Long-term safety of tezepelumab in patients with asthma: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Tezepelumab has demonstrated its effectiveness in patients with asthma, but its safety, especially for long-term use, needs to be further explored. This systematic review and meta-analysis aimed to determine the safety of long-term use of tezepelumab in patients with asthma. DATA SOURCES: A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. STUDY SELECTIONS: Randomized controlled trials (RCTs) on treatment of asthma with tezepelumab, compared with placebo, were reviewed. Studies were pooled to weighted mean differences (WMDs) and risk ratios (RRs), with 95% confidence intervals (CIs). RESULTS: Seven RCTs (enrolling 2050 participants) met the inclusion criteria. Serious adverse event (RR 0.74, 95% CI 0.57 to 0.95), upper respiratory tract infection (RR 0.73, 95% CI 0.55 to 0.96), and asthma (RR 0.61, 95% CI 0.48 to 0.76) were more frequent in the placebo groups. There was no statistically significant difference in the proportion of patients with at least one adverse event (AE), AEs leading to discontinuation of study treatment, all-cause death, influenza, bronchitis, nasopharyngitis, headache, and hypertension between the two groups. CONCLUSION: Long-term (12-52 wk) use of tezepelumab in patients with asthma does not increase the incidence of adverse events.

Nomogram model of serum thymidine kinase 1 combined with ultrasonography for prediction of central lymph node metastasis risk in patients with papillary thyroid carcinoma pre-surgery.

Objective: The aim of this study was to develop a nomogram, using serum thymidine kinase 1 protein (STK1p) combined with ultrasonography parameters, to early predict central lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) pre-surgery. Methods: Patients with PTC pre-surgery in January 2021 to February 2023 were divided into three cohorts: the observation cohort (CLNM, n = 140), the control cohort (NCLNM, n = 128), and the external verification cohort (CLNM, n = 50; NCLNM, n = 50). STK1p was detected by an enzyme immunodot-blot chemiluminescence analyzer and clinical parameters were evaluated by ultrasonography. Results: A suitable risk threshold value for STK1p of 1.7 pmol/L was selected for predicting CLNM risk by receiver operating characteristic (ROC) curve analysis. Multivariate analysis identified the following six independent risk factors for CLNM: maximum tumor size >1 cm [odds ratio (OR) = 2.406, 95% confidence interval (CI) (1.279-4.526), p = 0.006]; capsule invasion [OR = 2.664, 95% CI (1.324-5.360), p = 0.006]; irregular margin [OR = 2.922; 95% CI (1.397-6.111), p = 0.004]; CLN flow signal [OR = 3.618, 95% CI (1.631-8.027), p = 0.002]; tumor-foci number ≥2 [OR = 4.064, 95% CI (2.102-7.859), p < 0.001]; and STK1p ≥1.7 pmol/L [OR = 7.514, 95% CI (3.852-14.660), p < 0.001]. The constructed nomogram showed that the area under the ROC curve for the main dataset was 0.867 and that for the validation dataset was 0.830, exhibiting effectivity, and was recalculated to a total score of approximately 383. Through monitoring the response post-surgery, all patients were assessed as tumor-free at 12 months post-surgery, which was significantly associated with a reduction in STK1p to disease-free levels. Conclusion: We demonstrate for the first time that a novel nomogram including STK1p combined with ultrasonography can assist in the clinical prevention of CLNM, by facilitating timely, individualized prophylactic CLNM dissection, thereby reducing the risk of secondary surgery and the probability of recurrence.

Mesenchymal Stem Cells on Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The Coronavirus disease-2019 (COVID-19) pandemic continues, and the death toll continues to surge. This meta-analysis aimed to determine the efficacy of mesenchymal stem cells (MSCs) on mortality in patients with COVID-19. METHODS: A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of COVID-19 with MSCs, compared with placebo or blank, were reviewed. Studies were pooled to risk ratios (RRs), with 95% confidence intervals (CIs). RESULTS: Seventeen RCTs (enrolling 1019 participants) met the inclusion criteria. MSCs showed significant effect on 28-day mortality (RR 0.76, 95% CI 0.62 to 0.93; P = 0.008). There was no statistically significant difference in 60-day mortality (RR 0.87, 95% CI 0.70 to 1.09; P = 0.22), and 90-day mortality (RR 0.91, 95% CI 0.72 to 1.15; P = 0.44) between the two groups. CONCLUSIONS: MSCs significantly reduced 28-day mortality in patients with COVID-19. The long-term effect of MSCs on mortality require further study.

Benefits of Macitentan in Patients with Pulmonary Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: This systematic review and meta-analysis aimed to determine the efficacy of macitentan in patients with pulmonary hypertension (PH). Methods: A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of PH with macitentan, compared with placebo or blank, were reviewed. Studies were pooled to weighted mean differences (WMDs) and risk ratios (RRs), with 95% confidence intervals (CIs). Results: Six RCTs (enrolling 1,003 participants) met the inclusion criteria. Macitentan showed significant effects on 6-min walk distance (6MWD) (WMD 12.06 m, 95% CI 2.12 to 21.99 m), pulmonary vascular resistance (PVR) (WMD -186.51 dyn·s/cm-5, 95% CI -232.72 to -140.29 dyn·s/cm-5), mean pulmonary artery pressure (mPAP) (WMD -3.20 mmHg, 95% CI -5.93 to -0.47 mmHg), N-terminal pro-brain natriuretic peptide (NT-proBNP) (WMD -232.47 ng/L, 95% wCI -318.22 to -146.72 ng/L), and cardiac index (WMD 0.39 L/min/m2, 95% CI 0.20 to 0.58 L/min/m2). Conclusion: Macitentan significantly improved 6MWD, PVR, mPAP, NT-proBNP, and cardiac index in patients with PH. Macitentan should be further validated in patients with PH.

Long-term safety of macitentan in patients with pulmonary hypertension: A meta-analysis of randomised controlled trials.

BACKGROUND: Macitentan has demonstrated its effectiveness in patients with pulmonary hypertension (PH), but its safety, especially for long-term use, needs to be further explored. This systematic review and meta-analysis aimed to determine the safety of long-term use of macitentan in patients with PH. METHODS: A systematic search was made of PubMed, Embase, Cochrane Library and clinicaltrials.gov, without language restrictions. Randomised controlled trials (RCTs) on treatment of PH with macitentan, compared with placebo, were reviewed. Estimated effects of included studies were pooled as risk ratios (RRs), with 95% confidence intervals (CIs). RESULTS: Six RCTs (enrolling 1003 participants) met the inclusion criteria. Anaemia (RR 3.86, 95% CI 2.05-7.30), headache (RR 1.52, 95% CI 1.02-2.26) and bronchitis (RR 2.24, 95% CI 1.30-3.87) were more frequent in the macitentan groups. There was no statistically significant difference in the proportion of patients with at least one adverse event (AE) or serious adverse event (SAE), AEs leading to discontinuation of study treatment, all-cause death, right ventricular failure (RVF) and peripheral oedema between the two groups. CONCLUSIONS: The long-term use of macitentan is safe for patients with PH, although with a higher risk of anaemia, headache and bronchitis.

Selexipag in Patients With Pulmonary Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Despite the availability of treatments for all subgroups of pulmonary hypertension (PH), the prognosis for PH remains poor. This systematic review and meta-analysis aimed to determine the efficacy and safety of selexipag in patients with PH. A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of PH with selexipag, compared with placebo or blank, were reviewed. Studies were pooled to weighted mean differences (WMDs) and risk ratios (RRs), with 95% confidence intervals (CIs). Selexipag was safe and significantly improved hospitalization for worsening of PH, WHO FC, mPAP, NT-proBNP, and cardiac index in patients with PH. Selexipag should be considered in patients with pulmonary arterial hypertension or chronic thromboembolic PH.

Benefits of plasma exchange on mortality in patients with COVID-19: a systematic review and meta-analysis.

OBJECTIVE: The COVID-19 pandemic continues, and the death toll continues to surge. This systematic review and meta-analysis aimed to determine the efficacy of therapeutic plasma exchange (TPE) on mortality in patients with COVID-19. METHODS: A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Controlled clinical trials on treatment of COVID-19 with TPE, compared with standard of care, were reviewed. Studies were pooled according to risk ratios (RRs) and weighted mean differences, with 95% confidence intervals (CIs). RESULTS: A total of six trials (enrolling 343 participants) met the inclusion criteria. Therapeutic plasma exchange showed significant effect on mortality (RR 0.41, 95% CI 0.24 to 0.69; P = 0.0008). CONCLUSION: TPE significantly reduced mortality in hospitalized patients with moderate-to-critical COVID-19. Plasma exchange therapy should be considered for patients with COVID-19.

Benefits of LAMA in patients with asthma-COPD overlap: A systematic review and meta-analysis.

PURPOSE: A systematic review and meta-analysis to determine the efficacy of long-acting muscarinic antagonist (LAMA) in patients with asthma-COPD overlap (ACO) was conducted. METHODS: A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of ACO with LAMA, compared with placebo or blank, were reviewed. RESULTS: Six RCTs (enrolling 1151 participants) met the inclusion criteria. LAMA showed significant effects on forced expiratory volume in 1 s (FEV1) (WMD 98.31 mL, 95% CI 94.32 to 102.30 mL), forced vital capacity (FVC) (WMD 128.00 mL, 95% CI 121.89 to 134.12 mL), peak expiratory flow (PEF) (WMD 20.60 L/min, 95% CI 19.90 to 21.29 L/min), and rescue medicine use (WMD -0.67 puffs/day, 95% CI -1.11 to -0.23 puffs/day). CONCLUSIONS: The addition of LAMA significantly improved lung function and rescue medicine use in patients with asthma-COPD overlap.