Aetiology of Community-Acquired Pneumonia and the Role of Genetic Host Factors in Hospitalized Patients in Cyprus.

Community-acquired pneumonia (CAP) remains the leading cause of hospitalization among infectious disease in Europe, and a major cause of morbidity and mortality. In order to determine and characterize the aetiology of CAP in hospitalized adults in Cyprus, respiratory and blood samples were obtained from hospitalized patients with CAP, and analyzed using Multiplex Real-Time PCR/RT-PCR, and ID/AMR enrichment panel (RPIP) analysis. Probe-based allelic discrimination was used to investigate genetic host factors in patients. The aetiology could be established in 87% of patients. The most prevalent viral pathogens detected were influenza A, SARS-CoV-2, and human rhinovirus. The most common bacterial pathogens detected were Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae. Antimicrobial resistance genes were identified in 23 patients. S. aureus was the most common AMR correlated strain in our study. A positive correlation was detected between bacterial infections and the NOS3 rs1799983 G allele and the FCGR2A rs1801274 G allele. A positive correlation was also detected between the TNF-α rs1800629 A allele and sepsis, while a negative correlation was detected with the ACE rs1799752 insertion genotype and the severity of pneumonia. In conclusion, the targeted NGS panel approach applied provides highly sensitive, comprehensive pathogen detection, in combination with antimicrobial resistance AMR insights that can guide treatment choices. In addition, several host factors have been identified that impact the disease progression and outcome.

Predicting malignant pleural effusion during diagnostic pleuroscopy with biopsy: A prospective multicentre study.

BACKGROUND AND OBJECTIVE: Pleuroscopy with pleural biopsy has a high sensitivity for malignant pleural effusion (MPE). Because MPEs tend to recur, concurrent diagnosis and treatment of MPE during pleuroscopy is desired. However, proceeding directly to treatment at the time of pleuroscopy requires confidence in the on-site diagnosis. The study's primary objective was to create a predictive model to estimate the probability of MPE during pleuroscopy. METHODS: A prospective observational multicentre cohort study of consecutive patients undergoing pleuroscopy was conducted. We used a logistic regression model to evaluate the probability of MPE with relation to visual assessment, rapid on-site evaluation (ROSE) of touch preparation and presence of pleural nodules/masses on computed tomography (CT). To assess the model's prediction accuracy, a bootstrapped training/testing approach was utilized to estimate the cross-validated area under the receiver operating characteristic curve. RESULTS: Of the 201 patients included in the study, 103 had MPE. Logistic regression showed that higher level of malignancy on visual assessment is associated with higher odds of MPE (OR = 34.68, 95% CI = 9.17-131.14, p < 0.001). The logistic regression also showed that higher level of malignancy on ROSE of touch preparation is associated with higher odds of MPE (OR = 11.63, 95% CI = 3.85-35.16, p < 0.001). Presence of pleural nodules/masses on CT is associated with higher odds of MPE (OR = 6.61, 95% CI = 1.97-22.1, p = 0.002). A multivariable logistic regression model of final pathologic status with relation to visual assessment, ROSE of touch preparation and presence of pleural nodules/masses on CT had a cross-validated AUC of 0.94 (95% CI = 0.91-0.97). CONCLUSION: A prediction model using visual assessment, ROSE of touch preparation and CT scan findings demonstrated excellent predictive accuracy for MPE. Further validation studies are needed to confirm our findings.

Pulmonary Mucormycosis (Zygomycosis) Presenting as an Infective Exacerbation of Chronic Obstructive Pulmonary Disease.

Mucormycosis is a life-threatening fungal infection whose incidence has been rising recently, mainly due to the increasing use of immunosuppressive and corticosteroid treatment. In previous decades, mucormycosis was associated with a very poor prognosis as mortality was approximately 100%. Mortality rates reported in recent literature have only slightly improved despite the availability of targeted therapy with amphotericin B. Pulmonary mucormycosis is characteristically encountered in severely immunocompromised hosts, while rhino-orbital disease is often seen in individuals with diabetes mellitus. We report a rare case of fulminant pulmonary mucormycosis as an exceptionally rare complication of corticosteroid treatment in a 76-year-old patient with chronic obstructive pulmonary disease (COPD) and diabetes. The patient had presented with typical symptoms of an infective COPD exacerbation. The interesting aspects of our case were the absence of malignancy or immunosuppression, the isolation of Rhizomucor species, and the fungal invasion of the pleura and pericardium. Unfortunately, our patient died on the 49th day of hospitalisation, despite appropriate treatment. LEARNING POINTS: Pulmonary mucormycosis in patients with known respiratory disease may mimic an exacerbation of their lung disease, thus delaying diagnosis.Pulmonary mucormycosis can complicate corticosteroid treatment in elderly individuals with other predisposing factors, which is an emerging clinical concern.Pulmonary mucormycosis remains a potentially fatal disease, although early diagnosis and appropriate medical and surgical management can improve outcomes.

Rapid on-site evaluation with the Hemacolor rapid staining method of medical thoracoscopy biopsy specimens for the management of pleural disease.

BACKGROUND AND OBJECTIVE: Medical thoracoscopy (MT) is useful for the management of pleural disease. Rapid on-site evaluation (ROSE) of transbronchial needle aspirates proved to be useful during bronchoscopy. We aimed to evaluate the diagnostic performance of ROSE of MT biopsy specimens and thoracoscopists' impression of the macroscopic appearance and assess the intermodality agreement between ROSE and final histopathologic diagnosis. METHODS: Sixty two patients with exudative pleural effusions further investigated with MT were enrolled. MT was performed under local anaesthesia and conscious sedation, using the rigid pleuroscope. ROSE with the Hemacolor rapid staining method of the biopsy specimens was performed. Thoracoscopists' impression of the macroscopic appearance was recorded. The final diagnosis was established following histopathological examination. RESULTS: Thoracoscopic pleural biopsies were diagnosed in 61 patients (98.4%). Group A (n = 25) consisted of patients with malignancy and group B (n = 37) with benign disorders. Area under the curve of ROSE for the diagnosis of malignancy was 0.86 (95% CI: 0.76-0.96, P < 0.001), with a sensitivity of 79.17%, specificity of 94.59%, diagnostic accuracy of 88.5%, positive predictive value of 90.5% and negative predictive value of 87.5%. Intermodality agreement between ROSE and histopathology was good (κ ± SE = 0.615 ± 0.084, P < 0.001). Area under the curve of the thoracoscopists' impression of macroscopic appearance was 0.72 (95% CI: 0.58-0.85, P = 0.001), with a sensitivity of 100%, specificity of 44.7%, positive predictive value of 53.33% and negative predictive value of 100%. CONCLUSION: Rapid on-site evaluation during MT was found to have high accuracy for predicting malignancy. ROSE can provide the thoracoscopist with an on-site preliminary diagnosis, especially in cases with inconclusive macroscopic appearance.

A rare clinical case - Solitary fibrous tumor of the pleura.

We present a case of a 58 years old man with a large heterogeneous and well circumscribed soft tissue mass arising from the right pleural surface, found at a computer tomography of his chest. This mass after complete resection through a right lateral open thoracotomy, proved to be a Solitary Fibrous Tumor, previously known as 'benign mesothelioma'. This tumor is usually discovered at routine chest X-rays since patients are either asymptomatic or report atypical symptoms. Only 10-20% of the published cases report a malignant solitary fibrous tumor, however, definite diagnosis can only be made after complete resection which is the proposed diagnostic algorithm for these cases.

C-reactive protein, procalcitonin, clinical pulmonary infection score, and pneumonia severity scores in nursing home acquired pneumonia.

BACKGROUND: Patients with nursing home acquired pneumonia (NHAP) present a distinct group of lower respiratory track infections with different risk factors, clinical presentation, and mortality rates. OBJECTIVES: To evaluate the diagnostic value of clinical pulmonary infection score (CPIS), C-reactive protein, and procalcitonin and to compare the accuracy of pneumonia severity scores (confusion, urea nitrogen, breathing frequency, blood pressure, ≥ 65 y of age [CURB-65]; pneumonia severity index; NHAP index; systolic blood pressure, multilobar involvement, albumin, breathing frequency, tachycardia, confusion, oxygen, arterial pH [SMART-COP]; and systolic blood pressure, oxygen, age > 65 y, breathing frequency [SOAR]) in predicting in-patient mortality from NHAP. METHODS: Nursing home residents admitted to the hospital with acute respiratory illness were enrolled in the study. Subjects were classified as having NHAP (Group A) or other pulmonary disorders (Group B). Clinical, imaging, and laboratory data were assessed to compute CPIS and severity scores. C-reactive protein and procalcitonin were measured by immunonephelometry and immunoassay, respectively. RESULTS: Fifty-eight subjects were diagnosed with NHAP (Group A) and 29 with other pulmonary disorders (Group B). The mean C-reactive protein ± SD was 16.38 ± 8.6 mg/dL in Group A and 5.2 ± 5.6 mg/dL in Group B (P < .001). The mean procalcitonin ± SD was 1.52 ± 2.75 ng/mL in Group A and 0.24 ± 0.21 ng/mL in Group B (P = .001). The mean CPIS ± SD was 5.4 ± 1.2 in Group A and 2.3 ± 1.5 in Group B (P < .001). At a cutoff value of 0.475 ng/mL, procalcitonin had a sensitivity of 83% and a specificity of 72%. At a cutoff value of 8.05 mg/dL, C-reactive protein had a sensitivity of 81% and a specificity of 79%. Procalcitonin and C-reactive protein levels were significantly higher in Gram-positive NHAP. The in-patient mortality was 17.2% in Group A. Procalcitonin levels were 4.67 ± 5.4 ng/mL in non-survivors and 0.86 ± 0.9 ng/mL in survivors (P < .001). The area under the curve for procalcitonin in predicting in-patient mortality was 0.84 (95% CI 0.70-0.98, P = .001). A procalcitonin level upon admission > 1.1 ng/mL was an independent predictor of in-patient mortality. Of the pneumonia severity scores, CURB-65 showed greater accuracy in predicting in-patient mortality (area under the curve of 0.68, 95% CI 0.53-0.84, P = .06). CONCLUSIONS: CPIS, procalcitonin, and C-reactive protein are reliable for the diagnosis of NHAP. Procalcitonin and CURB-65 are accurate in predicting in-patient mortality in NHAP.

Clinical prediction of pulmonary embolism in respiratory emergencies.

INTRODUCTION: The initial management of suspected pulmonary embolism (PE) is commonly done in respiratory departments, but is based on clinical prediction rules developed in other settings. OBJECTIVE: To determine the accuracy of established prediction rules for PE in patients with respiratory emergencies. DESIGN: A prospective study MATERIALS AND METHODS: Patients presenting to respiratory emergency department with acute symptoms and signs suggestive of PE (n=183) and subsequently admitted to hospital were prospectively enrolled. Wells' rule, original and revised Geneva scores, their components separately, and other common clinical parameters were recorded during admission. PE was diagnosed by perfusion lung scanning, computed tomographic pulmonary angiography, lower limb venous ultrasonography, magnetic resonance pulmonary angiography, and/or pulmonary angiography. RESULTS: PE was confirmed in 52 and ruled out in 131 patients. Tachycardia, atelectasis, elevated hemidiaphragm, clinical signs of deep-venous thrombosis, physician perception that PE is the likeliest diagnosis, previous thromboembolism, chest pain, and absence of chronic obstructive pulmonary disease or cough were associated with the presence of PE. These significant parameters could be combined for accurate pre-test PE prediction, with a newly devised combinatorial tool exhibiting the highest area under curve [0.92 (95% CI: 0.87-0.97)], followed by Wells' rule [0.86 (95% CI 0.79-0.92)], the revised Geneva score [0.83 (95% CI 0.77-0.90)], and the original Geneva score [0.75 (95% CI 0.68-0.83)]. CONCLUSION: Wells' rule and the revised Geneva score are more useful in diagnosing PE in respiratory emergencies. A newly devised prediction tool can be of even greater accuracy in this patient population.

Diagnostic value of triggering receptor expressed on myeloid cells-1 and C-reactive protein for patients with lung infiltrates: an observational study.

BACKGROUND: Differential diagnosis of patients with lung infiltrates remains a challenge. Triggering receptor expressed on myeloid cells (TREM)-1 is a neutrophil and monocyte receptor up-regulated during infection. The aim of this study was to evaluate the diagnostic accuracy of TREM-1 and of C-reactive protein (CRP) from patients with lung infiltrates to discern community acquired lung infections. METHODS: 68 patients admitted to a medical ward with acute respiratory illness were enrolled in the study. Neutrophil and monocyte TREM-1 expression were measured by flow cytometry, sTREM-1 by an enzyme immunoassay and C-reactive protein by nephelometry. Clinical pulmonary infection score was recorded. RESULTS: 34 patients were diagnosed with bacterial community acquired pneumonia (group A) and 34 with non-bacterial pulmonary disease (group B). Median serum TREM-1 concentration was 102.09 pg/ml in group A and lower than 15.10 pg/ml (p < 0.0001) in group B. Mean±SE neutrophil TREM-1 expression was 4.67 ± 0.53 MFI in group A and 2.64 ± 0.25 MFI (p = 0.001) in group B. Monocyte TREM-1 expression was 4.2 ± 0.42 MFI in group A and 2.64 ± 0.35 MFI (p = 0.007) in group B and mean±SE CRP was 18.03 ± 2 mg/ml in group A and 7.1 ± 1.54 mg/ml (p < 0.001) in group B. A cut-off of 19.53 pg/ml of sTREM-1 with sensitivity 82.6% and specificity 63% to discriminate between infectious and non-infectious pulmonary infiltrates was found. sTREM-1 at admission greater than 180 pg/ml was accompanied with unfavourable outcome. CONCLUSION: TREM-1 myeloid expression and sTREM-1 are reliable markers of bacterial infection among patients with pulmonary infiltrates; sTREM-1 is a predictor of final outcome.

Silver nitrate through flexible bronchoscope in the treatment of bronchopleural fistulae.

OBJECTIVE: Bronchopleural fistula is a severe complication after pneumonectomy or lobectomy. Local application of silver nitrate to seal bronchopleural fistulae was reported once 25 years ago with considerable success but was never repeated. We aimed to develop and evaluate a concrete technique of applying silver nitrate through a flexible bronchoscope to treat bronchopleural fistulae in central airways. METHODS: Consecutive patients with small (5 mm) fistulae. Among the 11 treated patients (median fistula diameter 3 mm, range 2-5 mm), treatment failure was observed in 2 patients in whom treatment was attempted early (15 days postsurgery). In the remaining 9 patients, treatment success was achieved (81.8% success rate) after a median of 2.5 (range 1-10) applications of silver nitrate. After 11 (0.5-24) months of follow-up, no relapse was observed among successfully treated fistulae. CONCLUSION: The local application of silver nitrate through a flexible bronchoscopic brush produced a burn and healing process on the mucosa of small bronchopleural fistulae of the central airways, leading to effective and lasting treatment in most cases.

A central role for tumor-derived monocyte chemoattractant protein-1 in malignant pleural effusion.

BACKGROUND: Tumor cells in malignant pleural effusions (MPEs) are an important source of monocyte chemoattractant protein (MCP)-1. However, the role of tumor-derived MCP-1 in the pathogenesis and progression of MPE has not been determined. METHODS: B16 mouse skin melanoma cells, which are deficient in MCP-1 expression, and mouse Lewis lung cancer (LLC) cells, which express high levels of MCP-1, were engineered to stably express MCP-1 and short hairpin RNAs (shRNAs) targeting the MCP-1 transcript, respectively. Cells were injected into the pleural cavities of syngeneic immunocompetent mice, and MPE volume and pleural tumors were quantified at necropsy (day 14). MCP-1 and other mediators were determined by cytometric bead array and enzyme-linked immunosorbent assay, and mononuclear and endothelial cells were identified by immunolabeling of F4/80 and factor VIII-related antigen respectively. Mouse survival was assessed using Kaplan-Meier analysis. Vascular permeability in mice with MPE was assessed using albumin-binding Evans blue. Statistical tests were two-sided. RESULTS: LLC cells expressing shRNA against MCP-1 elaborated less than 5% of the MCP-1 level in cells expressing nonspecific shRNA (control cells), and intrapleural delivery of these cells resulted in less MPE (mean MPE volume = 86 and 585 muL, respectively; difference = 499 muL; 95% confidence interval [CI] = 331 to 669 muL; P < .001), reduced MCP-1 levels in the pleural fluid, and lower mortality than when control cells were delivered. Overexpression of MCP-1 in intrapleurally injected B16 melanoma cells led to increased MPE and reduced survival. In mice with MPE, MCP-1 was a potent inducer of vascular permeability, mononuclear recruitment, and, in pleural tumors, of angiogenesis. CONCLUSION: MCP-1 produced by tumor cells is an important determinant of their capacity to induce the formation of MPE and may be a useful target for the treatment of malignant pleural disease.

Exclusive diagnostic contribution of the histology specimens obtained by 19-gauge transbronchial aspiration needle in suspected malignant intrathoracic lymphadenopathy.

BACKGROUND: Transbronchial needle aspiration (TBNA) performed with a 19-gauge needle provides both cytologic and histologic specimens. However, the diagnostic yield for malignancy gained by histologic examination is unclear. Moreover, this kind of needle is often reserved only for selected cases, in part due to fear for complications. The primary aim of this study was to investigate the diagnostic contribution for malignancy added by histologic to the cytologic specimen examination. The secondary aim was to evaluate the safety of using a 19-gauge needle routinely in all patients. METHODS: Consecutive patients presenting with mediastinal and/or hilar lymph node enlargement of > or = 1 cm, in whom suspicion for malignancy was raised, underwent TBNA with a 19-gauge needle. Patients with negative aspirate test results underwent surgical investigation. RESULTS: Among 77 patients who were examined, 66 had malignant intrathoracic lymphadenopathy. TBNA proved malignancy in 58 patients, whereas it missed the diagnosis in 8 patients (sensitivity, 87.9%; negative predictive value, 57.9%). TBNA established the diagnosis in 94% of patients with small cell lung cancer (SCLC), and in 88% of patients with non-SCLC (p = 0.7). Exclusive diagnosis was obtained in 36.4% of patients by histology (compared with 18.2% of patients by cytology [p = 0.06]), representing an increase of 35.3% in the diagnostic yield of TBNA over sole cytology examination. No major complication occurred. CONCLUSIONS: Histology specimens obtained exclusively with a 19-gauge TBNA needle enabled diagnosis in about 36% of patients with malignant intrathoracic lymphadenopathy. The routine use of a 19-gauge needle is safe.