Epidemiology and Survival of Malignant Central Airway Obstruction in Lung Cancer Identified on Cross-Sectional Imaging.

BACKGROUND: The prevalence of malignant central airway obstruction at diagnosis and its 5-year incidence are largely unknown, as are basic epidemiological data pertaining to this serious condition. To address these data limitations, we retrospectively collected data from the cohort of patients diagnosed with lung cancer at our institution in 2015 and followed cohort patients 5 years forward, until 2020. METHODS: We reviewed index PET/CT or CT scans at the time of lung cancer diagnosis to identify the presence, subtype, and severity of malignant central airway obstruction as well as progression/development over the next 5 years. RESULTS: The prevalence of malignant central airway obstruction affecting the airway lumen by 25% or greater was 17%, and its 5-year incidence of development was 8.2%. Notable associations from the multivariate analysis included a younger age and a stepwise increase in obstruction with increasing stage of disease. Squamous cell carcinoma and small-cell lung cancer were the 2 histologic subtypes with the strongest association with obstruction. The presence of malignant central airway obstruction either at time of diagnosis or on follow-up imaging was associated with significantly shortened survival (multivariate Cox proportional HR for MCAO=1.702, P<0.001). CONCLUSION: This study provides the first systematic characterization of fundamental epidemiological data on malignant central airway obstructions at a tertiary cancer center in the United States. This data is important to inform research directions and funding efforts of this serious complication. It also serves as a baseline value against which to compare for future studies.

Correlation of Bronchoscopy and CT in Characterizing Malignant Central Airway Obstruction.

BACKGROUND: Malignant Central Airway Obstruction (MCAO) presents a significant challenge in lung cancer management, with notable morbidity and mortality implications. While bronchoscopy is the established diagnostic standard for confirming MCAO and assessing obstruction subtype (intrinsic, extrinsic, mixed) and severity, Computed Tomography (CT) serves as an initial screening tool. However, the extent of agreement between CT and bronchoscopy findings for MCAO remains unclear. METHODS: To assess the correlation between bronchoscopy and CT, we conducted a retrospective review of 108 patients at Roswell Park Comprehensive Cancer Center, analyzing CT and bronchoscopy results to document MCAO presence, severity, and subtype. RESULTS: CT correctly identified MCAO in 99% of cases (107/108). Agreement regarding obstruction subtype (80.8%, Cohen's κ = 0.683, p < 0.001), and severity (65%, Quadratic κ = 0.657, p < 0.001) was moderate. CT tended to equally overestimate (7/19) and underestimate (7/19) the degree of obstruction. CT was also poor in identifying mucosal involvement in mixed MCAO. CONCLUSIONS: CT demonstrates reasonable agreement with bronchoscopy in detecting obstruction. Nevertheless, when CT indicates a positive finding for MCAO, it is advisable to conduct bronchoscopy. This is because CT lacks reliability in determining the severity of obstruction and identifying the mucosal component of mixed disease.

Post-Operative Outcomes of Pre-Thoracic Surgery Respiratory Muscle Training vs Aerobic Exercise Training: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To compare the postoperative outcomes of preoperative respiratory muscle training (RMT) with a device to preoperative aerobic exercise training (AET) in patients undergoing thoracic surgeries (cardiac and lung). DATA SOURCES: PubMed, EMBASE, Cochrane, and Web of Science were comprehensively searched upon inception to 9/2020. STUDY SELECTION: All randomized control studies, including preoperative RMT and preoperative AET compared with a non-training control group, were included. DATA EXTRACTION: The meta-analysis was performed for outcomes including postoperative pulmonary complications (PPC), pneumonia, postoperative respiratory failure (PRF), hospital length of stay (HLOS), and mortality. We performed a network meta-analysis based on Bayesian random-effects regression models. DATA SYNTHESIS: A total of 25 studies, 2070 patients were included in this meta-analysis. Pooled data for the patients who performed RMT with a device showed a reduction in PPCs, pneumonia, PRF with odds ratio (OR) of 0.35 (P value .006), 0.38 (P value .002), and 0.22 (P value .008), respectively. Pooled data for the patients who performed AET showed reduction in PPC, pneumonia with a OR of 0.33 (P value <.00001) and OR of 0.54 (P value .01), respectively. HLOS was decreased by 1.69 days (P value <.00001) by performing RMT and 1.79 days (P value .0008) by performing AET compared with the usual group. No significant difference in all-cause mortality compared with usual care in both RMT and AET intervention groups. No significant difference in the incidence of PRF compared with usual group in RMT + AET and AET alone intervention groups (OR 0.32; P=.21; OR 0.94; P=.87). Based on rank probability plots analysis, on network meta-analysis, RMT and AET ranked similarly on the primary outcome of PPC and secondary outcomes of pneumonia, PRF and HLOS. CONCLUSIONS: In thoracic surgeries, preoperative RMT is comparable with preoperative AET to prevent PPC, pneumonia, and PRF and reduce HLOS. It can be considered in patients in resource-limited settings.

RhoA/Rho-kinases in asthma: from pathogenesis to therapeutic targets.

Asthma is a chronic and heterogeneous disease characterised by airway inflammation and intermittent airway narrowing. The key obstacle in the prevention and treatment of asthma has been our incomplete understanding of its aetiology and biological mechanisms. The ras homolog family member A (RhoA) of the Rho family GTPases has been considered to be one of the most promising and novel therapeutic targets for asthma. It is well known that RhoA/Rho-kinases play an important role in the pathophysiology of asthma, including airway smooth muscle contraction, airway hyper-responsiveness, ß-adrenergic desensitisation and airway remodelling. However, recent advances have suggested novel roles for RhoA in regulating allergic airway inflammation. Specifically, RhoA has been shown to regulate allergic airway inflammation through controlling Th2 or Th17 cell differentiation and to regulate airway remodelling through regulating mesenchymal stem cell (MSC) differentiation. In this review, we evaluate the literature regarding the recent advances in the activation of RhoA/Rho-kinase, cytokine and epigenetic regulation of RhoA/Rho-kinase, and the role of RhoA/Rho-kinase in regulating major features of asthma, such as airway hyper-responsiveness, remodelling and inflammation. We also discuss the importance of the newly identified role of RhoA/Rho-kinase signalling in MSC differentiation and bronchial epithelial barrier dysfunction. These findings indicate the functional significance of the RhoA/Rho-kinase pathway in the pathophysiology of asthma and suggest that RhoA/Rho-kinase signalling may be a promising therapeutic target for the treatment of asthma.

Unusual Sign from an Unusual Cause: Wellens' Syndrome due to Myocardial Bridging.

It is vital to recognize correctly, chest pain of cardiac etiology. Most commonly, it is because of blood supply-demand inequity in the myocardium. However, the phenomenon of myocardial bridging as a cause of cardiac chest pain has come to attention reasonably recently. Herein, a coronary artery with a normal epicardial orientation develops a transient myocardial course. If the cardiac muscle burden is substantial, the respective artery gets compressed during each cycle of systole, thereby impeding blood flow in the artery. Hence, myocardial bridging has been attributed to as a rare cause of angina. In this case report, the authors discuss a patient in whom myocardial bridging turned out to be an elusive cause of angina. We wish to underscore the importance of being clinically mindful of myocardial bridging when assessing a patient with angina.

Strongyloides Hyperinfection and Miliary Tuberculosis Presenting with Syndrome of Inappropriate Antidiuretic Hormone Secretion in a Malnourished Patient.

Strongyloides stercoralis (S. stercoralis) is an intestinal nematode endemic to tropical regions. An accelerated infection, known as a hyperinfection, occurs in immunocompromised patients, most commonly those treated chronically with glucocorticoids or those who have human T cell leukemia virus-1 (HTLV-1) infection. We describe a 67-year-old Hispanic female who presented with complaints of decreased oral intake and fatigue since three months. Hyponatremia on initial presentation was attributed to syndrome of inappropriate antidiuretic hormone (SIADH) secretion and managed with fluid restriction. Computed tomography (CT) of the chest revealed multiple pulmonary nodules suggestive of miliary tuberculosis, however, sputum acid-fast bacilli (AFB) smears were negative. Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) was performed and specimens sent for AFB testing. A concurrent endoscopy with biopsy was done to evaluate dysphagia. Both respiratory and gastrointestinal (GI) specimens were positive for Strongyloides stercoralis. Treatment with ivermectin and prophylactic antibiotics was started. The patient developed septic shock and had multiple episodes of gastrointestinal bleeding. Despite aggressive management, she expired. Subsequently, cultures for Mycobacterium tuberculosis (MTB) were positive and the autopsy demonstrated evidence of MTB infection in the lungs, liver, and lymph nodes. This case illustrates the importance of considering co-infection with Strongyloides stercoralis in patients with MTB, both associated with depressed cellular immunity.

Solitary Fibrous Tumor of Pleura Invading into the Left Atrium via Pulmonary Vein.

A 67-year-old woman came to the hospital because of difficulty in breathing. After an initial clinical assessment, contrast-enhanced computerized tomography (CT) of the chest revealed a well-circumscribed heterogeneous mass arising from the pleura adjacent to the superior and medial left pulmonary artery. The mass was invading the pulmonary vein and entering the left atrium. Histopathology of the biopsy of the mass was suggestive of solitary fibrous tumor (SFT) of the pleura. The patient underwent pneumonectomy and resection of the left atrial mass with pericardial patch repair of the left atrium.

Macrophage polarization and allergic asthma.

Allergic asthma is associated with airway inflammation and airway hyperresponsiveness. Macrophage polarization has been shown to have a profound impact on asthma pathogenesis. On exposure to local microenvironments, recruited macrophages can be polarized into either classically activated (or M1) or alternatively activated (or M2) phenotypes. Macrophage polarization has been heavily associated with development of asthma. The process of regulation of macrophage polarization involves an intricate interplay between various cytokines, chemokines, transcriptional factors, and immune-regulatory cells. Different signals from the microenvironment are controlled by different receptors on the macrophages to initiate various macrophage polarization pathways. Most importantly, there is an increased attention on the epigenetic changes (eg, microRNAs, DNA methylation, and histone modification) that impact macrophage functional responses and M1/M2 polarization through modulating cellular signaling and signature gene expression. Thus, modulation of macrophage phenotypes through molecular intervention by targeting some of those potential macrophage regulators may have therapeutic potential in the treatment of allergic asthma and other allergic diseases. In this review, we will discuss the origin of macrophages, characterization of macrophages, macrophage polarization in asthma, and the underlying mechanisms regarding allergen-induced macrophage polarization with emphasis on the regulation of epigenetics, which will provide new insights into the therapeutic strategy for asthma.

Tale of a Wandering Lead: Late Atrial Lead Perforation into Right Lung following Pacemaker Implantation.

Cardiac perforation by a pacemaker lead is a rare complication of pacemaker implantation. Presentation can vary from chest pain and shortness of breath to the patient being completely asymptomatic. Diagnosis is usually made by high-resolution computed tomography (HRCT) scan of the chest. Electrocardiograph (EKG) usually shows the absence of a paced rhythm, but it doesn't provide a definitive diagnosis. We describe a case of late cardiac perforation by an atrial pacemaker lead with no signs or symptoms of pericardial tamponade.

Candida Tropicalis Cholangitis in a Patient Without Underlying Malignancy.

Candida tropicalis is a rare cause of acute cholangitis, predominantly seen in patients with underlying hematological malignancies. Here, we describe a case of acute cholangitis caused by mixed organisms (Candida tropicalis, Candida albicans, and Enterococcus durans) without a known risk factor.

Aryl Hydrocarbon Receptor Protects Lungs from Cockroach Allergen-Induced Inflammation by Modulating Mesenchymal Stem Cells.

Exposure to cockroach allergen leads to allergic sensitization and increased risk of developing asthma. Aryl hydrocarbon receptor (AhR), a receptor for many common environmental contaminants, can sense not only environmental pollutants but also microbial insults. Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity to modulate immune responses. In this study, we investigated whether AhR can sense cockroach allergens and modulate allergen-induced lung inflammation through MSCs. We found that cockroach allergen-treated AhR-deficient (AhR(-/-)) mice showed exacerbation of lung inflammation when compared with wild-type (WT) mice. In contrast, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an AhR agonist, significantly suppressed allergen-induced mouse lung inflammation. MSCs were significantly reduced in cockroach allergen-challenged AhR(-/-) mice as compared with WT mice, but increased in cockroach allergen-challenged WT mice when treated with TCDD. Moreover, MSCs express AhR, and AhR signaling can be activated by cockroach allergen with increased expression of its downstream genes cyp1a1 and cyp1b1. Furthermore, we tracked the migration of i.v.-injected GFP(+) MSCs and found that cockroach allergen-challenged AhR(-/-) mice displayed less migration of MSCs to the lungs compared with WT. The AhR-mediated MSC migration was further verified by an in vitro Transwell migration assay. Epithelial conditioned medium prepared from cockroach extract-challenged epithelial cells significantly induced MSC migration, which was further enhanced by TCDD. The administration of MSCs significantly attenuated cockroach allergen-induced inflammation, which was abolished by TGF-ß1-neutralizing Ab. These results suggest that AhR plays an important role in protecting lungs from allergen-induced inflammation by modulating MSC recruitment and their immune-suppressive activity.

Gallbladder perforation: A rare complication of enteric fever.

INTRODUCTION: Gallbladder perforation is a rare complication of acute calculous cholecystitis in adults. Perforation of gallbladder due to enteric fever is extremely rare condition. Pre-operative diagnosis is rarely made and mortality is high. PRESENTATION OF CASE: We report a case of acalculous gallbladder perforation following enteric fever in a 14-year-old boy, who presented as acute abdomen and responded very well after emergency laparotomy and cholecystectomy. DISCUSSION: Enteric fever is common in tropics and a common cause of bowel perforation. Acute cholecystitis is a rare complication of typhoid and gallbladder perforation is extremely rare complication. Ultrasound and CT lack specificity to detect gallbladder perforation. Diagnosis is usually made intra-operatively. Cholecystectomy is treatment of choice in such cases and provides good result. CONCLUSION: Gallbladder perforation secondary to enteric fever requires a high degree of clinical suspicion. In typhoid endemic region, it should be considered as a differential diagnosis in patient presenting with a history of prolonged fever and signs of peritonitis. Early diagnosis and immediate surgical intervention are very important in reducing the morbidity and mortality. Cholecystectomy is the choice with a good outcome.