Peripheral blood natural killer cells in sarcoidosis are associated with early cardiac involvement.

AIM: To evaluate the distribution of circulating immune cell subsets in peripheral blood of patients with sarcoidosis and investigate if there is an association with an underlying cardiac involvement. METHODS AND RESULTS: Eighty-five newly diagnosed treatment-naïve patients with sarcoidosis (50 women) were included in the study. All patients underwent a thorough cardiac investigation, including cardiac magnetic resonance imaging (CMR). Of all patients, 19 (23.53%) had myocardial involvement, and the NK subpopulation in these patients in peripheral blood was significantly decreased compared to patients without (n = 63, p = 0.001 and p = 0.003 respectively). The absolute number of NKT cells (CD3+CD16/56+ ) in patients with cardiac involvement was highly correlated with T2 map increased values in MRI (r = -686, p = 0.041) showing that low NKT cell count correlates with the inflammatory process of the heart. No difference in CD19, CD3, CD4, CD8 and CD3- NK cell counts was found between groups. Lung severity was not found to correlate with the number of NK cells. CONCLUSION: We found that low NK cell count in peripheral blood of patients with sarcoidosis is associated with cardiac involvement, and the number of NK-T cells correlates with CMR findings indicative of myocardial inflammation. This finding might have a potential clinical application in detecting clinically silent cardiac involvement in sarcoidosis and may also suggest potential targets for therapeutic interventions.

Update Overview of the Role of Angiopoietins in Lung Cancer.

Angiogenesis is a biological process that involves the formation of new blood vessels from the existing vasculature, and it plays a fundamental role in the development and progression of several types of cancer, including lung cancer. The angiopoietin/Tie2 ligand/receptor system orchestrates vascular integrity. In particular, Angiopoietin-1 activates the endothelial cell (EC)-specific receptor tyrosine kinase,Tie2,which is essential for preserving endothelial quiescence. On the other hand, Angiopoietin-2 acts as an inhibitor of the Angiopoietin-1/Tie2 signaling pathways, thus facilitating the destabilization of quiescent endothelium in cases of inflammation and cancer. Clinical studies have proven that high levels of Angiopoietin-2 indicate the development of non-small-cell lung carcinomas (NSCLC), while high levels of Angiopoietin-2 are strongly related to tumor angiogenesis, lymphangiogenesis, metastasis, and poor prognosis. Interestingly, the association of Angiopoietin-2 levels with the type of surgical approach makes Angiopoietin-2 a valuable factor in selecting the most suitable therapeutic strategy for lung cancer patients. The role of the Angiopoietin-1 and Angiopoietin-4 levels in NSCLC development requires further investigation. The present review focuses on the clinical impact of the Angiopoietin-1, Angiopoietin-2, and Angiopoietin-4 levels in patients diagnosed with NSCLC, emphasizing the interaction between them, and how they affect the development, progression, and metastasis of lung disease. Finally, it estimates the role of angiopoietins levels in the effective therapy of lung cancer patients.

Prospective evAluatIon foR inhalation devices in Greek patients with COPD and asthma: The PAIR study.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) and asthma remain a major health burden. Adherence to inhaled therapy is critical in order to optimize treatment effectiveness. Properly designed questionnaires can assess patients' satisfaction with their inhaler devices. PATIENTS AND METHODS: A total of 766 patients with COPD, asthma or Asthma-COPD Overlap (ACO) were initially enrolled. During their first visit, patients were classified into three groups (Diskus™, Elpenhaler®, Turbuhaler®). Patients completed the FSI-10 questionnaire on Day 0 and Day 60. Test-retest reliability was evaluated. RESULTS: A total of 705 patients completed the study. FSI-10 questionnaire had good test-retest reliability (Total Intraclass Correlation Coefficient: 0.86). All dry powder inhaler (DPIs) yielded satisfactory results. Median score of FSI-10 questionnaire in first visit (FSI-10-I) was significantly higher for patients receiving Elpenhaler® (45, 95% CI: 44 to 46) than patients receiving Diskus™ (42, 95% CI: 41 to 43) and Turbuhaler® (42, 95% CI: 41 to 43) (p < 0.001). Accordingly, median score of FSI-10 questionnaire in the final visit (FSI-10-II) was significantly higher for patients receiving Elpenhaler® (46, 95% CI: 45 to 47) than patients receiving Diskus™ (42, 95% CI: 41 to 43) and Turbuhaler® (43, 95% CI: 42 to 44) (p < 0.001). CONCLUSION: FSI-10 questionnaire had good test-retest reliability and thus can be used in the follow-up of patients with COPD, asthma and ACO. All DPIs were highly acceptable among all study groups. Elpenhaler® achieved significantly higher ratings than Diskus™ and Turbuhaler® in FSI-10 score and presented higher preference among patients with obstructive lung diseases.

Bronchoscopy-related outbreaks and pseudo-outbreaks: A systematic review.

OBJECTIVE: To identify and report the pathogens and sources of contamination associated with bronchoscopy-related outbreaks and pseudo-outbreaks. DESIGN: Systematic review. SETTING: Inpatient and outpatient outbreaks and pseudo-outbreaks after bronchoscopy. METHODS: PubMed/Medline databases were searched according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, using the search terms "bronchoscopy," "outbreak," and "pseudo-outbreak" from inception until December 31, 2022. From eligible publications, data were extracted regarding the type of event, pathogen involved, and source of contamination. Pearson correlation was used to identify correlations between variables. RESULTS: In total, 74 studies describing 23 outbreaks and 52 pseudo-outbreaks were included in this review. The major pathogens identified in these studies were Pseudomonas aeruginosa, Mycobacterium tuberculosis, nontuberculous mycobacteria (NTM), Klebsiella pneumoniae, Serratia marcescens, Stenotrophomonas maltophilia, Legionella pneumophila, and fungi. The primary sources of contamination were the use of contaminated water or contaminated topical anesthetics, dysfunction and contamination of bronchoscopes or automatic endoscope reprocessors, and inadequate disinfection of the bronchoscopes following procedures. Correlations were identified between primary bronchoscope defects and the identification of P. aeruginosa (r = 0.351; P = .002) and K. pneumoniae (r = 0.346; P = .002), and between the presence of a contaminated water source and NTM (r = 0.331; P = .004) or L. pneumophila (r = 0.280; P = .015). CONCLUSIONS: Continued vigilance in bronchoscopy disinfection practices remains essential because outbreaks and pseudo-outbreaks continue to pose a significant risk to patient care, emphasizing the importance of stringent disinfection and quality control measures.

Small Airways Dysfunction and Lung Hyperinflation in Long COVID-19 Patients as Potential Mechanisms of Persistent Dyspnoea.

BACKGROUND: Reticulation, ground glass opacities and post-infection bronchiectasis are present three months following hospitalisation in patients recovering from SARS-CoV-2 infection and are associated with the severity of acute infection. However, scarce data exist on small airways impairment and lung hyperinflation in patients with long COVID-19. AIM: To evaluate small airways function and lung hyperinflation in previously hospitalised patients with long COVID-19 and their association with post-COVID-19 breathlessness. METHODS: In total, 33 patients (mean ± SD, 53 ± 11 years) with long COVID-19 were recruited 149 ± 90 days following hospital discharge. Pulmonary function tests were performed and lung hyperinflation was defined as RV/TLC ≥ 40%. Small airways function was evaluated by measuring the closing volume (CV) and closing capacity (CC) using the single-breath nitrogen washout technique (SBN2W). RESULTS: CC was 115 ± 28% pred. and open capacity (OC) was 90 ± 19. CC was abnormal in 13 patients (39%), CV in 2 patients (6.1%) and OC in 9 patients (27%). Lung hyperinflation was present in 15 patients, whilst the mean mMRC score was 2.2 ± 1.0. Lung hyperinflation was associated with CC (r = 0.772, p = 0.001), OC (r = 0.895, p = 0.001) and mMRC (r = 0.444, p = 0.010). CONCLUSIONS: Long COVID-19 patients present with small airways dysfunction and lung hyperinflation, which is associated with persistent dyspnoea, following hospitalisation.

Pulmonary blastoma with submandibular, scrotum and adrenal metastases: case report.

A 62-year-old patient diagnosed with pulmonary blastoma with submandibular, scrotum and adrenal metastases was admitted to Sotiria General Hospital in Athens. No other such case has been published to date. The patient started receiving chemotherapy, but the scrotum metastasis grew rapidly and erupted. This led to sepsis despite surgical excision of infected and necrotic tissues and intravenous antibiotics. Treatment strategy in pulmonary blastoma should be defined by a multidisciplinary team, and surgical treatment should be considered as quickly as possible when such a tumor is suspected.

Baseline Ang-2 Serum Levels as a Predictive Factor for Survival in NSCLC and SCLC.

Angiopoietin-2 (Ang-2) has been implicated in the development of several types of cancer, including lung malignancy. In the present study, we examined the impact of Ang-2 serum concentration on the development, dissemination, and 5-year overall survival of NSCLC and SCLC. A total of 99 patients with lung cancer were tested. The OS of NSCLC and SCLC patients was estimated using Kaplan−Meier curves and compared through log-rank test. The median serum level of Ang-2 at baseline in both NSCLC and SCLC patients was significantly higher than that of controls (p < 0.0001). The Ang-2 serum concentration was not related to metastasis, neither in NSCLC nor in SCLC cases. The OS was found to be significantly shorter for stage IIIß NSCLC patients with a high baseline Ang-2 serum concentration (p = 0.012), while Cox regression analysis showed that Ang-2 is a significant independent factor for poor prognosis for stage IIIß NSCLC (hazard ratio = 2.97, 95% CI: 1.05−8.40, p = 0.04). The concentration of Ang-2 has no impact on the prognosis of SCLC. Ang-2 could be considered as a significant molecular marker that enables the prediction of NSCLC and SCLC development, and is involved in the poor prognosis of stage IIIß NSCLC.

High-flow versus conventional nasal cannula oxygen supplementation therapy and risk of hypoxia in gastrointestinal endoscopies: a systematic review and meta-analysis.

BACKGROUND: Gastrointestinal endoscopy (GIE) represents a mainstay diagnostic and therapeutic procedure in clinical practice. Hypoxemia constitutes a major complication for endoscopists. Emerging evidence supports the utilization of high-flow nasal cannula (HFNC) over conventional nasal cannula (CNC) for avoidance of hypoxemia. Our aim was to compare the hypoxemia risk in patients undergoing GIE with HFNC versus CNC oxygen supplementation recruited by randomized controlled trials (RCTs). METHODS: We searched in medical databases PubMed, EMBASE and Cochrane to identify RCTs investigating the abovementioned association. Enrolled studies were evaluated for risk of bias and inserted into a random effects model for meta-analysis; subgroup analyses and publication bias were also assessed. RESULTS: Out of 271 articles, five RCTs were eligible (patients n=2656, HFNC 1299 and CNC 1357). A statistically significant reduced relative risk (RR) of hypoxemia among HFNC patients was revealed (RR=0.18, CI95%: 0.05-0.61), whilst with high heterogeneity (I2:79.94%, p<0.01). Patients undergoing upper GIE with HFNC displayed a significantly lower hypoxemia risk (96%, p<0.001, I2:15.59%), even after exclusion of endoscopic retrograde cholangiopancreatography cases (RR:0.03, CI95%:0.01-0.21), albeit with higher heterogeneity (I2:41.82%).    . CONCLUSION: Patients undergoing upper GIE with HFNC experience significantly less hypoxemia burden than CNC counterparts. Further research is warranted to target optimal safety during endoscopy.Abbreviations: ASA, American Society of Anesthesiologists; ASGE, American Society for Gastrointestinal Endoscopy; BMI, Body Mass Index; CI, confidence interval; CNC, conventional nasal cannula; ERCP, endoscopic retrograde cholangiopancreatography; FiO2, fraction of inspired O2; GI, gastrointestinal; GIE, gastrointestinal endoscopies; HFNC, High-Flow nasal cannula; ICU, intensive care unit; PEEP, positive end-expiratory pressure; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analysis; RCTs, randomized control trials; RR, relative risk (or risk ratio).

High-Flow vs. Low-Flow Nasal Cannula in Reducing Hypoxemic Events During Bronchoscopic Procedures: A Systematic Review and Meta-Analysis.

Introduction: High-flow nasal cannula (HFNC) oxygenation method has been proven to be successful in oxygenation of patients with respiratory failure and has exhibited clinical superiority compared to low-flow nasal cannula (LFNC). Methods: We performed a systematic review and meta-analysis to evaluate the potential favorable impact of HFNC oxygenation during bronchoscopy and related procedures like endobronchial ultrasound-transbronchial needle aspiration. Only randomized control trials (RCTs) were included in the meta-analysis. Results: Six randomized control trials with 1,170 patients were included in this meta-analysis. Patients who underwent bronchoscopy with the use of high-flow nasal cannula experienced less hypoxemic events/desaturations, less procedural interruptions and pneumothoraxes compared to patients under low-flow nasal cannula treatment. This beneficial effect of HFNC in hypoxemic events was persistent 10 min after the end of procedure. Conclusion: The high-flow nasal cannula (HFNC) oxygenation method could reduce hypoxemic events and related peri- and post-bronchoscopic complications.

Greek Guidelines for the Management of COPD, a Proposal of a Holistic Approach Based on the needs of the Greek Community.

Despite that COPD remains one of the most common respiratory diseases worldwide, it can be managed effectively with certain treatments and, more importantly, be prevented by the early implementation of various measures. The pathology and pathophysiology of this disease continue to be studied, with new pharmacological and invasive therapies emerging. In this consensus paper, the Working Group of the Hellenic Thoracic Society aimed to consolidate the up-to-date information and new advances in the treatment of COPD. Local and international data on its prevalence are presented, with revised strategies on the diagnostic approach and the evaluation of risk assessment and disease severity classification. Emphasis is placed on the management and therapy of patients with COPD, covering both common principles, specialized modalities, and algorithms to distinguish between home care and the need for hospitalization. Although pharmacological treatment is commonly recognized in COPD, an integrative approach of pulmonary rehabilitation, physical activity, patient education, and self-assessment should be encountered for a comprehensive treatment, prevention of exacerbations, and increased quality of life in patients.

Triplet combination of carboplatin, irinotecan, and etoposide in the first-line treatment of extensive small-cell lung cancer: a single-institution phase II study.

Small-cell lung cancer is a rapidly progressive tumor and median survival is less than 10 months in patients with extensive stage of the disease. This study aims to evaluate the efficacy and tolerability of the carboplatin, etoposide, and irinotecan triplet as a first-line treatment in extensive small-cell lung cancer. Chemonaive patients with documented diagnosis of extensive small-cell lung cancer, performance status 0-2, and adequate organ function were eligible. Patients received triweekly carboplatin area under the curve 5 on day 1, irinotecan 150 mg/m on day 2, and etoposide 75 mg/m on days 1, 2, and 3 for up to six cycles. A total of 54 patients were enrolled. Forty-seven of 54 patients (87%) had a performance status of 0-1. The response rate was 75% and complete response was achieved in 10 of 54 patients (18%). The median time to progression was estimated at 8 months (95% confidence interval: 6.6-8.9) and median overall survival at 12 months (95% confidence interval: 10.3-13.9). Patients with one site of metastases had prolonged survival as compared with those with two or more sites. Normalization of lactate dehydrogenase values after treatment was not correlated to survival. Grade 3-4 neutropenia occurred in nine patients (16.7%) and grade 3 fetal thrombocytopenia in one patient (1.9%). Two toxic deaths (3.7%) were reported. The carboplatin, irinotecan, and etoposide triplet is a very effective and well-tolerated combination for the poor prognosis group of extensive-stage small-cell lung cancer patients.

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.

Bi-weekly administration of docetaxel and gemcitabine as first-line therapy for non-small cell lung cancer: a phase II study.

BACKGROUND: The standard treatment for advanced non-small cell lung cancer (NSCLC) currently consists of platinum-based, combination chemotherapy of limited efficacy and possible toxicity. The bi-weekly administration of docetaxel and gemcitabine for advanced NSCLC was evaluated in a phase II study (objective response rate, median survival, median duration of response and safety). PATIENTS AND METHODS: A total of 170 cycles were administered to 31 patients with advanced NSCLC and a median age of 66 years (range 47-75 years). Patients received docetaxel 80 mg/m2 and gemcitabine 1000 mg/m2 on days 1 and 14 of a 28-day cycle. RESULTS: Sixteen patients achieved a PR (16/31, 55.2%), 3 patients had SD (3/31, 10.3%) and 10 (10/31, 34.5%) had PD. The median time to disease progression was 3 months (range 0-12 months) with a mean survival of 10 months (range 3-31 months). Haematological and non-haematological toxic effects were generally mild to moderate and manageable: Grade 3 neurotoxicity and allergy occurred in 2 patients (6.4%) and 1 patient (3.2%), respectively. Peripheral neuropathy, mostly grades 1 and 2, was reported in 24 patients (77.4%). CONCLUSION: The bi-weekly administration of a docetaxel/gemcitabine combination with G-CSF support constitutes a tolerable and convenient regimen for the treatment of advanced NSCLC, with efficacy similar to that reported in other regimens.

Teratoma occupying the left hemithorax.

BACKGROUND: Teratomas are manifested with a great variety of clinical and radiological features, while sometimes they simply represent incidental findings. CASE PRESENTATION: A rare case of benign teratoma of the dermoid cyst type, in an adult 40-year-old female patient, is reported. The patient had presented recurrent pulmonary infections for the previous 2 months, persistent cough, and progressively aggravating dyspnea. A chest X-ray showed total atelectasis of the left lung, and the thoracic CT-scan revealed a huge mass, containing multiple elements of heterogeneous density, probably originating from the mediastinum, occupying the whole left hemithorax. The mass compressed the vital structures of the mediastinum, great vessels and airways, and a chest MRI was performed to accurately detect the anatomical relations. The patient underwent left thoracotomy and the tumor was totally resected. The size of the tumor was extremely large although no invasion to the vessels or to the airway had occurred. Adherence to the adjacent left pulmonary artery and left main bronchus was present, but without erosion or fistulization. The postoperative course was uneventful, while the histological examination confirmed a teratoma. CONCLUSION: A teratoma is a non-homogeneous pathological entity, clinically, radiologically or histologically. It is predominantly diagnosed between the second and fourth decade and the incidence is equal for both sexes. Symptoms are absent in one half of the patients. The case reported is noteworthy as the tumor appeared with total atelectasis of the left lung, and symptoms started 2 months prior to diagnosis. Total removal of the tumor is adequate treatment for this type of teratoma and the prognosis is excellent.

Carboplatin plus pemetrexed as first-line treatment of patients with malignant pleural mesothelioma: a phase II study.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rapidly progressive tumor that is increasing in frequency worldwide. Treatment options are limited, and response to chemotherapy is poor. The aim of this phase II study was to evaluate the activity of the carboplatin/pemetrexed combination as first-line chemotherapy in patients with unresectable MPM. PATIENTS AND METHODS: Chemotherapy-naive patients with histologically confirmed MPM and an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled. Treatment consisted of pemetrexed 500 mg/m2 and carboplatin area under the concentration-time curve of 5 mg/mL/min, both administered on day 1 of a 21-day cycle. The treatment continued until 6 cycles were completed or until unacceptable toxicity or disease progression were observed. RESULTS: A total of 62 patients were enrolled. Of these patients, 18 (29%) had a confirmed partial response, whereas the disease remained stable in 34 patients (54.9%) and progressed in 10 patients (16.1%). The median overall survival (OS) was estimated at 14 months (95% CI, 11.8-16.2 months), and the median time to progression was 7 months (95% CI, 5.8-8.2 months). The difference in median OS between the epithelial histologic subtype (16 months) and the sarcomatoid subtype (11 months) was statistically significant. CONCLUSION: This study confirmed the activity of the carboplatin/ pemetrexed combination in the first-line treatment of patients with MPM. It is a viable option, especially in cases in which side effects are generally anticipated.