboratory investigations, data on calcium and vitamin D supplementation as well as on treatment modalities and their reimbursement rate. Men comprised 5 to 10% of all DXA referrals. The main reasons for referral were low back pain and fractures. Most of the respondents used the International male reference database. The diagnosis of osteoporosis was based mainly on a T-score below −2.5 after the age of 50, but a few respondents added fractures as a necessary condition. Only 1/3 of men visiting DXA sites are expected to have normal BMD. A consensus for the use of laboratory investigations in male osteoporosis is practically lacking. Treatment modalities include alendronate, risedronate, zoledronate, denosumab, rhPTH and strontium (with some restrictions for the latter three). Data on treatment adherence and persistence are generally lacking except for Austria, Romania and Slovakia. The levels of reimbursement vary a lot across countries. Osteoporosis in men is an under-recognized problem in CEE countries, leading to a tremendous gap in the diagnosis and treatment.

Background: Osteopenia and osteoporosis are known chronic complications of inflammatory bowel diseases (IBD). It is known that areal bone mineral density (aBMD) does not sufficiently reflect bone strength and quality. The trabecular bone score (TBS) provides an indirect measurement of bone microarchitecture, independent of aBMD. Methods: The aim was to assess TBS and BMD of lumbar spine (LS) in IBD patients. Furthermore we analyzed the impact of clinical factors on TBS. The cohort consisted of consecutive IBD patients from tertiary IBD centre. Clinical characteristics i.e. age, gender, anthropometry, clinical behaviour, medication were recorded. The BMD was determined by dual-energy X-ray absorptiometry (DXA, Hologic Discovery) at the lumbar spine. TBS was determined by TBS Insight® software (Medimaps, France). Results: The cohort consisted of 84 IBD patients (53 with Crohn's disease (CD) and 31 with ulcerative colitis (UC)). The mean age was 42.0±14.2 years with the mean disease duration of 11.0±7.0 years. There were 14% (12/84) postmenopausal women, 8 patients (9.5%) were on long term corticosteroids and 21 CD patients had prior major IBD surgery. The percentage of patients with substitution of vitamin D (800IU) and calcium (0.5–1g) was similar between CD and UC (24.5% vs. 29.0%), none of the patients was on anti-porothic treatment. The mean LS BMD of the cohort was 0.964±0.113 g/cm2 and TBS 1.36±0.14. We observed significantly lower mean TBS LS in patients with fistulising CD compared to luminal CD, 1.36±0.09 and 1.47±0.05 (p=0.0039) respectively. No similar finding was observed using BMD. We did not observe any significant impact of clinical characteristics nor medication in UC patients. Conclusions: We observed that spine TBS can identify quality of bone mineral density in patients with Crohn's disease better than BMD itself. CD patients with severe disease are at higher risk of low bone mineral density.

Aim: The purpose of this study was to monitor ultrasound-detectable changes of median nerve in transverse section level of the carpal tunnel in hypothyroid patients with newly diagnosed, untreated autoimmune hypothyreosis. Material and methods: A cross sectional comparative study of patients with newly-diagnosed primary autoimunne hypothyroidism, where transverse section breadth of the median nerve in its entrance to the carpal tunnel (CSA) was measured. Values were compared with a control group of healthy subjects. Differences were statistically evaluated by unpaired t-test. Results: Absolute number of patients included in the study was 44 (empty set age 52.8 years, 14 males/30 females, empty set BMI 24.542 kg/m(2), empty set TSH 22.815 mU/l, fT4 11.756 pmol/l). The control group consisted of 44 subjects (empty set age 52.57 years, 14 males/30 females, empty set BMI 24.52 kg/m(2), empty set TSH 2.31 mU/l, empty set fT4 16,397 pmol/l). CSA was significantly higher in patients (empty set 0.098 cm(2)) compared to controls (empty set 0.072 cm(2), p < 0.001). In two hypothyroid patients, pathological increase of CSA (> 0.11 cm(2)) was in accordance with symptomatology of the carpal tunnel syndrome. Conclusion: Ultrasound findings documented occurrence of subclinical and clinical carpal tunnel syndrome in patients with primary hypothyroidism. If carpal tunnel syndrome occurs, thyroidal status should be evaluated to exclude possible hypothyroidism. Cross sectional area of median nerve evaluation with high frequency ultrasound could be considered an alternative modality for early detection of this neuropathy in patients with hypothyroidism.