Role of Optical Coherence Tomography in Vasculitis-Associated Pulmonary Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Identifying and understanding the microstructural changes within the wall of the pulmonary artery (PA) is crucial for elucidating disease mechanisms and guiding treatment strategies. We assessed the utility of optical coherence tomography (OCT) in identifying such changes within segmental/subsegmental PAs and compared the morphological variations in WHO group 4 pulmonary hypertension associated with Behcet Disease (BD), Takayasu arteritis (TA) and chronic thromboembolic pulmonary hypertension (CTEPH). Idiopathic pulmonary arterial hypertension (IPAH) patients served as controls.Methods and Results: A total of 197 cross-sectional images were analyzed from 20 consecutive patients. BD patients exhibited lower %wall area and mean wall thickness (MWT) compared with CTEPH, TA and, IPAH patients. TA patients showed a notably higher %wall area, which was significant in IPAH and BD patients. Variations in %wall area measurements were observed across distinct cross-sectional segments of the PA within individual patients (22% in CTEPH, 19% in BD, 16% in TA, 23% in IPAH patients). Intravascular webs, bands, and thrombi were observed in BD and CTEPH patients. OCT provided clear delineation of vascular wall calcifications and adventitial vasa vasorum. No procedure-related complications were observed. CONCLUSIONS: PA involvement differs among the various etiologies of PH, with the PA being heterogeneously affected. OCT offers promise in elucidating microstructural vascular wall changes and providing insights into disease mechanisms and treatment effects.

Quadriceps femoris muscle ultrasound in sarcoidosis: an observational case-control study.

BACKGROUND: Although loss of muscle mass may be associated with general weakness, intolerance to physical activity and fatigue, it is underestimated and poorly understood in patients with sarcoidosis. AIM: To compare the quadriceps femoris muscle (QFM) thickness measured by ultrasonography (US) between the female patients with sarcoidosis and controls, secondly to assess the correlation between the muscle strength, fatigue and QFM thickness. DESIGN: Observational, case-control study. SETTING: Physical Medicine and Rehabilitation Department of a University Hospital. POPULATION: Thirty-one women with sarcoidosis and 27 healthy volunteers were included in the study. METHODS: The participants were evaluated for the following outcomes: 1) handgrip strength; 2) QFM thickness measured using US; and 3) sonographic thigh adjustment ratio (STAR). The sarcoidosis group was also evaluated with the 30-second chair stand test (30s-CST) and Fatigue Severity Scale (FSS). RESULTS: The QFM thickness and STAR values of the patients with sarcoidosis were significantly lower than those of the controls (P=0.0001). However, no statistically significant difference was observed between the handgrip strengths of the groups (P=0.581). There was no statistically significant correlation between the STAR values and handgrip strength in the sarcoidosis group; however, there was a significant positive correlation between the STAR values and 30s-CST (r=0.467, P=0.008). CONCLUSIONS: Loss of muscle mass is one of the musculoskeletal conditions in patients with sarcoidosis that may be associated with nonspecific symptoms, such as general debility, intolerance to physical activity, and fatigue. In the present study, no difference was observed in hand grip strength between the groups, while we found that QFM thickness was affected in patients with sarcoidosis when compared to the controls. The ultrasonographic QFM evaluation seems to be an innovative tool which may be used at all stages of sarcoidosis patient follow-up. CLINICAL REHABILITATION IMPACT: The grip strength is a commonly used test to detect muscle weakness, but onset of a decrease in muscle mass in the lower extremities may occur earlier. Considering the increased burden of musculoskeletal problems in this population, performing 30s-CST and sonographic QFM thickness is practical methods to identify risky patients.

Six-minute stepper test for evaluating functional exercise capacity in patients with sarcoidosis.

BACKGROUND: Researchers and clinicians may benefit from alternative tests that do not require large physical spaces or corridors for simply evaluating functional exercise capacity in the clinical practice. OBJECTIVE: Aim of this study was to investigate whether six-minute stepper test (6MST) is a valid tool for measuring functional exercise capacity in patients with sarcoidosis. METHODS: Thirty-six patients with sarcoidosis and 18 healthy controls were evaluated with 6MST and six-minute walk test (6MWT). Patients performed 6MST twice. Cardiovascular and symptom responses to tests including heart rate, blood pressure, SpO2, levels of dyspnea and fatigue were recorded. RESULTS: Receiver operating characteristic (ROC) curve analysis revealed an area under the ROC curve of 0.74 for 6MST in identifying the patients and controls, indicating acceptable discriminative ability. Patients performed significantly worse in 6MST compared to controls (277±54 vs 349±87 steps; p<0.001). 6MST was able to explain 66% of variance in 6MWT (p<0.001), and there was a strong relationship between 6MWT and 6MST (r = 0.812). SpO2 responses to tests were similar, however, 6MST generated more severe heart rate, dyspnea and fatigue responses. Intraclass correlation coefficient calculated for initial and retest scores of 6MST was 0.990, indicating excellent test-retest reliability. However, there was a systematical improvement (∼4%) in retest 6MST scores. CONCLUSIONS: 6MST is a valid and reliable alternative test for measuring functional exercise capacity in sarcoidosis. 6MST may also help better testing the upper limits of cardiac system and physical endurance as it is more physically demanding than 6MWT.

Humoral and Cellular Immunity to Severe Acute Respiratory Syndrome Coronavirus-2 Vaccination in Patients with Sarcoidosis

Background: The coronavirus disease 2019 vaccine induces both antibody and T-cell immune responses and has been proven to be effective in preventing coronavirus disease 2019, including its severe disease form, in healthy individuals. However, the details of severe acute respiratory syndrome coronavirus-2 immunoglobulin-G antibody responses and severe acute respiratory syndrome coronavirus-2 specific T-cell responses in patients with sarcoidosis are unknown. Aim: To measure and compare antibody responses and T cell responses using enzyme-linked immunosorbent assays and interferon-gamma release assay in sarcoidosis patients infected with coronavirus disease 2019 and vaccinated with CoronaVac. Study Design: A prospective cohort study. Methods: A total of 28 coronavirus disease 2019 polymerase chain reaction test-positive sarcoidosis patients who were infected with severe acute respiratory syndrome coronavirus-2 in the past 6 months and did not have coronavirus disease 2019 vaccination and 28 sarcoidosis patients who were administered with 2 doses of CoronaVac and never had coronavirus disease 2019 were included in this study. The immune response levels of patients were determined by measuring the severe acute respiratory syndrome coronavirus-2 immunglobulinG and interferon-gamma levels in the blood of the patients by the enzyme-linked immunosorbent assays method and interferon-gamma release assay tests, respectively. Results: The mean age of the patients in the COVID-infected group was 48.1 ± 11.3, while the mean age of the patients in the vaccinated group was 55.6 ± 9.32. The mean time elapsed after infection was 97.32 ± 42.1 days, while 61.3 ± 28.7 days had passed since the second vaccination dose. In the COVID-infected group, immunoglobulin-G and interferon-gamma release tests were positive in 64.3% and 89.3% of the patients, respectively. In the vaccinated group, immunoglobulin-G was positive in 10.7% of the patients, and interferon-gamma release test was positive in 14.3%. Conclusion: Innate immune responses are better than adaptive immune responses in patients with sarcoidosis. The coronaVac vaccine is insufficient to generate humoral and cellular immunities in patients with sarcoidosis.

Renin-angiotensin system activation: may it increase frequency of obstructive sleep apnea in patients with autosomal dominant polycystic kidney disease?

PURPOSE: Renin-angiotensin system (RAS) hyperactivity is a common entity in both autosomal dominant polycystic kidney disease (ADPKD) and obstructive sleep apnea (OSA). We aimed to investigate the frequency of OSA in adults with ADPKD either with stages 3-4 or stages 1-2 chronic kidney disease (CKD) and evaluate the effect of RAS blockade on OSA in these patients. METHODS: This is a comparative, prospective, two-center clinical study. Eligible patients with ADPKD were enrolled in a polysomnography (PSG) study. Presence of OSA in patients with ADPKD was compared with individuals who underwent polisomnography study due to OSA symptoms. A subgroup analysis was performed in terms of the presence of OSA in ADPKD with eGFR values lower or higher than 60 ml/min/1.73 m2 (stages 3-4 and stages 1-2 CKD, respectively). RESULTS: Frequency of OSA (65%) was higher than in the general population and similar between the two groups (p = 0.367). Patients with ADPKD and eGFR ≥ 60 ml/min/1.73 m2 presented a similar frequency of OSA to the control group (p = 0.759). However, OSA was significantly more frequent in ADPKD with eGFR < 60 ml/min/1.73 m2 (p = 0.018). Subgroup analysis revealed that presence of OSA also was significantly higher in ADPKD with lower eGFR levels (eGFR < 60 ml/min/1.73 m2 and eGFR > 60 ml/min/1.73 m2) 14/17 (82%) and 12/23 (52%), respectively (p: 0.048). CONCLUSION: As kidney disease progresses, uremia and related factors of renal failure rather than RAS activation seem to play a more important role for the development of OSA in patients with ADPKD.

Investigation of the frequency of obstructive sleep apnoea syndrome in patients with subclinical hypothyroidism.

Background: The aim of this study is to determine the frequency of obstructive sleep apnoea syndrome (OSAS) in a study group with the diagnosis of subclinical hypothyroidism and in a control group without the diagnosis of subclinical hypothyroidism. This study compares these two groups in terms of demographic characteristics, chronic diseases and especially polysomnographic data. Methods: A total of 120 patients were included in this study. They consisted of 60 patients with newly diagnosed subclinical hypothyroidism and a control group of 60 patients with normal thyroid functions. Demographic, anthropometric, polysomnography data and Epworth Sleepiness Scale scores of the patients were recorded and compared. Results: Any significant difference in the frequency and severity of OSAS was not detected. A significant difference was found in the oxygen desaturation index (ODI), the apnoea-hypopnoea index (AHI) in rapid eye movement sleep, the AHI in supine sleep position and the arousal index of the group experiencing subclinical hypothyroidism with OSAS. Conclusion: This study showed that there was no increase in OSAS frequency in patients with subclinical hypothyroidism, but it demonstrated that the ODI and the arousal index were significantly increased in OSAS patients diagnosed with subclinical hypothyroidism. It is thought that the diagnosis and treatment of OSAS in these patients may be important in preventing cardiovascular complications.

SARS-CoV-2 antibody research in patients with unprovoked pulmonary embolism in COVID-19 pandemic period.

OBJECTIVE: Due to the coronavirus disease 2019 (COVID-19) pandemic, a significant increase has been observed in patients diagnosed with pulmonary embolism (PE) in our clinic. In addition to COVID-19-related PE, the increase in the number of patients with unprovoked or idiopathic PE was also noteworthy. Although it is not surprising that PE due to immobilization was observed in elderly patients and patients with comorbidities at risk for PE during the pandemic, it is important to investigate the increase in the number of unprovoked PE. Thus, we aimed to show that a previous COVID-19 infection may be a risk factor in these patients by examining the presence of severe acute respiratory syndrome-causing coronavirus (SARS-CoV-2) antibodies in patients diagnosed with unprovoked PE. MATERIALS AND METHODS: The participants of the study consisted of 45 consecutive patients who were diagnosed with PE in our clinic, had no risk factors for PE, were considered unprovoked (idiopathic) PE, and had no history of COVID-19. SARS-CoV-2 antibody titers were measured in the serum samples of the patients for detecting immunity as a result of encountering COVID-19. RESULTS: Of the 45 patients diagnosed with PE, 24 (53.3%) patients were diagnosed with computed tomography pulmonary angiogram (CTPA), and 21 (46.7%) patients were diagnosed with perfusion single-photon emission computed tomography (Q-SPECT/CT). Immunity acquired after encountering COVID-19 was checked with the NCP kit, which revealed positive results in 9 (20%) patients. CONCLUSION: It should be kept in mind that some of the patients diagnosed with idiopathic PE during the pandemic may have embolism due to asymptomatic COVID-19. In addition, it is now known that COVID-19 also creates a tendency toward thrombosis in asymptomatic patients.

Investigation of the ongoing pulmonary defects with perfusion-single photon emission computed tomography/computed tomography in patients under anticoagulant therapy for coronavirus disease 2019-induced pulmonary embolism.

OBJECTIVE: It was aimed to reveal the continuing perfusion defect rates in patients with a diagnosis of pulmonary embolism (PE) due to COVID-19 who have completed the third month of anticoagulant therapy but whose symptoms or laboratory elevations continue. METHODS: Patients with COVID-19 who were diagnosed with PE by Q-SPECT-CT between 1 September 2020 and 1 November 2021, who underwent control Q-SPECT/CT were included in the study. Demographic characteristics, laboratory findings, and first and second Q-SPECT/CT evaluation results of the patients were recorded. RESULTS: It was observed that the pulmonary defect continued in Q-SPECT/CT in the third month of anticoagulant treatment in 58.3% of the patients diagnosed with PE due to COVID-19, and new defects developed in 6.3%. The persistence rate of segment defects was higher than that of subsegment defects. It was observed that the defects persisted more frequently in patients with a history of hospitalization due to COVID-19. CONCLUSION: Perfusion defects may still be present in patients diagnosed with PE due to COVID-19 in the presence of persistent dyspnea/chest pain/D-dimer elevation after 3 months of treatment. Perfusion defect persistence rates are higher in defects more proximal to the subsegment level and in people with severe COVID-19, and extended treatment should be considered in these patients.

Significance of Cyclooxgenase-2 gene polymorphism and related miRNAs in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with a poor prognosis. The suppression of cyclooxygenase-2 (COX-2) expression has been known to impair vascular function in endothelial cells; however, the epigenetic factors that cause this are largely obscure. Our aim in this study was to examine the polymorphisms in the gene for COX-2 (PTGS2) and related miRNAs regulating its level in a single-center cohort of patients with PAH. METHOD: In this study, three SNPs and miRNAs (rs5275, rs689470, rs20417, miR-26b-5p, miR-146a-5p, and miR-101-5p) in the PTGS2 were screened in PAH and controls by qPCR. In addition, the COX-2 level was determined by immunoassay to examine the effects of epigenetic factors on its expression levels. RESULTS: The non-dominant genotypes of rs20417 and rs5275 were found to be related to PAH (OR = 8.56, 95% CI = 3.39-21.63, p < 0.0001 and OR = 7.82, 95% CI = 3.30-18.53, p < 0.0001, respectively). We also observed a significant increase in the miR-26b-5p and miR-146a-5p levels in PAH patients (2.18 and 2.35-fold, respectively; for both, p < 0.05). In addition, it was found that SNPs influenced the COX-2, miR-26b-5p, and miR-146a-5p levels in PAH. A negative correlation was also found between COX-2 levels and miR-26b-5p and miR-146a-5p. CONCLUSIONS: As conventional drug therapies may cause lower COX-2 levels, the development of new genetic or epigenetic biomarkers is crucially important for early diagnosis and prognosis. The presence of minor alleles for rs5275 and rs689470 might also be considered as a significant risk factor for developing PAH. Furthermore, locus-specific miRNAs, such as miR-26b-5p and miR-146a-5p, seem to play a critical role in the regulation of PTGS2 expression.

Atorvastatin attenuates pulmonary fibrosis in mice and human lung fibroblasts, by the regulation of myofibroblast differentiation and apoptosis.

Statins have anti-inflammatory and antifibrotic effects in addition to cholesterol-lowering effect. We aimed to investigate the effect of atorvastatin (ATR) in fibrotic mouse lung and human lung fibroblasts (MRC5s). Pulmonary fibrosis was induced by a single dose of bleomycin by intratracheal instillation in adult mice. ATR was administered (20 mg/kg ip) to mice with healthy and pulmonary fibrosis for 10 days from Day 7 of the experiment. Mice were dissected on the 21st day. The levels of alpha-smooth muscle actin (α-SMA), pSMAD2/3, LOXL2, and p-Src were determined by Western blot analysis in the lungs. Furthermore, a group of MRC5 was differentiated into myofibroblasts by transforming growth factor-beta (TGF-ß). Another group of MRC5s was treated with 10 µM ATR at 24 h after TGF-ß stimulation. Cells were collected at 0, 24, 48, and 72 h. The effects of ATR on myofibroblast differentiation, apoptosis, and TGF-ß and Wnt/ß-catenin signaling activations were examined by Western blot analysis and flow cytometry in MRC5s. ATR attenuated pulmonary fibrosis by regulating myofibroblast differentiation and interstitial accumulation of collagen, by acting on LOXL2, p-Src, and pSMAD2/3 in mice lungs. Additionally, it blocked myofibroblast differentiation via reduced TGF-ß and Wnt/ß-catenin signaling and decreased α-SMA in MRC5s stimulated with TGF-ß. Moreover, ATR caused myofibroblast apoptosis via caspase-3 activation. ATR treatment attenuates pulmonary fibrosis in mice treated with bleomycin. It also inhibits fibroblast/myofibroblast activation, by both reducing myofibroblasts differentiation and inducing myofibroblast apoptosis.

Clinical efficacy, safety, tolerability, and survival outcome of long-term inhaled iloprost treatment in the management of pulmonary arterial hypertension: Data from prospective multicenter observational OPTION study.

OBJECTIVE: To evaluate clinical efficacy, safety and tolerability of long-term inhaled iloprost treatment in the daily practice for the management of pulmonary arterial hypertension (PAH). METHODS: A total of 115 patients with PAH on inhaled iloprost treatment were included. New York Heart Association (NYHA) functional class, brain natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and 6-minute walk distance (6MWD) were recorded at baseline and at 3rd to 24th month visits. Safety and tolerability of iloprost treatment were also evaluated during follow-up, as were the survival, clinical worsening, and the related risk factors. RESULTS: The treatment was associated with an increase in the percentage NYHA functional class II (from 0.0% at enrolment to 36.2% at 24th month visit) patients but no significant difference was noted in 6MWD values. Clinical worsening was observed in 63.5% patients, while survival rate was 69.6%. NT-proBNP levels were significantly higher in non-survivors than in survivors (p=0.042). Cox regression analysis revealed the association of female sex [odds ratio (OR)=0.318; 95% confidence interval (CI), 0.128-0.792; p=0.014] and scleroderma-related PAH (OR=0.347; 95% CI, 0.140-0.860; p=0.022) with significantly lower risk (3.14 fold and 2.88 fold, respectively) of mortality. CONCLUSION: Our findings indicate favorable efficacy, safety, and tolerability of long-term iloprost treatment in the management of PAH, whereas improved NYHA functional class was not accompanied with a significant change in 6MWD values. Patient age was a risk factor for clinical worsening, while female sex, scleroderma subtype, and lower NT-proBNP levels were associated with significantly lower mortality risk.

Investigation of perfusion defects by Q-SPECT/CT in patients with mild-to-moderate course of COVID-19 and low clinical probability for pulmonary embolism.

OBJECTIVE: Pulmonary embolism is a severe source of mortality and morbidity in patients with severe and critical coronavirus disease 2019. It is not yet clear whether the tendency to thrombosis is increased in the mild-to-moderate course of COVID-19. Our research aims to show the clinical benefit of Q-SPECT/CT in diagnosing PD in outpatients treated with mild-to-moderate course of COVID-19 and to determine the frequency of perfusion defects in these patients having relatively lower risk. METHODS: All patients who underwent Q-SPECT/CT with suspicion of embolism were examined retrospectively. Only patients with low clinical probability and mild-to-moderate course of COVID-19 for PE were included in the study. The patients were evaluated comparatively as those with and without perfusion defects. Patients were divided into laboratory suspicion, clinical suspicion, or clinical and laboratory suspicion. RESULTS: In outpatients with mild-to-moderate COVID-19 with low clinical probability for PE, PD without CT abnormality was detected with a rate of 36.6% with Q-SPECT/CT performed for complaints of high D-dimer and/or dyspnea. None of the patients had PD at more proximal level than the segment level. PD with no concomitant CT abnormality was observed with a rate of 56.5% in patients with both clinical and laboratory suspicion. For D-dimer = 0.5 mg/dL cut-off sensitivity is 85%, for D-dimer = 1.5 mg/dL cut-off specificity 81%. CONCLUSION: Thrombosis tendency is also present in outpatients with mild-to-moderate COVID-19, and these patients should also be offered anticoagulant prophylaxis during the COVID-19 period.

Increased frequency of obstructive sleep apnea in the patients with systemic sclerosis.

INTRODUCTION: Sleep problems, including obstructive sleep apnea (OSA), profoundly affect quality of life in patients with systemic sclerosis (SSc). This study aimed to determine the prevalence of OSA in patients with SSc and the factors affecting OSA. METHODS: Consecutive patients with SSc lung involvement who were referred to the "Outpatient Service for Interstitial Lung Disease" in our university hospital between 2015 and 2017 were included in the study. All patients completed the Epworth Sleepiness Scale (ESS) and underwent examination including body mass index (BMI), measurement of waist circumference, upper respiratory tract examination, and polysomnography (PSG). Spirometry, carbon monoxide diffusion test (DLCO), and 6-min walking distance were also performed. RESULTS: Of 38 patients, mean age 51.3 ± 11.6 years, 35 were women (92%). Mean apnea-hypopnea index (AHI) was 11 ± 15 (median 5.5) and prevalence of OSA was 58%. Mild OSA was found in 13 (34%) of patients, moderate OSA in 6 (16%), and severe OSA in 3 (8%). Significant relationships were found between age (p = 0.02), waist circumference (p = 0.01), presence of witnessed apneas (p = 0.005), and presence of OSA. CONCLUSIONS: Compared with the general population, the prevalence of OSA is increased in women with SSc. Patients with older age, those with increased waist circumference, and those reporting witnessed apneas should be studied for OSA.

Frequency of Obstructive Sleep Apnea in Stage I and II Sarcoidosis Subjects Who Had No Corticosteroid Therapy.

OBJECTIVES: The number of studies on the frequency of obstructive sleep apnea (OSA) in subjects with sarcoidosis is low. Therefore, we aimed to investigate the frequency and predictors of OSA in subjects with clinically stable stage I and II sarcoidosis who were not taking corticosteroid and/or immunosuppressive drugs. We also evaluated restless legs syndrome (RLS) and periodic leg movements in sleep (PLMS). MATERIALS AND METHODS: Subjects with clinically stable stage I and II sarcoidosis and not receiving corticosteroid and/or immunosuppressive therapy were included in the study. Upper airway examination, lung function tests (forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1], diffusing capacity of the lungs for carbon monoxide [DLCO]), and polysomnography were performed on all subjects. In addition, subjects' Epworth Sleepiness Scale (ESS) scores and the Pittsburgh Sleep Quality Index (PSQI) were recorded. RESULTS: Of the total number of 46 sarcoidosis subjects (35 women, 11 men; age: 44.4±10.7 years; body mass index (BMI): 29.3±5 kg/m2), 28 (60.9%) were detected with OSA (67.8% mild OSA). The recorded ESS score of the subjects was low (2.6±3.2), whereas the sleep quality was poor in 36.9% of these subjects. Rapid eye movements (REM) related OSA was diagnosed in 14.2% of the OSA subjects. Age was the only factor related to OSA diagnosis in a logistic regression analysis (p=0.048). None of the subjects were diagnosed with RLS and PLMS. CONCLUSION: OSA is common in stage I and II sarcoidosis subjects who did not receive corticosteroid therapy. The frequency of OSA diagnosis increases as the age of the subjects increases. Therefore, sarcoidosis subjects should be evaluated for OSA throughout the follow-up.

Evaluating the effectiveness of anti-tuberculosis treatment by detecting Mycobacterium tuberculosis 85B messenger RNA expression in sputum.

BACKGROUND: The antigen 85 complex (85B) is secreted in large quantities from growing mycobacteria and the presence of bacterial mRNA is an indicator of cell viability. The quantitative detection of 85B mRNA expression levels can be used to assess the success of anti-tuberculosis treatment outcomes to detect viable mycobacteria cells. Therefore, we evaluated the levels of 85B mRNA of Mycobacterium tuberculosis strains in patients with pulmonary tuberculosis. METHODS: Thirty patients with primary tuberculosis were included in this study. The sputum specimens of patients were collected on days 0, 15, and 30 days and were cultured and evaluated by 85B mRNA-based RT-qPCR. RESULTS: Overall, 23 of the studied tuberculosis strains were susceptible to the primary anti-tuberculosis antibiotics used in this study, 7 were resistant. By the 30th day of treatment, 85B mRNA was detected in only one of the susceptible strains, but in all 7 of the resistant strains, though the relative gene expression varied between the strains. This difference between the susceptible and resistant strains at day 30 was statistically significant (p < 0.05). CONCLUSION: 85B mRNA expression levels could be used to follow up on primary tuberculosis cases. 85B mRNA seems to be a good diagnostic marker for monitoring anti-tuberculosis treatment outcomes.

Increased frequency of obstructive sleep apnea syndrome in Behçet's syndrome patients with superior vena cava syndrome.

OBJECTIVES: Superior vena cava syndrome (SVCS) is a medical emergency which can also be seen in Behçet's syndrome (BS). Having noted that BS patients with SVCS frequently complained of sleep disturbances, snoring and sleep apnea, suggesting obstructive sleep apnea (OSA), we formally surveyed the risk for OSA among BS patients. METHODS: We studied 28 patients, all male, with SVCS (Group 1), 129 with vascular involvement without a SVCS (Group 2) and 151 with no vascular involvement (Group 3). In addition, 100 apparently healthy individuals (Group 4) were studied. The Berlin questionnaire (BQ), a validated screening tool with a high sensitivity and modest specificity that identifies individuals with high-risk for OSA, was administered to all study participants. RESULTS: The study groups were similar with regard to age (Group 1, mean age: 44.3±9.7; Group 2, mean age: 41.5±8.7, Group 3, mean age: 40.4±9.4 and Group 4, mean age: 42.1±9.4) mean body mass index and the frequency of hypertension and other comorbidities. The frequency of those patients at high-risk for OSA according to the BQ was 57%, 17%, 17% and 11% in Groups 1, 2, 3 and 4, respectively (p<0.05). Age-adjusted ORs of OSA compared to healthy controls (Group 4) was 11.00 (95%CI: 4.01-30.07) for Group 1, 1.78 (95%CI: 0.81-3.94) for Group 2, 1.92 (95%CI: 0.90-4.14) for Group 3. CONCLUSIONS: BS patients with SVCS are at high risk for OSA. This is probably due to the external pressure of the significant presence of venous collaterals that surround the upper airways. Our results should be further confirmed by polysomnography, and future research should be carried out to clarify the causes of this association.

Changes in inflammatory mediators as a result of intermittent hypoxia in obstructive sleep apnea syndrome.

BACKGROUND: Inflammation plays an important role in obstructive sleep apnea syndrome (OSAS). The objective of this study was to investigate the relationship of serum C-reactive protein (CRP), pentraxin-3 (PTX-3), procalcitonin (ProCT), interleukin-33 (IL-33) and its soluble receptor ST2 (sST2) with the syndrome severity and to show theirs importance as biomarkers. METHODS: This study comprises a total of 84 identical (sex and age wise) cases. Full-night polysomnography was performed in each patient. OSAS diagnosis and severity index being based on the widely used criterion known as Apnea Hypopnea Index(AHI). Subgroups were as follows: 24(AHI < 5) controls, 28 mild-moderate OSAS(AHI 5-30) and 32 severe OSAS(AHI > 30). RESULTS: PTX-3, IL-33 and sST2 receptors were significantly higher in OSAS groups than the control group (P < .001). However, both CRP and ProCT levels were similar in all subjects. There was a positive correlation between PTX-3 and BMI (r = 0.446; P < .01), ODI (r = 0.555; P < .01), IL-33 (r = 0.348; P = .001) and sST2 (r = 326; P = .002), while there was a negative correlation with minimum SaO2 (r = -0.672; P < .01) in patient group. PTX-3 as a predictor of OSAS showed highest specificity (%91.7) and sensitivity (%91.7) (P < .001). CONCLUSIONS: PTX-3 can be a new indicator reflecting the inflammatory state in patients with OSAS. Since patients with OSAS could have more hypoxic state during sleep, we found higher PTX-3 level in those patients and a negative correlation between PTX-3 and minimum SaO2 , which could explain that PTX-3 levels can increase with the severity of disease. Our results suggest that PTX-3 as an inflammatory biomarker may play a crucial role as an indicator of syndrome severity in OSAS.

Re-initiation of biologics after the development of tuberculosis under anti-TNF therapy.

The use of anti-TNF agents is associated with an increased risk of tuberculosis (TB) and anti-TNF agents are stopped when active TB develops. However, discontinuation of treatment can result in flare of the underlying disease. The charts of 22 patients who developed active TB among a cohort of 2754 patients using anti-TNF agents between 2001 and 2013 were reviewed retrospectively. Patients restarting biologics during further follow-up were identified. One patient with miliary TB died within 1 month. A biologic agent was restarted in 16 of the remaining 21 patients (76 %). The most frequently re-initiated biologic agent was etanercept (n = 6) followed by rituximab (n = 5) and interferon-alpha (n = 3). Biologic treatment was re-initiated during anti-TB treatment in four patients and after completing TB treatment in 12 patients. The median follow-up after restarting biologics was 53 (IQR: 40-75) months. TB re-occurred in one patient with Behçet's syndrome, who initially received etanercept due to severe sight-threatening uveitis at the third month of anti-TB treatment followed by canakinumab 15 months later along with methotrexate, cyclosporine and corticosteroids. After a second course of 9 months TB therapy this patient is currently stable on interferon-alpha for 33 months. Restarting of anti-TNF agents and other biologic agents, even during TB treatment, seems to be possible among patients who had previously developed TB under anti-TNF treatment. However, the risk of re-development of TB infection mandates careful follow-up.

Factors affecting the tuberculosis risk in patients receiving anti-tumor necrosis factor-α treatment.

BACKGROUND: Tumor necrosis factor (TNF)-α inhibitors are known to increase the risk of tuberculosis (TB). OBJECTIVES: To examine the factors associated with an increased risk of TB in patients receiving anti-TNF-α treatment (aTNF-α-T). METHOD: Of 3,094 patients who received aTNF-α-T between 2003 and 2013, a total of 1,964 subjects with a follow-up time longer than 6 months were identified and included in this retrospective analysis. Potential risk factors for the development of TB in patients receiving aTNF-α-T were evaluated. RESULTS: Of the 1,964 patients, 1,009 (51%) were male and 955 (49%) were female, with a mean age of 39.7 ± 13.9 years. The primary conditions requiring aTNF-α-T included ankylosing spondylitis (n = 875), rheumatoid arthritis (n = 711), Behçet's disease (n = 83), and others (n = 295). Sixteen patients [8 (50%) males and 8 (50%) females; 5 (31.2%) with pulmonary TB and 11 (68.8%) with extrapulmonary TB] developed TB, with a corresponding TB incidence of 466/100,000. No significant associations were found between age, gender, smoking history, pack-years of smoking, isoniazid (INH) chemoprophylaxis, type of anti-TNF-α agent, use of other immunosuppressive drugs, and the risk of TB (p > 0.05). Multivariate logistic regression analysis showed a significantly higher risk of TB in patients diagnosed with Behçet's disease, and a significantly lower risk of TB in patients with a tuberculin skin test wheal ≥10 mm in diameter (p < 0.05). CONCLUSION: aTNF-α-T is associated with an increased risk of pulmonary or extrapulmonary TB, even when follow-up protocols and INH chemoprophylaxis are implemented, and TB often develops in the later stages of treatment. The risk of TB was higher in patients with Behçet's disease and lower in patients who had a strong tuberculin skin test reaction.