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The New England Journal of Medicine Jun 2023In patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT), a calcineurin inhibitor plus methotrexate has been a standard prophylaxis against... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT), a calcineurin inhibitor plus methotrexate has been a standard prophylaxis against graft-versus-host disease (GVHD). A phase 2 study indicated the potential superiority of a post-transplantation regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil.
METHODS
In a phase 3 trial, we randomly assigned adults with hematologic cancers in a 1:1 ratio to receive cyclophosphamide-tacrolimus-mycophenolate mofetil (experimental prophylaxis) or tacrolimus-methotrexate (standard prophylaxis). The patients underwent HSCT from an HLA-matched related donor or a matched or 7/8 mismatched (i.e., mismatched at only one of the , , , and loci) unrelated donor, after reduced-intensity conditioning. The primary end point was GVHD-free, relapse-free survival at 1 year, assessed in a time-to-event analysis, with events defined as grade III or IV acute GVHD, chronic GVHD warranting systemic immunosuppression, disease relapse or progression, and death from any cause.
RESULTS
In a multivariate Cox regression analysis, GVHD-free, relapse-free survival was significantly more common among the 214 patients in the experimental-prophylaxis group than among the 217 patients in the standard-prophylaxis group (hazard ratio for grade III or IV acute GVHD, chronic GVHD, disease relapse or progression, or death, 0.64; 95% confidence interval [CI], 0.49 to 0.83; P = 0.001). At 1 year, the adjusted GVHD-free, relapse-free survival was 52.7% (95% CI, 45.8 to 59.2) with experimental prophylaxis and 34.9% (95% CI, 28.6 to 41.3) with standard prophylaxis. Patients in the experimental-prophylaxis group appeared to have less severe acute or chronic GVHD and a higher incidence of immunosuppression-free survival at 1 year. Overall and disease-free survival, relapse, transplantation-related death, and engraftment did not differ substantially between the groups.
CONCLUSIONS
Among patients undergoing allogeneic HLA-matched HSCT with reduced-intensity conditioning, GVHD-free, relapse-free survival at 1 year was significantly more common among those who received cyclophosphamide-tacrolimus-mycophenolate mofetil than among those who received tacrolimus-methotrexate. (Funded by the National Heart, Lung, and Blood Institute and others; BMT CTN 1703 ClinicalTrials.gov number, NCT03959241.).
Topics: Adult; Humans; Bronchiolitis Obliterans Syndrome; Cyclophosphamide; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Methotrexate; Mycophenolic Acid; Neoplasm Recurrence, Local; Tacrolimus; Unrelated Donors; Hematologic Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37342922
DOI: 10.1056/NEJMoa2215943 -
Respirology (Carlton, Vic.) Jun 2021In chronic obstructive pulmonary disease (COPD), exacerbations (ECOPD), characterized by an acute deterioration in respiratory symptoms, are fundamental events impacting... (Review)
Review
In chronic obstructive pulmonary disease (COPD), exacerbations (ECOPD), characterized by an acute deterioration in respiratory symptoms, are fundamental events impacting negatively upon disease progression, comorbidities, wellbeing and mortality. ECOPD also represent the largest component of the socioeconomic burden of COPD. ECOPDs are currently defined as acute worsening of respiratory symptoms that require additional therapy. Definitions that require worsening of dyspnoea and sputum volume/purulence assume that acute infections, especially respiratory viral infections, and/or exposure to pollutants are the main cause of ECOPD. But other factors may contribute to ECOPD, such as the exacerbation of other respiratory diseases and non-respiratory diseases (e.g., heart failure, thromboembolism). The complexity of worsening dyspnoea has suggested a need to improve the definition of ECOPD using objective measurements such as blood counts and C-reactive protein to improve accuracy of diagnosis and a personalized approach to management. There are three time points when we can intervene to improve outcomes: acutely, to attenuate the length and severity of an established exacerbation; in the aftermath, to prevent early recurrence and readmission, which are common, and in the long-term, establishing preventative measures that reduce the risk of future events. Acute management includes interventions such as corticosteroids or antibiotics and measures to support the respiratory system, including non-invasive ventilation (NIV). Current therapies are broad and better understanding of clinical phenotypes and biomarkers may help to establish a more tailored approach, for example in relation to antibiotic prescription. Other unmet needs include effective treatment for viruses, which commonly cause exacerbations. Preventing early recurrence and readmission to hospital is important and the benefits of interventions such as antibiotics or anti-inflammatories in this period are not established. Domiciliary NIV in those patients who are persistently hypercapnic following discharge and pulmonary rehabilitation can have a positive impact. For long-term prevention, inhaled therapy is key. Dual bronchodilators reduce exacerbation frequency but in patients with continuing exacerbations, triple therapy should be considered, especially if blood eosinophils are elevated. Other options include phosphodiesterase inhibitors and macrolide antibiotics. ECOPD are a key component of the assessment of COPD severity and future outcomes (quality of life, hospitalisations, health care resource utilization, mortality) and are a central component in pharmacological management decisions. Targeted therapies directed towards specific pathways of inflammation are being explored in exacerbation prevention, and this is a promising avenue for future research.
Topics: Bronchodilator Agents; Disease Progression; Humans; Noninvasive Ventilation; Pulmonary Disease, Chronic Obstructive; Quality of Life
PubMed: 33893708
DOI: 10.1111/resp.14041 -
Italian Journal of Pediatrics Feb 2023Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children. This document aims to update the consensus document... (Review)
Review
Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children. This document aims to update the consensus document published in 2014 to provide guidance on the current best practices for managing bronchiolitis in infants. The document addresses care in both hospitals and primary care. The diagnosis of bronchiolitis is based on the clinical history and physical examination. The mainstays of management are largely supportive, consisting of fluid management and respiratory support. Evidence suggests no benefit with the use of salbutamol, glucocorticosteroids and antibiotics with potential risk of harm. Because of the lack of effective treatment, the reduction of morbidity must rely on preventive measures. De-implementation of non-evidence-based interventions is a major goal, and educational interventions for clinicians should be carried out to promote high-value care of infants with bronchiolitis. Well-prepared implementation strategies to standardize care and improve the quality of care are needed to promote adherence to guidelines and discourage non-evidence-based attitudes. In parallel, parents' education will help reduce patient pressure and contribute to inappropriate prescriptions. Infants with pre-existing risk factors (i.e., prematurity, bronchopulmonary dysplasia, congenital heart diseases, immunodeficiency, neuromuscular diseases, cystic fibrosis, Down syndrome) present a significant risk of severe bronchiolitis and should be carefully assessed. This revised document, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of acute bronchiolitis.
Topics: Infant, Newborn; Child; Infant; Humans; Child, Preschool; Bronchiolitis; Hospitalization; Risk Factors; Albuterol; Respiratory Syncytial Virus Infections
PubMed: 36765418
DOI: 10.1186/s13052-022-01392-6 -
European Respiratory Review : An... Dec 2022Lower respiratory infections include acute bronchitis, influenza, community-acquired pneumonia, acute exacerbation of COPD and acute exacerbation of bronchiectasis. They... (Review)
Review
Lower respiratory infections include acute bronchitis, influenza, community-acquired pneumonia, acute exacerbation of COPD and acute exacerbation of bronchiectasis. They are a major cause of death worldwide and often affect the most vulnerable: children, elderly and the impoverished. In this paper, we review the clinical presentation, diagnosis, severity assessment and treatment of adult outpatients with lower respiratory infections. The paper is divided into sections on specific lower respiratory infections, but we also dedicate a section to COVID-19 given the importance of the ongoing pandemic. Lower respiratory infections are heterogeneous entities, carry different risks for adverse events, and require different management strategies. For instance, while patients with acute bronchitis are rarely admitted to hospital and generally do not require antimicrobials, approximately 40% of patients seen for community-acquired pneumonia require admission. Clinicians caring for patients with lower respiratory infections face several challenges, including an increasing population of patients with immunosuppression, potential need for diagnostic tests that may not be readily available, antibiotic resistance and social aspects that place these patients at higher risk. Management principles for patients with lower respiratory infections include knowledge of local surveillance data, strategic use of diagnostic tests according to surveillance data, and judicious use of antimicrobials.
Topics: Adult; Child; Humans; Aged; COVID-19; Respiratory Tract Infections; Community-Acquired Infections; Bronchitis; Pneumonia; Acute Disease; Anti-Infective Agents; Hospitals; Anti-Bacterial Agents
PubMed: 36261157
DOI: 10.1183/16000617.0092-2022 -
Annals of Internal Medicine Jun 2021Antimicrobial overuse is a major health care issue that contributes to antibiotic resistance. Such overuse includes unnecessarily long durations of antibiotic therapy in... (Review)
Review
DESCRIPTION
Antimicrobial overuse is a major health care issue that contributes to antibiotic resistance. Such overuse includes unnecessarily long durations of antibiotic therapy in patients with common bacterial infections, such as acute bronchitis with chronic obstructive pulmonary disease (COPD) exacerbation, community-acquired pneumonia (CAP), urinary tract infections (UTIs), and cellulitis. This article describes best practices for prescribing appropriate and short-duration antibiotic therapy for patients presenting with these infections.
METHODS
The authors conducted a narrative literature review of published clinical guidelines, systematic reviews, and individual studies that addressed bronchitis with COPD exacerbations, CAP, UTIs, and cellulitis. This article is based on the best available evidence but was not a formal systematic review. Guidance was prioritized to the highest available level of synthesized evidence.
BEST PRACTICE ADVICE 1
BEST PRACTICE ADVICE 2
BEST PRACTICE ADVICE 3
BEST PRACTICE ADVICE 4
Topics: Anti-Bacterial Agents; Bacterial Infections; Bronchitis; Cellulitis; Community-Acquired Infections; Cystitis; Drug Administration Schedule; Female; Humans; Male; Pneumonia, Bacterial; Prescription Drug Overuse; Primary Health Care; Pulmonary Disease, Chronic Obstructive; Pyelonephritis
PubMed: 33819054
DOI: 10.7326/M20-7355 -
American Family Physician Nov 2020
Review
Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; Bronchitis; Humans
PubMed: 33118784
DOI: No ID Found -
Chest Jul 2022Organizing pneumonia (OP), characterized histopathologically by patchy filling of alveoli and bronchioles by loose plugs of connective tissue, may be seen in a variety... (Review)
Review
Organizing pneumonia (OP), characterized histopathologically by patchy filling of alveoli and bronchioles by loose plugs of connective tissue, may be seen in a variety of conditions. These include but are not limited to after an infection, drug reactions, radiation therapy, and collagen vascular diseases. When a specific cause is responsible for this entity, it is referred to as "secondary OP." When an extensive search fails to reveal a cause, it is referred to as "cryptogenic OP" (previously called "bronchiolitis obliterans with OP"), which is a clinical, radiologic, and pathologic entity classified as an interstitial lung disease. The clinical presentation of OP often mimics that of other disorders, such as infection and cancer, which can result in a delay in diagnosis and inappropriate management of the underlying disease. The radiographic presentation of OP is polymorphous but often has subpleural consolidations with air bronchograms or solitary or multiple nodules, which can wax and wane. Diagnosis of OP sometimes requires histopathologic confirmation and exclusion of other possible causes. Treatment usually requires a prolonged steroid course, and disease relapse is common. The aim of this article is to summarize the clinical, radiographic, and histologic presentations of this disease and to provide a practical diagnostic algorithmic approach incorporating clinical history and characteristic imaging patterns.
Topics: Bronchiolitis Obliterans; Cryptogenic Organizing Pneumonia; Humans; Lung; Lung Diseases, Interstitial; Pneumonia
PubMed: 35038455
DOI: 10.1016/j.chest.2021.12.659 -
Missouri Medicine 2021Plastic Bronchitis (PB) is a rare pulmonary condition characterized by the presence of casts in the trachea or bronchial tree. While there are many individual cases... (Review)
Review
PURPOSE OF STUDY
Plastic Bronchitis (PB) is a rare pulmonary condition characterized by the presence of casts in the trachea or bronchial tree. While there are many individual cases reported in pediatric and adult populations, no thorough reviews of pediatric and adult cases of PB exist in the literature. The purpose of this article is to conduct a comprehensive review of PB regarding presentation, diagnosis, pathophysiology, and treatments.
ETIOLOGY
In the pediatric population, PB can be attributed to pediatric cardiothoracic surgeries such as Fontan procedures, infections, inflammatory processes, acute chest syndrome, or iatrogenic processes. In the adult population, PB can be idiopathic or due to infections, anatomic variations in lymphatic vessels, surgeries, medications, or other comorbidities.
PATHOPHYSIOLOGY
The pathophysiology of PB is still widely unknown; however, associations with inflammatory diseases and cardiac surgery have been proposed. There are two types of cast formations found in plastic bronchitis: Type I casts are associated with inflammatory diseases and Type II casts are associated with surgical procedures.
TREATMENT
Historically, PB has been treated by a variety of pharmacological methods including the use of corticosteroids and mucolytics. Recently, the treatment paradigm has shifted towards procedures such as lymphatic embolization, duct ligation, and stent grafting.
CONCLUSIONS
The information available regarding PB is still sparse, hence future research is necessary for further understanding of the disease. Due to its numerous presentations and disease associations, awareness of plastic bronchitis, and its treatment options is essential for primary care providers and respiratory specialists.
Topics: Adrenal Cortex Hormones; Adult; Bronchitis; Child; Fontan Procedure; Humans; Lymphatic Vessels; Plastics
PubMed: 34373673
DOI: No ID Found