Comparison of clinical features of cystic fibrosis patients eligible but not on CFTR modulators to ineligible for CFTR modulators.

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs target the underlying defect and improve CFTR function. They are a part of standard care in many countries, but not all patients are eligible for these drugs due to age and genotype. Here, we aimed to determine the characteristics of non-eligible patients for CFTR modulators in the CF registry of Turkey (CFRT) to highlight their clinical needs. METHODS: This retrospective cohort study included CF patient data from the CFRT in 2021. The decision of eligibility for the CFTR modulator was determined according to the 'Vertex treatment-Finder' on the Vertex® website. Demographic and clinical characteristics of patients were compared between eligible (group 1) and ineligible (group 2) groups for CFTR modulators. RESULTS: Among the study population (N = 1527), 873 (57.2%) were in group 1 and 654 (42.8%) were in group 2. There was no statistical difference between groups regarding sex, meconium ileus history, diagnoses via newborn screening, FEV1 z-score, CF-associated complications, organ transplant history, and death. Patients in group 2 had a higher incidence of pancreatic insufficiency (87.7% vs. 83.2%, p = .010), lower median height z-scores (-0.87 vs. -0.55, p < .001), lower median body mass index z-scores (-0.65 vs. -0.50, p < .001), longer days receiving antibiotics due to pulmonary exacerbation (0 [interquartile range, IQR: 0-2] vs. 0 [IQR: 0-7], p = 0.001), and more non-invasive ventilation support (2.6% vs. 0.9%, p = 0.008) than patients in group 1. CONCLUSION: The ineligible group had worse clinical outcomes than the eligible group. This highlights their need for life-changing drugs to improve clinical outcomes.

Impact of posaconazole prophylaxis and antifungal treatment on BAL GM performance in hematology malignancy patients with febrile neutropenia: a real life experience.

BACKGROUND: Diagnostic accuracy of galactomannan measurements is highly variable depending on the study population, diagnostic procedures, and treatment procedures. We aimed to evaluate the effect of posaconazole prophylaxis and empiric antifungal treatment upon diagnostic accuracy of GM measurements in bronchoalveolar lavage (BAL), bronchial lavage (BL), and serum in hematological malignancy population. METHODS: Patients hospitalized in a single tertiary care center with hematologic malignancies undergoing fiberoptic bronchoscopy (FOB) with a preliminary diagnosis of IPA were retrospectively included. RESULTS: In all the study population (n = 327), AUC for BAL, BL, and serum GM were as follows: 0.731 [0.666-0.790], 0.869 [0.816-0.912], and 0.610 [0.540-0.676] with BL samples having the best diagnostic value. GM measurements in patients under posaconazole prophylaxis (n = 114) showed similar diagnostic performance. While specificity was similar between patients with and without posaconazole prophylaxis, sensitivity of GM measurements was lower in patients with prophylaxis. Analyses with patient classified according to antifungal treatment at the time of FOB procedure (n = 166) showed a decreased diagnostic accuracy in serum GM and BAL GM measurements related with the duration of treatment. However, BAL, BL, and serum GM measurements presented similar sensitivity and specificity in higher cut-off values in longer durations of antifungal treatment. CONCLUSION: Our study shows that posaconazole prophylaxis and active short-term (3 days) antifungal treatment do not significantly affect overall diagnostic performance of GM measurements in bronchoalveolar lavage and bronchial lavage samples. However, using different cut-off values for patients receiving active treatment might be suggested to increase sensitivity.

Serum Krebs von den Lungen-6: promising biomarker to differentiate CPFE from IPF.

Background   Combined pulmonary fibrosis and emphysema (CPFE) has been recognised as a phenotype of pulmonary fibrosis. We aimed to compare serum surfactant protein-A (SP-A), surfactant protein-D (SP-D) and Krebs von den Lungen-6 (KL-6) levels, functional parameters, in CPFE and  IPF (idiopathic pulmonary fibrosis) patients. Methods Patients diagnosed with 'CPFE' and 'IPF' were consecutively included in 6 months as two groups. The patients with connective tissue diseases are excluded. Results           In this study, 47 patients (41 males, 6 females) with CPFE (n = 21) and IPF (n = 26) with a mean age of 70.12 ± 8.75 were evaluated. CPFE patients were older, had more intense smoking history, had lower DLCO/VA, lower FVC, and worse six-minute walking distance than the IPF group (p=0.005, p=0.027, p=0.02, p<0.001, p=0.001, respectively). Serum KL-6 levels were higher in CPFE group compared to IPF group [264.70 U/ml (228.90-786) vs 233.60 (101.8-425.4), p<0.001]. Serum KL-6 levels of 245.4 U/ml and higher have 81% sensitivity and 73% specificity for the discrimination of CPFE from IPF. Conclusions   Our study has shown that serum KL-6 level is a promising biomarker to differentiate CPFE from IPF. In CPFE cases respiratory and functional parameters are worse than those of pure fibrosis cases.

Tocilizumab treatment in COVID-19: A prognostic study using propensity score matching.

BACKGROUND: The potential role of interleukin-6 (IL-6) in coronavirus disease 2019 (COVID-19) pneumonia provides the rationale for investigating IL-6 signaling inhibitors. OBJECTIVES: To evaluate and report treatment responses to tocilizumab (TCZ) in COVID-19 patients and compare mortality outcomes with those of standard care. MATERIAL AND METHODS: Patients hospitalized with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, diagnosed with reverse transcription polymerase chain reaction (RT-PCR) between March 2020 and April 2021, were enrolled in this single-center retrospective cohort study. Propensity score matching was performed in order to reduce confounding effects secondary to imbalances in receiving TCZ treatment. RESULTS: A total of 364 patients were included in this study. Two hundred thirty-six patients received standard care, while 128 patients were treated with TCZ in addition to standard care (26 (20.3%) patients received a dose of 400 mg intravenously once, while 102 (79.7%) patients received a total dose of 800 mg intravenously). In the propensity score-matched population, less noninvasive mechanical ventilation (p = 0.041) and mechanical ventilation support (p = 0.015), and fewer deaths (p = 0.008) were observed among the TCZ-treated patients. The multivariate adjusted Cox regression model showed a significantly higher survival rate among TCZ patients compared to controls (hazard ratio (HR): 0.157, 95% confidence interval (95% CI): 0.026-0.951; p = 0.044). The hazard ratio for mortality in the TCZ group was 0.098 (95% CI: 0.030-0.318; p = 0.0001 using log-rank test). CONCLUSIONS: This study determined that TCZ treatment in COVID-19 patients was associated with better survival, reduced need for mechanical ventilation and reduced hospital-associated mortality.

Is serum iron responsive protein-2 level associated with pulmonary functions and frequent exacerbator phenotype in COPD?

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) exacerbations contribute to the overall severity in individual patients because they are associated with airway inflammation, pulmonary function loss, decreased quality of life and increased mortality. Although, identifying frequent exacerbator patients is important due to severe outcomes associated with frequent exacerbator phenotype in COPD patients there is no single biomarker which can differentiate this phenotype. Iron responding protein-2 (IRP2) is the protein product of IREB2 gene, which is a COPD susceptibility gene that regulates cellular iron homeostasis and has a key role in hypoxic conditions. Previous research indicates that IREB2 expression in lung tissue is associated with spirometric measurements and emphysema in COPD. In this study, our aim was to investigate whether serum IRP2 levels were associated with frequent exacerbator phenotype, to evaluate whether IRP2 levels in serum are associated with pulmonary functions and selected systemic inflammation biomarkers. MATERIALS AND METHODS: Designed as a single tertiary care center based, crosssectional study, included high risk (GOLD C, D) COPD patients who admitted to outpatient clinic consecutively between December 2015 and July 2016. RESULT: The study included 80 COPD patients. Serum IRP2 levels were negatively correlated with FEV1 ml (r= -0.25, p= 0.02) and body weight (r= -0.35, p= 0.002) but not with markers of systemic inflammation. COPD patients with at least one exacerbation history in the last year tended to have higher IRP2 levels than patients without any exacerbation [12.3 (IQR 25-75: 10.4- 17.1) vs 10.5 (IQR 25-75: 8.8-18.5), p= 0.06]. CONCLUSIONS: Serum IRP2 level is significantly correlated with FEV1 mL but not with FEV1 % predicted and cannot be used to differentiate frequent exacer bator patients. Although IREB2 gene expressions in lung tissue and bronchoalveolar lavage results have significant associations with emphysema and FEV1/FVC, FEV1 %predicted in COPD patients, our results suggests serum IRP2 level is not as promising.

Diagnostic performance of EBUS-TBNA and its interrelation with PET-CT in patients with extra-thoracic malignancies.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established diagnostic tool for lung cancer, sarcoidosis, and suspected metastatic extra-thoracic malignancy (ETM). Patients with primary ETM often have hypermetabolic mediastinal/hilar lymph node enlargement in the PET-scan done for initial staging or post treatment followup. We aimed to determine the diagnostic performance of EBUS-TBNA and the relationship between PET-SUV values and diagnosis of malignancy metastasis in patients with ETM. MATERIALS AND METHODS: Results of EBUS-TBNA in ETM patients with suspected MLN metastasis were retrospectively analysed (May 2016 to July 2019). Non-malign results were confirmed for surgery or clinical/radiological followup. Lymph nodes with a high FDG-uptake (SUV > 2.5, MLN) were reported as suspicious for metastasis. RESULT: Of the 588 EBUS procedures, 109 were included in the analysis. Patient' mean age was 62.5 ± 10.1 years; there were 35 men and 74 women. Primary malignancies were breast cancer in 33, gastrointestinal in 23, female genital tract in 17, head and neck in 14, genitourinary cancer in 13, malignant melanoma in 6, sarcoma in 2 and kaposi sarcoma in 1. According to EBUS-TBNA smear and cell block histopathologic evaluations, 16 patients' results (14.7%) were malignant compatible with metastasis of ETM. Among the 93 patients with non-malignant diagnosis, EBUS-TBNA revealed a granulomatous lympadenitis compatible with sarcoid reaction in 7 and tuberculosis in 2. A total of 9 patients underwent surgical procedures after EBUSTBNA, with a definitive histological diagnosis of granulomatous lymphadenitis in 2, malignancy in 5 and, reactive lymph node in 2. Overall sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of EBUS-TBNA were 76.19% (95% CI 52.83-91.78), 100% (95% CI 95.89-100.00), 100%, 94.62% (95% CI 89.12-97.12) and 95.4%, respectively. CONCLUSIONS: EBUS-TBNA sampling has high diagnostic performance. Histopathological confirmation requirement for MLN should be kept in mind in patients with ETM, even they have negative EBUS results.

The Outcome of Antifungal Prophylaxis with Posaconazole in Patients with Acute Myeloid Leukemia: A Single-Center Study

Objective: Invasive fungal infections (IFIs) are a significant cause of morbidity and mortality among neutropenic patients undergoing chemotherapy for acute myeloid leukemia (AML) and stem cell transplantation. The aim of this study was to evaluate the real-life impact of posaconazole prophylaxis. Materials and Methods: Eighty-four adult patients were included with AML under remission induction chemotherapy and posaconazole prophylaxis. The 34 patients in the control group did not receive primary antifungal prophylaxis. The period between June 2006 and January 2009, when antifungal prophylaxis was not administered (control group), was retrospectively compared to the period between December 2010 and May 2012 when primary oral posaconazole prophylaxis was administered in similar conditions (posaconazole group) according to the use of antifungal agents for treatment, breakthrough infections, galactomannan performance, and the necessity for performing bronchoalveolar lavage (BAL) procedures. Results: The two groups were compared according to the use of antifungal agents; progression to a different antifungal agent was found in 34/34 patients (100%) in the control group and in 9/84 patients (11%) in the posaconazole group (p<0.001). There were four breakthrough IFIs (4/84, 4.8%) in the posaconazole group and 34 IFIs in the control group (p<0.001). In addition, 15/34 patients (44%) in the control group required BAL compared to 11/84 patients (13%) in the posaconazole group (p<0.001). Posaconazole treatment was discontinued within 7-14 days in 7/84 patients (8.3%) due to poor oral compliance related to mucositis after chemotherapy. Conclusion: Posaconazole appears to be effective and well-tolerated protection against IFIs for AML patients.

Association between serum neopterin, obesity and daytime sleepiness in patients with obstructive sleep apnea.

OBJECTIVE: Obesity and obstructive sleep apnea (OSA) and systemic inflammation may interact through biochemical pathways. Neopterin (NP) is a monocyte/macrophage activation marker produced by macrophages in response to interferon-gamma secreted by activated T-lymphocytes. This study examines the association between NP, obesity and OSA. PATIENTS AND METHODS: The study included 22 newly diagnosed OSA (+) patients and 18 OSA (-) patients. Subjects with history of coronary artery disease, transplant patients, history of alcohol and drug abuse, history of HIV and any other significant medical illnesses such as active infections, autoimmune disease, malignancy, liver disease, pulmonary disease (COPD, asthma,...), neuromuscular disease, patients on immunomodulating therapy or HMG-CoA reductase inhibitors were excluded. RESULTS: There were no significant differences in age, body mass index (BMI), and smoking habits of the OSA (+) patients and OSA (-) patients. Serum NP levels did not show any significant difference between the OSA (+) patients and OSA (-) patients, however, NP levels were positively correlated with BMI (r=0.320, p=0.044). There was no significant correlation between NP and any of the polysomnographic parameters. The result of stepwise regression analyses (r(2)=0.320, p<0.001) showed that high serum NP levels (p=0.004) and apnea-hypopnea index (AHI) were a risk factor for elevated Epworth sleepiness score, independent of BMI. CONCLUSION: We suggest that serum NP levels correlate with BMI. There was a significant relationship between serum NP levels and excessive daytime sleepiness in OSA patients.

Low-grade urinary albumin excretion in normotensive/non-diabetic obstructive sleep apnea patients.

Previous studies have indicated that high levels of urinary albumin excretion (UAE) are associated with an increased incidence of cardiovascular morbidity and mortality. This study examined the association between UAE and obstructive sleep apnea syndrome (OSAS). The study included 35 newly diagnosed OSAS patients and 11 nonapneic controls. Subjects with diabetes mellitus, hypertension, a history of renal failure, cardiac failure, coronary heart disease, collagen tissue disease, high serum creatinine, and urinary infection, and who use angiotensin-converting enzyme inhibitors and were women were excluded from the study. A single void morning urine sample at the baseline examination was used to measure UAE. There were no significant differences in the age, body mass index (BMI), and smoking habits of the OSAS patients and controls. UAE of the OSAS group was significantly higher than that of the control group (23.3 +/- 6.1 microg/min vs. 6.5 +/- 2.1 microg/min, respectively; P = 0.002). UAE was positively correlated to length of time spent at an oxygen saturation of <90% (r = 0.503, P = 0.002) and BMI (r = 0.361, P = 0.033). Regression analyses (r (2) = 0.504, P < 0.0001) showed that the length of time spent at an oxygen saturation of <90% (P < 0.0001) was risk factor for UAE, independent of age and BMI. Our study supports the notion that low-grade UAE is associated with non-hypertensive/non-diabetic OSAS, independent of age and BMI. Low-grade UAE may be a marker for subclinical vascular damage that predisposes OSAS patients to future cardiovascular disease.

Can clinical factors be determinants of bone metastases in non-small cell lung cancer?

OBJECTIVE: The aim of this study was to investigate the correlations among symptoms, laboratory findings of bone metastasis and whole body bone scanning (WBBS) and the frequency of occurrence of bone metastases MATERIALS AND METHODS: Hundred and six patients who were diagnosed with non-small cell lung cancer (NSCLC) between June 2001 and September 2005 were investigated retrospectively. Bone pain, detection of bone tenderness on physical examination, hypercalcemia and increased serum alkaline phosphatase were accepted clinical factors of bone metastases. Presence of multiple asymmetric lesions in WBBS was also accepted as bone metastases. Subjects whose clinical factors and WBBS indicated doubtful bone metastases were evaluated with magnetic resonance and/or biopsy. RESULTS: Occurrence of bone metastases was 31.1% among all patients. Bone metastases were determined in 21 (52.5%) of 40 patients who had at least one clinical factor. Asymptomatic bone metastases without any clinical factors were established in 11.3% of all NSCLC patients and 15.3% of 26 operable patients. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the clinical factors of bone metastases were 63.6, 73.9, 52.5, 81.8 and 70.7% respectively. There was no significant relationship between histologic type and bone metastases. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of WBBS in detection of bone metastases were 96.9, 86.3, 76.2, 98.4, 89.6% respectively. CONCLUSION: Sensitivity and specificity of the clinical factors of bone metastases are quite low. Routine WBBS prevented futile thoracotomies. Therefore, routine WBBS should be performed in all NSCLC patients, even in the absence of bone-specific clinical factors.

An unusual reason of parotid gland enlargement; parotid gland tuberculosis.

Although pulmonary tuberculosis is common in Turkey, parotid gland tuberculosis is rarely seen. A 39 years old female presented with left side swelling on her face. The diagnosis was made excisional biopsy. Histologic examination of the operative specimen revealed necrotising granuloma concordant with tuberculosis.