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Rheumatology (Oxford, England) Nov 2023To evaluate the effectiveness and safety of current treatment strategies for the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome.
OBJECTIVES
To evaluate the effectiveness and safety of current treatment strategies for the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome.
METHODS
A protocolized systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed. Three databases were searched for reports on treatment strategies for VEXAS. Data from the included publications was extracted and a narrative synthesis was performed. Treatment response was recorded as complete (CR), partial (PR) or none (NR) depending on changes in clinical symptoms and laboratory parameters. Patient characteristics, safety data and previous treatments were analysed.
RESULTS
We identified 36 publications with a total of 116 patients; 113 (98.3%) were male. The identified reports included azacytidine (CR 9/36, 25%; PR 14/36, 38.9%), Janus kinase inhibitors (JAKi) (CR 11/33, 33%; PR 9/33, 27.3%), tocilizumab (CR 3/15, 20%; PR 6/15, 40%), allogeneic stem cell transplantation (CR 6/7, 85.7%; one patient died), anakinra (CR 4/5, 80%; NR 1/5, 20%), canakinumab (CR 1/2, 50%; PR 1/2, 50%) and glucocorticoid monotherapy (CR 1/6, 16.7%; PR 4/6, 66.7%). Individual reports were available for TNF inhibitors, rituximab and MTX. Data on adverse events were available for 67 patients (67/116, 57.8%) and included: pneumonia (12/67, 17.9%), other infections (9/67, 13.4%), venous thromboembolisms (6/67, 8.9%), cytopenias (4/67, 5.9%), and acute (4/67, 5.9%) and chronic graft-vs-host-disease (2/67, 2.9%).
CONCLUSION
Current data on VEXAS treatment are limited and inhomogeneous. Treatment decisions should be individualized. For the devolvement of treatment algorithms clinical trials are needed. Adverse events remain a challenge, especially an elevated risk for venous thromboembolism associated to JAKi treatment should be carefully considered.
Topics: Humans; Male; Female; Algorithms; Azacitidine; Bronchiolitis Obliterans Syndrome; Databases, Factual; Janus Kinase Inhibitors; Mutation
PubMed: 37233149
DOI: 10.1093/rheumatology/kead240 -
World Journal of Pediatrics : WJP Jan 2024Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000... (Review)
Review
BACKGROUND
Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years, representing a major global healthcare burden. There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life. A multidisciplinary consensus development group comprising experts in epidemiology, infectious diseases, respiratory medicine, and methodology aims to develop the current consensus to address clinical issues of RSV infections in children.
DATA SOURCES
The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, using variations in terms for "respiratory syncytial virus", "RSV", "lower respiratory tract infection", "bronchiolitis", "acute", "viral pneumonia", "neonatal", "infant" "children", and "pediatric".
RESULTS
Evidence-based recommendations regarding diagnosis, treatment, and prevention were proposed with a high degree of consensus. Although supportive care remains the cornerstone for the management of RSV infections, new monoclonal antibodies, vaccines, drug therapies, and viral surveillance techniques are being rolled out.
CONCLUSIONS
This consensus, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections. Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.
Topics: Child; Humans; Respiratory Syncytial Virus Infections; Consensus; Respiratory Syncytial Viruses; Bronchiolitis; Respiratory Tract Infections; Hospitalization
PubMed: 38064012
DOI: 10.1007/s12519-023-00777-9 -
Clinical Infectious Diseases : An... Mar 2023The management of patients with prolonged viral shedding and coronavirus disease 2019 symptoms remains unclear. Combining antivirals, as practiced in other infections,...
The management of patients with prolonged viral shedding and coronavirus disease 2019 symptoms remains unclear. Combining antivirals, as practiced in other infections, is theoretically advantageous. We present a case of persistent, symptomatic severe acute respiratory syndrome coronavirus 2 infection and associated organizing pneumonia that was successfully treated with an extended course of combination antiviral therapy.
Topics: Humans; COVID-19; SARS-CoV-2; Organizing Pneumonia; Antiviral Agents; Immunocompromised Host
PubMed: 36281907
DOI: 10.1093/cid/ciac847 -
Lung Dec 2022Lung transplantation has developed significantly in recent years, but post-transplant care and patients' survival still need to be improved. Moreover, organ shortage... (Review)
Review
Lung transplantation has developed significantly in recent years, but post-transplant care and patients' survival still need to be improved. Moreover, organ shortage urges novel modalities to improve the quality of unsuitable lungs. Cytokines, the chemical mediators of the immune system, might be used for diagnostic and therapeutic purposes in lung transplantation. Cytokine monitoring pre- and post-transplant could be applied to the prevention and early diagnosis of injurious inflammatory events including primary graft dysfunction, acute cellular rejection, bronchiolitis obliterans syndrome, restrictive allograft syndrome, and infections. In addition, preoperative cytokine removal, specific inhibition of proinflammatory cytokines, and enhancement of anti-inflammatory cytokines gene expression could be considered therapeutic options to improve lung allograft survival. Therefore, it is essential to describe the cytokines alteration during inflammatory events to gain a better insight into their role in developing the abovementioned complications. Herein, cytokine fluctuations in lung tissue, bronchoalveolar fluid, peripheral blood, and exhaled breath condensate in different phases of lung transplantation have been reviewed; besides, cytokine gene polymorphisms with clinical significance have been summarized.
Topics: Humans; Cytokines; Lung Transplantation; Bronchiolitis Obliterans; Graft Rejection; Transplantation, Homologous
PubMed: 36348053
DOI: 10.1007/s00408-022-00588-1 -
The Lancet. Infectious Diseases Jan 2023Seasonal epidemics of respiratory syncytial virus (RSV) cause a clinically significant burden of disease among young children. Non-pharmaceutical interventions targeted... (Observational Study)
Observational Study
Epidemiology of respiratory syncytial virus in children younger than 5 years in England during the COVID-19 pandemic, measured by laboratory, clinical, and syndromic surveillance: a retrospective observational study.
BACKGROUND
Seasonal epidemics of respiratory syncytial virus (RSV) cause a clinically significant burden of disease among young children. Non-pharmaceutical interventions targeted at SARS-CoV-2 have affected the activity of other respiratory pathogens. We describe changes in the epidemiology of RSV among children younger than 5 years in England since 2020.
METHODS
Surveillance data on RSV infections, comprising laboratory-confirmed cases, proportion of positive tests, hospital admissions for RSV-attributable illness, and syndromic indicators for RSV-associated disease (emergency department attendances for acute bronchitis or bronchiolitis, non-emergency health advice telephone service [NHS 111] calls for cough, general practitioner [GP] in-hours consultations for respiratory tract infections, and GP out-of-hours contacts for acute bronchitis or bronchiolitis) were analysed from Dec 29, 2014 to March 13, 2022, for children younger than 5 years. Data were extracted from national laboratory, clinical, and syndromic surveillance systems. Time-series analyses using generalised linear models were used to estimate the effect of non-pharmaceutical interventions targeting SARS-CoV-2 on RSV indicators, with absolute and relative changes calculated by comparing observed and predicted values.
FINDINGS
RSV-associated activity was reduced for all RSV indicators during winter 2020-21 in England, with 10 280 (relative change -99·5% [95% prediction interval -100·0 to -99·1]) fewer laboratory-confirmed cases, 22·2 (-99·6%) percentage points lower test positivity, 92 530 (-80·8% [-80·9 to -80·8]) fewer hospital admissions, 96 672 (-73·7% [-73·7 to -73·7]) fewer NHS 111 calls, 2924 (-88·8% [-90·4 to -87·2]) fewer out-of-hours GP contacts, 91 304 (-89·9% [-90·0 to -89·9]) in-hours GP consultations, and 27 486 (-85·3% [-85·4 to -85·2]) fewer emergency department attendances for children younger than 5 years compared with predicted values based on winter seasons before the COVID-19 pandemic. An unprecedented summer surge of RSV activity occurred in 2021, including 11 255 (1258·3% [1178·3 to 1345·8]) extra laboratory-confirmed cases, 11·6 percentage points (527·3%) higher test positivity, 7604 (10·7% [10·7 to 10·8]) additional hospital admissions, 84 425 (124·8% [124·7 to 124·9]) more calls to NHS 111, 409 (39·0% [36·6 to 41·8]) more out-of-hours GP contacts, and 9789 (84·9% [84·5 to 85·4]) more emergency department attendances compared with the predicted values, although there were 21 805 (-34·1% [-34·1 to -34·0]) fewer in-hours GP consultations than expected. Most indicators were also lower than expected in winter 2021-22, although to a lesser extent than in winter 2020-21.
INTERPRETATION
The extraordinary absence of RSV during winter 2020-21 probably resulted in a cohort of young children without natural immunity to RSV, thereby raising the potential for increased RSV incidence, out-of-season activity, and health-service pressures when measures to restrict SARS-CoV-2 transmission were relaxed.
FUNDING
None.
Topics: Humans; Child; Infant; Child, Preschool; COVID-19; Sentinel Surveillance; Pandemics; Laboratories, Clinical; SARS-CoV-2; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; England; Bronchiolitis; Bronchitis; Seasons
PubMed: 36063828
DOI: 10.1016/S1473-3099(22)00525-4 -
Current Pediatric Reviews 2024Acute bronchiolitis is a viral infection of the lower respiratory tract affecting infants aged under 12 months, variably presenting with respiratory distress, diffuse...
BACKGROUND
Acute bronchiolitis is a viral infection of the lower respiratory tract affecting infants aged under 12 months, variably presenting with respiratory distress, diffuse crackles and inflammatory wheezing. The main causative agent is Respiratory Syncytial Virus (RSV). The diagnosis is clinical and treatment mainly supportive. Despite the availability of more than 30 international guidelines, consistent management recommendations are lacking and considerable variability in patients' care persists among different providers.
OBJECTIVE
To review and describe current knowledge about epidemiology, physiopathology, clinic, diagnosis and management of acute bronchiolitis, with particular emphasis on updated evidence and future perspectives in terms of treatment and prevention.
METHODS AND RESULTS
We searched Cochrane for systematic reviews and PubMed for scientific articles published in the last 10 years, using a combination of the following search terms: "bronchiolitis", "respiratory syncytial virus", "epidemiology", "risk factors", "severity", "diagnosis", "clinic", "diagnostic imaging", "management", "asthma", "wheezing", "bronchodilator", "steroids", "hypertonic saline", "oxygen", "blood gas analysis", "HHHFNC", "rehydration", "enteral feeding", "parenteral hydration", "prevention", "vaccine" and "COVID-19 or SARS-CoV2". We accordingly performed a deep and extensive selection of the most updated and considerable literature on the matter, summarizing the most significant evidence concerning all aspects of acute bronchiolitis (epidemiology, clinic, diagnosis, management and prevention). Furthermore, we examined references and available guidelines from UK, USA, Canada, Italy and Spain. Results are extensively discussed below.
CONCLUSION
Although acute bronchiolitis has been a widely known disease for decades, its therapeutic approach remained unchanged and essentially limited to respiratory and metabolic support. Despite the abundance of studies, there is no significant evidence concerning therapeutic alternatives (e.g. steroids, inhaled hypertonic solution), which are therefore not recommended. According to most recent data, "acute bronchiolitis" definition encompasses a plethora of different clinical entities related to each subject's genetic and immune predisposition. Therefore, future research should focus on the precise characterization of such subcategories in order to individualize therapeutic management and ensure the most appropriate evidence-based care.
Topics: Infant; Humans; RNA, Viral; Systematic Reviews as Topic; Bronchiolitis; Bronchodilator Agents; Risk Factors; Respiratory Syncytial Virus Infections
PubMed: 37873951
DOI: 10.2174/0115733963267129230919091338 -
Clinical Cancer Research : An Official... Mar 2023Acute and chronic GVHD remain major causes of transplant-related morbidity and mortality (TRM) after allogeneic hematopoietic cell transplantation (alloHCT). We have...
PURPOSE
Acute and chronic GVHD remain major causes of transplant-related morbidity and mortality (TRM) after allogeneic hematopoietic cell transplantation (alloHCT). We have shown CD83 chimeric antigen receptor (CAR) T cells prevent GVHD and kill myeloid leukemia cell lines. In this pilot study, we investigate CD83 expression on GVHD effector cells, correlate these discoveries with clinical outcomes, and evaluate critical therapeutic implications for transplant recipients.
EXPERIMENTAL DESIGN
CD83 expression was evaluated among circulating CD4+ T cells, B-cell subsets, T follicular helper (Tfh) cells, and monocytes from patients with/without acute or chronic GVHD (n = 48 for each group), respectively. CD83 expression was correlated with survival, TRM, and relapse after alloHCT. Differential effects of GVHD therapies on CD83 expression was determined.
RESULTS
CD83 overexpression on CD4+ T cells correlates with reduced survival and increased TRM. Increased CD83+ B cells and Tfh cells, but not monocytes, are associated with poor posttransplant survival. CD83 CAR T eliminate autoreactive CD83+ B cells isolated from patients with chronic GVHD, without B-cell aplasia as observed with CD19 CAR T. We demonstrate robust CD83 antigen density on human acute myeloid leukemia (AML), and confirm potent antileukemic activity of CD83 CAR T in vivo, without observed myeloablation.
CONCLUSIONS
CD83 is a promising diagnostic marker of GVHD and warrants further investigation as a therapeutic target of both GVHD and AML relapse after alloHCT.
Topics: Humans; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Leukemia, Myeloid, Acute; Pilot Projects; Receptors, Chimeric Antigen; Recurrence; Transplantation, Homologous
PubMed: 36622700
DOI: 10.1158/1078-0432.CCR-22-2837 -
BMJ Open Respiratory Research Jul 2021To assess the published evidence to establish the efficacy and safety of high flow oxygen cannula (HFNC) as respiratory support for children up to 24 months of age with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To assess the published evidence to establish the efficacy and safety of high flow oxygen cannula (HFNC) as respiratory support for children up to 24 months of age with bronchiolitis within acute hospital settings.
METHODS
We searched eight databases up to March 2021. Studies including children up to 24 months of age with a diagnosis of bronchiolitis recruited to an randomised controlled trial were considered in the full meta-analysis. At least one arm of the study must include HFNC as respiratory support and report at least one of the outcomes of interest. Studies were identified and extracted by two reviewers. Data were analysed using Review Manager V.5.4.
RESULTS
From 2943 article titles, 308 full articles were screened for inclusion. 23 studies met the inclusion criteria, 15 were included in the metanalyses. Four studies reported on treatment failure rates when comparing HFNC to standard oxygen therapy (SOT). Data suggests HFNC is superior to SOT (OR 0.45, 95% CI 0.36 to 0.57). Four studies reported on treatment failure rates when comparing HFNC to continuous positive airways pressure (CPAP). No significant difference was found between CPAP and HFNC (OR 1.64, 95% CI 0.96 to 2.79; p=0.07). Four studies report on adverse outcomes when comparing HFNC to SOT. No significant difference was found between HFNC & SOT (OR 1.47, 95% CI 0.54 to 3.99).
CONCLUSION
HFNC is superior to SOT in terms of treatment failure and there is no significant difference between HFNC and CPAP in terms of treatment failure. The results suggest HFNC is safe to use in acute hospital settings.
Topics: Bronchiolitis; Cannula; Child; Continuous Positive Airway Pressure; Humans; Oxygen; Oxygen Inhalation Therapy; Randomized Controlled Trials as Topic
PubMed: 34326153
DOI: 10.1136/bmjresp-2020-000844 -
EBioMedicine Sep 2023Patients diagnosed with environmental/occupational bronchiolitis obliterans (BO) over the last 2 decades often present with an indolent evolution of respiratory symptoms... (Review)
Review
Patients diagnosed with environmental/occupational bronchiolitis obliterans (BO) over the last 2 decades often present with an indolent evolution of respiratory symptoms without a history of high-level, acute exposure to airborne toxins. Exertional dyspnea is the most common symptom and standard clinical and radiographic evaluation can be non-diagnostic. Lung biopsies often reveal pathological abnormalities affecting all distal lung compartments. These modern cases of BO typically exhibit the constrictive bronchiolitis phenotype of small airway remodeling, along with lymphocytic inflammation. In addition, hypertensive-type remodeling of intrapulmonary vasculature, diffuse fibroelastosis of alveolar tissue, and fibrous thickening of visceral pleura are frequently present. The diagnosis of environmental/occupational BO should be considered in patients who present with subacute onset of exertional dyspnea and a history compatible with prolonged or recurrent exposure to environmental toxins. Important areas for future studies include development of less invasive diagnostic approaches and testing of novel agents for disease prevention and treatment.
Topics: Humans; Bronchiolitis Obliterans; Biopsy; Dyspnea; Phenotype
PubMed: 37598462
DOI: 10.1016/j.ebiom.2023.104760 -
Thoracic Surgery Clinics May 2022Chronic lung allograft dysfunction (CLAD) is a syndrome of progressive lung function decline, subcategorized into obstructive, restrictive, and mixed phenotypes. The... (Review)
Review
Chronic lung allograft dysfunction (CLAD) is a syndrome of progressive lung function decline, subcategorized into obstructive, restrictive, and mixed phenotypes. The trajectory of CLAD is variable depending on the phenotype, with restrictive and mixed phenotypes having more rapid progression and lower survival. The mechanisms driving CLAD development remain unclear, though allograft injury during primary graft dysfunction, acute cellular rejection, antibody-mediated rejection, and infections trigger immune responses with long-lasting effects that can lead to CLAD months or years later. Currently, retransplantation is the only effective treatment.
Topics: Allografts; Bronchiolitis Obliterans; Chronic Disease; Graft Rejection; Humans; Lung; Lung Transplantation; Primary Graft Dysfunction; Retrospective Studies
PubMed: 35512941
DOI: 10.1016/j.thorsurg.2021.11.004