ABSTRACT
Preterm infants with oxygen supplementation are at high risk for bronchopulmonary dysplasia (BPD), a neonatal chronic lung disease. Inflammation with macrophage activation is central to the pathogenesis of BPD. CXCL10, a chemotactic and pro-inflammatory chemokine, is elevated in the lungs of infants evolving BPD and in hyperoxia-based BPD in mice. Here, we tested if CXCL10 deficiency preserves lung growth after neonatal hyperoxia by preventing macrophage activation. To this end, we exposed Cxcl10 knockout (Cxcl10-/-) and wild-type mice to an experimental model of hyperoxia (85% O2)-induced neonatal lung injury and subsequent regeneration. In addition, cultured primary human macrophages and murine macrophages (J744A.1) were treated with CXCL10 and/or CXCR3 antagonist. Our transcriptomic analysis identified CXCL10 as a central hub in the inflammatory network of neonatal mouse lungs after hyperoxia. Quantitative histomorphometric analysis revealed that Cxcl10-/- mice are in part protected from reduced alveolar. These findings were related to the preserved spatial distribution of elastic fibers, reduced collagen deposition, and protection from macrophage recruitment/infiltration to the lungs in Cxcl10-/- mice during acute injury and regeneration. Complimentary, studies with cultured human and murine macrophages showed that hyperoxia induces Cxcl10 expression that in turn triggers M1-like activation and migration of macrophages through CXCR3. Finally, we demonstrated a temporal increase of macrophage-related CXCL10 in the lungs of infants with BPD. In conclusion, our data demonstrate macrophage-derived CXCL10 in experimental and clinical BPD that drives macrophage chemotaxis through CXCR3, causing pro-fibrotic lung remodeling and arrest of alveolarization. Thus, targeting the CXCL10-CXCR3 axis could offer a new therapeutic avenue for BPD.
PMID:37876024 | PMC:PMC10594718 | DOI:10.1186/s41232-023-00301-6
23:08
PubMed articles on: Cardio-Oncology
Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection
Redox Biol. 2023 Nov;67:102894. doi: 10.1016/j.redox.2023.102894. Epub 2023 Oct 6.
BACKGROUND: Recent studies suggested a relationship between Takotsubo syndrome (TTS) and malignancy. However, clinical outcomes of TTS associated with cancer have not been assessed completely. This study was aimed to investigate the outcomes of patients with TTS and cancer.
METHODS: We performed a systematic review and meta-analysis to evaluate the clinical outcomes of TTS in patients with and without malignancy. We systematically reviewed and analyzed 14 studies (189,210 patients) published in PubMed and Cochrane Library databases until December 2022. The primary outcome was all-cause mortality at the longest follow-up.
RESULTS: The prevalence of current or previous malignancy in patients with TTS was 8.7% (16,461 patients). Patients with TTS and malignancy demonstrated a higher risk of mortality at the longest follow-up than those with TTS alone (odds ratio [OR], 2.41; 95% confidence interval [CI]; 1.95-2.98; P < 0.001). Moreover, cancer was significantly associated with an increased risk of in-hospital or 30-day mortality (OR 2.36; 95% CI, 1.67-3.33; P < 0.001), shock (OR 1.42; 95% CI, 1.30-1.55; P < 0.001), mechanical respiratory support (OR 1.68; 95% CI, 1.59-1.77; P < 0.001), arrhythmia (OR 1.27; 95% CI, 1.21-1.34; P < 0.001), and major adverse cardiac events (OR 1.69; 95% CI, 1.18-2.442; P < 0.001).
CONCLUSIONS: This study revealed significant associations between previous or active cancer and an increased risk of all-cause mortality and in-hospital adverse events in patients with TTS.
PMID:37840966 | PMC:PMC10570743 | DOI:10.3389/fcvm.2023.1244808
CXCL10 deficiency limits macrophage infiltration, preserves lung matrix, and enables lung growth in bronchopulmonary dysplasia
Inflamm Regen. 2023 Oct 24;43(1):52. doi: 10.1186/s41232-023-00301-6.
The number of meta-analyses of aggregate data has dramatically increased due to the facility of obtaining data from publications and the development of free, easy-to-use, and specialised statistical software. Even when meta-analyses include the same studies, their results may vary owing to different methodological choices. Assessment of the replication of meta-analysis provides an example of the variation of effect 'naturally' observed between multiple research projects. Reproducibility of results has mostly been reported using graphical descriptive representations. A quantitative analysis of such results would enable (i) breakdown of the total observed variability with quantification of the variability generated by the replication process and (ii) identification of which variables account for this variability, such as methodological quality or the statistical analysis procedures used. These variables might explain systematic mean differences between results and dispersion of the results. To quantitatively characterise the reproducibility of meta-analysis results, a bivariate linear mixed-effects model was developed to simulate both mean results and their corresponding uncertainty. Results were assigned to several replication groups, those assessing the same studies, outcomes, treatment indication and comparisons classified in the same replication group. A nested random effect structure was used to break down the total variability within each replication group and between these groups to enable calculation of an intragroup correlation coefficient and quantification of reproducibility. Determinants of variability were investigated by modelling both mean and variance parameters using covariates. The proposed model was applied to the example of meta-analyses evaluating direct oral anticoagulants in the acute treatment of venous thromboembolism.
PMID:37846195 | DOI:10.1002/jrsm.1676
Clinical outcomes of takotsubo syndrome in patients with cancer: a systematic review and meta-analysis
Front Cardiovasc Med. 2023 Sep 29;10:1244808. doi: 10.3389/fcvm.2023.1244808. eCollection 2023.
BACKGROUND: Venous thromboembolism (VTE) is a potentially preventable serious complication in lung cancer patients undergoing thoracic surgery. We examined the risk and timing of VTE following surgery for primary non-small cell lung cancer (NSCLC).
METHODS: in the Danish Lung Cancer Registry. VTE events in the year after surgery were assessed by stage, patient characteristics, and surgical procedure.
RESULTS: We identified 13,197 patients who underwent surgery for NSCLC in 2003-2021 (mean age 67.6 years, 50% female); 10,524 (79.7%) had stage I-II NSCLS and 2673 (20.3%) had stage III-IV. During one-year follow-up, there were 335 VTE events, yielding a rate of 2.87 events/100 person-years and an absolute risk of 3.3% (95% CI 2.3-4.0). VTE risk increased with advancing cancer stage (1.8% for stage I versus 4.1% for stage IV), but varied little by pathological type, sex, and comorbidity level. Bilobectomy was associated with highest VTE risk (4.8%, 95% CI 3.2-6.9), followed by pneumonectomy (3.6%, 95% CI 2.5-5.1). The hazard of VTE was highest during the first three months after surgery, whereafter it declined. For stage IV cancer hazards increased again after six months. At one-year, all-cause death was 12.6% (95% CI: 12.0-13.1 %).
CONCLUSIONS: Among patients undergoing surgery for NSCLC, 3.3% developed VTE, most commonly within 3 months postoperatively. Prolonged thromboprophylaxis could be considered, particularly in those with advanced cancer stage and undergoing extended resections.
PMID:37890818 | DOI:10.1016/j.athoracsur.2023.10.015
PubMed articles on: Cancer & VTE/PE
A framework to characterise the reproducibility of meta-analysis results with its application to direct oral anticoagulants in the acute treatment of venous thromboembolism
Res Synth Methods. 2023 Oct 17. doi: 10.1002/jrsm.1676. Online ahead of print.
OBJECTIVES: To determine if the duration of invasive mechanical ventilation (IMV) was associated with hospital-acquired venous thromboembolism (HA-VTE) among critically ill children.
DESIGN: A multicenter, matched case-control study as a secondary analysis of Children's Hospital Acquired Thrombosis (CHAT) Consortium registry.
SETTING: PICUs within U.S. CHAT Consortium participating centers.
PATIENTS: Children younger than 21 years old admitted to a PICU receiving IMV for greater than or equal to 1 day duration from January 2012 to March 2022 were included for study. Cases with HA-VTE were matched 1:2 to controls without HA-VTE by patient age groups: younger than 1, 1-12, and older than 12 years.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: The primary outcome was IMV duration in days. Descriptive data included demographics, anthropometrics, HA-VTE characteristics (i.e., type, location, and timing), central venous catheterization data, thromboprophylaxis practices, and Braden Q mobility scores. Descriptive, comparative, and associative (multivariate conditional logistic regression for HA-VTE) statistics were employed. A total of 152 cases were matched to 304 controls. Cases with HA-VTE were diagnosed at a median of 7 days (interquartile range [IQR], 3-16 d) after IMV. The HA-VTE were limb deep venous thromboses in 130 of 152 (85.5%) and frequently central venous catheterization-related (111/152, 73%). Cases with HA-VTE experienced a longer length of stay (median, 34 d [IQR, 18-62 d] vs. 11.5 d [IQR, 6-21 d]; p < 0.001) and IMV duration (median, 7 d [IQR, 4-15 d] vs. 4 d [IQR, 1-7 d]; p < 0.001) as compared with controls. In a multivariate logistic model, greater IMV duration (adjusted odds ratio, 1.09; 95% CI, 1.01-1.17; p = 0.023) was independently associated with HA-VTE.
CONCLUSIONS: Among critically ill children undergoing IMV, HA-VTE was associated with greater IMV duration. If prospectively validated, IMV duration should be included as part of prothrombotic risk stratification and future pediatric thromboprophylaxis trials.
PMID:37882641 | DOI:10.1097/PCC.0000000000003383
Risk and timing of venous thromboembolism after surgery for lung cancer: a nationwide cohort study
Ann Thorac Surg. 2023 Oct 25:S0003-4975(23)01073-1. doi: 10.1016/j.athoracsur.2023.10.015. Online ahead of print.
OBJECTIVE: Currently, immune checkpoint inhibitors (ICIs) therapy is one of the main methods of treatment in non-small cell lung cancer (NSCLC). This study aimed to explore the risk factors of VTE and evaluate the effect of ICIs on VTE in patients with NSCLC.
RESEARCH DESIGN AND METHODS: We retrospectively studied patients with NSCLC who were divided into VTE group and without VTE (Non-VTE) group. We identified the risk factors of VTE in NSCLC patients and evaluated the effect of ICIs on VTE in NSCLC patients.
RESULTS: We found that clinical stage III-IV (P = 0.015) and Khorana score (KS) ≥ 2 (P = 0.047) were independent risk factors for the occurrence of VTE in NSCLC, and treatment with ICIs reduced the risk of VTE occurrence (P = 0.028). There were no differences of survival rates in the 12-month (P = 0.449), 24-month (P = 0.412), or 36-month (P = 0.315) between the VTE and non-VTE groups. History of anti-angiogenic therapy (P = 0.033) and chronic obstructive pulmonary disease (COPD) (P = 0.046) were independent risk factors for VTE in NSCLC patients who were treated with ICIs.
CONCLUSION: This study suggests that we should strengthen anticoagulant therapy when using ICIs for NSCLC patients with a history of anti-angiogenic therapy and COPD.
PMID:37883026 | DOI:10.1080/17474086.2023.2276209
Hospital-Acquired Venous Thromboembolism and Invasive Mechanical Ventilation: A Report From the Children's Hospital Acquired Thrombosis Consortium
Pediatr Crit Care Med. 2023 Oct 26. doi: 10.1097/PCC.0000000000003383. Online ahead of print.
OBJECTIVE: To observe the effect of nurse-patient co-management mode on preventing venous thromboembolism (VTE) in lung cancer patients with carboplatin and gemcitabine chemotherapy after peripheral venipuncture central venous catheterization (PICC).
METHODS: 100 patients with lung cancer admitted to the 2nd Affiliated Hospital of Hainan Medical University from April 2020 to April 2022 were selected. All patients received a combination chemotherapy of carboplatin and gemcitabine and PICC catheterization. The patients were divided into an observation group and a control group by 1:1 simple random method, with 50 cases in each group. Patients in the control group were given routine nursing for lung cancer, and patients in the observation group were treated with nurse-patient co-management mode, and nursing intervention lasted for 2 months. General Comfort Questionnaire, self-management ability, quality of life, Self-care ability Scale, self-rating Anxiety Scale (SAS), and self-rating depression Scale were compared before and after intervention between the two groups. The recovery of immune ability indices (CD3+, CD3+CD4+, CD3+CD8+, CD3+CD4+/CD3+CD8+) in 2 groups were detected. Complications after PICC catheterization were recorded in the two groups.
RESULTS: After nursing, self-rating depression Scale and self-rating Anxiety Scale scores in both groups were significantly decreased, which were lower in the observation group than the control group (P < .001). After nursing, scores of self-concept, self-responsibility, self-care skills, and health knowledge level were significantly increased in both groups, which were higher in the observation group than control group (P < .001). After nursing, scores on the General Comfort Questionnaire, self-management scale, and quality of life were increased in both groups, which were higher in the observation group than control group (P < .0501). After nursing care, the immune competence indices of both patients increased significantly, and the immune indexes of CD3+, CD3+CD4+, and CD3+ CD4+/CD3+CD8+ in the observation group were significantly higher than those in the control group (P < .05). The total incidence of complications in the observation group was significantly lower than that in the control group (8.00% vs. 26.00%, P < .001), and the incidence of venous thromboembolism was significantly lower than that in the control group (2.00% vs. 14.00%, P < .001).
CONCLUSION: The nurse-patient co-management model has shown to be effective in reducing the incidence of venous thromboembolism in patients who have undergone PICC catheterization while receiving carboplatin and gemcitabine chemotherapy. This model also helps patients improve their self-care and self-management abilities, alleviates adverse psychological effects, and contributes to the recovery of their immune system.
PMID:37883756
Evaluating the effect of immune checkpoint inhibitors on venous thromboembolism in non-small cell lung cancer patients
Expert Rev Hematol. 2023 Oct 26:1-8. doi: 10.1080/17474086.2023.2276209. Online ahead of print.
ABSTRACT OBJECTIVE: To observe the effect of nurse-patient co-management mode on preventing venous thromboembolism (VTE) in lung cancer p...
