Substitution Urethroplasty with Buccal Mucosal Graft in the Management of Stricture of Vesicourethral Anastomosis or Membranous Urethra: Single-Institution Long-Term Experience with Perineal Approach and Endourethroplasty.

OBJECTIVE: To present long-term experience with buccal mucosa posterior urethroplasty (BMPU) for refractory posterior urethral stenosis (PUS) or vesicourethral anastomosis stenosis (VUAS) either by perineal approach (PA) or by endourethroplasty (EUP). MATERIALS AND METHODS: A single-center retrospective study of 38 consecutive patients operated on between 1999 and 2022. BMPU consisted of the transfer of onlay or tubular buccal mucosa grafts into dilated and/or incised strictures through an open or endourological approach. If VUAS or PUS recurred with short stenosis within the first 12 months after surgery, it was transected by a cold-knife direct vision internal urethrotomy (DVIU), referred to as an 'auxiliary' DVIU. The primary outcome was three-year stricture recurrence-free survival (SRFS). RESULTS: BMPU by perineal approach and EUP were performed in 27 (71%) and 11 (29%) patients, respectively. The three-year SRFS was 65% for the whole cohort, with rates of 63% for the perineal approach and 73% for endourological approach. With permitted auxiliary DVIU, three-year SRFS for the whole cohort was 81%. De novo incontinence occurred in 2 out of 18 preoperatively continent patients. Limitations include the retrospective nature of the single-center study and a small, heterogenous cohort of patients. CONCLUSIONS: We present two techniques of substitution urethroplasty with BMG in the management of PUS and VUAS with a low rate of recurrence or de novo incontinence. A novel endourological approach (EUP) is a promising minimally invasive alternative to the perineal approach.

Enhancing the utility of chromosome 6 and 8 testing in uveal melanoma biopsies.

BACKGROUND: The aim of this study was to evaluate the significance of testing the gain of chromosome 8 and the gain of chromosome 6 as prognostic markers in histopathological samples of enucleated eyes in with uveal melanoma. METHODS: This is a retrospective study of 54 enucleated eyes. The status of chromosomes 3, 8 and 6 was tested by CISH, and FISH was used in a few samples. A follow-up for the detection of metastases was conducted in all patients. The statistical significance of chromosomal abnormalities as a prognostic factor for the development of metastases was determined. RESULTS: The study group consists of 54 patients (average age 63 years), 28 men (51.9%) Monosomy 3 together with gain of chromosome 8 was found in 10 samples (18.5%). Both chromosomal abnormalities were detected in 6 (11%) patients. No chromosomal abnormality in 3 or 8 was detected in 21 (38.9%) patients. Abnormalities of chromosome 6 were present in 6 (11%) patients. Progression free survival after 5 years was 33.3% (95% CI 0.0; 83.3) in these patients. CONCLUSIONS: Our findings indicate a correlation between progression-free survival and the presence of changes in chromosome 3 and e 8 in uveal melanomas. The results underline the necessity of testing for both chromosomal aberrations.

Changes in Segmental Impedances and Selected Body Composition Parameters Assessed by Multi-Frequency Bioimpedance Analysis after Fluid Consumption in Healthy Young Population.

Objectives: Body composition (BC) analysis is a routine part of comprehensive public health care. Assessment of BC is more important source of information than BMI. Adherence to the standard measurement conditions is essential for the correct results. Our study aimed to examine the effect of acute fluid consumption on measures of body mass (BM), percentage of body fat (%BF), visceral fat (VF), percentage of body water (%BW), and impedance at 100 kHz (I100) and 20 kHz (I20) using segmental multi-frequency bioelectrical impedance analysis (SMF-BIA) in a general healthy population. Methods: 95 consecutive healthy normal-weight adults (42 men; 53 women) were involved in the study (mean ± s.d.; age 23.9±1.6 years; body mass 68.3±14.1 kg). All subjects underwent two separate series of body composition (BC) measurements at 0 (BASELINE), 30, 60, 90 min (POST): the first series after drinking 600 ml of isotonic carbohydrate/electrolyte drink (IST) and the second after no fluid administration (CON). Individual measurements were performed in the morning on two consecutive days. Results: In the IST group, BM, VF (both P<0.001), and %BF (P<0.05) increased significantly at 30 min POST compared to BASELINE. BM and VF remained elevated at 90 min POST (both P<0.001). %BW decreased significantly at 30 min POST (P<0.01) then increased at 60 min (P<0.001) and 90 min (P<0.01) POST. There were no significant changes in I100. I20 increased significantly at 30 min POST (P<0.001) then decreased at 60 min (P<0.001) and 90 min POST (P<0.01) compared to BASELINE. In the CON group, BM and VF decreased below BASELINE at 90 min POST (P<0.001), %BF, %BW and I100 did not change significantly. The difference between IST and CON was statistically significant for all POST measurement times only in BM and VF (both P<0.001). The VF results are also underlined by the detected impedance changes in the trunk area at 20 kHz (B20) and 100 kHz (B100) at 60 min and 90 min (both P<0.001). Conclusions: Our study suggests that segmental impedances and BC measurement in healthy young normal-weight adults requires strict adherence to fluid restriction at least 90 min before the measurement to avoid false impedance values and overestimation of BM and VF.

Tumor Necrosis Factor Inhibitor Monotherapy Versus Combination Therapy for the Treatment of Psoriatic Arthritis: Combined Analysis of European Biologics Databases.

OBJECTIVE: To investigate whether tumor necrosis factor inhibitor (TNFi) combination therapy with conventional synthetic disease-modifying antirheumatic drugs (csDMARD) is more effective for psoriatic arthritis (PsA) and/or improves TNFi drug survival compared to TNFi monotherapy. METHODS: Five PsA biologics cohorts were investigated between 2000 and 2015: the ATTRA registry (Czech Republic); the Swiss Clinical Quality Management PsA registry; the Hellenic Registry of Biologics Therapies (Greece); the University of Bari PsA biologics database (Italy); and the Bath PsA cohort (UK). Drug persistence was analyzed using Kaplan-Meier and equality of survival using log-rank tests. Comparative effectiveness was investigated using logistic regression with propensity scores. Separate analyses were performed on (1) the combined Italian/Swiss cohorts for change in rate of Disease Activity Score in 28 joints (DAS28); and (2) the combined Italian, Swiss, and Bath cohorts for change in rate of Health Assessment Questionnaire (HAQ). RESULTS: In total, 2294 patients were eligible for the drug survival analysis. In the Swiss (P = 0.002), Greek (P = 0.021), and Bath (P = 0.014) databases, patients starting TNFi in combination with methotrexate had longer drug survival compared to monotherapy, while in Italy the monotherapy group persisted longer (P = 0.030). In eligible patients from the combined Italian/Swiss dataset (n = 1056), there was no significant difference between treatment arms in rate of change of DAS28. Similarly, when also including the Bath cohort (n = 1205), there was no significant difference in rate of change of HAQ. CONCLUSION: Combination therapy of a TNFi with a csDMARD does not appear to affect improvement of disease activity or HAQ versus TNFi monotherapy, but it may improve TNFi drug survival.

Retrospective analysis of the incidence of pulmonary embolism in CT images in patients with a positive value of D-dimers.

AIM: The analysis of the correlation between D-dimer and positive finding of pulmonary embolism on CT-angiography. Determination of the cut-off value of D-dimers, which would lead to a reduction in the number of examinations on CT-angiography. MATERIALS AND METHODS: Patients who had positive D-dimer values in their blood tests and were examined using CT-angiography were included in the analysis. The relationship between the D-dimer value and the finding of pulmonary embolism on CT-angiography was analyzed. The analysis included 91 consecutive patients (46 women, 64,5 ± 18,8 years) examined from December 2019 to January 2020. RESULTS: The mean value of D-dimers in patients with proven pulmonary embolism on CT was statistically significantly higher than in patients without embolism (7,46 vs 2,93 mg/l; p < 0,001). Of the total number of patients examined on CT, pulmonary embolism was confirmed in 21 (23 %). We did not show a statistically significant difference in the incidence of pulmonary embolism in one sex (52 % female vs 48 % male; p = 1,000), nor the relationship between age and the incidence of pulmonary embolism (64,2 vs 64,5 years; p = 0,981). Based on ROC analysis, we determined a high probability of negative CT-angiography at the value of D-dimers up to 1,7 mg/l (negative predictive value 95,7 %). We also determined the value of D-dimers 3,5 mg/l, from which the probability of pulmonary embolism on CT is high (specificity 81,4 %). CONCLUSION: Based on a retrospective analysis of patients with measured values of D-dimers and objectification of the finding of pulmonary embolism on CT-angiography, we demonstrated a very low probability of pulmonary embolism at D-dimer values up to 1,7 mg/l. We also showed that at values above 3,5 mg/l, the probability of pulmonary embolism is high.

Prognostic Survival Factors of Hepatocellular Carcinoma Treated with Transarterial Chemoembolization.

PURPOSE: Identification of prognostic survival factors of hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) in a single center in 2005-2018. BACKGROUND: Transarterial chemoembolization in hepatocellular carcinoma is indicated in Barcelona Liver Cancer Clinic (BLCC) stage B. This stage includes a very large group of patients unsuitable for curative treatment, who are in a good clinical condition and do not show extra-hepatic spread. The aim of this retrospective analysis is to identify factors influencing patient survival and to divide the patients into subgroups based on these risk factors. MATERIALS AND METHODS: All patients with HCC indicated for TACE in complex oncological center in 2005-2018 were included in the analysis. The survival rates from the 1st TACE were evaluated in relation to HCC on computed tomography/magnetic resonance prior to the 1st TACE (size of the biggest lesion, single/multiple lesions, unilobar/bilobar involvement), presence and severity of liver disease (cirrhosis, Child-Pugh, portal vein thrombosis) and a combination of other invasive treatment (resection, percutaneous ablation) (single and multivariate analysis). The survival of HCC patients was compared according to the year of the dia-gnosis and the year of the 1st TACE (log-rank test). RESULTS: Out of 382 patients, 157 (29 women) of them were treated with TACE (540 TACEs in total, median 3 TACEs per patient). The most important risk factors for survival were the presence of portal vein thrombosis (hazard ratio (HR) = 3.279), bilobar involvement (HR = 2.257), lesion size (HR = 1.125/cm) and Child-Pugh B in chronic liver disease (HR = 1.922). Based on these risk factors, the patients were divided into 3 prognostic groups with different median survival (52.1 vs. 21.5 vs. 9.0 months). CONCLUSION: Based on the retrospective analysis, predictive factors of HCC survival after TACE were identified and the patients were divided into 3 prognostic groups based on these factors.

Vitamin D levels in IBD: a randomised trial of weight-based versus fixed dose vitamin D supplementation.

Objectives: Body weight is one of the factors affecting blood levels of 25-hydroxyvitamin D (25OHD). The aim of this study was to establish whether a vitamin D (vitD) weight-based dosing is more appropriate to a fixed daily dose in patients with inflammatory bowel disease (IBD).Materials/methods: This was an open label randomised trial. Patients with IBD were assigned to receive oral cholecalciferol at a dose of 28 IU/kg (IU/kg) or 2000 IU per day (IU/day) for 12 weeks during winter months. 25OHD plasma levels and other biochemical parameters were measured at baseline and after supplementation period. The primary outcome measure was 25OHD level after a follow-up period.Results: A total of 173 patients were analysed. The mean BMI was 25.5 ± 5.1 and initial mean 25OHD level was 62.7 ± 25.5 nmol/l. A similar increase (9.7 ± 26.9 vs 9.8 ± 26.7 nmol/l) in 25OHD levels occurred both in IU/kg and IU/day group. The proportion of subjects with normal and sub-normal levels following the substitution was comparable irrespective of body weight. The change in 25OHD level correlated positively only with the dose of vitD (p < .001) and negatively with the baseline 25OHD level (p < .001). A sustained 25OHD level of 75 nmol/l corresponds with a calculated daily vitD dose of 2034 IU.Conclusions: Weight-based dosing of vitamin D is not superior to a fixed dose in order to maintain stable 25OHD levels in IBD patients. Cholecalciferol dose of 2,000 IU/day is safe and sufficient during winter period.

Uveal melanoma - testing of abnormalities of chromosome 3 and 8 in the Czech Republic.

AIM: The aim of this cytogenetic study is to confirm the significance of chromosome 3 loss (monosomy 3) and of the gain of chromosome 8 as prognostic markers in histopathological samples of enucleated eyes with uveal melanoma in the Czech population. METHODS: This is a retrospective study of 52 enucleated eyes. Chromosome 3 and 8 status were tested by CISH, and in a few samples FISH was used. The correlation between monosomy 3 and gain of chromosome 8 and clinical features (histopathological type, size of the tumour) were evaluated. A follow up for the detection of metastases was conducted in all patients. The statistical significance of chromosomal abnormalities as a prognostic factor for the development of metastases was calculated. RESULTS: There were 52 patients, 27 men (51.9%) and 25 women (48.1%) enrolled in our study group. The mean age was 63 ± 14 years. Loss of the one copy of chromosome 3 (monosomy 3) was detected in 26 (50.0%) patients, monosomy 8 was present in 34.6% of patients with monosomy 3. After 5 years there were no metastases in 82% of patients without monosomy 3 as opposed to 40% of patients with monosomy 3. We confirmed a statistically significant association between progression free survival (PFS) and the presence of monosomy 3 (P=0.017). The association between PFS and gain of chromosome 8 was significant as well (0.010). CONCLUSIONS: Our data showed the association of progression-free survival with the presence of monosomy 3 in uveal melanomas. We provided a good prognostic value of monosomy 3 in uveal melanoma.

Short-term response in new users of anti-TNF predicts long-term productivity and non-disability: analysis of Czech ATTRA ankylosing spondylitis biologic registry.

Objectives: To assess the role of short-term response to first anti-TNF in long-term prediction of disability.Methods: In nationwide registry ATTRA, we identified ankylosing spondylitis patients starting anti-TNF between 01/2003 and 12/2016. Full disability and work impairment (WI; WPAI questionnaire) were predicted via the Cox- and lagged-parameter mixed-effect regression.Results: 2,274 biologicals-naïve patients newly indicated to anti-TNF were prospectively followed (6,333 patient-years; median follow-up 1.9 years). Reaching BASDAI < 4 (77.4%) and ASDAS-CRP < 2.1 (61.1%) after 3 months of anti-TNF both decreased the risk of future disability by ≈2.5-fold. ASDAS-CRP < 2.1 predicted non-disability better than BASDAI < 4 & CRP < 5 mg/L (p = 0.032). BASDAI < 4 & CRP < 5 mg/L was comparable to BASDAI < 4 (p = 0.941) and to BASDAI change by >50% or by >2 points (p = 0.902). ASDAS-CRP change >1.1 and >2.0 both failed to predict non-disability. Once on anti-TNF therapy, the strongest predictor of WI was Pain (SF36). Yearly increase in indirect costs remains below €3,000 in those reaching ASDAS-CRP < 2.1.Conclusions: Low disease activity measured by ASDAS-CRP ≤ 2.1 should be used to measure the outcome of new anti-TNF therapy. Continuous WI could be decreased through pain management.

Vitamin D supplementation dose needs to be higher in patients with inflammatory bowel disease: interventional study.

INTRODUCTION: Vitamin D (vitD) is a substance with an immunomodulatory effect. Its insufficiency has negative impact also on inflammatory bowel disease (IBD) where it is often present. The recommended daily intake for general population is 600 UI/day (units/day). What is the necessary dose for IBD patients remains unknown. The aim of the study was to verify whether the 2,000 IU/day of vitD is sufficient for maintaining sustained levels in these patients. METHODS: Patients with Crohns disease (CD) or ulcerative colitis (UC) were supplemented orally with 2,000 IU of cholecalciferol daily during winter time. The level of 25-hydroxyvitamin D (25OHD) was established at the beginning of substitution period (October to December) and in Month 4. Demographic data, Ca, P, parathormone levels, dose of vitD used, and patients compliance were observed. RESULTS: 108 patients with CD and UC (71/37) were analysed, out of them 51 females, average age 43.3 ± 16.2 years. The level of 25OHD increased from 60.2 ± 26.5 nmol/l to 68.1 ± 27.1 nmol/l (p < 0.001) during the period with the average substitution dose of vitD 1 858 ± 464 IU/day. 60.2 % of subjects complied with the recommended dosing of vitD. The dose of 1,820 IU vitD/day showed to be sufficient for maintaining sustained levels in the model. No changes of Ca, P serum levels occurred during observation period. CONCLUSIONS: Substitution doses of vitD recommended for general population are insufficient for IBD patients. A dose of up to 2,000/day, which is safe, is necessary to maintain normal levels of 25OHD. Noncompliance with the use of vitD is high.

Circulating S100 proteins effectively discriminate SLE patients from healthy controls: a cross-sectional study.

S100 proteins are currently being investigated as potential diagnostic and prognostic biomarkers of several cancers and inflammatory diseases. The aims of this study were to analyse the plasma levels of S100A4, S100A8/9 and S100A12 in patients with incomplete systemic lupus erythematosus (iSLE), in patients with established SLE and in healthy controls (HCs) and to investigate the potential utility of the S100 proteins as diagnostic or activity-specific biomarkers in SLE. Plasma levels were measured by ELISA in a cross-sectional cohort study of 44 patients with SLE, 8 patients with iSLE and 43 HCs. Disease activity was assessed using the SLEDAI-2K. The mean levels of all S100 proteins were significantly higher in SLE patients compared to HCs. In iSLE patients, the levels of S100A4 and S100A12 but not S100A8/9 were also significantly higher compared to HCs. There were no significant differences in S100 levels between the iSLE and SLE patients. Plasma S100 proteins levels effectively discriminated between SLE patients and HCs. The area under the curve (AUC) for S100A4, S100A8/9 and S100A12 plasma levels was 0.989 (95% CI 0.976-1.000), 0.678 (95% CI 0.563-0.792) and 0.807 (95% CI 0.715-0.899), respectively. S100 levels did not differentiate between patients with high and low disease activity. Only the S100A12 levels were significantly associated with SLEDAI-2K and with cSLEDAI-2K. S100 proteins were significantly higher in SLE patients compared HCs and particularly S100A4 could be proposed as a potential diagnostic biomarker for SLE.

Half-Fluence Photodynamic Therapy for Chronic Central Serous Chorioretinopathy: Predisposing Factors for Visual Acuity Outcomes.

BACKGROUND: Central serous chorioretinopathy (CSC) is characterised by a serous detachment of the neurosensory retina in the macula. Chronic CSC tends to affect older individuals with a less favourable visual outcome. Photodynamic therapy (PDT) with verteporfin is a possible therapeutic approach in cases of CSC with no tendency for spontaneous resorption. PDT has shown good anatomic and functional results in treating chronic CSC. For the purpose of diminishing side effects, modifications of the standard protocol were used. MATERIALS AND METHODS: This is a retrospective study of 32 eyes with CSC of 32 patients treated by half-fluence PDT. The patients underwent complete ophthalmology examination. On optical coherence tomography (OCT) we measured central retinal thickness (CRT), the outer nuclear layer (ONL), presence of subfoveolar detachment of retinal pigment epithelium (PED), disturbance of external limiting membrane (ELM), morphological changes in the inner segment/outer segment (IS/OS) line and retinal pigment epithelium (RPE) atrophy. We evaluated at baseline, 3 and 12 months after PDT. RESULTS: The mean BCVA at baseline was 0.41 ± 0.23 log MAR, the mean BCVA at 3 months was 0.24 ± 0.20 and at the end of the follow-up it was 0.23 ± 0.200. We observed statistically significant improvements of visual acuity after 3 and 12 months (p < 0.001, Wilcoxon test). The mean central retinal thickness at baseline was 373 ± 87 µm, the mean CRT after 3 months was 234 ± 42 µm and after 12 months 223 ± 39 µm. A significant reduction from baseline was seen after 3 months and 12 months (p < 0.001, Wilcoxon test). Baseline ONL reached 80 ± 27 µm, after 3 months it was 78 ± 20 and after 12 months it was 74 ± 20 µm. We observed a statistically significant change in diminishing the amount of PED after PDT after 3 months and after 12 months (p = 0.021, McNemar's test). We observed that in patients with RPE ablation, there is lower chance for the restitution of the IS/OS layer (p = 0.045, Mann-Whitney test). We observed a negative association between the improvement of visual acuity after 12 months and the presence of RPE ablation (p = 0.031, Mann-Whitney test). Restitution of ELM was significantly more often in patients with shorter duration of symptoms, (p = 0.027 after 3 months, p = 0.033 after 12 months after PDT, Spearman correlation). Neither ocular nor systemic adverse effects were observed during the follow-up period. CONCLUSIONS: Half-fluence PDT treatment has shown to be a usually safe and often effective therapy in patients with chronic CSC. This study suggests that the most important predictive factor is baseline visual acuity. The important anatomical change detected using OCT is a thinning of the outer nuclear layer. Nonetheless, other studies with a larger number of patients and a longer follow-up are required.

The relationship between synovitis quantified by an ultrasound 7-joint inflammation score and physical disability in rheumatoid arthritis - a cohort study.

BACKGROUND: Restoring normal physical functioning is a major therapeutic aim in the management of rheumatoid arthritis (RA). It is unknown, whether the extent of synovial inflammation quantified by musculoskeletal ultrasound (US) can predict current or future capacity for physical functioning. To answer this question we investigated the longitudinal relationship between physical function assessed by the health assessment questionnaire (HAQ) and the German 7-joint ultrasound score (US7S) in a prospective cohort of patients with RA. METHODS: Patients with RA (n = 185 (46 with incident and 139 with prevalent disease) were followed for 30.9 ± 9.1 months. Baseline and annual assessments comprised the disease activity score in 28 joints (DAS28), HAQ and US7S. The US7S includes semiquantitative measurements of synovitis assessed by greyscale (GS) and power Doppler (PD) in seven joints of the clinically dominant hand and foot, which are then aggregated in PD and GS synovitis sum-scores (PDsynSS and GSsynSS). A linear mixed-effect model was used to assess the longitudinal relationship between GSsynSS, PDsynSS and HAQ. We used standard and time-lag models to explore the association between HAQ, and GSsynSS, PDsynSS and DAS28 measured at the same time or at the previous visit 12 months ago, respectively. RESULTS: When the standard model was applied, in univariate analyses HAQ score was positively associated with GSsynSS and PDsynSS with ß coefficients significantly higher in incident than in prevalent disease. In multivariate analysis both synSSs were individually no longer significant predictors of HAQ score. When using the time-lag model, after adjustment for the previous DAS28 or HAQ score, both PDsynSS and GSsynSS were significantly and negatively associated with the current HAQ. CONCLUSIONS: US7 PD and GS synovitis sum-scores alone were positively associated with current functional status reflected by the HAQ in patients with RA, and this relationship was stronger in patients with early disease. When combined with the DAS28 or HAQ, US7 PD and GS synovitis sum-scores were predictive of the change in HAQ score over one year.

[Idiopathic pulmonary fibrosis prognostic factors - analysis of the Czech registry]. / Prognostické faktory idiopatické plicní fibrózy (IPF) - analýza Ceského registru IPF.

UNLABELLED: Idiopathic pulmonary fibrosis (IPF) is a rare, progressive and usually fatal form of idiopathic interstitial pneumonia. IPF is characterized by failure of alveolar re-epithelization, persistence of fibroblasts, deposition of extracellular matrix, and distortion of lung architecture, which ultimately results in respiratory failure.We analysed 202 consecutive patients with IPF diagnosed at the Departments of Pulmonary Diseases and Tuberculosis in the Czech Republic, who they were included in the nationwide Czech IPF registry. Our aim was to determine prognostic factors of IPF and outcome of the disease.There were 129 males and 73 females who were the median age 67 years. IPF was biopsy-proven in 66 (33 %) of patients. Median time from the first symptom to diagnosis was 12 months. Diagnosis was made in 57 patients (28.3 %) within 6 months from the onset of respiratory symptoms. 8 (4 %) patients had an acute exacerbation during the course of the disease.In uniparametric (univariate) analysis as prognostic factors associated with poorer survival were found: higher age, higher degree dyspnea scores, clubbing fingers, comorbidities (arterial hypertension, osteoporosis), patients without histology biopsy, and bronchoalveolar increased neutrophil count. We found these positive prognostic factors: higher levels of VC (vital capacity), TLC (total lung capacity) and DLCO (diffusing capacity for carbon monooxide).In multiparametric (multivariate) analysis as prognostic factors associated with mortality were found: higher age, higher degree of dyspnoe score. Increased lymphocytes in bronchoalveolar fluid, higher level of VC a DLCO were associated with better survival. There was no difference in survival of patients by sex, by smoking status. No significant difference in survival rates was found between IPF with and without emphysema, between the extent of fibrosis on HRCT (high resolution computed tomography) of thorax and mortality. Median survival was 51.6 months. 58 (28.7 %) patients died. The most frequent reason of dead was IPF progression with respiratory failure. KEY WORDS: Idiopathic pulmonary fibrosis; prognosis; treatment.

A tailored approach to reduce dose of anti-TNF drugs may be equally effective, but substantially less costly than standard dosing in patients with ankylosing spondylitis over 1 year: a propensity score-matched cohort study.

OBJECTIVE: To compare the effectiveness, safety and costs of standard versus individually tailored reduced doses of anti-tumour necrosis factor (TNF) drugs in patients with ankylosing spondylitis (AS) after achieving low-disease activity. METHODS: This was a single-centre prospective observational study performed within the ATTRA registry. The anti-TNF dose tapering strategy was chosen by treating physicians, without prespecified protocol. We used propensity score (PS) methodology to identify two cohorts of patients matched for relevant baseline characteristics who were treated with either reduced (n=53) or standard (n=83) doses of TNF inhibitors. One-year outcomes and costs of anti-TNF drugs were compared between both PS-matched cohorts. RESULTS: In the reduced dosing group, the median dose of TNF inhibitor corresponded to 0.67 and 0.5 of the standard dose initially and at 12 months respectively, and 21% of patients required return to standard dosing regimen. The mean change per year in Bath Ankylosing Spondylitis Activity Index, C-reactive protein , Health Assessment Questionnaire Disability Index and Bath AS functional index, as well as quality-adjusted life-year area under the curve were no different between both groups. The HR (95% CI) of reduced versus standard dosing group for relapse and any adverse event was 1.46 (0.66 to 3.19) and 0.56 (0.22 to 1.44), respectively. Mean difference (95% CI) in cost of anti-TNF drugs was €-4214 (-4707 to -3701) per year of treatment in favour of reduced dosing strategy. CONCLUSIONS: In patients with AS after reaching low-disease activity, a tailored approach to reduce doses of anti-TNF drugs produced similar clinical outcomes at 1 year, but was substantially less costly.

Serum tenascin-C discriminates patients with active SLE from inactive patients and healthy controls and predicts the need to escalate immunosuppressive therapy: a cohort study.

INTRODUCTION: The aim of this study was to examine whether circulating levels of the proinflammatory glycoprotein tenascin-C (TNC) are useful as an activity-specific or predictive biomarker in systemic lupus erythematosus (SLE). METHODS: Serum TNC levels were determined by enzyme-linked immunosorbent assay at inception visit in a prospective cohort of 59 SLE patients, and in 65 healthy controls (HC). SLE patients were followed for a mean of 11 months, disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) and British Isles Lupus Assessment Group disease activity index (BILAG-2004), clinical and laboratory data were recorded every 3-6 months, and changes in glucocorticoids (GC) and immunosuppressants (IS) were recorded serially. We examined cross-sectionally the relationships between serum concentrations of TNC and SLE status, SLEDAI-2 K scores, strata of disease activity, and levels of conventional biomarkers [anti-double-stranded DNA (dsDNA), anti-nucleosome antibodies, C3 and C4]. We also explored the utility of TNC levels for predicting disease flares, defined as (i) new/increased GC, (ii) new/increased GC or IS, and (iii) increase in SLEDAI by ≥3 or (iv) BILAG A or B flare. RESULTS: There was no significant difference in the mean levels of TNC between the SLE patients and HC. However, in SLE patients with active disease (SLEDAI ≥6), the TNC levels were significantly higher than in the HC (p = 0.004) or in patients with no/low disease activity (p = 0.004). In SLE patients, TNC levels were significantly associated with positivity of anti-dsDNA (p = 0.03) and anti-nucleosome antibodies (p = 0.008). Flares defined by a need to escalate immunosuppressive therapy were captured more frequently and earlier than flares defined by standard activity indices. Higher baseline levels of serum TNC presented a significantly greater risk of flare (i) [hazard ratio (HR) 1.39, 95% confidence interval (CI) 1.11-1.73] or (ii) (HR 1.25, 95% CI 1.02-1.52) but not of flares (iii) or (iv). The baseline serum TNC level was the single most important independent predictor of flare (i) compared with conventional biomarkers. CONCLUSIONS: TNC is not disease-specific, but it seems to indicate the activity of SLE and may predict the need to escalate immunosuppressive therapy. TNC levels may thus serve as a useful activity-specific and predictive biomarker in SLE.

In vitro antiproliferative and cytotoxic activities of novel kojic acid derivatives: 5-benzyloxy-2-selenocyanatomethyl- and 5-methoxy-2-selenocyanatomethyl-4-pyranone.

Some kojic acid (KA) derivatives and selenium containing compounds possess antiproliferative properties. The present study tested novel selenocyanatomethyl derivatives of KA for growth inhibitory and LDH cytotoxic activities. Human skin carcinoma (A431) and human breast carcinoma (MCF7) cells were treated with 5-benzyloxy-2-selenocyanatomethyl-4-pyranone (P763) and 5-methoxy-2-selenocyanatomethyl-4-pyranone (P764) in selected concentrations for 24, 48 and 72 h. Cell viability tests aimed at intracellular injury of mitochondria (MTT) and lysosomes (neutral red uptake, NR) revealed (a) higher growth inhibitory activity of the benzyloxy-selenocyanatomethyl derivative of KA (P763) compared with the methoxy derivative (P764) in both cell lines, (b) an intensified effect with time of exposure (MTT test only). The results demonstrate that NR cell survival/viability assay is more sensitive than the MTT test to detect subcellular changes induced by test compounds. Cell membrane integrity determined by LDH leakage confirmed an exaggerated cytotoxic effect of P763 but similar sensitivity of both cell lines to membrane injury. The ED50 values for all three tests used indicate that injury of intracellular mitochondria and lysosomes precedes the loss of membrane integrity. Cell growth inhibitory activities of new selenium containing kojic acid derivatives are preferentially aimed at the intracellular compartment rather than the plasma membrane and enlarge the group of antiproliferative active compounds.