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Scientific Reports Jun 2024In tuberculosis (TB), chest radiography (CXR) patterns are highly variable, mimicking pneumonia and many other diseases. This study aims to evaluate the efficacy of...
In tuberculosis (TB), chest radiography (CXR) patterns are highly variable, mimicking pneumonia and many other diseases. This study aims to evaluate the efficacy of Google teachable machine, a deep neural network-based image classification tool, to develop algorithm for predicting TB probability of CXRs. The training dataset included 348 TB CXRs and 3806 normal CXRs for training TB detection. We also collected 1150 abnormal CXRs and 627 normal CXRs for training abnormality detection. For external validation, we collected 250 CXRs from our hospital. We also compared the accuracy of the algorithm to five pulmonologists and radiological reports. In external validation, the AI algorithm showed areas under the curve (AUC) of 0.951 and 0.975 in validation dataset 1 and 2. The accuracy of the pulmonologists on validation dataset 2 showed AUC range of 0.936-0.995. When abnormal CXRs other than TB were added, AUC decreased in both human readers (0.843-0.888) and AI algorithm (0.828). When combine human readers with AI algorithm, the AUC further increased to 0.862-0.885. The TB CXR AI algorithm developed by using Google teachable machine in this study is effective, with the accuracy close to experienced clinical physicians, and may be helpful for detecting tuberculosis by CXR.
Topics: Humans; Deep Learning; Tuberculosis, Pulmonary; Radiography, Thoracic; Algorithms; Female; Male; Middle Aged; Adult; Area Under Curve
PubMed: 38942819
DOI: 10.1038/s41598-024-65703-z -
Nature Communications Jun 2024Dexamethasone is the standard of care for critically ill patients with COVID-19, but the mechanisms by which it decreases mortality and its immunological effects in this...
Dexamethasone is the standard of care for critically ill patients with COVID-19, but the mechanisms by which it decreases mortality and its immunological effects in this setting are not understood. Here we perform bulk and single-cell RNA sequencing of samples from the lower respiratory tract and blood, and assess plasma cytokine profiling to study the effects of dexamethasone on both systemic and pulmonary immune cell compartments. In blood samples, dexamethasone is associated with decreased expression of genes associated with T cell activation, including TNFSFR4 and IL21R. We also identify decreased expression of several immune pathways, including major histocompatibility complex-II signaling, selectin P ligand signaling, and T cell recruitment by intercellular adhesion molecule and integrin activation, suggesting these are potential mechanisms of the therapeutic benefit of steroids in COVID-19. We identify additional compartment- and cell- specific differences in the effect of dexamethasone that are reproducible in publicly available datasets, including steroid-resistant interferon pathway expression in the respiratory tract, which may be additional therapeutic targets. In summary, we demonstrate compartment-specific effects of dexamethasone in critically ill COVID-19 patients, providing mechanistic insights with potential therapeutic relevance. Our results highlight the importance of studying compartmentalized inflammation in critically ill patients.
Topics: Dexamethasone; Humans; COVID-19 Drug Treatment; COVID-19; SARS-CoV-2; Lung; Cytokines; Critical Illness; Male; Single-Cell Analysis; Female; Middle Aged; T-Lymphocytes; Aged; Lymphocyte Activation
PubMed: 38942804
DOI: 10.1038/s41467-024-49756-2 -
Journal of Cystic Fibrosis : Official... Jun 2024Data on the impact of liver transplantation (LT) in cystic fibrosis (CF) on lung function and exacerbations are limited. The objective of this study was to summarize the...
BACKGROUND
Data on the impact of liver transplantation (LT) in cystic fibrosis (CF) on lung function and exacerbations are limited. The objective of this study was to summarize the literature on lung function, nutritional status, survival, and complications following LT in people with CF.
METHODS
Three databases were searched until September 2023, to identify the impact of LT in CF. Lung transplant prior to LT and simultaneous liver-lung transplant were excluded. Pooled hazard ratios were calculated using random-effects models.
RESULTS
Thirty studies were included in this review, with 3 and 9 studies included in meta-analyses for nutritional status and lung function, respectively. Eighty-three percent of the studies used data that was more than a decade old. There was a significant increase in percent-predicted forced expiratory volume with mean change of 7.16 % (2.13, 12.19; p = 0.005) one year post-LT. Pulmonary exacerbations decreased in the short-term, however there was no significant change in body mass index (BMI). One-year survival post-LT ranged between 75 and 100 %, while five-year survival was lower at 64-89 %.
CONCLUSION
Existing data suggest that LT improves lung function in the short term and does not increase the likelihood of pulmonary exacerbations, despite ongoing immunosuppression in the setting of chronic lung infection.
PubMed: 38942722
DOI: 10.1016/j.jcf.2024.06.012 -
Clinical Radiology Jun 2024This study assesses the safety and efficacy of particle embolization during bronchial artery embolization (BAE) in patients with shunts between bronchial and...
AIM
This study assesses the safety and efficacy of particle embolization during bronchial artery embolization (BAE) in patients with shunts between bronchial and non-bronchial systemic arteries and the pulmonary artery.
METHODS
In this retrospective, single-center study, we analyzed 312 BAE procedures performed from June 2020 to April 2023. The patient cohort had shunts between bronchial and non-bronchial systemic arteries and the pulmonary artery. We meticulously collected and examined comprehensive data, including clinical characteristics, computed tomography (CT) imaging, and embolization procedural details.
RESULTS
Vascular shunts were identified in 49 patients. The etiologies of hemoptysis included post-TB sequelae (42.8%), bronchiectasis (26.5%), active TB (12.2%), aspergilloma (8.1%), bacterial pneumonia (4.1%), lung cancer (4.1%), and non-tuberculous mycobacterial infection (2%). The technical success rate of the procedures was 98%, with 149 out of 152 identified vessels successfully embolized. All patients experienced cessation or significant reduction of hemoptysis within 24 hours following the procedure. The clinical success rates were 97.9% at one month, 93.9% at six months, and 89.8% at one year. No shunt-related complications were detected.
CONCLUSION
BAE with particle embolization is a safe and effective treatment for hemoptysis, particularly in cases with complex shunts between bronchial and non-bronchial systemic arteries and the pulmonary artery.
PubMed: 38942705
DOI: 10.1016/j.crad.2024.06.003 -
Journal of Microbiology, Immunology,... Jun 2024The increasing prevalence of drug-resistant pathogens leads to delays in adequate antimicrobial treatment in intensive care units (ICU). The real-world influence of the...
The real-world impact of the BioFire FilmArray blood culture identification 2 panel on antimicrobial stewardship among patients with bloodstream infections in intensive care units with a high burden of drug-resistant pathogens.
BACKGROUND
The increasing prevalence of drug-resistant pathogens leads to delays in adequate antimicrobial treatment in intensive care units (ICU). The real-world influence of the BioFire FilmArray Blood Culture Identification 2 (BCID2) panel on pathogen identification, diagnostic concordance with conventional culture methods, and antimicrobial stewardship in the ICU remains unexplored.
METHODS
This retrospective observational study, conducted from July 2021 to August 2023, involved adult ICU patients with positive blood cultures who underwent BCID2 testing. The concordance between BCID2 and conventional culture results was examined, and its impact on antimicrobial stewardship was assessed through a comprehensive retrospective review of patient records by intensivists.
RESULTS
A total of 129 blood specimens from 113 patients were analysed. Among these patients, a high proportion of drug-resistant strains were noted, including carbapenem-resistant Klebsiella pneumoniae (CRKP) (57.1%), carbapenem-resistant Acinetobacter calcoaceticus-baumannii complex (100%), methicillin-resistant Staphylococcus aureus (MRSA) (70%), and vancomycin-resistant Enterococcus faecium (VRE) (100%). The time from blood culture collection to obtaining BCID2 results was significantly shorter than conventional culture (46.2 h vs. 86.9 h, p < 0.001). BCID2 demonstrated 100% concordance in genotype-phenotype correlation in antimicrobial resistance (AMR) for CRKP, carbapenem-resistant Escherichia coli, MRSA, and VRE. A total of 40.5% of patients received inadequate empirical antimicrobial treatment. The antimicrobial regimen was adjusted or confirmed in 55.4% of patients following the BCID2 results.
CONCLUSIONS
In the context of a high burden of drug-resistant pathogens, BCID2 demonstrated rapid pathogen and AMR detection, with a noticeable impact on antimicrobial stewardship in BSI in the ICU.
PubMed: 38942661
DOI: 10.1016/j.jmii.2024.06.004 -
Heart, Lung & Circulation Jun 2024The impact of sex on outcomes following surgical aortic valve replacement (SAVR) remains unclear. It has been proposed that females experience inferior outcomes, but...
BACKGROUND
The impact of sex on outcomes following surgical aortic valve replacement (SAVR) remains unclear. It has been proposed that females experience inferior outcomes, but this has yet to be conclusively established, particularly in the long term. The objective of this study is to identify discrepancies in postoperative outcomes between males and females following SAVR to better inform consideration for surgical intervention.
METHOD
We retrospectively reviewed the outcomes of 4,927 patients who underwent SAVR from 2004 to 2018 at our centre. In total, 531 propensity-matched males and females were included in the final analysis. The primary outcome was mortality at any point during the follow-up period. Secondary outcomes included various measures of postoperative morbidity. Follow-up duration was 15 years.
RESULTS
In SAVR all-comers, females experienced inferior short-term mortality, but equivalent mid-term and long-term mortality. Rates of mediastinal bleeding, sternal wound infections, sepsis, heart failure, and pacemaker insertion were all equivalent between the sexes; however, males experienced a higher rate of acute kidney injury and readmission for stroke at the longest follow-up while females experienced a longer intensive care unit and hospital length of stay. In a sub-analysis of isolated SAVR, males and females experienced equivalent early, mid, and late mortality. Of note, a trend towards increased aortic valve reoperation was noted in females at the longest follow-up.
CONCLUSIONS
Males and females experience equivalent long-term mortality following isolated SAVR. Sex is not an independent risk factor of poor outcomes post-SAVR; however, the increased preoperative risk profile of females requires diligent consideration.
PubMed: 38942621
DOI: 10.1016/j.hlc.2024.03.006 -
The Lancet. Public Health Jul 2024The COVID-19 pandemic disrupted health-care delivery, including difficulty accessing in-person care, which could have increased the need for strong pharmacological pain...
BACKGROUND
The COVID-19 pandemic disrupted health-care delivery, including difficulty accessing in-person care, which could have increased the need for strong pharmacological pain relief. Due to the risks associated with overprescribing of opioids, especially to vulnerable populations, we aimed to quantify changes to measures during the COVID-19 pandemic, overall, and by key subgroups.
METHODS
For this interrupted time-series analysis study conducted in England, with National Health Service England approval, we used routine clinical data from more than 20 million general practice adult patients in OpenSAFELY-TPP, which is a a secure software platform for analysis of electronic health records. We included all adults registered with a primary care practice using TPP-SystmOne software. Using interrupted time-series analysis, we quantified prevalent and new opioid prescribing before the COVID-19 pandemic (January, 2018-February, 2020), during the lockdown (March, 2020-March, 2021), and recovery periods (April, 2021-June, 2022), overall and stratified by demographics (age, sex, deprivation, ethnicity, and geographical region) and in people in care homes identified via an address-matching algorithm.
FINDINGS
There was little change in prevalent prescribing during the pandemic, except for a temporary increase in March, 2020. We observed a 9·8% (95% CI -14·5 to -6·5) reduction in new opioid prescribing from March, 2020, with a levelling of the downward trend, and rebounding slightly after April, 2021 (4·1%, 95% CI -0·9 to 9·4). Opioid prescribing rates varied by demographics, but we found a reduction in new prescribing for all subgroups except people aged 80 years or older. Among care home residents, in April, 2020, parenteral opioid prescribing increased by 186·3% (153·1 to 223·9).
INTERPRETATION
Opioid prescribing increased temporarily among older people and care home residents, likely reflecting use to treat end-of-life COVID-19 symptoms. Despite vulnerable populations being more affected by health-care disruptions, disparities in opioid prescribing by most demographic subgroups did not widen during the pandemic. Further research is needed to understand what is driving the changes in new opioid prescribing and its relation to changes to health-care provision during the pandemic.
FUNDING
The Wellcome Trust, Medical Research Council, The National Institute for Health and Care Research, UK Research and Innovation, and Health Data Research UK.
Topics: Humans; England; COVID-19; Interrupted Time Series Analysis; Analgesics, Opioid; Male; Female; Middle Aged; Aged; Adult; Practice Patterns, Physicians'; Drug Prescriptions; Young Adult; Cohort Studies; Adolescent; Aged, 80 and over; Pandemics
PubMed: 38942555
DOI: 10.1016/S2468-2667(24)00100-2 -
Progress in Molecular Biology and... 2024Repurposing pharmaceuticals is a technique used to find new, alternate clinical applications for approved drug molecules. It may include altering the drug formulation,... (Review)
Review
Repurposing pharmaceuticals is a technique used to find new, alternate clinical applications for approved drug molecules. It may include altering the drug formulation, route of administration, dose or the dosage regimen. The process of repurposing medicines starts with screening libraries of previously approved drugs for the targeted disease condition. If after an the initial in silico, in vitro or in vivo experimentation, the molecule has been found to be active against a particular target, the molecule is considered as a good candidate for clinical trials. As the safety profile of such molecules is available from the previous data, significant time and resources are saved. These advantages of drug repurposing approach make it especially helpful for finding treatments for rapidly evolving conditions including bacterial infections. An ever-increasing incidence of antimicrobial resistance, owing to the mutations in bacterial genome, leads to therapeutic failure of many approved antibiotics. Repurposing the approved drug molecules for use as antibiotics can provide an effective means for the combating life-threatening bacterial diseases. A number of drugs have been considered for drug repurposing against bacterial infections. These include, but are not limited to, Auranofin, Closantel, and Toremifene that have been repurposed for various infections. In addition, the reallocation of route of administration, redefining dosage regimen and reformulation of dosage forms have also been carried out for repurposing purpose. The current chapter addresses the drug discovery and development process with relevance to repurposing against bacterial infections.
Topics: Drug Repositioning; Humans; Bacterial Infections; Animals; Anti-Bacterial Agents
PubMed: 38942533
DOI: 10.1016/bs.pmbts.2024.03.031 -
The American Journal of Medicine Jul 2024
Topics: Humans; COVID-19; Sleep Apnea, Obstructive; SARS-CoV-2; Post-Acute COVID-19 Syndrome
PubMed: 38942494
DOI: 10.1016/j.amjmed.2024.03.021 -
Life Sciences Jun 2024The study evaluated the antiviral effect of Verapamil against respiratory syncytial virus (RSV) and investigated its underlying mechanism.
AIMS
The study evaluated the antiviral effect of Verapamil against respiratory syncytial virus (RSV) and investigated its underlying mechanism.
MATERIALS AND METHODS
RSV-infected BALB/c mice were treated with Verapamil. Body weight, survival rates, viral load, lung damage, inflammatory factors, and the expression of RSV fusion (F) protein were analyzed. In cellular studies, intracellular Ca and viral titers were measured in the presence of Verapamil, Calcium Chloride, and EGTA. A time-of-addition assay assessed the antiviral effect of Verapamil.
KEY FINDINGS
Mice infected with RSV and treated with Verapamil exhibited a significant decrease in weight loss, an increase in survival rates, and reductions in viral titers, RSV F protein expression, inflammatory responses, and lung tissue injury. Verapamil reduced intracellular calcium levels, which correlated with reduced viral titers. The addition of calcium chloride reversed the anti-viral effects mediated by Verapamil, while EGTA potentiated them. The antiviral activity of Verapamil was observed during the early phase of RSV infection, likely by blocking Ca channels and inhibiting virus replication.
SIGNIFICANCE
Verapamil effectively inhibits RSV infection by blocking calcium channels and reducing intracellular calcium levels, thereby impeding viral replication. Thus, Verapamil shows promise as a treatment for RSV.
PubMed: 38942358
DOI: 10.1016/j.lfs.2024.122877