Screening for pulmonary arterial hypertension in patients with systemic sclerosis in the era of new pulmonary arterial hypertension definitions.

OBJECTIVES: This study compares the performance of three composite pulmonary arterial hypertension (PAH) screening tools in a real-life SSc cohort, according to both the previous 2015 ESC/ERS guideline and the recent 2022 ESC/ERS guideline haemodynamic criteria. METHODS: Consecutive SSc patients without a previous diagnosis of pulmonary hypertension (PH) were screened for PAH using the European Society of Cardiology/European Respiratory Society (ESC/ERS), DETECT, and Australian Scleroderma Interest Group (ASIG) algorithms. Right heart catheterisation (RHC) referral performances for PAH were compared according to the 2022 ESC/ERS PAH criteria. RESULTS: Thirty-five of the 81 patients required RHC; 15 (18.5%) according to ESC/ERS, 27 (33.3%) according to DETECT, and 25 (31%) according to ASIG. The final diagnoses were no-PH in 17 patients, WHO group 1 PH (PAH) in 8 patients, WHO group 2 PH in 8 patients, and WHO group 3 PH in 2 patients. When the hemodynamic criteria of the previous ESC/ERS guideline were applied, only one patient was diagnosed with PAH. The sensitivities of the algorithms for the diagnosis of PAH were 62.5% for ESC/ERS, 75% for DETECT, 87.5% for ASIG according to the 2022 ESC/ERS guideline definition, and 100% for all according to the previous ESC/ERS guideline. CONCLUSIONS: With the recent criteria, PAH diagnosis in patients with SSc increased by 1.8-fold. Current algorithms for screening PAH are less sensitive with these revised criteria. Although the ASIG algorithm seems more sensitive, it can still miss the diagnosis. The multimodal/algorithmic approach seems to be the best option for predicting PAH.

The role of an activity monitor in the objective evaluation of patients with pulmonary hypertension.

INTRODUCTION: Patients with pulmonary hypertension (PH) show no symptoms at rest, but symptoms are triggered by physical activities. OBJECTIVES: The primary aim of our study was to assess physical activity of patients with PH by using an activity monitor. The secondary aim was to evaluate the correlation between the activity monitor parameters and 6-min walk distance (6MWD), activity of daily living (ADL), quality of life, WHO functional class and PH classification. METHODS: Thirty-eight patients with pulmonary arterial hypertension (PAH) and seven patients with chronic thromboembolic PH were included in the study. Physical activity was assessed using a SenseWear arm band. A 6-min walk test was performed. Daily living activities were assessed using the 'nottingham extended activity of daily living index' (NEADL). For quality of life assessments, 'Minnesota living with heart failure' (MLHF) and 'Short form-36' (SF-36) surveys were used. RESULTS: Physical activity, exercise capacity, quality of life and contribution to ADL were lower in patients with PH. These data were associated with the 6MWD, quality of life and ADL index scores. We also found weak and moderate correlations between activity monitor data and SF-36 sub-group scores, MLHF and NEADL scores (P < 0.05). For the group with PAH, idiopathic PAH patients had more exercise capacity and total energy expenditure compared with patients with scleroderma-associated PAH. CONCLUSION: Correlation between activity monitor data and 6MWD, most of SF-36 sub-group scores, MLHF scores and NEADL index scores suggest that activity monitor can be used in the evaluation of patients with PH.

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.

Relationship Between Abnormalities on High-Resolution Computerized Tomography, Pulmonary Function, and Bronchoalveolar Lavage in Progressive Systemic Sclerosis.

 Introduction and aim: Progressive systemic sclerosis (pSS) is a multisystemic connective tissue disease characterized by fibrosis of the skin and internal organs including lung. The mechanisms that leads to progressive lung fibrosis in scleroderma remain obscure. In this study, we aimed to investigate the correlation between HRCT findings and patients' clinical and functional status and the degree of alveolitis based on the BAL resultsMaterials and methods: 65 patients with pSS were evaluated. Thoracic HRCT, pulmonary function tests, and dyspnea measurements were applied, and BAL was performed. The parenchymal abnormalities identified on HRCT were coded, and  scored according to Warrick et al. RESULTS: Among parameters investigated, a correlation was found between the number of segments with subpleural cysts and the duration of disease. Also there was a correlation between the HRCT score and patient age whereas no correlation was detected between the duration of the disease, manifestation of the symptoms, and the x-ray findings. A correlation was found between the percentage of neutrophils detected in BAL and the extent of the honeycombing on HRCT. CONCLUSION: This study showed a strong correlation between the extent of x-ray abnormalities and FVC, RV, and DLCO, as well as an increase in the percentage of BAL fluid neutrophils in patients with SSc-PI.

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.

Evaluation of the Practice Pattern of Medical Patients' VTE Prophylaxis With a Standard Risk Assessment Model Form: MERAM Study.

Hospitalized acutely ill patients face high risk for venous thromboembolism (VTE) unless appropriate thromboprophylaxis is applied. This study aimed to determine VTE prophylaxis practices for inpatients in Turkey and to evaluate the impact of physicians' training via a modified "Standard Medical Patients' VTE Risk Assessment Model (MERAM)." A total of 607 inpatients included in this national multicenter noninterventional observational registry were evaluated in terms of demographics, VTE risk, and preventive measures at 2 consecutive cross-sectional visits. Physicians were asked to complete a questionnaire on current VTE method risk assessment and other models including MERAM. The VTE prophylaxis rates significantly increased from 49.4% to 62.4% between visits (P < .05). The lack of risk evaluation decreased from 74.6% to 19.5% (P < .001). Percentage of physicians using prophylaxis and use of MERAM increased between visits. Physician training proved effective for providing general "awareness" of VTE prophylaxis and led to higher rates of risk assessment model-based appropriate VTE prophylaxis.

Pulmonary tuberculosis incidence in Turkish prisons: importance of screening and case finding strategies.

INTRODUCTION: The purpose of this study was to evaluate the burden of pulmonary tuberculosis in 10 prisons mostly located in the Marmara Region of Turkey, and to compare them with the country incidence. PATIENTS AND METHODS: All the inmates in ten prisons mostly located in the four cities in the Marmara Region of Turkey were enrolled in this study. Tuberculosis screening was done between January 2006-January 2007. Radiological screening for tuberculosis was performed by the mobile X-ray system and it was followed by bacteriological analysis of sputum for tuberculosis suspects. Four physicians evaluated the X-rays independently. RESULTS: Four thousand six hundred and fifteen prisoners were detected by radiological screening. Three hundred and one (7%) of them were female and 4314 (93%) were male, age range was between 14-72 years. Age ranges of female and male prisoners were 16-59 and 14-72 respectively. 398/4615 (8.6%) were young adults inmates with an age range of 14-18. Radiological abnormalities consistent with tuberculosis were found in 130 chest X-rays and followed by sputum bacteriology. Smear and culture positive pulmonary tuberculosis diagnosed in five out of 130, were all male with mean age 33 ± 10 years. Tuberculosis prevalence in the prisons was found to be 108/100.000 which was four times higher than the overall incidence of tuberculosis in Turkey in the year which the present study was conducted. CONCLUSION: Prisoners are one of the most important risk groups with high burden of tuberculosis in Turkey. This result highlights the need for adequate case- finding strategies in prisons.

A retrospective case-control study, factors affecting treatment outcomes for pulmonary tuberculosis in istanbul, Turkey.

BACKGROUND: Tuberculosis is a public health problem and its transmission is a threat to the community. AIMS: The aim of this study was to determine the factors influencing the treatment outcomes and the effectiveness of the National Tuberculosis Program (NTP) in relation to the application of the directly observed treatment, short-course (DOTS) program in various sites in Istanbul, Turkey. STUDY DESIGN: Case-Control Study. METHODS: A case-control study was used, where cases and controls were randomly selected from the Turkish Tuberculosis National Database, which includes complete data on treatment outcomes for patients recorded in the database from January 1, 2006 to December 31, 2009 and had one year follow-up. RESULTS: The case group was composed of 464 patients with adverse outcome, while the control group was composed of 441 patients who had been cured of disease. Factors associated with adverse treatment outcome were >65 years of age (OR: 3.39 (1.99-5.76)) ; male gender (OR:2.11 (1.49-2.99)); born outside Turkey (OR: 5.48 (2.13-14.04)); co-morbidity (OR: 1.85 (1.29-2.65)); bilateral radiologic lesions (OR: 2.07 (1.41-3.00); previous treatment history (OR: 3.99 (2.78-5.74)); 3(rd) month positive microscopy (OR: 4.96 (3.04-8.09)) and any H&R +/- others multidrug resistant (MDR) resistance (OR: 22.64 (6.92-74.08)). There was no association between the adverse treatment outcome and the application site of direct observation treatment, short course (DOTS) delivery and the supervisors. CONCLUSION: Our findings indicate similar quality in DOTS application and supervision among patients with or without adverse treatment outcomes. However, patients with certain characteristics should be carefully monitored and aggressively treated.

The functional SLC11A1 gene polymorphisms are associated with sarcoidosis in Turkish population.

Sarcoidosis (SA) is an immune-mediated multisystemic disorder of unknown etiology characterized by the accumulation of lymphocytes, mononuclear phagocytes and epithelioid cell granulomas involved in different organs and tissues. The belief that genetics contribute to SA etiology is supported by twin studies, disease clustering in families and racial differences in incidence rates. Involvements of SLC11A1 in macrophage function and activation, makes it an attractive candidate gene for immune-mediated and infectious diseases. We investigated the association between SA and four polymorphisms of the SLC11A1 gene, including a single nucleotide change in intron 4 (INT4); a nonconservative single-base substitution at codon 543 (D543N); a TGTG deletion in the 3' untranslated region; and the functional (GT)(n) repeat polymorphism in the 5' region, in 95 Turkish SA patients and 150 healthy controls, by using amplification refractory mutation system-polymerase chain reaction and sequencing. We found significant association between SA and INT4 G/C allele frequency (P = 0.0000; odds ratio 2.75; 95% confidence interval 1.68-4.52) and 5'(GT)(n) allele 2/3 frequency (P = 0.0000; odds ratio 2.69; 95% confidence interval 1.61-4.47) suggesting that SLC11A1 might be a plausible candidate gene for SA.

Survival in progressive systemic sclerosis with pulmonary involvement: a single-center experience in Istanbul, Turkey.

The objective of the current study was to determine survival and factors that affect survival in progressive systemic sclerosis (SSc) with pulmonary involvement. A total of 102 SSc patients with pulmonary involvement, diagnosed between 1994 and 2008, enrolled into the study. Pulmonary involvement was defined based on the presence of interstitial changes on high-resolution CT (HRCT). Demographical, clinical, radiological, and laboratory data of the patients were found from patient records and were used for the evaluation of survival. The mean age of the patients at diagnosis was 50 ± 12 years. In follow-up, 22 (21.5%) patients were deceased. The mean age of the patients at death was 55 ± 12 years. Seventy-eight percent of known causes of mortality were related to pulmonary complications. After any initial systemic manifestation of disease, the mean survival was 447 ± 27 months and 5, 10, 15, and 20 year survival rates were 99, 92, 83, and 72%, respectively. The mean survival after initial pulmonary manifestation was 269 ± 23 months and 5, 10 and 15 year survival rates were 91, 73 and 57%, respectively. Mean survival was 113 ± 5 months, and 5- and 10-year survival rates after the lung involvement detected with HRCT were 85 and 66%, respectively. Pulmonary artery hypertension, disease onset after the age of 40, and honeycombing on HRCT were associated with poor survival. Our data suggest that pulmonary involvement is the most important determinant factor for poor prognosis in patients with SSc. Therefore, echocardiography, pulmonary function tests, and HRCT should be performed in early stages of the disease for early diagnosis of pulmonary artery hypertension and lung involvement before irreversible vascular and interstitial changes exist.

Clinical presentations and diagnostic work-up in sarcoidosis: a series of Turkish cases (clinics and diagnosis of sarcoidosis).

Sarcoidosis is an idiopathic granulomatous disease. It usually affects the lung. The diagnosis may be problematic since the known causes of granulomatous inflammation must be excluded. This multicenter study aimed to evaluate the clinical presentations and diagnostic approaches of sarcoidosis. The study protocol was sent via internet, and the participants were asked to send the information (clinical, radiological and diagnostic) on newly diagnosed sarcoidosis cases. 293 patients were enrolled within two years. Pulmonary symptoms were found in 73.3% of the patients, and cough was the most common one (53.2%), followed by dyspnea (40.3%). Constitutional symptoms were occured in half of the patients. The most common one was fatigue (38.6%). The most common physical sign was eritema nodosum (17.1%). The most common chest radiograhical sign was bilateral hilar lymphadenomegaly (78.8%). Staging according to chest X-ray has revealed that most of the patients were in Stage I and Stage II (51.9% and 31.7%, respectively). Sarcoidosis was confirmed histopathologically in 265 (90.4%) patients. Although one-third of the bronchoscopy was revealed normal, mucosal hyperemi (19.8%) and external compression of the bronchial wall (16.8%) were common abnormal findings. The 100% success rate was obtained in mediastinoscopy among the frequently used sampling methods. Transbronchial biopsy was the most frequently used method with 48.8% success rate. Considering sarcoidosis with its most common and also rare findings in the differential diagnosis, organizing the related procedures according to the possibly effected areas, and the expertise of the team would favour multimodality diagnosis.

Extrapulmonary involvement in patients with sarcoidosis in Turkey.

BACKGROUND AND OBJECTIVE: Extrapulmonary sarcoidosis is common, and is almost always associated with concomitant thoracic involvement. Extrapulmonary manifestations vary on the basis of gender, age at presentation and ethnicity. The aim of this study was to investigate extrapulmonary involvement in patients with sarcoidosis in Turkey. METHODS: This study was conducted by Turkish Thoracic Society Clinical Problems Study Group. New cases of sarcoidosis between 1 June 2004 and 31 May 2006 were recorded on electronic case record forms sent to all potential investigators and information about extrapulmonary involvement was collected. RESULTS: One hundred and nineteen of 293 patients (83 female, 36 male, mean age = 45 ± 12 years) had extrapulmonary involvement in this study (40.6%). The median time to diagnosis was 6 months and this was longer than patients with just thoracic sarcoidosis (P = 0.001). Extrapulmonary symptoms were present in 181 (61.8%) patients, and skin lesions, arthralgia and back pain were the commonest (33.4%, 20.8% and 16.4%, respectively). Incidence of organ involvement was independent of age with the exception of ocular involvement, which was higher in those under the age of 40 years (P = 0.007). CONCLUSIONS: Skin and peripheral lymph node involvement were the most common sites of extrapulmonary involvement and ocular involvement was more common in those under the age of 40 years in patients with sarcoidosis in a Turkish population.

Sarcoidosis mimicking lymphoma on positron emission tomography-computed tomography in two patients treated for lymphoma: two case reports.

INTRODUCTION: Sarcoidosis is a granulomatous disease that mostly involves the lungs. Its association with malignancies has been well documented. Several mechanisms have been proposed that may underlie this concurrence including triggering tumour antigens and defective cellular immunity. CASE PRESENTATIONS: We briefly review the literature on malignancy associated sarcoidosis and report two female lymphoma patients of 49 and 56 years of age who, during their course of disease, developed sarcoidosis that was misinterpreted as a lymphoma relapse on positron emission tomography-computed tomography. CONCLUSION: We hypothesise that T cell dysfunction and exposure to tumour associated antigens might be the underlying mechanisms of development of sarcoidosis in patients with lymphoma. Positron emission tomography-positive lesions do not always indicate malignancy and therefore a tissue biopsy is always mandatory to confirm the diagnosis.

3p abnormalities in peripheral lymphocytes in small cell lung cancer.

3p abnormalities are the most frequent chromosome abnormalities in small cell lung cancer (SCLC). To date these abnormalities have only been observed in cells derived from tumor tissues. It is thought that cancer-related chromosome abnormalities in peripheral lymphocytes could help to predict cancer development, prognosis, and future metastasis. We report clonal and nonclonal 3p abnormalities in the peripheral lymphocytes of two patients with SCLC. A standard T-lymphocyte culture method and GTL banding technique were applied to the samples, and various clonal and nonclonal chromosome 3 abnormalities, i.e., -3, del(3)(p24), del(3)(p21), del(3)(p11), del(3)(q22), inv(3)(p14q29), and inv(3)(q21q29) were observed. Efforts have been made to understand if there are cancer-related chromosome abnormalities in lymphocytes and the suitability of these abnormalities to predict cancer development or metastases. As far as we know, this is the first report on chromosome 3 abnormalities in lymphocytes. Since 3p abnormalities are specific for SCLC, it is important to show that these cancer-related abnormalities can be found in blood cells.

The oxidant-antioxidant balance in systemic sclerosis cases with interstitial lung involvement.

We aimed to assess the plasma oxidant and antioxidant levels in systemic sclerosis (SS) patients with interstitial lung involvement. Twenty-seven female SS patients and 17 healthy female volunteers were included in the study. Plasma levels of oxidants and antioxidants levels were studied of two groups. The median oxidant and antioxidant levels in study and control groups were, MDA 5.2 +/- 0.4/3.7 +/- 0.5 nmol/ml (P < 0.001), NO 45.4 +/- 3.7/34.2 +/- 2.9 nmol/l (P < 0.001), SOD 25.6 +/- 2.3/24.6 +/- 2.0 U/ml (P > 0.05), catalase 99.9 +/- 9.9/140.0 +/- 10.0 U/ml (P < 0.001), vitamin E 20.5 +/- 1.3/22.6 +/- 2.0%mg (P < 0.001), vitamin C 70.6 +/- 8.7/83.5 +/- 7.3 mg/dl (P < 0.001), respectively. There was also no correlation between plasma levels of oxidants-antioxidants levels and disease duration, duration of pulmonary signs, pulmonary function test values, HRCT scores in SS patients (P > 0.05). In our study, the oxidant burden in SS patients with interstitial lung involvement was found to be increased; however no correlation was detected between the severity of lung involvement and oxidant-antioxidant levels.