Effects of 1-year tofacitinib therapy on angiogenic biomarkers in rheumatoid arthritis.

OBJECTIVES: Cardiovascular (CV) morbidity and mortality, and perpetuated synovial angiogenesis have been associated with RA. In our study we evaluated angiogenic factors in relation to vascular inflammation and function, and clinical markers in RA patients undergoing 1-year tofacitinib therapy. METHODS: Thirty RA patients treated with either 5 mg or 10 mg twice daily tofacitinib were included in a 12-month follow-up study. Eventually, 26 patients completed the study and were included in data analysis. Levels of various angiogenic cytokines (TNF-α, IL-6), growth factors [VEGF, basic fibroblast (bFGF), epidermal (EGF), placental (PlGF)], cathepsin K (CathK), CXC chemokine ligand 8 (CXCL8), galectin-3 (Gal-3) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) were determined at baseline, and at 6 and 12 months after initiating tofacitinib treatment. In order to assess flow-mediated vasodilation, common carotid intima-media thickness (ccIMT) and carotid-femoral pulse-wave velocity, ultrasonography was performed. Synovial and aortic inflammation was also assessed by 18F-fluorodeoxyglucose-PET/CT. RESULTS: One-year tofacitinib therapy significantly decreased IL-6, VEGF, bFGF, EGF, PlGF and CathK, while it increased Gal-3 production (P < 0.05). bFGF, PlGF and NT-proBNP levels were higher, while platelet-endothelial cell adhesion molecule 1 (PECAM-1) levels were lower in RF-seropositive patients (P < 0.05). TNF-α, bFGF and PlGF correlated with post-treatment synovial inflammation, while aortic inflammation was rather dependent on IL-6 and PECAM-1 as determined by PET/CT (P < 0.05). In the correlation analyses, NT-proBNP, CXCL8 and Cath variables correlated with ccIMT (P < 0.05). CONCLUSIONS: Decreasing production of bFGF, PlGF or IL-6 by 1-year tofacitinib therapy potentially inhibits synovial and aortic inflammation. Although NT-proBNP, CXCL8 and CathK were associated with ccIMT, their role in RA-associated atherosclerosis needs to be further evaluated.

The effects of immersion in 42℃ radon, natrium, calcium, bicarbonate content thermal-mineral water on chronic low back pain. Controlled, follow-up study.

In our minimized follow-up trial with 137 participants with chronic low back pain, one group of participants received regular outpatient care, and the other group received balneotherapy by immersion in 42℃ thermal-mineral water in addition to regular outpatient care on 15 occasions for 3 weeks. Pain on movement and at rest on the 0-100 mm visual analogue scale (VAS), Oswestry index, the number of participants evaluating the symptoms clinically acceptable (Patient Acceptable Symptom State, PASS) and the EuroQol-5D-5L (EQ-5D-5L) quality of life questionnaire were assessed at basal time (at week 0) and after balneotherapy (at weeks 3 and 12). The VAS pain scores, the Oswestry index, the EQ-5D-5L index and the EQ-VAS significantly improved in the balneotherapy group after treatment at week 3 (p < 0.001) and week 12 (p < 0.001) compared to baseline, with a significant between group difference at week 3 (p < 0.001) and week 12 (p < 0.001). The pain VAS score on movement was 66.82 ± 11.48, 26.69 ± 21.49, and 20.09 ± 23.29 in the balneotherapy group, and 63.67 ± 14.77, 67.35 ± 15.44, and 70.23 ± 18.26 in the control group at the consecutive visits. The PASS increased in both groups at week 3 and week 12 compared to the baseline, with a significant between-group difference at week 3 and week 12 for the balneotherapy group. Our results suggest the therapeutic efficacy of immersion in 42℃ thermal mineral water on chronic low back pain.ClinicalTrials.gov Identifier: NCT05342051.

Characterization of bone metabolism in hungarian psoriatic arthritis patients: a case-control study.

BACKGROUND: Skeletal manifestations are predominant in psoriatic arthritis (PsA). The aim of this cross-sectional, case-control study is the complex assessment of areal and volumetric bone mineral density (BMD), fracture risk, vitamin D status and bone turnover markers, and its association with disease-related variables. METHODS: Lumbar spine (L1-L4) and femoral neck (FN) areal, and distal radius (DR) volumetric BMD, 10-year probability of major and hip osteoporotic fracture as assessed by the fracture risk assessment (FRAX) tool, markers of bone metabolism and disease activity were assessed. RESULTS: Upon comparison of the disease and age- and sex-matched control groups, there was a statistically significant difference in FN areal (0.952 (0.607-1.292) g/cm2 vs. 1.016 (0.760-1.550) g/cm2; p = 0.001) and DR total volumetric (284.3 (138.9-470.3) mg/cm3 vs. 367.0 (287.0-412.0) mg/cm3; p < 0.001) BMD, 10 year probability for major osteoporotic (3.7% (0.7-32%) vs. 2.6% (0-17.5%); p = 0.003) and hip (0.4% (0-16%) vs. 0.05% (0-6.1%); p = 0.002) fracture and 25-hydroxyvitamin D status (47.5 (10-120) nmol/L vs. 64 (10-137; p < 0.001) nmol/L). As compared to areal assessment, volumetric BMD measurements identified a significantly higher number of patients with low bone mineral density (T-Score ≤ - 1.00) (34% vs. 88%, p < 0.001). Upon multiple linear regression analysis, disease activity score, as determined by DAS28 assessment, was an independent predictor of 10-year probability for major osteoporotic fracture (B (95%CI) = 1.351 (0.379-2.323); p = 0.007). CONCLUSION: In the studied PsA cohort, disease activity was an independent predictor of 10-year probability for a major osteoporotic fracture, and complemented assessment of volumetric and areal BMD assured better efficacy at identifying those with low bone mineral density.

Peripheral quantitative computed tomography in the assessment of bone mineral density in anti-TNF-treated rheumatoid arthritis and ankylosing spondylitis patients.

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<0.017 after Bonferroni's correction). Trabecular QCT BMD at baseline (p=0.015) and cortical QCT BMD after 12 months (p=0.005) were inversely determined by disease activity at baseline in the full cohort. Trabecular QCT BMD at baseline also correlated with CTX (p=0.011). In RA, CRP negatively (p=0.014), while SOST positively (p=0.013) correlated with different QCT parameters. In AS, RANKL at baseline (p=0.014) and after 12 months (p=0.007) correlated with cortical QCT BMD. In the full cohort, 12-month change in QTRABBMD was related to TNF inhibition together with elevated VITD-0 levels (p=0.031). Treatment and lower CATHK correlated with QCORTBMD changes (p=0.006). In RA, TNF inhibition together with VITD-0 (p<0.01) or CATHK-0 (p=0.002), while in AS, treatment and RANKL-0 (p<0.05) determined one-year changes in QCT BMD. 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.

Correction to: Assessment of cervical spine involvement in rheumatoid arthritis patients in the era of biologics: a real-life, cross-sectional MRI study.

In the original article, the first author's given name and family name were interchanged as provided by the authors in the original manuscript.

Assessment of cervical spine involvement in rheumatoid arthritis patients in the era of biologics: a real-life, cross-sectional MRI study.

Cervical spine involvement may lead to severe complications in rheumatoid arthritis (RA). In the era of modern therapies, atlantoaxial subluxation (AAS) may be rare; however, it may still be detected in asymptomatic patients. The onset of myelopathy can occur at any time. Altogether 49 female RA patients were included. Among them, 15 were methotrexate treated, biologic free, while 34 patients received biologics. The patients had no cervical pain or any neurological symptoms. We assessed the first (C1) and second (C2) cervical vertebrae by 3 T magnetic resonance imaging (MRI). In addition to AAS, we also determined odontoid erosion or periodontal soft tissue thickening. We associated our MRI findings with clinical, laboratory parameters, and hand radiography. We detected anterior AAS and soft tissue thickening in one-quarter, while odontoid erosions in eight (16%) of RA patients. There were no significant differences among the therapeutic subgroups. No posterior or vertical AAS was seen. Anterior AAS was associated with higher degree of inflammation, soft tissue thickening was seen at younger age, while odontoid erosions were associated with van der Heijde-Sharp scores of the hand. None of the patients had any lesions requiring surgery. The presence of cervical involvement in RA patients with 10-11 years of disease duration is still an important and frequent phenomenon. Higher disease activity and erosive disease are associated with atlantoaxial involvement. 3 T MRI is a sensitive method to assess AAS, as well as soft tissue lesions and odontoid erosions.

Effects of 1-year anti-TNF-α therapy on vascular function in rheumatoid arthritis and ankylosing spondylitis.

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.

Assessment of cognitive function in female rheumatoid arthritis patients: associations with cerebrovascular pathology, depression and anxiety.

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.

The effects of Tiszasüly and Kolop mud pack therapy on knee osteoarthritis: a double-blind, randomised, non-inferiority controlled study.

The aim of this non-inferiority study was to evaluate and compare the effects of Tiszasüly and Kolop mud pack therapy on pain, function and quality of life in patients with knee osteoarthritis. In this double-blind, randomised, follow-up study, 60 patients with knee osteoarthritis were treated with either Tiszasüly hot mud pack (group 1) or with Kolop hot mud pack (group 2) on 10 occasions for 2 weeks (10 working days). One hundred millimetre visual analogue scale (VAS) for knee pain, the Western Ontario and McMaster Universities Arthritis Index (WOMAC), the Knee injury and Osteoarthritis Outcome Score (KOOS), the Lequesne Index for physical function and EuroQoL-5D for quality-of-life measurements were recorded at baseline, at the end of treatment (week 2) and 3 months later (week 12). In both groups, all measured parameters improved significantly from the baseline until the end of treatment and during the follow-up period (p < 0.05). There were no significant differences between the groups in terms of the WOMAC, KOOS, EQ-5D and Lequesne Index at any visits. Knee pain improved in both groups at week 2 and week 12; the only significant difference visible between the groups was at the end of the treatment in favour of the Tiszasüly mud pack group (p = 0.009). Tiszasüly and Kolop mud packs both have a favourable effect on knee pain, physical function and quality of life in patients with knee osteoarthritis. Our results proved non-inferiority of Tiszasüly mud pack.

Comparative study of shockwave therapy and low-level laser therapy effects in patients with myofascial pain syndrome of the trapezius.

The objective of the study was to compare the effects of shockwave therapy and laser therapy on pain, neck functionality, and quality of life in patients with myofascial pain syndrome of the trapezius. 61 patients (> 18 years) were randomly allocated to two treatment groups: (1) 31 patients received soft laser therapy once daily in a 3-week period for a total of 15 sessions, (2) 30 patients received shockwave therapy once in a week for 3 weeks, totalling 3 treatments. Resting pain and pain tolerance were assessed by a 100 mm visual analogue scale; functional status and quality of life were measured by specific questionnaires (Neck Disability Index, SF-36) before and after the 3-week therapy and at the 15th week follow-up visit. All measured parameters improved significantly in both groups at week 3 and week 15. Comparing the two groups, patients receiving shockwave therapy demonstrated significantly better changes in pain tolerance (mean between-group differences at visit 1-0 = 14.911, 95% CI = 2.641-27.182, mean between-group differences at visit 2-0 = 17.190, 95% CI = 4.326-30.055 in the left trapezius), neck functionality (mean between-group differences at visit 1- 0 = 0.660, 95% CI = - 1.933 to 3.253, mean between-group differences at visit 2-0 = 1.072, 95% CI = - 2.110 to 4.254), and in all domains using SF-36 QoL questionnaire. The only parameter in which the laser group showed significantly higher benefits was at week 15 for resting pain (mean between-group differences at visit 2-0 = - 1.345, 95% CI = - 14.600 to 11.910). The results of our study point to a conclusion that both laser and shockwave therapy are effective in myofascial pain syndrome, though we found shockwave therapy to be somewhat more beneficial. Clinical trial registration number NCT03436459 ( https://clinicaltrials.gov/ct2/show/NCT03436459 ).

Correction to: The effects of the calcium-magnesium-bicarbonate content in thermal mineral water on chronic low back pain: a randomized, controlled follow-up study.

The original article mistakenly displays each set of author names in the wrong order, i.e., first names as last names and vice versa. The author correct names are: Tamás Gáti, Ildikó Katalin Tefner, Lajos Kovács, Katalin Hodosi, Tamás Bender. The original article has been corrected.

The effects of the calcium-magnesium-bicarbonate content in thermal mineral water on chronic low back pain: a randomized, controlled follow-up study.

The aim of this study was to investigate the effects of balneotherapy on chronic low back pain. This is a minimized, follow-up study evaluated according to the analysis of intention to treat. The subjects included in the study were 105 patients suffering from chronic low back pain. The control group (n = 53) received the traditional musculoskeletal pain killer treatment, while the target group (n = 52) attended thermal mineral water treatment for 3 weeks for 15 occasions on top of the usual musculoskeletal pain killer treatment. The following parameters were measured before, right after, and 9 weeks after the 3-week therapy: the level of low back pain in rest and the level during activity are tested using the Visual Analog Scale (VAS); specific questionnaire on the back pain (Oswestry); and a questionnaire on quality of life (EuroQual-5D). All of the investigated parameters improved significantly (p < 0.001) in the target group by the end of the treatment compared to the base period, and this improvement was persistent during the follow-up period. There were no significant changes in the measured parameters in the control group. Based on our results, balneotherapy might have favorable impact on the clinical parameters and quality of life of patients suffering from chronic low back pain.

[The shades of anti-Jo1 positive antisynthetase syndrome in a Hungarian cohort]. / Az anti-Jo-1-pozitív antiszintetáz szindróma jellegzetességei gondozott betegeink alapján.

INTRODUCTION: In idiopathic inflammatory myopathies, the presence of anti-Jo-1 antibody defines a distinct clinical phenotype (myositis, arthritis, interstitial lung disease, Raynaud's phenomenon fever, mechanic's hands), called antisynthetase syndrome. AIM: To determine the demographic data as well as clinical, laboratory and terapeutical features of anti-Jo1 positive patients, followed by the department of the authors. METHOD: The medical records of 49 consecutive anti-Jo1 patients were reviewed. RESULTS: Demographic and clinical results were very similar to those published by other centers. Significant correlation was found between the anti-Jo-1 titer and the creatine kinase and C-reactive protein levels. Distinct laboratory results measured at the time of diagnosis of the disease (C-reactive protein, antigen A associated with Sjogren's syndrome, positive rheumatoid factor), and the presence of certain clinical symptoms (fever, vasculitic skin) may indicate a worse prognosis within the antisyntetase positive patient group. CONCLUSION: In the cases above more agressive immunosuppressive therapy may be required.

Add-on Sacubitril/Valsartan Therapy Induces Left Ventricular Remodeling in Non-responders to Cardiac Resynchronization Therapy to a Similar Extent as in Heart Failure Patients Without Resynchronization.

INTRODUCTION: Non-responders to cardiac resynchronization therapy (CRT-NR) have poor prognosis. Sacubitril/valsartan (SV) treatment improved the outcome of patients with heart failure with reduced left ventricular (LV) ejection fraction (HFrEF) in randomized trials with no data on the specific cohort of CRT-NRs. The aim of this study was to compare the echocardiographic and biomarker changes in CRT-NR patients treated with versus without SV, and in patients with HFrEF on SV therapy. METHODS: CRT-NR patients initiated on SV (group I), CRT-NR patients on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) (group II), and patients with HFrEF (without CRT) initiated on SV (group III) were identified in our heart failure (HF) registry. CRT-NR was defined as < 10% improvement in left ventricular ejection fraction (LV EF) 6 months after the implantation. Echocardiographic parameters and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at baseline and at the end of follow-up were compared. RESULTS: A total of 275 patients (group I, 70; group II, 70; and group III, 135) were included. After a follow-up of 7.54 ± 1.8 months (mean ± standard deviation [SD]), LV EF (%) increased in group I (25.2 ± 5.7 versus 29.4% ± 6.7; p < 0.001) and in group III (26.6 ± 6.4 versus 29.9 ± 6.7; p < 0.001). LV end-systolic diameters (mm) decreased in group I (56.6 ± 9.0 versus 54.3 ± 8.7; p = 0.004) and in group III (55.9 ± 9.9 versus 54.3 ± 11.2; p = 0.021). The levels of NT-proBNP (pg/mL) decreased in group I (2058.86 [1041.07-4502.51] versus 1121.55 [545-2541]; p < 0.001) and in group III (2223.35 [1233.03-4795.96] versus 1123.09 [500.38-2651.27]; p < 0.001). The extent of improvement was similar in groups I and III (p > 0.05). No significant changes were detected in group II. CONCLUSION: SV therapy induced similar improvements in echocardiographic parameters and in NT-proBNP levels in CRT-NR patients and in patients with HFrEF without resynchronization.

Technically Challenging Percutaneous Interventions of Chronic Total Occlusions Are Associated with Enhanced Platelet Activation.

Percutaneous coronary intervention (PCI) is a frequently performed treatment option for recanalization in patients with chronic total occlusion (CTO). As CTO-PCIs are often complicated and challenging for interventionalists, the stressful and damaging nature of the procedure can be remarkable, thus platelets can be easily activated. Our aim was to investigate the effect of CTO-PCI on platelet activation and the expression of selected circulating microRNAs (miR) of platelet and endothelium origin after CTO-PCI. In this study, 50 subjects after CTO-PCI were enrolled. Blood samples were obtained before PCI, at 2 days and 3-6 months after the procedure to measure the degree of platelet activation and the level of plasma miR-223, miR-181b, and miR-126. Patients were divided based on the characteristics of the intervention. Patients with higher Japanese CTO scores and longer duration of PCI showed significantly elevated platelet P-selectin positivity (p = 0.004 and p = 0.013, respectively) 2 days after the procedure compared to pre-PCI and increased concentration of soluble P-selectin 3-6 months after the intervention (higher Japanese CTO score: p = 0.028 and longer duration of PCI: p = 0.023) compared to baseline values. Shorter total stent length caused a significantly lower miR-181b expression at 3-6 months after the intervention (p = 0.031), while no difference was observed in miR-223 and miR-126. One stent thrombosis occurred during the follow-up period. Although these technically challenging CTO-PCIs may cause enhanced platelet activation right after the intervention and long-term endothelial cell dysfunction, these interventions are not associated with more adverse clinical events.

Immune-related adverse events of anti-PD-1 immune checkpoint inhibitors: a single center experience.

Objectives: Immune checkpoint inhibitors (ICIs) stimulate antitumor immune responses and, in parallel, they might trigger autoimmune and other immunopathological mechanisms eventually leading to immune-related adverse events (irAE). In our study, we assessed patients with malignancies who underwent anti-PD-1 treatment at the University of Debrecen, Clinical Center. Patients and methods: Between June 2017 and May 2021, 207 patients started ICI treatment at our university. A total of 157 patients received nivolumab and 50 were treated with pembrolizumab. We looked for factors associated with the development of irAEs. In addition to correlation studies, we performed binary logistic regression analysis to determine, which factors were associated with irAEs. We also performed Forward Likelihood Ratio (LR) analysis to determine independent prognostic factors. Results: At the time of data analysis, the mean duration of treatment was 2.03 ± 0.69 years. ROC analysis determined that 9 or more treatment cycles were associated with a significantly higher risk of irAEs. A total of 125 patients received ≥9 treatment cycles. Three times more patients were treated with nivolumab than pembrolizumab. Of the 207 patients, 66 (32%) developed irAEs. Among the 66 patients who developed irAEs, 36 patients (55%) developed one, 23 (35%) developed two, while 7 (10%) developed three irAEs in the same patient. The most common irAEs were thyroid (33 cases), dermatological (25 cases), pneumonia (14 cases) and gastrointestinal complications (13 cases). Patients who developed irAEs received significantly more treatment cycles (21.8 ± 18.7 versus 15.8 ± 17.4; p=0.002) and were younger at the start of treatment (60.7 ± 10.8 versus 63.4 ± 10.1 years; p=0.042) compared to patients without irAEs. Pembrolizumab-treated patients developed more but less severe irAEs compared to those receiving nivolumab. Conclusion: ICI treatment is very effective, however, irAEs may develop. These irAEs might be related to the number of treatment cycles and the type of treated malignancy.

Effect of tofacitinib therapy on angiotensin converting enzyme activity in rheumatoid arthritis.

Introduction: The Renin-Angiotensin-Aldosterone system (RAAS) has been implicated in the regulation of the cardiovascular system and linked to rheumatoid arthritis (RA). Little information has become available on the effects of Janus kinase (JAK) inhibition on RAAS. Here we studied the effects of 12-month tofacitinib treatment on angiotensin converting enzyme (ACE), ACE2 production and ACE/ACE2 ratios in RA along with numerous other biomarkers. Patients and methods: Thirty RA patients were treated with tofacitinib in this prospective study. Serum ACE concentrations were assessed by ELISA. ACE2 activity was determined by a specific quenched fluorescent substrate. ACE/ACE2 ratios were calculated. We also determined common carotid intima-media thickness (ccIMT), brachial artery flow-mediated vasodilation (FMD) and carotid-femoral pulse-wave velocity (cfPWV) by ultrasound. C-reactive protein (CRP), rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) were also determined. All measurements were performed at baseline, as well as after 6 and 12 months of tofacitinib treatment. Results: After the dropout of 4 patients, 26 completed the study. Tofacitinib treatment increased ACE levels after 6 and 12 months, while ACE2 activity only transiently increased at 6 months. The ACE/ACE2 ratio increased after 1 year of therapy (p < 0.05). Logistic regression analyses identified correlations between ACE, ACE2 or ACE/ACE2 ratios and RF at various time points. Baseline disease duration also correlated with erythrocyte sedimentation rate (ESR) (p < 0.05). One-year changes of ACE or ACE2 were determined by tofacitinib treatment plus ACPA or RF, respectively (p < 0.05). Conclusion: JAK inhibition increases serum ACE and ACE/ACE2 ratio in RA. Baseline inflammation (ESR), disease duration and ACPA, as well as RF levels at various time points can be coupled to the regulation of ACE/ACE2 ratio. The effect of tofacitinib on RAAS provides a plausible explanation for the cardiovascular effects of JAK inhibition in RA.

Effects of various types of ultrasound therapy in hip osteoarthritis - a double-blind, randomized, controlled, follow-up study.

PURPOSE: To compare the effects of various types of ultrasound therapy (UST) on pain, function, and quality of life in patients with hip osteoarthritis. METHODS: Seventy-one patients receiving conventional physiotherapy (exercise, massage, and balneotherapy), were randomly allocated into four treatment groups: (1) continuous UST, (2) pulsed UST, (3) UST combined with transcutaneous electrical nerve stimulation (TENS), (4) placebo UST. We evaluated the hip pain (Visual Analog Scale), medication use, functional impairment (Western Ontario and McMaster Universities Arthritis Index; 6-minute walking test) and quality of life (SF-36) before, right after the treatments, and at 3 months follow-up. RESULTS: Resting pain improved significantly in all treatment groups at the follow-up visit compared to baseline (p (group1-4) ≤0.002). The proportion of patients achieving Minimal Clinically Important Improvement (MCII) in function at month 3 was the highest in group 3 (73%). The 6-minute walking test significantly improved in each group during the follow-up period (p (group1-4) ≤ 0.025). Pain (p (group1-4) ≤ 0.014) and general health domains of the SF-36 showed the greatest improvement (p (group 2-4) ≤ 0.018). CONCLUSIONS: There was no difference among the effects of various types of UST on pain, function, and quality of life in the treatment of hip osteoarthritis. Additional ultrasound treatment is not likely to increase the effect of the conventional therapy on pain and function in hip osteoarthritis.

Severity and prognostic factors of SARS-CoV-2-induced pneumonia: The value of clinical and laboratory biomarkers and the A-DROP score.

Introduction: Numerous clinical and laboratory scores that include C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase (LDH), interleukin 6 (IL-6), procalcitonin (PCT), blood urea nitrogen (BUN), creatinine levels and oxygenation (PaO2 and SaO2) have been used for the prognosis of COVID-19. In addition, composite scores have been developed for the assessment of general state and risk in community-acquired pneumonia (CAP) that may be applied for COVID-19 as well. In this study, we assessed severity and potential prognostic risk factors for unfavorable outcome among hospitalized COVID-19 patients. We also applied the A-DROP general scoring system used in CAP to COVID-19. Patients and methods: Altogether 233 patients admitted to our center with COVID-19 were included in the study. Clinical status, several laboratory biomarkers described above, indicators of oxygenation were determined at hospital admission. We also applied the A-DROP composite scoring system that includes Age (≥ 70 years in males and ≥ 75 years in females), Dehydration (BUN ≥ 7.5 mmol/l), Respiratory failure (SaO2 ≤ 90% or PaO2 ≤ 60 mmHg), Orientation disturbance (confusion) and low blood Pressure (systolic BP ≤ 90 mmHg) to COVID-19. Results: At the time of admission, most patients had elevated CRP, LDH, ferritin, D-dimer, and IL-6 levels indicating multisystemic inflammatory syndrome (MIS). Altogether 49 patients (21.2%) required admission to ICU, 46 (19.7%) needed ventilation and 40 patients (17.2%) died. In the binary analysis, admission to ICU, the need for ventilation and death were all significantly associated with the duration of hospitalization, history of hypertension or obesity, confusion/dizziness, as well as higher absolute leukocyte and neutrophil and lower lymphocyte counts, elevated CRP, PCT, LDH, ferritin, IL-6, BUN, and creatinine levels, low PaO2 and SaO2 and higher A-DROP score at the time of admission (p < 0.05). Conclusion: Numerous laboratory biomarkers in addition to obesity, dizziness at the time of admission and the history of hypertension may predict the need for ICU admission and ventilation, as well as mortality in COVID-19. Moreover, A-DROP may be a suitable scoring system for the assessment of general health and disease outcome in COVID-19.

Effect of invasive therapeutic coronary interventions on endothelial cell activation and thrombin generation in patients with chronic total coronary occlusion.

BACKGROUND: Percutaneous coronary intervention (PCI) is commonly used treatment for chronic total occlusion (CTO). PCI can be performed in two different ways using wire escalation (WE) or subintimal dissection and reentry (DR) technique. During both procedures patients are treated with anticoagulants, however a substantial activation of coagulation cascade is expected, which may affect clinical outcome. OBJECTIVES: Our aim was to compare the impact of WE and DR techniques regarding endothelial cell activation and thrombin formation. METHODS: Fifty patients after CTO-PCI were enrolled into this study. Blood samples were obtained before PCI, at 48 h and 3-6 months after the intervention to measure soluble endothelium-specific markers and to investigate thrombin generation. RESULTS: Twenty-nine patients were treated with WE, 21 received DR. In the DR group, soluble VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular cell adhesion molecule-1) concentrations were gradually elevated and remained significantly increased at 3-6 months (p = 0.006 and p = 0.037, respectively) compared to pre-PCI. Furthermore, significant decrease in lagtime (p = 0.004) and time to peak (p = 0.002) with a substantial increment in peak thrombin (p = 0.001) were observed in these patients. In contrast, no significant alteration was found in the WE cohort. Clinical complications (myocardial infarction, stroke, thrombosis, revascularization) did not occur in the first 9 months of follow-up period in either group. CONCLUSION: Although DR intervention induces more thrombin generation with a larger degree of endothelium activation compared to WE, this technique does not cause more clinical complications.