Comparative Efficacy and Safety of Neoadjuvant Immunotherapy with Nivolumab vs. Pembrolizumab in Resectable Non-Small Cell Lung Cancer: A Systematic Review.

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. Immunotherapy has emerged as a promising treatment option due to its favorable toxicity profile. However, selecting the most appropriate immunotherapeutic agent for neoadjuvant use-aimed at curative intent in early-stage NSCLC-based on efficacy and safety remains a critical question. This review aims to compare the efficacy and safety profiles of nivolumab and pembrolizumab when used as neoadjuvant treatments in NSCLC. A systematic review was conducted across PubMed, Scopus, Wiley Online Library, ProQuest Dissertations and Theses Global, and Google Scholar, utilizing the search terms "Nivolumab OR Pembrolizumab AND Neoadjuvant Immunotherapy AND non-small cell lung cancer." Out of 1444 retrieved studies, 4 retrospective studies met the inclusion criteria by providing comparative data on nivolumab and pembrolizumab within the same study cohorts. Despite the critical risk of bias and the evidence quality ranging from moderate to very low across these studies, both nivolumab and pembrolizumab demonstrated efficacy rates exceeding 30% and maintained favorable safety profiles. There is no observed superiority between nivolumab and pembrolizumab in terms of efficacy and safety for the neoadjuvant treatment of early-stage NSCLC.

Effects of menopause and fat mass in asthmatic inflammation.

INTRODUCTION: Female hormones and obesity have an impact on women with asthma. We aimed to describe how these components affect asthma inflammatory processes. METHODS: Sex hormones [FSH, LH, estradiol (E2), estrone (E1), testosterone and Δ4 androstenedione (A4)] and serum IL1ß, IL13, IL17a, IL-5, IL6, TNF-a were measured from 11 to18 pre- and postmenopausal women with asthma. RESULTS: Premenopausal normal weight women revealed higher levels of IL5 and IL17a than obese women on both days of the menstrual cycle (IL5: D1: 6.4 vs 1.4 pg/ml, p = .036 and D14: 3 vs 1.4 pg/ml, p = .045 and IL17a: D1: 13.7 pg/ml vs 10.6 pg/ml and D14: 12.4 pg/ml vs 10.6 pg/ml, p = .009, respectively). In premenopausal women on D1, Δ4 Androstenedione was positively correlated with IL1ß (p = .016, r = 0.733), whereas on D14, Estradiol with IL1ß (p = .009, r = -.768) and TNF-a with Testosterone (p = .004, r = -0.816), and Δ4 Androstenedione (p = .002, r = -0.841) negatively. In postmenopausal women, TNF-a was negatively associated with FSH (p = .004, r = -0.638), but positively with Testosterone (p = .025, r = 0.526) and IL10 also positively with Estradiol (p = .007, r = 0.610). CONCLUSION: Obesity shows a protective role in asthma through the suppression of IL5 and IL17. Estrogens seem to inhibit Th1 and Th2 inflammation, while androgens have a dual role with negative and positive correlations with neutrophilic biomarkers.

Urban thoracic trauma: diagnosis and initial treatment of non-cardiac injuries in adults.

This comprehensive review aims to delineate the prevailing non-cardiac thoracic injuries occurring in urban environments following initial on-site treatment and subsequent admission to hospital emergency departments. Our study involved a rigorous search within the PubMed database, employing key phrases and their combinations, including "thoracic injury," "thoracic trauma," "haemothorax," "lung contusion," "traumatic pneumothorax," "rib fractures," and "flail chest." We focused on original research articles and reviews. Non-cardiac thoracic injuries exhibit a high prevalence, often affecting poly-trauma patients, and contributing to up to 35% of polytrauma-related fatalities. Furthermore, severe thoracic injuries can result in a substantial 5% mortality rate. This review provides insights into clinical entities such as lung contusion, traumatic haemothorax, pneumothorax, rib fractures, and sternal fractures. Thoracic injuries represent a frequent and significant clinical concern for emergency department physicians and thoracic surgeons, warranting thorough understanding and timely intervention.

PD-L1 assessment in lung cancer biopsies-pitfalls and limitations.

The programmed cell death-ligand 1 (PD-L1) protein expression on tumor cells predicts the efficacy of immunotherapy in patients with non-small cell lung cancer. However, the assessment of PD-L1 expression on tumor cells has limited power for selecting patients for immunotherapy due to intra-tumoral heterogeneity and inter-tumoral heterogeneity of PD-L1 expression, the inter-observer variability in scoring PD-L1 staining, and reproducibility. These difficulties and pitfalls in interpreting the PD-L1 assessment are discussed in detail in this review.

Segmentectomy versus lobectomy. Which factors are decisive for an optimal oncological outcome?

Low-dose computed tomography is being used for lung cancer screening in high-risk groups. Detecting lung cancer at an early stage improves the chance of optimal treatment and increases overall survival. This article compares segmentectomy vs. lobectomy as surgical options, in the case of stage I non-small cell lung carcinoma, ideally IA. To compare the 2 previously referred strategies, data were collected from articles (40 studies were reviewed), reviews, and systematic analyses in PubMed Central, as well as reviewing recent literature. Segmentectomy could be an equal alternative to lobectomy in early-stage NSCLC (tumour < 2 cm). It could be preferred for patients with a low cardiopulmonary reserve, who struggle to survive a lobectomy. As far as early-stage NSCLC is concerned, anatomic segmentectomy is an acceptable procedure in a selective group of patients. For better tumour and stage classification, a systematic lymph node dissection should be performed.

The Perioperative Use of Levosimendan as a Means of Optimizing the Surgical Outcome in Patients with Severe Heart Insufficiency Undergoing Cardiac Surgery.

BACKGROUND: Postoperative myocardial dysfunction following cardiac surgery is a relatively common occurrence. Levosimendan, a calcium sensitizer and inotropic drug, has shown potential in improving outcomes for patients with low preoperative ejection fraction (EF) and myocardial dysfunction after cardiac surgery. This study aims to evaluate the efficacy of levosimendan in optimizing the surgical outcome for such patients. METHODS: A retrospective analysis was conducted on 314 patients with preoperative severe heart failure who underwent cardiac surgery. Among them, 184 patients received perioperative adjunctive therapy with levosimendan, while a comparable group of 130 patients received conventional treatment. RESULTS: The use of levosimendan demonstrated several advantages in postoperative outcomes. It significantly improved short- and long-term survival rates after cardiac surgery, enhanced hemodynamic stability, reduced the requirement for inotropic support, and facilitated faster weaning from ventilator support. Patients who received levosimendan reported reduced angina and dyspnea symptoms, as well as fewer postoperative arrhythmias. Furthermore, levosimendan helped minimize myocardial injury inevitable after cardiac surgery. The levosimendan group also exhibited a notable reduction in hospital readmissions. CONCLUSIONS: This study provides evidence of several benefits associated with the perioperative use of levosimendan. However, further prospective randomized studies are warranted to standardize and comprehensively document the other perioperative therapies, in order to validate these findings and establish stronger conclusions.

Perioperative Application of Levosimendan Optimizes Postoperative Renal Function and Organ Perfusion in Patients with Severe Heart Failure.

Background: Renal dysfunction and impaired organ perfusion are common concerns following cardiac surgery. Levosimendan, a calcium sensitizer inotropic drug, is investigated in this study for its potential to improve postoperative renal function and organ perfusion in patients with low preoperative ejection fraction and severe myocardial dysfunction after cardiac surgery. Methods: A retrospective analysis was conducted on 314 patients with preoperative heart failure who underwent cardiac surgery. Among them, 184 patients received perioperative adjunctive therapy with levosimendan, while 130 patients with similar characteristics received conventional treatment. Results: The perioperative administration of levosimendan resulted in a significantly lower need for renal replacement therapy (p < 0.001) and improvements in the serum creatinine levels, glomerular filtration rate, and creatinine clearance. Similarly, the C-reactive protein levels, blood pH, and lactic acid levels showed comparable improvements. Conclusions: The use of levosimendan was associated with a significant enhancement in postoperative renal function and a reduction in the need for renal replacement therapy. Furthermore, it resulted in a decrease in the extent of organ malperfusion. Postoperative inflammatory reactions and metabolic balance also exhibited improvements.

Cardiovascular Diseases in COPD: From Diagnosis and Prevalence to Therapy.

Chronic obstructive pulmonary disease (COPD) is considered one of the leading causes of mortality. Cardiovascular comorbidities are diagnosed often in COPD patients, not only because of the common risk factors these two diseases share, but also because of the systemic inflammation which characterizes COPD and has deleterious effects in the cardiovascular system. The comorbid cardiovascular diseases in COPD result in several difficulties in the holistic treatment of these patients and affect outcomes such as morbidity and mortality. Several studies have reported that mortality from cardiovascular causes is common among COPD patients, while the risk for acute cardiovascular events increases during COPD exacerbations and remains high for a long time even after recovery. In this review, we focus on the prevalence of cardiovascular comorbidities in COPD patients, presenting the evidence regarding the interaction of the pathophysiological pathways which characterize each disease. Furthermore, we summarize information regarding the effects of cardiovascular treatment on COPD outcomes and vice versa. Finally, we present the current evidence regarding the impact of cardiovascular comorbidities on exacerbations, quality of life and survival of COPD patients.

Global initiative for chronic obstructive lung disease (GOLD) recommendations: strengths and concerns for future needs.

Chronic obstructive pulmonary disease (COPD) is already the third leading cause of death worldwide and simultaneously a major cause of morbidity and mortality. Global initiative for Chronic Obstructive Lung Disease (also known as GOLD) committee, has been created in 1997 to increase the awareness regarding the burden of COPD. GOLD recommendations have been contributing to diagnosis, managementz, and therapy of COPD since 2001. Through these years, by reviewing published articles, GOLD aimed to provide state-of-the-art information not only for pulmonologists, but also for non-respiratory physicians, and to encourage research on COPD. From 2011, GOLD annual reports have changed the way of COPD evaluation from based entirely on spirometric parameters to more clinical indices, such as the assessment of symptoms and dyspnea alongside with exacerbations. Moreover, according to recent developments in pathophysiology of COPD, there is a trend in identifying new preclinical stages, contributing to prevention and early COPD treatment. In the field of therapeutic algorithms, changes turn to a more personalized approach. However, it is not clear in what extent this personalized disease management would be feasible and the real challenge for current recommendations is to include more patient characteristics such as comorbidities and multidimensional scores in disease evaluation.

Lung Metastatectomy: Can Laser-Assisted Surgery Make a Difference?

BACKGROUND: Resection of lung metastases with curative intention in selected patients is associated with prolonged survival. Laser-assisted resection of lung metastases results in complete resection of a high number of lung metastases, while preserving lung parenchyma. However, data concerning laser lung resections are scarce and contradictory. The aim of this study was to conduct a systematic review to evaluate the utility of laser-assisted pulmonary metastasectomy. METHODS: An electronic search in MEDLINE (via PubMed), complemented by manual searches in article references, was conducted to identify eligible studies. RESULTS: Fourteen studies with a total of 1196 patients were included in this metanalysis. Laser-assisted surgery (LAS) for lung metastases is a safe procedure with a postoperative morbidity up to 24.2% and almost zero mortality. LAS resulted in the resection of a high number of lung metastases with reduction of the lung parenchyma loss in comparison with conventional resection methods. Survival was similar between LAS and conventional resections. CONCLUSION: LAS allows radical lung-parenchyma saving resection of a high number of lung metastases with similar survival to conventional methods.

Can Chest Ultrasound Replace Chest X-ray in Thoracic Surgery?

Background: There is growing evidence that supports the use of chest ultrasound (CUS) versus conventional chest X-ray (CXR) in order to diagnose postoperative complications. However, data regarding its use after thoracic surgery are scarce and contradictory. The aim of this study was to conduct a systematic review to evaluate the accuracy of CUS after thoracic surgery. Methods: An electronic search in MEDLINE (via PubMed), complemented by manual searches in article references, was conducted to identify eligible studies. Results: Six studies with a total of 789 patients were included in this meta-analysis. Performing CXR decreased in up to 61.6% of cases, with the main reasons for performing CXR being massive subcutaneous emphysema or complex hydrothorax. Agreement between CUS and routine-based therapeutic options was, in some studies, up to 97%. Conclusions: The selectively postoperative use of CUS may reduce the number of routinely performed CXR. However, if CUS findings are inconclusive, further radiological examinations are obligatory.

Blood eosinophils in COPD: friend or foe?

INTRODUCTION: The pathogenesis of chronic obstructive pulmonary disease (COPD) is highly complex and the underlying cellular and molecular mechanisms remain poorly understood. AREAS COVERED: COPD has been traditionally associated with neutrophilic inflammation of the bronchi, but in the last decade, studies have demonstrated that eosinophils may also migrate into the lower airways of patients with COPD and their increased numbers can be noticed during exacerbations as well as stable disease. In this review, we present clinical characteristics of eosinophilic COPD, as well as the role of eosinophils as a biomarker-guided therapy in COPD. A systematic research using the database of Pubmed up to February 2021 was performed. The terms we searched were eosinophilic inflammation, COPD, COPD phenotypes, COPD exacerbations, corticosteroids in COPD, and monoclonal antibodies in COPD. EXPERT OPINION: Blood eosinophil levels show strong potential as a prognostic and theragnostic biomarker in the clinical management of COPD being at the moment the most reliable biomarker. The lack of a certain cutoff value of blood eosinophils as guidance for treatment with ICS and biologic therapies and the uncertainty regarding the stability of eosinophilia and eosinophilic phenotype through the course of COPD remain as unmet dilemmas and problems.

Device use errors among patients with asthma and COPD and the role of training: a real-life study.

Background and objectives: Administration of inhaled medication for asthma and COPD is often difficult and incorrect device use is associated with unfavorable outcomes. We aimed to evaluate device use errors in asthma and COPD patients and to associate incorrect use with the patient's characteristics and medical history.Methods: Demographics and medical history were recorded. The use of each prescribed device was evaluated according to predefined steps.Results: 607 patients (49.9% male, median age (IQR) 63 (51, 70) years performed 663 demonstrations (56 patients were using 2 different types of devices). 51.4% were treated for asthma and 48.6% for COPD. 79.6% of demonstrations were performed using DPIs. Errors were documented on 41.2% of demonstrations and were associated with the type of device, p < 0.001. Elderly patients were less frequently using their devices correctly compared to younger patients, 50.8% vs 62.2%, respectively, p = 0.007. Correct demonstrations were more among asthmatics compared to COPD patients 63.1% vs 54.5%, p = 0.024. Incorrect use was associated with more acute exacerbations in the preceding year [median(IQR), 1(0, 2) vs 1(0, 1)], for incorrect and correct use, respectively, p < 0.001. Upon demonstration, 15.5% of patients have never been trained (i.e., undergone actual demonstrations and observation while using their device) by anyone. Errors occurred more frequently among patients who reported not to be trained compared to those who were trained, 67.0% vs 14.6%, respectively, p < 0.001. The commonest error was associated with the inspiration maneuver and accounted for the 48.3% of errors in the DPIs and 53.0% of errors in the MDIs.Conclusion: Device use errors are common and associated with unfavorable outcomes. Trained patients were more likely to use the device correctly.

Bronchoscopic diagnosis and treatment of endobronchial carcinoid: case report and review of the literature.

Carcinoid tumours are rare neuroendocrine neoplasms that mostly occur in younger adults with low tendencies to metastasise. Based on their histological characteristics, they are divided into typical and atypical subtypes. The most common presenting symptoms are due to central airway obstruction. The first step in the diagnostic assessment should be a computed tomography (CT) scan, as it provides information both for local tumour extent and lymph node involvement. Bronchoscopy is the main tool for histological confirmation, evaluation of bronchial wall invasion and removal of endobronchial manifestation with subsequent resolution of atelectasis. Endobronchial ultrasound may be necessary to rule out lymph node metastasis. Somatostatin receptor scintigraphy in combination with CT can rule out further metastatic disease.Surgical resection using parenchyma-sparing techniques remains the gold standard for treatment. For selected patients, endobronchial therapy could be an alternative for minimal invasiveness. Long-term follow-up is suggested due to the high likelihood of recurrence.Here, we describe our clinical experience in a 35-year-old male patient who originally presented with haemoptysis and a central polypoid tumour in the left main bronchus revealed by a CT scan. The histological characteristics were indicative of a typical carcinoid. The patient was treated using an endobronchial approach only. No complications and no recurrences have been observed in a follow-up of 2 years.

Prevalence, distribution and clinical significance of joints, muscles and bones in sarcoidosis: an 18F-FDG-PET/CT study.

OBJECTIVES: In Sarcoidosis joints-muscles-bones (JMBs) localizations are of the least common. 18F-FDG-PET/CT imaging revolutionized detection of JMBs involvement by adding metabolic activity information and allowing for a comprehensive, whole-body mapping of the disease. AIM AND METHODS: This study investigated prevalence, distribution, and clinical significance of JMBs sarcoidosis in 195 consecutive patients that underwent 18F-FDG PET/CT examination. RESULTS: Joint and bone involvement were encountered in 15% of patients with a mean of the maximum-standardized-uptake-value (SUVmax) of 6.1. Most common location was the axial skeleton. Hypercalciuria was significantly more frequent in patients with osseous involvement (p = 0.003). Muscle activity (SUVmax = 2.4) was encountered in 20% of the patients, most frequently in treatment-naïve (p = 0.02). The muscles of the lower extremities were affected the most. Muscle and bone localization coexist in 50% of the cases. JMBs disease was almost asymptomatic, not related to chronicity but to pulmonary, nodal, and systemic disease. Long-term follow-up and treatment response of affected patients confirmed sarcoidosis. CONCLUSION: 18F-FDG-PET/CT revealed JMBs localizations and coexistence with other organ sites supporting the concept that sarcoidosis is a systemic disease. By allowing an integrative interpretation of multi-organ involvement in the context of a pattern highly suggestive of sarcoidosis, it strongly keeps-off the diagnosis of malignancy.

Sirtuin 1: Endocan and Sestrin 2 in Different Biological Samples in Patients with Asthma. Does Severity Make the Difference?

BACKGROUND: Sestrin 2, Endocan, and Sirtuin 1 are distinct molecules with some biologic actions associated with asthma pathophysiology. The aim of the present study was to determine the molecular level differences attributable to underlying asthma severity. METHODS: We initially recruited 85 asthmatics with a wide spectrum of severity. All of the patients were optimally treated according to current guidelines. Demographics, test results of lung function, and treatment regimes of all patients were recorded. Sestrin 2, Endocan, and Sirtuin 1 were measured in different biological samples (sputum with two processing methods and serum). RESULTS: A total of 60 patients (35 with severe asthma) were analyzed, since 25 patients failed to produce an adequate sample of sputum. Patients with severe asthma showed significantly higher values for Sestrin 2 [pg/mL], measured in both sputum supernatant and cell pellet, compared to those with mild to moderate asthma [9524 (5696, 12,373) vs. 7476 (4265, 9273) p = 0.029, and 23,748 (15,280, 32,742) vs. 10,084 (3349, 21,784), p = 0.008, respectively]. No other significant differences were observed. No significant associations were observed between biomarkers, inflammatory cells, and lung function. CONCLUSION: Sestrin 2 is increased in patients with severe asthma as part of a mechanism that may modify structural alterations through the imbalance between oxidative stress and antioxidant activity.