Elif Kupeli

Genetic Mutations in Turkish Population With Pulmonary Embolism and Deep Venous Thrombosis

Venous thromboembolism (VTE) is a universal health hazard. Inherited and acquired risk factors increase the risk of VTE. We evaluated the relationship between factor V (G1691A, A1090G, and A1299G), prothrombin (PT G20210A), methylenetetrahydrofolate reductase (MTHFR C677T) mutations, plasminogen activator inhibitor 1 (PAI-1 -675) polymorphism, and VTE in Turkish population. In all, 80 patients with VTE and 104 controls were included. Heterozygous factor V Leiden (FVL) mutation was significantly higher among patients (P = .04) with allele frequency of 6.3% (P = .01). Heterozygous PT G20210A mutation was also significantly higher among patients (P = .001) with allele frequency of 6.9% (P = .003). MTHFR 677TT genotype was significantly higher in patients (P = .009) with allele frequency of 23.8% (P = .005). No significant difference was found in FV A1090G and FV A1299G mutation rate as well as PAI-1 genotypes and their allele frequencies (P > .05). Thus, frequencies of FV G1691A, PT G20210A, and MTHFR C677T mutations are higher in patients with VTE. FV A1090G, FV A1299G mutations, and PAI-1 gene polymorphisms may not be a risk factor for VTE in Turkish population.

Pleural effusion following ventriculo-pleural shunt: Case reports and review of the literature

Ventriculo-pleural shunt (VPLS) is an acceptable alternative in the management of hydrocephalus. Imbalance between the production and absorption of cerebrospinal fluid an lead to formation of pleural effusion in patient with VPLS and on occasion produce symptoms. Pleural effusion could be a transudate or a non-specific exudate. We report our experience with this modality in relation to formation of pleural effusion and review the literature to make recommendation for its management. Information related to patients’ demographics, smoking history, prior pulmonary and occupational history, indication, duration and complications of the VPLS and their management was gathered to substantiate current recommendation with our experience.

Diagnostic Accuracy of Cytokine Levels (TNF-α, IL-2 and IFN-γ) in Bronchoalveolar Lavage Fluid of Smear-Negative Pulmonary Tuberculosis Patients

Background: The determination of cytokine concentrations in serum and bronchoalveolar lavage fluid (BALF) may contribute to the diagnosis of tuberculosis (TB) since cytokines have been ascribed an important role in TB pathogenesis. Objective: To assess the diagnostic accuracy of TNF-α, IFN-γ and IL-2 levels in serum and BALF of smear-negative pulmonary TB patients. Method: BALF was obtained from the affected lobe in patients with smear-negative TB or other pulmonary diseases (OPD), and from the right middle lobe in healthy controls. ELISA and a nephelometric method were used to detect cytokine and albumin levels. Results: TNF-α levels in BALF were significantly elevated in the TB group (n = 15) compared with the OPD patients (n = 40) and controls (n = 17; p < 0.001). Although these three cytokines correlated well with each other in BALF (p < 0.0001, and r ≧ 0.7, respectively), BALF IL-2 and IFN-γ levels were not significantly different among the groups (p > 0.05). BALF TNF-α or IFN-γ levels were significantly higher in patients with cavitary disease (n = 11) versus those without (n = 61; p < 0.05). However, no significant difference was found between cavitary (n = 7) and non-cavitary TB in cytokine levels (p > 0.05). Neither gender nor smoking status showed any statistical differences in cytokines in the groups (p > 0.05). Sensitivity and specificity of BALF TNF-α were found to be 73 and 76%, respectively. The positive and negative predictive values for BALF TNF-α were 44 and 91%, respectively. Conclusion: In cases of smear-negative TB, BALF TNF-α can be a useful tool to identify healthy subjects rather than smear-negative TB patients.

Pulmonary complications in renal recipients after transplantation.

BACKGROUND Renal transplantation is the most common type of solid organ transplantation. Recipients are susceptible to a variety of pulmonary complications, in particular during intense immunosuppression therapy. OBJECTIVE To evaluate pulmonary complications during the first year after renal transplantation. MATERIALS AND METHODS Medical records were reviewed retrospectively for all patients who underwent renal transplantation between 2007 and 2010. Data pertinent to pulmonary complications were obtained including patient demographics, findings at chest radiography and pulmonary function testing, concentrations of C-reactive protein and albumin, and white blood cell count. RESULTS The study included 136 patients (71.3% men), with mean (SD) age of 36.3 (12.2) years. The most frequently prescribed immunosuppression therapy included prednisolone plus cyclosporine, tacrolimus, or rapamycin. Fifteen patients developed complications during the first year after surgery including respiratory infections in 12 (80%), namely, bacterial pneumonia in 10 (66.6%), and tuberculosis (caused by Mycobacterium tuberculosis) in 2 (33.3%). Pneumonia developed within the first 5 months after transplantation in 6 patients, and tuberculosis after the third month. Microbiologic agents were detected in 3 of the 6 patients (20%), and empyema, postoperative atelectasis, and pulmonary embolism, respectively, in the other 3 patients. No association was observed between complications and baseline pulmonary function test results. C-reactive protein concentration was significantly increased in patients with pulmonary complications. No invasive procedures were performed to diagnose complications, all of which resolved with appropriate treatment. CONCLUSION Pulmonary infections are a primary complication in renal transplant recipients, and are observed most frequently in the first 6 months after surgery. Immunosuppression therapy is the most likely cause of these complications, and rigorous monitoring of drug concentrations is essential. An invasive diagnostic approach may not always be necessary to determine the early specific therapy.

Pulmonary infections in transplant recipients.

PURPOSE OF REVIEW Hematopoietic stem cell as well as solid-organ transplantation is being carried out with increasing frequency throughout the world. Lower respiratory tract infections (LRTIs) remain a common life-threatening complication faced by the transplant recipients. The purpose of this review is to provide up-to-date information on pulmonary infections among the transplant recipients, especially emphasizing the endemicity of microorganisms, epidemiology, work-up of infections, and principles of their management. RECENT FINDINGS A lower respiratory tract infection such as pneumonia is the most frequent of all the infections and is associated with high morbidity and mortality. Factors increasing the risk of pulmonary infections include surgical techniques, immune status, chemoradiotherapy, alloimmune mechanisms between the host and the graft, and the environment. A high degree of suspicion, computed tomography (CT) scan of the chest, and flexible bronchoscopy are required in most to establish the diagnosis. SUMMARY Proper management of LRTI in transplant recipients requires a high degree of suspicion, thorough knowledge of the epidemiology and endemicity of the suspected organisms, CT scan of the chest, and expertise at bronchoscopy. Utmost teamwork among transplant physicians, infectious disease specialist, and bronchoscopist is essential.

Transbronchial needle aspiration "by the books"

BACKGROUND: Training for advanced bronchoscopic procedures is acquired during the interventional pulmonology (IP) Fellowship. Unfortunately a number of such programs are small, limiting dissemination of formal training. OBJECTIVE: We studied success of conventional transbronchial needle aspiration (C-TBNA) in the hands of physicians without formal IP training. METHODS: A technique of C-TBNA was learned solely from the literature, videos and practicing on inanimate models at “Hands-On” courses. Conventional TBNA with 21 and/or 19 gauge Smooth Shot Needles (Olympus®, Japan) was performed on consecutive patients with undiagnosed mediastinal lymphadenopathy. RESULTS: Thirty-four patients (male 23), mean age 54.9 ± 11.8 years underwent C-TBNA. Twenty-two patients had nodes larger than 20 mms. Suspected diagnoses were malignancy in 20 and nonmalignant conditions in 14. Final diagnoses were malignancy 17, sarcoidosis 4, reactive lymph nodes 12, and tuberculosis 1. Final diagnosis was established by C-TBNA in 14 (11 malignancy, 3 sarcoidosis; yield 41.1%), mediastinoscopy in 14, transthoracic needle aspiration in 3, peripheral lymph node biopsies in 2 and by endobronchial biopsy in 1. Nodal size had an impact on outcome (P = 0.000) while location did not (P = 0.33). C-TBNA was positive in 11/20 when malignancy was suspected (yield 55%), while 3/14 when benign diagnosis was suspected (yield 21.4%) (P = 0.05). Sensitivity, specificity, PPV, NPV, and diagnostic accuracy were 66.6%, 100%, 100%, 65%, and 79.4%, respectively. There were no complications or scope damage. CONCLUSION: Conventional-TBNA can be learned by the books and by practicing on inanimate models without formal training and results similar to those published in the literature could be achieved.

Diagnostic utility of flexible bronchoscopy in recipients of solid organ transplants.

BACKGROUND Solid organ transplant (SOT) recipients are prone to develop pulmonary complications (PC) due to their immunocompromised state. Flexible bronchoscopy (FB) is frequently performed to diagnose the nature of these complications. The aim of this study was to evaluate the diagnostic utility of FB in SOT recipients with suspected PC. METHOD We examined the medical records of patients who underwent FB between 2000 and 2010; patients who received SOT were included patient demographics, transplantation type, primary diagnoses, thorax computed tomography results, total blood count and chemistries, immunosuppressant therapies, indication, results, specimen cultures, as well as suspected and final diagnoses were recorded. RESULTS Among 1368 either liver or kidney transplant recipients 61 subjects including 49 male patients of overall mean age 42.8±12 years underwent FB. FB was performed for lung infiltrates (n=42), lung nodules (n=2), atelectasis (n=1), bronchopleural fistula (n=1), stridor (n=1), mediastinal lymphadenopathy (n=2), pleural effusion (n=1), fever (n=9), and/or hemoptysis (n=2). FB was unremarkable in 17. Other findings were as follows: increased secretions (n=24), chronic mucosal changes (n=7), endobronchial lesion (n=1), edematous mucosa (n=3), submucosal narrowing (n=1), necrotic plaque (n=2), hemorrhage (n=2), tracheal stenosis (n=1), and/or friable mucosa (n=3). We performed bronchial washings (n=56) and/or bronchoalveolar lavage (n=5). In 24 patients the microorganisms were Mycobacterium tuberculosis, Staphylococcus aureus, Moraxella catharralis, Candida albicans, Klebsiella pneumonia, Escherichia coli, Streptococcus pneumonia, Stenotrofomonas maltofilia, Aspergillus fumigatus, and Pseudomonas aerigunosa. In 34 patients a final diagnosis was established using FB (diagnostic yield, 55.7%). Thirty-one patients had received tacrolimus (10.5±5.3 ng/ng/mL); 22 cyclosporine (187.1±79.3 ng/mL); and 8, sirolimus (6.2±2.2 ng/mL). No significant difference was observed between high versus low drug levels and the culture results (P>.05). CONCLUSION Suspected pulmonary infection is the most common indication for FB in SOT recipients. It may identify the causative organism in more than 30% of patients and should be considered in the presence of a lung infection.

Bony bridge of a bifid rib.

A 21-year-old man presents with 3 days of cough and hemoptysis. A chest x-ray reveals a congenital anomaly.

Hyperhomocysteinemia Due to Pernicious Anemia Leading to Pulmonary Thromboembolism in a Heterozygous Mutation Carrier

Pulmonary thromboembolism is a life-threatening condition resulting mostly from lower extremity deep-vein or pelvic-vein thrombosis. A 46-year-old woman was admitted to hospital with pain on the right side of the chest and hemoptysis. On laboratory analysis, D-dimer level was elevated. Computed tomographic pulmonary angiography revealed intravascular filling defects due to thrombi in right lower lobe pulmonary segmental arteries. Screening for thrombophilic states was normal except for heterozygous mutations of both prothrombin and methylene tetrahydrofolate reductase (MTHFR 677) genes. Homocysteine level was high, and vitamin B12 level and serum ferritin level were reduced. Serum antiparietal antibody was positive, and therefore, pernicious anemia was diagnosed along with iron-deficiency anemia. After the diagnoses were established, enoxaparin followed by warfarin was started in addition to oral vitamin B12, pyridoxine, thiamine, folic acid, and ferroglycine sulfate supplementation. At the end of 8 weeks of the replacement therapy, vitamin B12, folate, and homocysteine levels and red cell volume were found to be normal, with complete resolution of the thrombus confirmed by repeat computed tomographic pulmonary angiography. We conclude that hyperhomocysteinemia due to vitamin B12 deficiency associated with pernicious anemia might have decreased the threshold for thrombosis. In addition, the presence of heterozygous prothrombin and methylene tetrahydrofolate reductase mutations might serve as synergistic cofactors triggering pulmonary thromboembolism.

Tracheobronchopathia osteochondroplastica: a review of the literature

Tracheobronchopathia osteochondroplastica (TBPOCP) is an uncommon benign condition affecting the lumen of tracheobronchial tree and characterized by abnormal chondrification and ossification. TBPOCP is more frequent than it has been reported, as it can be asymptomatic or present with non‐specific respiratory symptoms.