Peptidylarginine Deiminase (PAD) Inhibitor Optimization through Displacement of a Trapped Water Molecule.

Excess protein citrullination, a post-translational modification converting arginine to citrulline, has been associated with a range of autoimmune and neurological disorders, as well as cancers. Protein citrullination is mediated by the peptidylarginine deiminase enzyme family (PAD1-4), and inhibition of one or several PAD isozymes in combination may offer a therapeutic approach to targeting these diseases. Building upon the discovery of PAD-PF2, an allosteric inhibitor of PAD1-4, herein, we report on the optimization of potency and pharmacokinetic properties while minimizing hERG channel liabilities within this novel chemical series.

Tracheobronchoplasty for Excessive Dynamic Airway Collapse and Tracheobronchomalacia: A Comparative Analysis of Distinct Airway Disorders.

Background: Excessive dynamic airway collapse (EDAC) and tracheobronchomalacia (TBM) are distinct etiologies of excessive central airway collapse; EDAC is characterized by excessive anterior displacement of the posterior membrane, while TBM is due to weakness of the cartilaginous rings. We compare outcomes after tracheobronchoplasty across these two pathologies.

Methods: This was a single-center retrospective study including patients who underwent tracheobronchoplasty between 2018-2023.

Procedure-free survival after therapeutic bronchoscopy in patients with central airway obstruction.

Background: Central airway obstruction (CAO) poses a significant risk of respiratory failure, often necessitating urgent intervention. Therapeutic bronchoscopy is a well-established method for palliation or definitive management of CAO. Although similar therapeutic maneuvers are employed for benign and malignant CAO, the long-term effectiveness and influencing factors are not fully described.

An international survey on the practice patterns of intrapleural enzymatic therapy for complicated parapneumonic effusions and empyema.

Background: Pleural space infection is a common clinical problem in thoracic medicine and is associated with significant morbidity and mortality. Prior studies have described multiple treatment strategies in the management of complicated parapneumonic effusions (CPPEs) and empyema. As a result, significant variation likely exists in clinical practice patterns amongst healthcare providers around the world.

Patterns of HER2 expression and genomic correlates in lung cancer, with a focus on preanalytical variables impacting immunohistochemical staining results.

Aims: Fam-trastuzumab deruxtecan-nxki (T-DXd) was recently approved for advanced stage or metastatic solid tumours with human epidermal growth factor receptor 2 (HER2) immunohistochemical (IHC) 3+ staining. Data on HER2 IHC testing and knowledge of genomic correlates in lung cancer are scarce. This study analyses genomic characteristics of HER2-expressing tumours and addresses issues with preanalytical variables for lung cancer specimens.

Tunneled Pleural Catheters: An Effective Nonsurgical Alternative for Nonexpandable Lung in Chronic Pleural Infection.

Background: Open window thoracostomy (OTW) is the standard of care for debilitated patients with chronic pleural infection and nonexpandable lungs (NEL) who are not candidates for major surgical intervention. Tunneled pleural catheters (TPC) offer tremendous treatment potential in this setting based on their efficacy in malignant pleural effusion and NEL. We aim to assess the efficacy, safety, and health care utilization of TPC in this setting.

Rapid Pleurodesis in Patients With Chronic Noninfectious Pleural Effusion: Twenty Years of Real-world Performance Data.

Background: Small cohort studies have shown rapid pleurodesis protocol's (RPP) effectiveness and capacity to expedite pleurodesis for malignant pleural effusion (MPE). This study intends to evaluate the effectiveness of the RPP in inducing pleurodesis in patients with pleural effusions from either malignant or benign etiologies.

Methods: In this single-center, retrospective cohort study spanning 2 decades, we assessed patients with recurrent symptomatic chronic noninfectious pleural effusion, both benign and malignant.

Airway Stents for Excessive Central Airway Collapse: A Randomized Controlled Open-label Trial.

Background: Short-term airway stent placement (stent evaluation) has been employed to evaluate whether patients with excessive central airway collapse (ECAC) will benefit from tracheobronchoplasty. Although retrospective studies have explored the impact of stent placement on ECAC, prospective randomized controlled trials are absent.

Methods: This was a randomized open-label trial comparing patients receiving airway stent placement and standard medical treatment (intervention group) versus standard medical treatment alone (control group) for ECAC.

Considerations for instituting pediatric pulmonary embolism response teams: A tool kit.

The incidence of pediatric pulmonary embolism (PE) has increased by 200 % in the last decade, but at a single center, it is still infrequent. Given the unique epidemiologic features of pediatric PE, diagnosis is often delayed, and the management is empiric, based on individual physician experience or preference. Thus, there is a strong need for center-specific uniform management of pediatric PE patients.

Beneficial Effects of Dietary Flaxseed on Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD), a significant cause of chronic liver disease, presents a considerable public health concern. Despite this, there is currently no treatment available. This study aimed to investigate dietary flaxseed in the JCR:LA-corpulent rat strain model of NAFLD.

Considerations for choosing an optimal animal model of cardiovascular disease.

The decision to use the optimal animal model to mimic the various types of cardiovascular disease is a critical one for a basic scientist. Clinical cardiovascular disease can be complex and presents itself as atherosclerosis, hypertension, ischemia/reperfusion injury, myocardial infarcts, and cardiomyopathies, amongst others. This may be further complicated by the simultaneous presence of two or more cardiovascular lesions (for example, atherosclerosis and hypertension) and co-morbidities (i.

Cardiomyocyte and endothelial cells play distinct roles in the tumour necrosis factor (TNF)-dependent atrial responses and increased atrial fibrillation vulnerability induced by endurance exercise training in mice.

Aims: Endurance exercise is associated with an increased risk of atrial fibrillation (AF). We previously established that adverse atrial remodelling and AF susceptibility induced by intense exercise in mice require the mechanosensitive and pro-inflammatory cytokine tumour necrosis factor (TNF). The cellular and mechanistic basis for these TNF-mediated effects is unknown.

Preoperative Workup of Patients With Excessive Central Airway Collapse: Does Stent Evaluation Serve a Role?

Background: Tracheobronchoplasty (TBP) is a definitive anatomic intervention for patients with severe symptomatic expiratory central airway collapse. Although stent evaluations have been described for surgical workup, current literature does not address if improvement during stent evaluation is sustained after TBP. We compared health-related quality of life (HRQOL) and functional status responses after airway stenting to those post-TBP.

Pleural Disease in Acute COVID-19 Pneumonia: A Single Center Retrospective Cohort Study.

Background: Pleural diseases encompass pleural effusion and pneumothorax (PTX), both of which were uncommon in coronavirus disease of 2019 (COVID-19). We aimed to describe the frequency, characteristics, and main outcomes of these conditions in patients with COVID-19 pneumonia.

Methods: We performed a retrospective cohort analysis of inpatients with COVID-19 pneumonia between January 1, 2020 and January 1, 2022, at Beth Israel Deaconess Medical Center in Boston, Massachusetts.

Tracheobronchoplasty yields long-term anatomy, function, and quality of life improvement for patients with severe excessive central airway collapse.

Objectives: This study examines the long-term anatomic and clinical effects of tracheobronchoplasty in severe excessive central airway collapse.

Methods: Included patients underwent tracheobronchoplasty for excessive central airway collapse (2002-2016). The cross-sectional area of main airways on dynamic airway computed tomography was measured before and after tracheobronchoplasty.

Stent Evaluation for Expiratory Central Airway Collapse: Does the Type of Stent Really Matter?

Background: Careful selection of patients with expiratory central airway collapse (ECAC) that may benefit from tracheobronchoplasty (TBP) can be aided by a short-term airway stent evaluation. This can be performed with either silicone Y-stents (SYSs) or uncovered self-expanding metallic airway-stents (USEMAS). No direct comparison has been made between these 2 stent types.