Pseudoaneurysm as an Etiological Cause of Hemoptysis in Extensive Tuberculosis.

Hemoptysis is a life-threatening emergency and a possible first sign of pulmonary tuberculosis. Minor hemoptysis, as a possible clinical aspect of adult tuberculosis, usually has limited course and in most cases, is resolved with antitubercular therapy. However, massive hemoptysis is a life-threatening condition associated with a mortality rate of >50% in the absence of well-timed and proper handling. Hence, prompt diagnosis and early interventions are essential. In this study, we present a rare case of pseudoaneurysm causing massive hemoptysis in a patient with pulmonary tuberculosis.

Risk factors and severity of functional impairment in long COVID: a single-center experience in Croatia.

AIM: To determine the frequency of common symptoms in long COVID and their effect on the quality of life, and to determine the factors contributing to a more severe long COVID. METHODS: The study enrolled 266 patients who were either referred to long-COVID outpatient clinic or were inpatients undergoing rehabilitation. The data were collected between December 2020 and May 2021. We evaluated the symptoms experienced during acute and long COVID and comorbidities. Functional status was assessed with Post Covid Functional Status (PCFS). RESULTS: The final sample consisted of 261 patients. After acute COVID-19 period (>4 weeks), almost 80% of patients had impaired functional status. Only 21.5% reported no functional impairment (0 on PCFS scale). A higher PCFS score was associated with female sex (P<0.001) and oxygen therapy requirement during acute disease (P=0.001). However, it was not associated with having a pre-existing lung disease (P=0.749). Disease severity did not pose a risk for developing a more severe long COVID. CONCLUSION: Women were at greater risk for developing greater functional impairment in long COVID, although we have no explanation why. Malignant disease and hypertension also presented a risk factor for greater functional impairment. More studies are warranted to determine if patients with certain lung disease are more susceptible to long COVID.

QuantiFERON-TB Gold In-Tube Test in the Diagnosis of Latent Tuberculosis Infection in Arthritis Patients Treated with Tumor Necrosis Factor Antagonists.

The aim of this study was to investigate the role of the QuantiFERON-TB Gold In-Tube test (QFT-GIT) in detecting latent tuberculosis in immunocompromised patients before introducing tumor necrosis factor (TNF-α) antagonists. The study included 300 subjects of similar age. The study group comprised of 150 QuantiFERON (QFT) positive subjects with rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis and psoriatic arthritis, while control group comprised of 150 QFT negative respondents with the same diseases. Exhaustive medical history was documented for all patients. Screening tests were performed including QFT-GIT, tuberculin skin test (TST), chest radiography and detection of Mycobacterium tuberculosisin sputum culture 2 times. A positive QFT-GIT test result, regardless of TST result, was considered as an indication for latent tuberculosis infection (LTBI) treatment. Results of this study showed good correlation between the conclusive results of QFT-GIT and TST. All study group patients had normal clinical findings, normal radiologic findings and negative results of sputum microbiological analysis during the course of prophylaxis and after its completion and during the course of biological therapy. Conversion of positive QFT-GIT test to negative was observed in 4% of study group patients, while QFT negative respondents remained negative. There was a statistically significant positive correlation between QFTGIT, TST results and patient age, smoking habit and contact with tuberculosis. Study results showed that along with good clinical evaluation and detailed medical history, it is important to conduct testing in order to avoid disease progression or unnecessary isoniazid prophylaxis.

Evaluation of Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry in Identification of Nontuberculous Mycobacteria.

BACKGROUND/AIMS: Species-level identification of nontuberculous mycobacteria (NTM) is important in making decisions about the necessity and choice of antimicrobial treatment. The reason is predictable clinical significance and the susceptibility profile of specific NTM species. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is recognized as a diagnostic tool for routine identification of bacteria and yeasts in the clinical laboratory based on protein fingerprint analysis. The aim of the study was to evaluate MALDI-TOF MS in the identification of NTM. METHODS: A total of 25 NTM isolates from liquid cultures were identified with both polymerase chain reaction (PCR)-based hybridization assay and MALDI-TOF MS at the University Hospital Center Zagreb. RESULTS: PCR-based hybridization assay identified 96% (24/25) and MALDI-TOF MS 80% (20/25) of tested NTM isolates. Five isolates with no reliable MALDI-TOF MS identification belonged to the Mycobacterium avium-intracellulare complex. Seventy percent (14/20) of NTM isolates successfully identified with MALDI-TOF MS had a score higher than 2.0, indicating reliable species identification. CONCLUSION: MALDI-TOF MS is a promising tool for the identification of NTM. With a further improvement of the protein extraction protocol, especially regarding the M. avium-intracellulare complex, MALDI-TOF MS could be an additional standard method for identification of NTM.

Value of rapid aetiological diagnosis in optimization of antimicrobial treatment in bacterial community acquired pneumonia.

In 80 adult patients with community acquired pneumonia (CAP) conventional microbiological methods, polymerase chain reaction (PCR) and serum C-reactive protein (CRP) levels were performed and the appropriateness of the empirical antimicrobial treatment was evaluated according to bacterial pathogen detected. The aetiology was determined in 42 (52.5%) patients, with Streptococcus pneumoniae as the most common pathogen. PCR applied to bronchoalveolar lavage (BAL) provided 2 and PCR on sputum samples 1 additional aetiological diagnosis of CAP The mean CRP values in the S. pneumoniae group were not significantly higher than in the group with other aetiological diagnoses (166.89 mg/L vs. 160.11 mg/L, p = 0.457). In 23.8% (10/42) of patients with determined aetiology, the empirical antimicrobial treatment was inappropriate. PCR tests need further investigation, particularly those for the atypical pathogens, as they are predominant in inappropriately treated patients. Our results do not support the use of CRP as a rapid test to guide the antimicrobial treatment in patients with CAP.

Necrotising sarcoid granulomatosis of the spinal cord: case report.

We report a patient who presented with leg weakness and cervical lymphadenopathy. Thoracical magnetic resonance imaging showed an inhomogenously increased signal in the thickened portion of the cord. Multilevel laminectomy and spinal cord biopsy revealed granulomatous infiltrations with necrosis. Review of the histopathological finding established the diagnosis of necrotising sarcoid granulomatosis (NSG) of the spinal medulla, cytological FNA diagnosis of the neck lymph node was granulomatous inflammation with necrosis, but histopathological analysis of the same neck lymph node disclosed granulomatous inflammation without necrosis. On further radiographic chest evaluation mediastinal lymphadenopathy was found. Immunophenotyping of lymphocytes in bronchoalveolar lavage fluid (BALF) was indicative of sarcoidosis. After the administration of corticosteroid therapy the patient's clinical condition improved, and laryngeal and mediastinal lymph nodes subsided with minor changes remaining in the spinal medulla, which, based upon MR assessment, were considered to be irreversible. To our knowledge, this is the first described case with finding of granulomatous inflammation with and without vasculitis in various organs, consistent with the Churg's study who believes NSG to be a histological variant of sarcoidosis.

Lymphomatoid granulomatosis in a 23-year-old man--cytological and histological typing and rapid response to steroid and cyclophosphamide combination therapy.

Lymphomatoid granulomatosis (LG) is currently called as extranodal angiocentric and angiodestructive immunoproliferative disorder with various degrees of histological differentiation and disease severity. Histological grading and clinical manifestations are due to number of atypical large EBV + B-lymphatic cells. We report the case of a 23-year-old man clinically presented with fever, sweating, and physical intolerance, and bilateral pulmonary infiltrates of nodular type and destructive changes on the chest X-ray, previously treated with antituberculotics for 1.5 month. As the disease showed progression, diagnostic procedures extended to transbronchial lung biopsy and percutaneous fine needle aspiration with cytological and histological analysis of collected specimens, all being not conclusive enough. LG was confirmed by open lung biopsy, followed by induction of corticosteroids and cyclophosphamide therapy. Very good clinical, functional and radiomorphologic improvement was achieved in a few weeks, and remission of disease maintained in long term follow-up.

[Pulmonary Langerhans' cell histiocytosis--case report]. / Plucna histiocitoza Langerhansovih stanica--prikaz bolesnika.

Authors report a case of a 29-year old patient with pulmonary Langerhans' cell histiocytosis who presented with chest pain as a consequence of rib osteolytic process. We carried out a diagnostic work-up which included laboratory and radiographic analysis, lung function tests, bronchoscopy, cytologic and pathologic analysis. After reaching the diagnosis, corticosteroid therapy was introduced with long-term follow-up. In this report, we included a brief review of pulmonary Langerhans' cell histiocytosis.

[Thyroid transcription factor-1 in pulmonary cytology]. / TTF-1 u plucnoj citologiji.

UNLABELLED: Currently it is necessary to define in almost each case whether a carcinoma is a small or non-small cell carcinoma, adenocarcinoma, pulmonary or metastatic in origin. Thyroid transcription factor-1 (TTF-1) was positive in more than 80% of primary pulmonary adenocarcinomas and in none from the sites other than the thyroid. Mucinous bronchioloalveolar carcinomas are usually negative. Immunocytochemistry with a panel of cytokeratins (CK) 7 and 20, along with TTF-1, is recommended for identification of the origin of adenocarcinoma in pulmonary cytology. OBJECTIVE: The aim of the study was to assess the value of TTF-1 reactivity in adenocarcinomas determined by immunocytochemistry in different pulmonary cytologic specimens. METHODS AND RESULTS: Cytologic specimens of 83 patients with adenocarcinomas were analyzed. Immunocytochemistry was performed with a panel of antibodies: TTF-1, CK7, CK20 in all cases and CK5/6 if necessary. The study included 17 different bronchoscopic samples (aspirates, brushes, transbronchial FNA), 14 transthoracic FNA, 27 pleural effusions and 25 FNA of peripheral lymph nodes. TTF-1 was positive in 26/83 (31.3%) and negative in 47/83 (68.7%) samples. All TTF-1 positive adenocarcinomas were also CK7 positive, thus being conclusive of pulmonary origin. In TTF-1 negative group, pulmonary origin was proven in 10/57 (17.5%) adenocarcinomas, whereas 18/57 (31.6%) adenocarcinomas were metastatic; in 29/57 (50.9%) adenocarcinomas other diagnostic procedures failed to prove their origin. CK20 positivity with CK7 negativity was conclusive of metastatic gastrointestinal adenocarcinoma. DISCUSSION: Numerous reports support TTF-1 expression in adenocarcinoma as being highly specific for pulmonary origin, if thyroid is excluded. We were able to identify 36/83 (43.4%) adenocarcinomas as pulmonary adenocarcinomas. Among them, only 31.3% were TTF-1 positive. In our study, about 60% of adenocarcinomas with uncertain origin were in the groups of pleural effusions and lymph nodes. In these groups, cytologic diagnosis of adenocarcinoma often provided evidence of the carcinoma expansion, aggressive behavior and poor differentiation, and served as a guideline for patient management. In the studies of mixed pulmonary adenocarcinomas, TTF-1 expression was lower in poorly differentiated segments as well as in the areas with bronchioloalveolar pattern. One explanation for the high percentage of TTF-1 negative adenocarcinomas in our material is morphological selection of adenocarcinomas of presumably non-pulmonary origin before immunocytochemistry. CONCLUSION: TTF-1 in a panel with cytokeratins is specific for differentiation of the origin of adenocarcinomas. TTF-1 negative finding in adenocarcinomas does not exclude pulmonary origin, but only points to other diagnostic procedures for definitive diagnosis.

[Bronchiolitis obliterans with organizing pneumonia in a patient treated with amiodarone]. / Bronchiolitis obliterans s organiziranom pneumonijom u bolesnika lijecenog amiodaronom.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a well-defined clinicopathological entity. The aetiology of BOOP is generally unknown, although it has been associated with specific diseases or various pharmaceutical drugs. The amiodarone is one of them. We report a patient with BOOP secondary to amiodarone therapy, who presented with cough, fever and sputum production, dyspnoea and night sweats lasting for two months. A chest radiograph showed bilateral patchy and interstitial infiltrates. Lymphocyte phenotyping of bronchoalveolar lavage fluid showed decreased ratio of CD4+:CD8+ lymphocytes. Transbronchial lung biopsy established the diagnosis of BOOP. After stopping amiodarone therapy, symptoms disappeared and the chest radiograph remained normal within two months.

Progressive form of pulmonary Langenharns' cell histiocytosis in a female adult non-smoker.

Little is known about the cause, nature, treatment and prognosis of pulmonary Langerhans' cell histiocytosis (LCH) in adults. We report the case of a 44-year-old female non-smoker suffering from pulmonary histiocytosis who after a 7-year remission period relapsed with both lung and bone disease. Using a combination of corticosteroids, methotrexate and bone irradiation treatment, the patient achieved total disease remission. The patient was a non-smoking female who has had long-term and swift remission of the disease on two occasions.

Cellular and humoral immunity to purified protein derivative (PPD) in PPD skin reactive and nonreactive patients with pulmonary tuberculosis: comparative analysis of antigen-specific lymphocyte proliferation and IgG antibodies.

AIM: To evaluate in vitro reactivity against tuberculin purified protein derivative (PPD) in patients with active pulmonary tuberculosis scoring either positive or negative upon intradermal PPD application (PPD-DTH). METHOD: Two groups of patients with pulmonary tuberculosis, 22 PPD+ and 22 PPD-, were studied. Peripheral blood mononuclear cells (PBMC) were assayed for in vitro proliferation to PPD antigen, phytohaemagglutin, concanavalin A, and pokeweed mitogens. In the proliferation assay PBMC were incubated in a medium supplemented with serum (20% concentration) from healthy donors, autologous serum, or allogenic serum. Anti-PPD IgG concentration in patients sera were analyzed by ELISA. CD3+ lymphocytes from 10 patients in each group were tested for the expression of surface activation markers (HLA-DR and CD25/IL-2 receptors) by flow cytometry. RESULTS: PPD- patients showed clinically and radiologically more advanced forms of pulmonary tuberculosis as compared with PPD+ patients. PBMC from both groups of patients proliferated in response to PPD effectively, but significantly higher de novo DNA synthesis was observed in PPD+ patients (p<0.001). Proliferative activity was not affected by the type of the serum supplement (autologous or allogenic) in the culture medium. Mitogen stimulation elicited similar proliferative responses in both groups. Similar percentages of T-lymphocytes and T-lymphocytes expressing CD25 activation markers were observed in both groups of patients. There was a borderline difference in the percentage of CD3+HLA-DR+ lymphocytes between these two groups of patients (p=0.05). At 1:1000 serum dilution a significant difference (p=0.002) in anti-PPD IgG concentrations was found between PPD- and PPD+ patients. CONCLUSION: Patients with active pulmonary tuberculosis with a more favorable clinical course have a more potent specific cell-mediated immunity to PPD (positive skin reactivity in vivo and significantly greater lymphocyte proliferative response in vitro) than patients with a clinically more severe form of the disease. The concentration of PPD specific IgG in the serum appears to be higher in patients with relatively more severe forms of the disease.