Multiple treatment interruptions and protecting HIV-specific CD4 T cells enable durable CD8 T cell response and viral control.

Human Immunodeficiency Virus (HIV) remains a global health challenge, and novel approaches to improve HIV control are significantly important. The cell and gene therapy product AGT103-T was previously evaluated (NCT04561258) for safety, immunogenicity, and persistence in seven patients for up to 180 days post infusion. In this study, we sought to investigate the impact of AGT103-T treatment upon analytical treatment interruptions (ATIs).

Safety and durability of AGT103-T autologous T cell therapy for HIV infection in a Phase 1 trial.

Unlabelled: The cell and gene therapy product AGT103-T was designed to restore the Gag-specific CD4+ T cell response in persons with chronic HIV disease who are receiving antiretroviral therapy. This autologous, genetically engineered cell product is under investigation in a Phase 1 clinical trial (NCT03215004). Trial participants were conditioned with cyclophosphamide approximately 1 week before receiving a one-time low (< 10 genetically modified CD4+ T cells) or high (≥10 genetically modified CD4+ T cells) dose of AGT103-T, delivering between 2 and 21 million genetically modified cells per kilogram (kg) body weight.

Consensus Statements on Deployment-Related Respiratory Disease, Inclusive of Constrictive Bronchiolitis: A Modified Delphi Study.

Background: The diagnosis of constrictive bronchiolitis (CB) in previously deployed individuals, and evaluation of respiratory symptoms more broadly, presents considerable challenges, including using consistent histopathologic criteria and clinical assessments.

Research Question: What are the recommended diagnostic workup and associated terminology of respiratory symptoms in previously deployed individuals?

Study Design And Methods: Nineteen experts participated in a three-round modified Delphi study, ranking their level of agreement for each statement with an a priori definition of consensus. Additionally, rank-order voting on the recommended diagnostic approach and terminology was performed.

Mosaic Attenuation Pattern: A Guide to Analysis with HRCT.

Mosaic attenuation pattern is commonly encountered on high-resolution computed tomography and has myriad causes. These diseases may involve small airways, vessels, alveoli, or interstitium, with some involving compartmental combinations. Small airways disease is caused by cellular bronchiolitis, infiltrated by inflammatory cells or constrictive bronchiolitis, resulting in fibrosis of the small airways.

Demystifying idiopathic interstitial pneumonia: time for more etiology-focused nomenclature in interstitial lung disease.

Introduction: A major focus of interstitial lung disease (ILD) has centered on disorders termed idiopathic interstitial pneumonias (IIPs) which include, among others, idiopathic pulmonary fibrosis, idiopathic nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, and respiratory bronchiolitis-interstitial lung disease.

Areas Covered: We review the radiologic and histologic patterns for the nine disorders classified by multidisciplinary approach as IIP, and describe the remarkable amount of published epidemiologic, translational, and molecular studies demonstrating their associations with numerous yet definitive environmental exposures, occupational exposures, pulmonary diseases, systemic diseases, medication toxicities, and genetic variants.

Expert Opinion: In the 21st century, these disorders termed IIPs are rarely idiopathic, but rather are well-described radiologic and histologic patterns of lung injury that are associated with a wide array of diverse etiologies.

Autologous Stem Cell Transplantation in the Treatment of Pulmonary Light Chain Deposition Disease.

Light chain deposition disease is a rare condition that results in the deposition of light chains in organs and their subsequent dysfunction. It is often the consequence of unchecked light chain production by a plasma cell clone. Rarely does it manifest with solely pulmonary involvement, especially in the young otherwise healthy patient.

Non-Infectious Granulomatous Lung Disease: Imaging Findings with Pathologic Correlation.

Non-infectious granulomatous lung disease represents a diverse group of disorders characterized by pulmonary opacities associated with granulomatous inflammation, a relatively nonspecific finding commonly encountered by pathologists. Some lesions may present a diagnostic challenge because of nonspecific imaging features; however, recognition of the various imaging manifestations of these disorders in conjunction with patients' clinical history, such as age, symptom onset and duration, immune status, and presence of asthma or cutaneous lesions, is imperative for narrowing the differential diagnosis and determining appropriate management of this rare group of disorders. In this pictorial review, we describe the pathologic findings of various non-infectious granulomatous lung diseases as well as the radiologic features and high-resolution computed tomography imaging features.

A comprehensive assessment of environmental exposures and the medical history guides multidisciplinary discussion in interstitial lung disease.

Background: Multidisciplinary discussion (MDD) is widely recommended for patients with interstitial lung disease (ILD), but published primary data from MDD has been scarce, and factors influencing MDD other than chest computed tomography (CT) and lung histopathology interpretations have not been well-described.

Methods: Single institution MDD of 179 patients with ILD.

Results: MDD consensus clinical diagnoses included autoimmune-related ILD, chronic hypersensitivity pneumonitis, smoking-related ILD, idiopathic pulmonary fibrosis, medication-induced ILD, occupation-related ILD, unclassifiable ILD, and a few less common pulmonary disorders.

Complex obstructive lung disease - A diagnostic and management conundrum.

Rheumatoid arthritis (RA) is a common autoimmune disease most well-known for its inflammatory, destructive polyarthropathy. Extraarticular manifestations of the disease may involve the respiratory system, including interstitial lung disease, pleural disease, pulmonary vascular abnormalities, and airways disease. Smoking is highly prevalent in the RA population, and may even have a synergistic effect in disease development and progression.

Induction of homeostatic biological parameters in reward deficiency as a function of an iron-free multi-nutrient complex: Promoting hemoglobinization, aerobic metabolism, viral immuno-competence, and neuroinflammatory regulation.

Background: A common neurological condition worldwide is Reward Deficiency Syndrome (RDS) leading to both substance and non-substance addictive behaviors, that must be combatted by integrating both central nervous system and peripheral nervous system biological approaches. Integrity of hemoglobin is a crucial determining factor for the overall health functions. Nutrient repletion therapy should be a fundamental strategy to restore the healthy properties of blood.

Combined Pulmonary Fibrosis and Emphysema: Pulmonary Function Testing and a Pathophysiology Perspective.

Combined pulmonary fibrosis and emphysema (CPFE) has been increasingly recognized over the past 10-15 years as a clinical entity characterized by rather severe imaging and gas exchange abnormalities, but often only mild impairment in spirometric and lung volume indices. In this review, we explore the gas exchange and mechanical pathophysiologic abnormalities of pulmonary emphysema, pulmonary fibrosis, and combined emphysema and fibrosis with the goal of understanding how individual pathophysiologic observations in emphysema and fibrosis alone may impact clinical observations on pulmonary function testing (PFT) patterns in patients with CPFE. Lung elastance and lung compliance in patients with CPFE are likely intermediate between those of patients with emphysema and fibrosis alone, suggesting a counter-balancing effect of each individual process.

Interstitial Lung Disease and Pulmonary Fibrosis: A Practical Approach for General Medicine Physicians with Focus on the Medical History.

Interstitial lung disease (ILD) and pulmonary fibrosis comprise a wide array of inflammatory and fibrotic lung diseases which are often confusing to general medicine and pulmonary physicians alike. In addition to the myriad of clinical and radiologic nomenclature used in ILD, histopathologic descriptors may be particularly confusing, and are often extrapolated to radiologic imaging patterns which may further add to the confusion. We propose that rather than focusing on precise histologic findings, focus should be on identifying an accurate etiology of ILD through a comprehensive and detailed medical history.

Radiologist Performance in the Detection of Pulmonary Embolism: Features that Favor Correct Interpretation and Risk Factors for Errors.

Purpose: This study aimed to assess the factors contributing toward accurate detection and erroneous interpretation of pulmonary embolism (PE).

Materials And Methods: Over 13 months, all computed tomography pulmonary angiography studies were retrospectively rereviewed by a chest radiologist. Two additional chest radiologists assessed cases with disagreement between the first interpretation and rereview.

Transcriptomic evidence of immune activation in macroscopically normal-appearing and scarred lung tissues in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease manifested by overtly scarred peripheral and basilar regions and more normal-appearing central lung areas. Lung tissues from macroscopically normal-appearing (IPFn) and scarred (IPFs) areas of explanted IPF lungs were analyzed by RNASeq and compared with healthy control (HC) lung tissues. There were profound transcriptomic changes in IPFn compared with HC tissues, which included elevated expression of numerous immune-, inflammation-, and extracellular matrix-related mRNAs, and these changes were similar to those observed with IPFs compared to HC.

Clinical-Radiologic-Pathologic Correlation of Smoking-Related Diffuse Parenchymal Lung Disease.

The direct toxicity of cigarette smoke and the body's subsequent response to this lung injury leads to a wide array of pathologic manifestations and disease states that lead to both reversible and irreversible injury to the large airways, small airways, alveolar walls, and alveolar spaces. These include emphysema, bronchitis, bronchiolitis, acute eosinophilic pneumonia, pulmonary Langerhans cell histiocytosis, respiratory bronchiolitis, desquamative interstitial pneumonia, and pulmonary fibrosis. Although these various forms of injury have different pathologic and imaging manifestations, they are all part of the spectrum of smoking-related diffuse parenchymal lung disease.

Castleman Disease of the Thorax: Clinical, Radiologic, and Pathologic Correlation: From the Radiologic Pathology Archives.

Castleman disease is a complex lymphoproliferative disease pathologically divided into two subtypes, the hyaline vascular variant (HVV) and the plasma cell variant (PCV). The HVV is the most common, is thought to represent a benign neoplasm of lymph node stromal cells, and is treated with surgical resection. It is most commonly found in the mediastinum, where it classically appears as a unicentric, avidly enhancing mass at computed tomography (CT) and magnetic resonance imaging.