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Current Opinion in Virology Jun 2024
PubMed: 38941708
DOI: 10.1016/j.coviro.2024.101425 -
Scientific Reports Jun 2024Helminth infections lead to an overdispersion of the parasites in humans as well as in animals. We asked whether early immune responses against migrating Ascaris larvae...
Helminth infections lead to an overdispersion of the parasites in humans as well as in animals. We asked whether early immune responses against migrating Ascaris larvae are responsible for the unequal distribution of worms in natural host populations and thus investigated a susceptible versus a resistant mouse strain. In mice, the roundworm larvae develop until the lung stage and thus early anti-Ascaris immune responses against the migrating larvae in the liver and lung can be deciphered. Our data show that susceptible C57BL/6 mice respond to Ascaris larval migration significantly stronger compared to resistant CBA mice and the anti-parasite reactivity is associated with pathology. Increased eosinophil recruitment was detected in the liver and lungs, but also in the spleen and peritoneal cavity of susceptible mice on day 8 post infection compared to resistant mice. In serum, eosinophil peroxidase levels were significantly higher only in the susceptible mice, indicating functional activity of the recruited eosinophils. This effect was associated with an increased IL-5/IL-13 production by innate lymphoid cells and CD4 T cells and a pronounced type 2 macrophage polarization in the lungs of susceptible mice. Furthermore, a comparison of wildtype BALB/c and eosinophil-deficient dblGATA-1 BALB/c mice showed that eosinophils were not essential for the early control of migrating Ascaris larvae. In conclusion, in primary infection, a strong local and systemic type 2 immune response during hepato-tracheal helminth larval migration is associated with pathology rather than protection.
Topics: Animals; Ascariasis; Larva; Mice; Th2 Cells; Mice, Inbred BALB C; Lung; Ascaris; Eosinophils; Mice, Inbred C57BL; Mice, Inbred CBA; Liver; Female
PubMed: 38942904
DOI: 10.1038/s41598-024-65281-0 -
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 -
Haemophilia : the Official Journal of... Jun 2024Acquired haemophilia A (AHA) is a bleeding disorder caused by autoantibody development against factor VIII (FVIII). Studies on AHA have mainly focused on patients...
INTRODUCTION
Acquired haemophilia A (AHA) is a bleeding disorder caused by autoantibody development against factor VIII (FVIII). Studies on AHA have mainly focused on patients treated at specialist centres.
AIM
To determine the incidence, clinical characteristics and outcomes of AHA in an unselected population-based patient cohort from Finland.
METHODS
This retrospective observational cohort comprised all cases diagnosed with AHA in Finland between 2006 and 2019. Patients were identified by the two central laboratories performing FVIII antibody testing in Finland, the Finnish Red Cross Blood Service and HUSLAB. Clinical details were collected from all hospitals and healthcare units where patients were treated. This study was performed in conjunction with the AHA in the Nordics study.
RESULTS
The median incidence of AHA was 0.65 per million per year (range 0.19-1.27). Fifty-five patients were identified, with a median age of 76 years and an even sex ratio (51% women). When diagnosed, all had bleeding symptoms with severe bleeds in 92%. First-line immunosuppressive treatment regimens included steroid monotherapy in 31% of cases, steroids and a cytotoxic agent in 51% and a rituximab-based regimen in 16%. Clinical remission was achieved in 71% of cases, and 15% had relapses. Mortality was 13% for bleeds and 9% for treatment-related infections. Overall survival was 64% for 1 year and 56% for 2 years after diagnosis.
CONCLUSIONS
In a nationwide population-based cohort study, we discovered a lower incidence of AHA than previously reported. Mortality among patients with AHA was high, calling for the consideration of updated treatment strategies.
PubMed: 38941448
DOI: 10.1111/hae.15037 -
Medicine Jun 2024The aim of this study is to delineate the distinctive high-resolution computed tomography features of pulmonary cryptococcosis in non-HIV-infected patients. This...
The aim of this study is to delineate the distinctive high-resolution computed tomography features of pulmonary cryptococcosis in non-HIV-infected patients. This retrospective analysis encompasses high-resolution computed tomography scans from 58 patients with histologically confirmed pulmonary cryptococcosis, focusing on the diagnostic challenges and the factors that lead to misdiagnosis. Analysis of computed tomography scans from these patients indicated that nodular or mass-like presentations were evident in 32 cases (55.2%), consolidation presentations in 7 cases (12.1%), and mixed presentations in 19 cases (32.8%). Lesions were predominantly located in the lower lobes of the lungs (40 cases, 69.0%) and in peripheral zones (55 cases, 94.8%). Notable radiographic signs included the presence of the burr sign in 55 cases (94.8%), lobulation sign in 53 cases (91.4%), halo sign in 53 cases (91.4%), and air bronchogram in 46 cases (79.0%). Moreover, 24 cases (41.4%) exhibited necrosis or cavitation, mediastinal lymphadenopathy was noted in 6 cases (10.3%), and pleural effusion was present in 5 cases (8.6%). Lesions were devoid of calcification. Pulmonary cryptococcosis ought to be contemplated in the differential diagnosis when computed tomography imaging exhibits patterns including, but not limited to, lower lobe and peripheral distribution, a broad base abutting the pleura, clustered growth with a propensity for fusion, air bronchogram within lesions, and peripheral halo sign.
Topics: Humans; Male; Female; Retrospective Studies; Middle Aged; Cryptococcosis; Tomography, X-Ray Computed; Lung Diseases, Fungal; Adult; Aged; Lung; Young Adult
PubMed: 38941424
DOI: 10.1097/MD.0000000000038671