Immune checkpoint inhibitor-related adverse cardiac events in patients with lung cancer: a systematic review and meta-analysis.

BACKGROUND: Although people are more and more aware of the cardiotoxicity caused by immune checkpoint inhibitors (ICIs) in the treatment of lung cancer, its incidence rate has not been systematically analyzed. This study aims to evaluate the incidence of cardiotoxicity related to the ICI therapies for lung cancer, so as to enhance clinicians' attention to cardiotoxicity, implement proper prevention and intervention for high-risk patients, and minimize the risk of cardiac dysfunction during and after completion of therapy. METHODS: We conducted a systematic literature search for relevant publications in PubMed and Scopus from inception to 19 April 2022. Pooled incidence and risk ratios with 95% confidence intervals (95% CIs) for cardiotoxicity events were calculated. RESULTS: A total of 37 studies covering 38 trials, including 14,342 patients, were identified. The pooled risk ratios of incidence of any cardiac AEs were 1.944 [95% CI 0.8-4.725] (Single ICI versus chemotherapy), 1.677 [95% CI 1.065-2.64] (Single ICI plus chemotherapy versus chemotherapy), and 0.478 [95% CI 0.127-1.798] (Single ICI versus Dual ICI). The incidence of myocarditis and arrhythmia were 0.003[95%CI 0.002-0.006] and 0.014[95%CI 0-0.037], respectively. CONCLUSION: Single ICI did not increase the risk of cardiotoxicity compared with chemotherapy, and single ICI plus chemotherapy increased the risk of cardiotoxicity by 67% compared with chemotherapy alone. Combination immunotherapy did not increase the risk of cardiotoxicity compared with single ICI.

Adverse Effects Associated With Currently Commonly Used Antifungal Agents: A Network Meta-Analysis and Systematic Review.

Background: Invasive fungal infections (IFI) is an important contributing factor in morbidity and mortality of immunocompromised and critically ill patients. Although the therapeutic effects of these drugs on IFI have been well documented, the long-term use of antifungal agents has raised concerns about drug tolerability and treatment-related toxicity risks. Methods: We searched articles published before June 30, 2020 in four electronic databases: Web of Science, Cochrane Library, embase and PubMed. Results: 66 trials were determined to meet our inclusion criteria, providing data on 18,230 participants. We sorted out 23 AEs by system organ classes and six laboratory AEs, 13 of these were used to construct 13 network meta-analyses. Compared with LAmB, anidulafungin, caspofungin, micafungin, fluconazole, and posaconazole had a significantly low incidence of discontinuation of therapy due to AEs (OR = 0.24 (0.09,0.65), 0.24 (0.13,0.43), 0.32 (0.19,0.52), 0.38 (0.23,0.62) and 0.35 (0.17,0.69), respectively). Conclusion: We found that echinocandins are the most tolerated antifungal agents with high safety. The AEs of triazole drugs are mainly concentrated on the increase in liver enzymes, nervous system disorders, especially visual disorders, gastrointestinal disorders, and cardiac diseases. LAmB is the least tolerated and has the most abundant AEs.

Blood eosinophil count-guided corticosteroid therapy and as a prognostic biomarker of exacerbations of chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and dyspnea, as well as an increase in the number of leukocytes in the airways, lungs, and pulmonary vessels. A 'One size fits all' approach to COPD patients with different clinical features may be considered outdated. The following are the two major objectives of this meta-analysis: the first is to determine if blood eosinophil counts (BEC) can serve as a prognostic biomarker of COPD outcomes, and the second is to determine which level of BEC is effective for inhaled corticosteroid (ICS) treatment. METHODS: We searched articles published before 15 May 2021 in the following four electronic databases: Web of Science, Cochrane Library, EMBASE, and PubMed. RESULTS: A total of 42 studies, comprising a sampling of 188,710 subjects, were summarized and compared in this meta-analysis. The rate ratio (RR) of exacerbations of COPD (ECOPD) between ICS and non-ICS treatment was statistically significant for the COPD patients with a baseline BEC ⩾ 2% or ⩾ 200 cells/µl, RR = 0.82 (0.73, 0.93) or 0.79 (0.70, 0.89) respectively, while the RR of ECOPD between ICS and non-ICS treatment was statistically insignificant for the COPD patients with baseline BEC < 2% or <200 cells/µl, RR = 0.97 (0.87, 1.08) or 0.97 (0.86, 1.08), suggested that ICS therapy was beneficial to the improvement of ECOPD in patients with a baseline BEC ⩾ 2% or BEC ⩾ 200 cells/µl. CONCLUSION: Our research shows that a BEC ⩾ 200 cells/µl or ⩾2% is likely to become the cutoff value of ICS treatment for ECOPD. Moreover, we believe that the baseline BEC can be used as a biomarker for predicting ECOPD. The stability of BEC requires special attention.

Association of ß-blocker use with survival and pulmonary function in patients with chronic obstructive pulmonary and cardiovascular disease: a systematic review and meta-analysis.

AIMS: The aim of this study was to clarify the effect of ß-blockers (BBs) on respiratory function and survival in patients with chronic obstructive pulmonary disease with cardiovascular disease (CVD), as well as the difference between the effects of cardioselective and noncardioselective BBs. METHODS AND RESULTS: We searched for relevant literature in four electronic databases, namely, PubMed, EMBASE, Cochrane Library, and Web of Science, and compared the differences in various survival indicators between patients with chronic obstructive pulmonary disease taking BBs and those not taking BBs. Forty-nine studies were included, with a total sample size of 670 594. Among these, 12 studies were randomized controlled trials (RCTs; seven crossover and five parallel RCTs) and 37 studies were observational (including four post hoc analyses of data from RCTs). The hazard ratios (HRs) of chronic obstructive pulmonary disease exacerbation between patients with chronic obstructive pulmonary disease who were not treated with BBs and those who were treated with BBs, cardioselective BBs, and noncardioselective BBs were 0.77 [95% confidence interval (CI) 0.67, 0.89], 0.72 [95% CI 0.56, 0.94], and 0.98 [95% CI 0.71, 1.34, respectively] (HRs <1 indicate favouring BB therapy). The HRs of all-cause mortality between patients with chronic obstructive pulmonary disease who were not treated with BBs and those who were treated with BBs, cardioselective BBs, and noncardioselective BBs were 0.70 [95% CI 0.59, 0.83], 0.60 [95% CI 0.48, 0.76], and 0.74 [95% CI 0.60, 0.90], respectively (HRs <1 indicate favouring BB therapy). Patients with Chronic obstructive pulmonary disease treated with cardioselective BBs showed no difference in ventilation effect after the use of an agonist, in comparison with placebo. The difference in mean change in forced expiratory volume in 1 s was 0.06 [95% CI -0.02, 0.14]. CONCLUSION: The use of BBs in patients with chronic obstructive pulmonary disease is not only safe but also reduces their all-cause and in-hospital mortality. Cardioselective BBs may even reduce chronic obstructive pulmonary disease exacerbations. In addition, cardioselective BBs do not affect the action of bronchodilators. Importantly, BBs reduce the heart rate acceleration caused by bronchodilators. BBs should be prescribed freely when indicated in patients with chronic obstructive pulmonary disease and heart disease.

Effect of alectinib versus crizotinib on progression-free survival, central nervous system efficacy and adverse events in ALK-positive non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Lung cancer is the most common malignant tumor, and it remains the major cause of cancerrelated death worldwide. Anaplastic lymphoma kinase fusion gene-rearrangement (ALK-positive) nonsmall cell lung cancer (NSCLC) is a unique subgroup that accounts for 3-7% of NSCLC cases. Over the last few years, the introduction of several ALK inhibitors has completely altered the treatment of advanced ALK-positive NSCLC and significantly improved the prognosis for patients. Crizotinib was the first ALK inhibitor developed, and it has demonstrated systemic efficacy and strongly improved outcomes in NSCLC patients with ALK-positive when compared with chemotherapy. Alectinib was designed specifically to be a more potent and selective anti-ALK therapeutic agent that could bypass crizotinib resistance. This study aims to evaluate the different efficacies of alectinib and crizotinib on progression-free survival (PFS), central nervous system (CNS) progression and adverse events (AEs) in NSCLC patients with ALK-positive. METHODS: We searched for relevant literature in four electronic databases: PubMed, EMBASE, Cochrane Library, and Web of Science. The hazard ratio (HR) was calculated, and the effect of alectinib and crizotinib on PFS was evaluated. The quality of the studies was assessed using the Cochrane Risk of Bias tool. Publication bias was assessed using the Begg rank correlation test and the Egger weighted linear regression test. We performed the sensitivity analysis using the method of "removing one study". All analyses were performed in STATA. RESULTS: Ten studies were included, and the total sample size was 2,377. Alectinib showed significant PFS superiority over crizotinib. The pooled HR =0.41 (95% CI: 0.29-0.53) indicated that the alectinib therapy group did have significantly longer PFS than that of the crizotinib group. Based on 5 clinical trials, the cumulative incidence of CNS progression for patients treated with alectinib at 6 months (10%, 95% CI: 5-16%) and 12 months (16%, 95% CI: 9-24%) was calculated. Based on 7 clinical studies, the risk of AEs related to treatment with alectinib was determined: alectinib was associated with 28 cases of AE grade ≤2 and 9 cases of AE grade ≥3; among the top 4 incidences of AE grade ≥3, were blood creatine phosphokinase increased 5.6%, ALT increased 2.5%, AST increased 2.4% and Anemia 1.8%. CONCLUSIONS: Alectinib significantly prolongs PFS and it better controls CNS metastases than crizotinib and good toxicity characteristics in the first-line treatment of NSCLC patients with ALK-positive.

The incidence and relative risk of adverse events in patients treated with bisphosphonate therapy for breast cancer: a systematic review and meta-analysis.

BACKGROUND: Adjuvant bisphosphonates reduce the rate of breast cancer recurrence in the bone and improve breast cancer survival. However, the risk of adverse events associated with bisphosphonate therapy for breast cancer remains poorly defined. METHODS: A literature search was conducted using the PubMed, EMBASE, Cochrane and Web of Science libraries. Risk ratio (RR) was calculated to evaluate the adverse events of the meta-analytic results. Osteonecrosis of the jaw (ONJ) incidence was calculated using the random effect model (D+L pooled) for meta-analysis. RESULTS: A total of 47 studies comprising 20,607 patients were included; 23 randomized controlled studies (RCTs) provided data of adverse events for bisphosphonate therapy versus without bisphosphonates. Bisphosphonates were significantly associated with influenza-like illness (RR = 4.52), fatigue (RR = 1.08), fever (RR = 1.82), dyspepsia (RR = 1.25), anorexia (RR = 1.29), and urinary tract infection (RR = 1.32). No differences were observed in other adverse events. We combined the incidence of ONJ in 24 retrospective studies to analyze the incidence of ONJ using bisphosphonates. The pooled probability of ONJ toxicity in the bisphosphonates group was 2%. CONCLUSIONS: Bisphosphonates were significantly associated with influenza-like illness, fatigue, fever, dyspepsia, anorexia, and urinary tract infection. Furthermore, bisphosphonates increase the risk of ONJ toxicity.