Value of Dynamic Computed Tomography Myocardial Perfusion in CAD: A Systematic Review and Meta-analysis.

AIMS: Dynamic stress computed tomography (CT) perfusion is a non-invasive method for quantifying myocardial ischemia by assessing myocardial blood flow (MBF). In this meta-analysis, we evaluated the diagnostic accuracy of dynamic CT perfusion for the detection of significant coronary artery disease (CAD) across various CT scanners, obese patients, and its prognostic value. METHODS AND RESULTS: We systematically searched PubMed, Embase, Web of Science, and Cochrane library for published studies evaluating the accuracy of CT myocardial perfusion in diagnosing functional significant ischemia by invasive fractional flow reserve. The diagnostic performance of dynamic CT perfusion in detecting ischemia was evaluated using a summary receiver operating characteristic (sROC) curve. A total of 23 studies underwent meta- analysis. In myocardial region without ischemia, MBF was measured at 1.44 ml/min/g (95% confidence interval [CI]: 1.13-1.75), while in region with ischemia, it was 0.94 ml/min/g (95% CI: 0.80-1.08) (p<0.001). On the patient-based analysis, the area under the sROC curve of CT-MBF was 0.93, with a sensitivity of 0.84 and specificity of 0.88. Differences in CT type (dual source vs. single source), and body mass index (BMI) did not significantly affect the diagnostic performance. The pooled hazard ratio of dynamic CT perfusion for predicting adverse events was 4.98 (95%CI: 2.08-11.93, p=<0.001, I2=61%, p for heterogeneity = 0.07). CONCLUSIONS: Dynamic CT perfusion has high diagnostic performance in the quantitative assessment of ischemia and detection of functional myocardial ischemia as defined by invasive FFR, and may be useful in risk stratification of CAD patients.

Improved diagnostic accuracy with three lung tumor markers compared to six-marker panel.

Background: Combining multiple tumor markers increases sensitivity for lung cancer diagnosis in the cost of false positive. However, some would like to check as many as tumor markers in the fear of missing cancer. We though to propose a panel of fewer tumor markers for lung cancer diagnosis. Methods: Patients with suspected lung cancer who simultaneously underwent all six tests [carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA), squamous cell carcinoma-associated antigen (SCC), neuron-specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP), and sialyl Lewis-X antigen (SLX)] were included. Tumor markers with significant impact on the lung cancer in a logistic regression model were included in our panel. Area under the curve (AUC) was compared between our panel and the panel of all six. Results: We included 1,733 [median 72 years, 1,128 men, 605 women, 779 (45%) confirmed lung cancer]. Logistic regression analysis suggested CEA, CYFRA, and NSE were independently associated with the lung cancer diagnosis. The panel of these three tumor markers [AUC =0.656, 95% confidence interval (CI): 0.630-0.682, sensitivity 0.650, specificity 0.662] had better (P<0.001) diagnostic performance than six tumor markers (AUC =0.575, 95% CI: 0.548-0.602, sensitivity 0.829, specificity 0.321). Conclusions: Compared to applying all six markers (at least one marker above the upper limit of normal), the panel with three markers (at least one marker above the upper limit of normal) led to a better predictive value by lowering the risk of false positives.

Immune checkpoint inhibitors for metastatic uveal melanoma: a meta-analysis.

Several studies have evaluated immune checkpoint inhibitors (ICIs) for metastatic uveal melanoma; however, the efficacy of ICIs in the previous studies varied greatly. In this systematic review, we searched for prospective or retrospective studies on single or dual-ICIs for metastatic uveal melanoma treatment. A random-effect model meta-analysis with generic inverse-variance was conducted, and 36 articles representing 41 cohorts of 1414 patients with metastatic uveal melanoma were included. The pooled outcomes were as follows: objective response rate (ORR) was 5.6% (95% confidence interval [95%CI] 3.7-7.5%; I2, 36%), disease control rate (DCR) was 32.5% (95% CI 27.2-37.7%; I2, 73%), median progression-free survival was 2.8 months (95% CI 2.7-2.9 months; I2, 26%), and median overall survival (OS) was 11.2 months (95% CI 9.6-13.2 months; I2, 74%). Compared to single-agent ICI, dual ICI led to better ORR (single-agent: 3.4% [95% CI 1.8-5.1]; dual-agent: 12.4% [95% CI 8.0-16.9]; P < 0.001), DCR (single-agent: 29.3%, [95% CI 23.4-35.2]; dual-agent: 44.3% [95% CI 31.7-56.8]; P = 0.03), and OS (single-agent: 9.8 months [95% CI 8.0-12.2]; dual-agent: 16.3 months [95% CI 13.5-19.7]; P < 0.001). Our analysis provided treatment outcomes as described above. Dual-ICIs appear better than single-agent ICIs for the treatment of metastatic uveal melanoma.

Real-world evidence of efficacy of pembrolizumab plus chemotherapy and nivolumab plus ipilimumab plus chemotherapy as initial treatment for advanced non-small cell lung cancer.

BACKGROUND: For advanced non-small cell lung cancer (NSCLC), combination therapies including a PD-1 inhibitor plus chemotherapy or a PD-1 inhibitor, CTLA-4 inhibitor, and chemotherapy are standard first-line options. However, data directly comparing these regimens are lacking. This study compared the efficacy of pembrolizumab plus chemotherapy (CP) against nivolumab plus ipilimumab and chemotherapy (CNI) in a real-world setting. METHODS: In this multicenter retrospective study, we compared the efficacy and safety of CP and CNI as first-line therapies in 182 patients with stage IIIB-IV NSCLC. Primary outcomes were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included the response rate (RR) and safety profiles. Kaplan-Meier survival curves and Cox proportional hazards models were utilized for data analysis, adjusting for confounding factors such as age, gender, and PD-L1 expression. RESULTS: In this study, 160 patients received CP, while 22 received CNI. The CP group was associated with significantly better PFS than the CNI group (median 11.7 vs. 6.6 months, HR 0.56, p = 0.03). This PFS advantage persisted after propensity score matching to adjust for imbalances. No significant OS differences were observed. Grade 3-4 adverse events occurred comparably, but immune-related adverse events were numerically more frequent in the CNI group. CONCLUSIONS: In real-world practice, CP demonstrated superior PFS compared with CNI. These findings can inform treatment selection in advanced NSCLC.

ILD-GAP combined with the monocyte ratio could be a better prognostic prediction model than ILD-GAP in patients with interstitial lung diseases.

BACKGROUND: The ILD-GAP scoring system is known to be useful in predicting prognosis in patients with interstitial lung disease (ILD). An elevated monocyte count was associated with increased risks of IPF poor prognosis. We examined whether the ILD-GAP scoring system combined with the monocyte ratio (ILD-GAPM) is superior to the conventional ILD-GAP model in predicting ILD prognosis. METHODS: In patients with ILD treated between April 2013 and April 2017, we were retrospectively assessed the relationships between baseline clinical parameters, including age, sex, Charlson Comorbidity Index score (CCIS), ILD diagnosis, blood biomarkers, pulmonary function test results, and disease outcomes. In ILD patients were included idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia (iNSIP), collagen vascular disease-related interstitial pneumonia (CVD-IP), chronic hypersensitivity pneumonitis (CHP), and unclassifiable ILD (UC-ILD). We also assessed the ability to predict prognosis was compared between the ILD-GAP and ILD-GAPM models. RESULTS: A total of 179 patients (mean age, 73 years) were assessed. All of them were taken pulmonary function test, including percentage predicted diffusion capacity for carbon monoxide. ILD patients included 56 IPF cases, 112 iNSIP and CVD-IP cases, 6 CHP cases and 5 UC-ILD cases. ILD-GAPM provided a greater area under the receiver-operating characteristic curve (0.747) than ILD-GAP (0.710) for predicting 3-year ILD-related events. Furthermore, the log-rank test showed that the Kaplan-Meier curves in ILD-GAPM were significantly different by stage (P = 0.015), but not by stage in ILD-GAP (P = 0.074). CONCLUSIONS: The ILD-GAPM model may be a more accurate predictor of prognosis for ILD patients than the ILD-GAP model.

Efficacy and safety of macrolide therapy for adult asthma: A systematic review and meta-analysis.

BACKGROUND: The evidence for macrolide therapy in adult asthma is not properly established and remains controversial. We conducted a systematic review and meta-analysis to examine the efficacy and safety of macrolide therapy for adult asthma. METHODS: We searched randomized controlled trials from MEDLINE via the PubMed, CENTRAL, and Ichushi Web databases. The primary outcome was asthma exacerbation. The secondary outcomes were serious adverse events (including mortality), asthma-related quality of life (symptom scales, Asthma Control Questionnaire, and Asthma Quality of Life Questionnaire), rescue medication (puffs/day), respiratory function (morning peak expiratory flow, evening peak flow, and forced expiratory volume in 1 s), bronchial hyperresponsiveness, and minimum oral corticosteroid dose. Of the 805 studies, we selected seven studies for the meta-analysis, which was conducted using a random-effects model. SYSTEMATIC REVIEW REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN000050824). RESULTS: No significant difference between macrolide and placebo for asthma exacerbations was observed (risk ratio 0.71, 95 % confidence interval [CI] 0.46-1.09; p = 0.12). Macrolide therapy for adult asthma showed a significant improvement in rescue medication with short-acting beta-agonists (mean difference -0.41, 95 % CI -0.78 to -0.04; p = 0.03). Macrolide therapy did not show more serious adverse events (odd ratio 0.61, 95 % CI 0.34-1.10; p = 0.10) than those with placebo. The other secondary outcomes were not significantly different between the macrolide and placebo groups. CONCLUSIONS: Macrolide therapy for adult asthma may be more effective than placebo and could be a treatment option.

Pregnancy outcomes in patients with familial Mediterranean fever: systematic review and meta-analysis.

OBJECTIVE: The relationship between FMF and pregnancy outcomes remains unclear. This systematic review and meta-analysis aimed to clarify this association. METHODS: Electronic databases-PubMed, Web of Science, Cochrane, and EMBASE-were searched on 20 December 2022, using specific search terms. Case-control, cohort, and randomized clinical trial studies comparing patients with FMF and healthy controls were considered eligible. We excluded systematic reviews, meta-analyses, case series with fewer than five cases, republished articles without new findings on pregnancy outcomes, studies targeting paternal FMF, and those not published in English. The results were summarized in the form of odds ratios (ORs) and 95% CIs, using a random-effects model. This study was registered in the University hospital Medical Information Network Clinical Trials Registry (Japan) as UMIN000049827. RESULTS: The initial electronic search identified 611 records, of which 9 were included in this meta-analysis (177 735 pregnancies, 1242 with FMF, and 176 493 healthy controls). FMF was significantly associated with increased odds of preterm deliveries (OR, 1.67; 95% CI, 1.05-2.67; I2 = 22%) and insignificantly associated with increased odds of fetal growth restriction (OR, 1.45; 95% CI, 0.90-2.34; I2 = 0%) and hypertensive disorders during pregnancy (OR, 1.28; 95% CI, 0.87-1.87; I2 = 0%). CONCLUSION: FMF was significantly associated with preterm delivery and insignificantly associated with fetal growth restriction and hypertensive disorders. All of the included studies were observational studies. Treatment characteristics were not fully collected from the articles, and further analysis of treatments for FMF in pregnancy is still warranted.

Treatment-related adverse events, including fatal toxicities, in patients with solid tumours receiving neoadjuvant and adjuvant immune checkpoint blockade: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Incorporating immune checkpoint blockade into perioperative cancer therapy has improved clinical outcomes. However, the safety of immune checkpoint blockade needs better evaluation, given the chances of more prolonged disease-free survival. We aimed to assess how adding immune checkpoint blockade to perioperative therapy affects treatment-related adverse events. METHODS: For this systematic review and meta-analysis, we searched PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library from database inception until Aug 8, 2023, for randomised controlled trials that assessed the addition of immune checkpoint blockade to neoadjuvant or adjuvant therapy for cancer, reported treatment-related deaths, and had a design in which the experimental group assessed immune checkpoint blockade in combination with the therapy used in the control group. Meta-analysis was done to pool odds ratios (ORs) of treatment-related deaths, any grade and grade 3-4 treatment-related adverse events, serious adverse events, and adverse events leading to treatment discontinuation. The protocol is registered with PROSPERO, CRD42022343741. FINDINGS: 28 randomised controlled trials with 16 976 patients were included. The addition of immune checkpoint blockade was not significantly associated with increased treatment-related deaths (OR 1·76, 95% CI 0·95-3·25; p=0·073), consistent across immune checkpoint blockade subtype (I2=0%). 40 fatal toxicities were identified across 9864 patients treated with immune checkpoint blockade, with pneumonitis being the most common (six [15·0%]); 13 fatal toxicities occurred among 7112 patients who were not treated with immune checkpoint blockade. The addition of immune checkpoint blockade increased the incidence of grade 3-4 treatment-related adverse events (OR 2·73, 95% CI 1·98-3·76; p<0·0001), adverse events leading to treatment discontinuation (3·67, 2·45-5·51; p<0·0001), and treatment-related adverse events of any grade (2·60 [1·88-3·61], p<0·0001). The immune checkpoint blockade versus placebo design primarily used as adjuvant therapy was associated with increased incidence of treatment-related deaths (4·02, 1·04-15·63; p=0·044) and grade 3-4 adverse events (5·31, 3·08-9·15; p<0·0001), whereas the addition of immune checkpoint blockade in the neoadjuvant setting was not associated with increased incidence of treatment-related death (1·11, 95% CI 0·38-3·29; p=0·84) or grade 3-4 adverse events (1·17, 0·90-1·51; p=0·23). INTERPRETATION: The addition of immune checkpoint blockade to perioperative therapy was associated with an increase in grade 3-4 treatment-related adverse events and adverse events leading to treatment discontinuation. These findings provide safety insights for further clinical trials assessing neoadjuvant or adjuvant immune checkpoint blockade therapy. Clinicians should closely monitor patients for treatment-related adverse events to prevent treatment discontinuations and morbidity from these therapies in earlier-stage settings. FUNDING: None.

Right ventricular myocardial fibrosis evaluated by extracellular volume fraction by magnetic resonance imaging in patients with repaired tetralogy of Fallot: a meta-analysis.

OBJECTIVE: The objective of this meta-analysis was to assess the clinical utility of anomalous discoveries on cardiac magnetic resonance, particularly the right ventricular extracellular volume (RV-ECV), among individuals who underwent surgical repair for Tetralogy of Fallot (rTOF). METHODS: We conducted a systematic search of electronic databases including PubMed, Web of Science Core Collection, Cochrane advanced search, and EMBASE. Our analysis involved a comparison of ECV levels between rTOF patients and controls, as well as an evaluation of the predictive value of ECV for future adverse events. RESULTS: We identified 16 eligible studies that encompassed 856 rTOF patients and 283 controls. Our meta-analysis showed a significant increase in LV-ECV among rTOF patients compared to control subjects (MD = 2.63, 95%CI: 1.35 to 3.90, p < 0.0001, I2 = 86%, p for heterogeneity < 0.00001). Moreover, RV-ECV was found to be substantially higher in patients compared to LV-ECV. Our meta-analysis also revealed a significant association between RV-ECV and adverse events (HR = 1.15, 95% CI: 1.04 to 1.27, p = 0.005, I2 = 0%, p for heterogeneity = 0.62), while LV-ECV did not show any significant association with adverse events (HR = 1.12, 95% CI: 0.92 to 1.36, p = 0.16, I2 = 0%, p for heterogeneity = 0.46). CONCLUSION: The results of this meta-analysis on RV-ECV confirmed the presence of RV fibrosis as one of the prognostic factors in rTOF patients.

Serum heme oxygenase-1 as a prognostic biomarker in patients with acute exacerbation of interstitial lung disease.

Serum heme oxygenase (HO)-1 level has been reported as a clinically reliable diagnostic biomarker for acute exacerbation of interstitial lung disease (ILD); however, its utility for predicting mortality among these patients is unclear. Serum HO-1 levels of patients newly diagnosed with acute exacerbation of ILD were measured at the time of initiating steroid pulse therapy. The relationship between serum HO-1 and various other serum biomarkers, change in HRCT findings, and disease prognosis at 12 weeks after diagnosis of acute exacerbation was evaluated in 51 patients, of whom 17 (33%) had idiopathic pulmonary fibrosis (IPF). Serum HO-1 was higher in patients with acute exacerbation of IPF than in patients with acute exacerbation of other ILDs. Serum HO-1 levels were higher in patients who died within these 12 weeks than in survivors. Among age, sex, comorbidities, IPF diagnosis, HRCT findings, and blood biomarkers, serum HO-1 was a primary predictor of 12-week mortality. In 41 patients who underwent repeat HRCT, serum HO-1 was higher in patients with honeycomb progression than in those without. Serum HO-1 measurement could be useful for evaluating disease mortality and morbidity of patients with acute exacerbation of ILDs.

Whole-genome sequencing predicting phenotypic antitubercular drug resistance: meta-analysis.

BACKGROUND: For simultaneous prediction of phenotypic drug susceptibility test (pDST) for multiple anti-tuberculosis drugs, the whole genome sequencing (WGS) data can be analyzed using either catalogue-based approach, wherein one causative mutation suggests resistance, (e.g., WHO catalog) or non-catalogue-based approach using complicated algorithm (e.g., TB-profiler, machine learning). The aim was to estimate the predictive ability of WGS-based tests with pDST as the reference, and to compare the two approaches. METHODS: Following the systematic literature search, the diagnostic test accuracies for 14 drugs were pooled using a random-effect bivariate model. RESULTS: Out of 779 articles, 44 articles with 16,821 specimens for meta-analysis and 13 articles not for meta-analysis were adopted. The areas under summary receiver operating characteristic curve suggested "excellent" (0.97-1.00) for 2 drugs (isoniazid 0.975, rifampicin 0.975), "very good" (0.93-0.97) for 8 drugs (pyrazinamide 0.946, streptomycin 0.952, amikacin 0.968, kanamycin 0.963, capreomycin 0.965, para-aminosalicylic acid 0.959, levofloxacin 0.960, ofloxacin 0.958), and "good" (0.75-0.93) for 4 drugs (ethambutol 0.926, moxifloxacin 0.896, ethionamide 0.878, prothionamide 0.908). The non-catalogue-based and catalogue-based approaches had similar ability for all drugs. CONCLUSION: WGS accurately identifies isoniazid and rifampicin resistance. For most drugs, positive WGS results reliably predict pDST positive. The two approaches had similar ability.

The Complex Interaction between Proton Pump Inhibitors and Cancer Treatment.

We have read the article authored by Rizzo et al [...].

Cardiotoxicity Associated with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) have shown significant efficacy in various cancers, including non-small cell lung cancer, small cell lung cancer, melanoma, classical Hodgkin lymphoma, head and neck squamous cell carcinoma, urothelial cancer, and renal cell carcinoma [...].

The Effectiveness and Safety of Long-Term Macrolide Therapy for COPD in Stable Status: A Systematic Review and Meta-Analysis.

Background: Chronic obstructive pulmonary disease (COPD) is a prevalent condition with fewer treatments available as the severity increases. Previous systematic reviews have demonstrated the benefits of long-term macrolide use. However, the therapeutic differences between different macrolides and the optimal duration of use remain unclear. Methods: A systematic review and meta-analysis were conducted to assess the effectiveness of long-term macrolide use in reducing COPD exacerbations, compare the therapeutic differences among macrolides, and determine the appropriate treatment duration. Four databases (PubMed, Cochrane Library, Web of Science, and ICHU-SHI) were searched until 20 March 2023, and a random-effects model was used to calculate the pooled effect. Results: The meta-analysis included nine randomized controlled trials involving 1965 patients. The analysis revealed an odds ratio (OR) of 0.34 (95% confidence interval [CI] 0.19, 0.59, p < 0.001) for the reduction in exacerbation frequency. Notably, only azithromycin or erythromycin showed suppression of COPD exacerbations. The ORs for reducing exacerbation frequency per year and preventing hospitalizations were -0.50 (95% CI: -0.81, -0.19; p = 0.001) and 0.60 (95% CI: 0.3, 0.97; p = 0.04), respectively. Statistical analyses showed no significant differences between three- and six-month macrolide prescriptions. However, studies involving a twelve-month prescription showed an OR of 0.27 (95% CI: 0.11, 0.68; p = 0.005; I2 = 81%). Although a significant improvement in St George's Respiratory Questionnaire (SGRQ) total scores was observed with a mean difference of -4.42 (95% CI: -9.0, 0.16; p = 0.06; I2 = 94%), the minimal clinically important difference was not reached. While no adverse effects were observed between the two groups, several studies have reported an increase in bacterial resistance. Conclusions: Long-term use of azithromycin or erythromycin suppresses COPD exacerbations, and previous studies have supported the advantages of a 12-month macrolide prescription over a placebo.

Clinical Utility of Computed Tomography-Derived Myocardial Extracellular Volume Fraction: A Systematic Review and Meta-Analysis.

BACKGROUND: Computed tomography (CT)-derived extracellular volume fraction (ECV) is a noninvasive method to quantify myocardial fibrosis. Although studies suggest CT is a suitable measure of ECV, clinical use remains limited. OBJECTIVES: A meta-analysis was performed to determine the clinical value of CT-derived ECV in cardiovascular diseases. METHODS: Electronic database searches of PubMed, Web of Science Core Collection, Cochrane advanced search, and EMBASE were performed. The most pivotal analysis entailed the comparison of ECV ascertained through CT-ECV among the control, aortic stenosis, and cardiac amyloidosis cohorts. The diagnostic test accuracy for detecting cardiac amyloidosis was assessed using summary receiver-operating characteristics curve. RESULTS: Pooled CT-derived ECV values were 28.5% (95% CI: 27.3%-29.7%) in the control, 31.9 (95% CI: 30.2%-33.8%) in the aortic stenosis, and 48.9% (95% CI: 44.5%-53.3%) in the cardiac amyloidosis group. ECV was significantly elevated in aortic stenosis (P = 0.002; vs controls) but further elevated in cardiac amyloidosis (P < 0.001; vs aortic stenosis). CT-derived ECV had a high diagnostic accuracy for cardiac amyloidosis, with sensitivity of 92.8% (95% CI: 86.7%-96.2%), specificity of 84.8% (95% CI: 68.6%-93.4%), and area under the summary receiver-operating characteristic curve of 0.94 (95% CI: 0.88-1.00). CONCLUSIONS: This study is the first comprehensive systematic review and meta-analysis of CT-derived ECV evaluation in cardiac disease. The high diagnostic accuracy of CT-ECV suggests the usefulness of CT-ECV in the diagnosis of cardiac amyloidosis in preoperative CT planning for transcatheter aortic valve replacement.