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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 -
Respiratory Care Jun 2024
Topics: Humans; Pulmonary Medicine; Respiratory Therapy
PubMed: 38942596
DOI: 10.4187/respcare.12174 -
RNA (New York, N.Y.) Jun 2024SARS-CoV-2, the causative virus of the COVID-19 pandemic, follows SARS and MERS as recent zoonotic coronaviruses causing severe respiratory illness and death in humans....
SARS-CoV-2, the causative virus of the COVID-19 pandemic, follows SARS and MERS as recent zoonotic coronaviruses causing severe respiratory illness and death in humans. The recurrent impact of zoonotic coronaviruses demands a better understanding of their fundamental molecular biochemistry. Nucleoside modifications, which modulate many steps of the RNA lifecycle, have been found in SARS-CoV-2 RNA, although whether they confer a pro- or anti-viral effect is unknown. Regardless, the viral RNA-dependent RNA polymerase will encounter these modifications as it transcribes through the viral genomic RNA. We investigated the functional consequences of nucleoside modification on the pre-steady state kinetics of SARS-CoV-2 RNA-dependent RNA transcription using an in vitro reconstituted transcription system with modified RNA templates. Our findings show that N6-methyladenosine and 2'O-methyladenosine modifications slow the rate of viral transcription at magnitudes specific to each modification, which has the potential to impact SARS-CoV-2 genome maintenance.
PubMed: 38942480
DOI: 10.1261/rna.079991.124 -
BMJ Open Quality Jun 2024WHO reported that neonatal hypothermia accounts for about 27% of newborn deaths worldwide. It is a serious concern in Ethiopia and other parts of sub-Saharan Africa; it...
BACKGROUND
WHO reported that neonatal hypothermia accounts for about 27% of newborn deaths worldwide. It is a serious concern in Ethiopia and other parts of sub-Saharan Africa; it poses a serious threat to global health, increasing morbidity and mortality. Hypothermic neonates are more likely to experience respiratory distress, infections and other issues that could result in longer hospital stays and delayed development. The objective of this quality improvement project was to minimise intensive medical treatments, maximise resource usage and enhance overall health outcomes for newborns at Gandhi Memorial Hospital by reducing neonatal hypothermia.
METHODS
Over 10 months (from 1 March 2021 to 30 January 2022), neonatal hypothermia incidence was assessed using Quality Supervision Mentoring Team and Health Management Information System data. Root cause analysis and literature review led to evidence-based interventions in a change bundle. After team training and neonatal intensive care unit (NICU) relocation, Plan-Do-Study-Act cycles tested the bundle. Close temperature monitoring and data collection occurred. Run charts evaluated intervention success against baseline data, informing conclusions about effectiveness.
RESULT
The quality improvement project reduced neonatal hypothermia in NICU admissions from a baseline median of 80.6% to a performance median of 30%.
CONCLUSION AND RECOMMENDATION
The quality improvement project at Gandhi Memorial Hospital effectively reduced neonatal hypothermia through interventions such as the temperature management bundle and NICU relocation, leading to improved patient care, fewer hypothermic neonates and enhanced body temperature management. Continuous monitoring, adherence to best practices, sharing success and outcome assessment are crucial for enhancing the project's effectiveness and sustaining positive impacts on neonatal hypothermia reduction and patient outcomes.
Topics: Humans; Ethiopia; Infant, Newborn; Quality Improvement; Hypothermia; Incidence; Intensive Care Units, Neonatal; Female; Male
PubMed: 38942436
DOI: 10.1136/bmjoq-2023-002656 -
Annals of Oncology : Official Journal... Jun 2024Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant...
Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA.
BACKGROUND
Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups.
PATIENTS AND METHODS
This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR).
RESULTS
Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004].
CONCLUSIONS
Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.
PubMed: 38942080
DOI: 10.1016/j.annonc.2024.05.541 -
Heart & Lung : the Journal of Critical... Jun 2024Aeorobic exercise is an essential component of the pulmonary rehabilitation program for patients with chronic obstructive pulmonary disease (COPD). Single-limb exercises... (Review)
Review
BACKGROUND
Aeorobic exercise is an essential component of the pulmonary rehabilitation program for patients with chronic obstructive pulmonary disease (COPD). Single-limb exercises are a type of aeorobic exercise that aims to increase patient tolerance by reducing the workload of the respiratory system.
OBJEKTIVES
The aim of our systematic review was to determine the effects of single-limb exercises on pulmonary function, dyspnea, fatigue, and muscle dysfunction in patients with COPD.
METHODS
Searches were performed using PubMed, Pedro, Google Scholar, MEDLINE, EMBASE, Scopus, Cochrane Library, Web of Science databases. Publications from the beginning to 2023 searched. Studies were selected by two authors by scanning the title, Mesh terms abstract in Rayyan QCRI software. Selected studies were subjected to full-text screening by applying selection criteria. Randomized controlled, case-control, cohort studies were included.
RESULTS
In the first screening according to mesh terms, 1011 articles were identified. After the screening criteria and duplicate articles were evaluated, 10 articles were included. This systematic review includes seven case-control, one randomized control trial (RCT), one cross-sectional, and one non-randomized study. A total of 157 patients with COPD received treatment in these studies. According to the Bakker scale, single-limb exercises have been shown to improve pulmonary function with strong evidence. There is strong evidence that single-limb exercises have no effect on dyspnea and fatigue in COPD patients. There is limited evidence that single-limb exercises have an effect on functional exercise capacity.
CONCLUSION
Single-limb exercise can advised in terms of improving pulmonary function in patients with COPD. Current systematic review has found single limb exercise has no effect on dyspnea and fatigue perception. No side effects were reported in the studies and these exercises can be considered safe.
PubMed: 38941773
DOI: 10.1016/j.hrtlng.2024.06.004 -
Heart & Lung : the Journal of Critical... Jun 2024Bradycardia and dysautonomia observed during SARS-Cov2 infection suggests involvement of the autonomic nervous system (ANS). Limited data exists on ANS dysregulation and...
BACKGROUND
Bradycardia and dysautonomia observed during SARS-Cov2 infection suggests involvement of the autonomic nervous system (ANS). Limited data exists on ANS dysregulation and its association with outcomes in patients with acute respiratory distress syndrome (ARDS) related to COVID-19 (C-ARDS) or other etiologies (NC-ARDS).
OBJECTIVES
We aimed to explore sympathovagal balance, assessed by heart rate variability (HRV), and its clinical prognostic value in C-ARDS compared with NC-ARDS.
METHODS
A single-center, prospective case-control study was conducted. Consecutive patients meeting ARDS criteria between 2020 and 2022 were included. HRV was assessed using 1-hour electrographic tracing during a stable, daytime period.
RESULTS
Twenty-four patients with C-ARDS and 19 with NC-ARDS were included. Age, sex and ARDS severity were similar between groups. The median heart rate was markedly lower in the C-ARDS group than in the NC-ARDS group (60 [53-72] versus 101 [91-112] bpm, p<.001). Most of HRV parameters were significantly increased in patients with C-ARDS. HRV correlated with heart rate only in patients with C-ARDS. A positive correlation was found between the low-to high-frequency ratio (LF/HF) and length of intensive care unit stay (r = 0.576, p<.001).
CONCLUSION
This study confirmed that C-ARDS was associated with marked bradycardia and severe ANS impairment, suggesting a sympathovagal imbalance with vagal overtone. Poor outcomes appeared to be more related to sympathetic rather than parasympathetic hyperactivation.
PubMed: 38941770
DOI: 10.1016/j.hrtlng.2024.06.014 -
International Emergency Nursing Jun 2024Older patients are more likely to be undertriaged as they often suffer from multiple diseases and complain of non-specific symptoms. Therefore, it is necessary to...
BACKGROUND
Older patients are more likely to be undertriaged as they often suffer from multiple diseases and complain of non-specific symptoms. Therefore, it is necessary to identify the characteristics of undertriaged older patients in emergency departments.
METHODS
This descriptive study retrospectively reviewed and analyzed the electronic medical records of older patients who visited the emergency department of a general hospital in Seoul between January and December 2019.
RESULTS
Approximately 29 % (n = 4,823) of older patients who visited the emergency department during the study period were classified as Korean Triage and Acuity Scale (KTAS) level 4 or 5, and approximately 8 % (n = 397) were undertriaged. Approximately 73 % (n = 288) of patients were hospitalized after visiting the emergency department. The undertriaged older patients exhibited nervous system symptoms such as dizziness and headache (28.8 %), cardiopulmonary symptoms such as chest discomfort, palpitations, and abdominal pain (28.4 %), head trauma (12.8 %), and respiratory symptoms such as cough and dyspnea (12.5 %).
CONCLUSION
Triage nurses in emergency departments should carefully triage older patients as their chief complaints can be non-specific. In particular, when older patients visit the emergency department and exhibit symptoms such as dizziness, abnormal pain, chest discomfort, palpitations, and head trauma, they are more likely to be admitted to the intensive care unit. Therefore, meticulous care for older patients showing these symptoms is essential.
PubMed: 38941741
DOI: 10.1016/j.ienj.2024.101477 -
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 -
British Dental Journal Jun 2024
Topics: Humans; Nose
PubMed: 38942879
DOI: 10.1038/s41415-024-7601-7