Progression-Free Survival as Early Efficacy Endpoint in Resectable Esophageal Cancer Treated With Neoadjuvant Therapy: A Systematic Review

To investigate literature-based evidence regarding progression-free survival (PFS) as an early efficacy endpoint in patients with resectable esophageal or gastroesophageal junction (GEJ) cancer receiving neoadjuvant therapy, this study identified large-scale randomized controlled trials (RCTs) with strict quality control. Twenty-four RCTs involving 7,514 patients were included. Trial-level correlation analysis was conducted to analyze the relationship between PFS hazard ratio (HR) and overall survival (OS) HR, Δ median PFS and Δ median OS. Correlation analysis at the neoadjuvant treatment arm level was performed between 1- to 5-year PFS and 5-year OS, median PFS and median OS. Subgroup analysis was performed in patients treated with standard neoadjuvant chemoradiotherapy (NCRT). The correlation was evaluated using the Pearson correlation coefficient r in weighted linear regression, with weight equal to patient size. In trial-level correlation, PFS were strongly associated with OS HR (r, 0.82 [95% confidence interval (CI), 0.42-0.97]) and Δ median survival (r, 0.83 [95% CI, 0.54-0.96]). In neoadjuvant treatment arms, there was a strong correlation between 1 to 5-year PFS rates and 5-year OS (r, 0.83-0.95), and median PFS and median OS (r, 0.97 [95% CI, 0.85-0.99]). NCRT subgroup analysis demonstrated acceptable consistency. In conclusion, we recommend PFS as an early efficacy endpoint in resected esophageal or GEJ cancer treated with neoadjuvant therapy.

The Value of Platelet-to-Lymphocyte Ratio as a Prognostic Marker in Cholangiocarcinoma: A Systematic Review and Meta-Analysis

The platelet-to-lymphocyte ratio (PLR), an inflammatory parameter, has shown prognostic value in several malignancies. The aim of this meta-analysis was to determine the impact of pretreatment PLR on the oncological outcome in patients with cholangiocarcinoma (CCA). A systematic literature search has been carried out in the PubMed and Google Scholar databases for pertinent papers published between January 2000 and August 2021. Within a random-effects model, the pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated to investigate the relationships among the PLR, overall survival (OS), and disease-free survival (DFS). Subgroup analysis, sensitivity analysis, and publication bias were also conducted to further evaluate the relationship. A total of 20 articles comprising 5429 patients were included in this meta-analysis. Overall, the pooled outcomes revealed that a high PLR before treatment is associated with impaired OS (HR = 1.14; 95% CI = 1.06–1.24; p < 0.01) and DFS (HR = 1.57; 95% CI = 1.19–2.07; p < 0.01). Subgroup analysis revealed that this association is not influenced by the treatment modality (surgical vs. non-surgical), PLR cut-off values, or sample size of the included studies. An elevated pretreatment PLR is prognostic for the OS and DFS of CCA patients. More high-quality studies are required to investigate the pathophysiological basis of the observation and the prognostic value of the PLR in clinical management as well as for patient selection.

Potential Association Between Changes in Microbiota Level and Lung Diseases: A Meta-Analysis

Objective:Lung microbiota is increasingly implicated in multiple types of respiratory diseases. However, no study has drawn a consistent conclusion regarding the relationship between changes in the microbial community and lung diseases. This study verifies the association between microbiota level and lung diseases by performing a meta-analysis.Methods:Literature databases, including PubMed, ISI Web of Science, Embase, Google Scholar, PMC, and CNKI, were used to collect related articles published before March 20, 2021. The standard mean deviation (SMD) and related 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup, sensitivity, and publication bias analyses were also conducted.Results:Six studies, comprising 695 patients with lung diseases and 176 healthy individuals, were included in this meta-analysis. The results indicated that the microbiota level was higher in patients with lung diseases than in healthy individuals (SMD = 0.39, 95% CI = 0.22–0.55, I2 = 91.5%, P &lt; 0.01). Subgroup analysis based on country demonstrated that the microbiota level was significantly higher in Chinese (SMD = 1.90, 95% CI = 0.87–2.93, I2 = 62.3%, P &lt; 0.01) and Korean (SMD = 0.24, 95% CI = 0.13–0.35, I2 = 78.7%, P &lt; 0.01) patients with lung diseases. The microbiota level of patients with idiopathic pulmonary fibrosis (IPF) (SMD = 1.40, 95% CI = 0.42–2.38, I2 = 97.3%, P = 0.005), chronic obstructive pulmonary disease (COPD) (SMD = 0.30, 95% CI = 0.09–0.50, I2 = 83.9%, P = 0.004), and asthma (SMD = 0.19, 95% CI = 0.06–0.32, I2 = 69.4%, P = 0.004) were significantly higher than those of the healthy group, whereas a lower microbiota level was found in patients with chronic hypersensitivity pneumonitis (CHP). The microbiota level significantly increased when the disease sample size was &gt;50. Subgroup analysis based on different microbiota genera, indicated that Acinetobacter baumannii and Pseudomonas aeruginosa were significantly increased in COPD and asthma diseases.Conclusion:We observed that patients with IPF, COPD, and asthma had a higher microbiota level, whereas patients with CHP had a lower microbiota level compared to the healthy individuals. The level of A. baumannii and P. aeruginosa were significantly higher in patients with COPD and asthma, and thus represented as potential microbiota markers in the diagnosis and treatment of lung diseases.

Subgroup analysis reveals higher reliability of the new comprehensive evaluation of Global Initiative for Chronic Obstructive Lung Disease 2019

To estimate the severity of the disease in outpatients with chronic obstructive pulmonary disease (COPD) in Hunan Province, China and use the subgroup analysis to evaluate the reliability of the new comprehensive evaluation of Global Initiative for Chronic Obstructive Lung Disease (GOLD). COPD outpatients from 12 medical centers in Hunan Province, China were stratified into groups A–D, and group D patients were further stratified into subgroups D1–D3 according to the GOLD 2016 and 2019 comprehensive assessment. Demography, clinical characteristics and medications were compared among groups. In 1017 COPD outpatients, the distribution from group A to D and subgroup D1 to D3 was 41 (4.0%), 249 (24.5%), 17 (1.7%), 710 (69.8%) and 214 (30.2%), 204 (28.7%), 292 (41.1%), according to GOLD 2016. In terms of demographic and clinical characteristics related to A–D groups, there was a significant difference in COPD assessment test (CAT), modified Medical British Research Council (mMRC), the clinical COPD questionnaire(CCQ), age, BMI, education level, smoking history, comorbidities, the course of chronic bronchitis/emphysema, number of exacerbations/hospitalisations in the previous year, treatment protocols, forced expiratory volume in one second (FEV1) % predicted, and FEV1/forced vital capacity (FVC) (p < 0.01). Furthermore, some patients in groups C–D regrouped to groups A–B were all C1 and D1 subgroups according to GOLD 2019. Comparing subgroup D1 with group B, subgroup D2 and subgroup D3, it was found that the demography, clinical characteristics and medications of subgroup D1 were the closest to group B, according to GOLD 2016 (p < 0.01). The disease severity of outpatients with COPD in Hunan Province was more pronounced in group B and D and patients in groups A–D had different demography, clinical characteristics and medications. Subgroup analysis can explain to a certain extent that GOLD2019’s new comprehensive assessment is more reliable than GOLD 2016.

Endoscopic Submucosal Dissection for Early Gastric Cancer in Elderly vs. Non-Elderly Patients: A Systematic Review and Meta-Analysis

ObjectiveThis study aimed to review the applicability and complications rate associated with endoscopic submucosal dissection (ESD) for early gastric cancer in elderly patients.MethodsDatabases of PubMed, Embase, CENTRAL, and ScienceDirect were searched till 15th April 2021. All types of studies comparing ESD in the elderly vs non-elderly were included. Subgroup analysis was conducted for the following groups: ≥80 years vs &lt;80 years, ≥75 years vs &lt; 75 years, and ≥65 years vs &lt;65 years.Results17 studies were included. Meta-analysis indicated no statistically significant difference in the en-bloc resection rates (OR: 0.92 95% CI: 0.68, 1.26 I2 = 8% p=0.62) and histological complete resection rates (OR: 0.93 95% CI: 0.75, 1.15 I2 = 26% p=0.50) between elderly and non-elderly patients. The results were non-significant even on subgroup analysis. Overall, we found a non-significant but a tendency of increased perforation rates in the elderly as compared to non-elderly patients (OR: 1.22 95% CI: 0.99, 1.52 I2 = 0% p=0.06). However, there was a significantly increased risk of perforation in elderly patients aged ≥80 years as compared to patients &lt;80 years (OR: 1.50 95% CI: 1.00, 2.24 I2 = 3% p=0.05). Bleeding rates were not different in the two groups (OR: 1.07 95% CI: 0.87, 1.32 I2 = 19% p=0.52). Pooled analysis indicated a statistically significantly increased risk of pneumonia in elderly patients (OR: 2.52 95% CI: 1.72, 3.70 I2 = 7% p&lt;0.00001). Length of hospital stay was reported only by five studies. Meta-analysis indicated no significant difference between the two study groups (MD: 0.67 95% CI: -0.14, 1.48 I2 = 83% p=0.10).ConclusionEn-bloc and histological complete resection rates do not differ between elderly and non-elderly patients undergoing ESD for early gastric cancer. Elderly patients have a small tendency of increased risk of perforation with significantly increased rates in the super-elderly (≥80 years of age). The risk of pneumonia is significantly higher in elderly patients but the rates of bleeding do not differ. The certainty of evidence is “very low” and there is a need for high-quality studies taking into account confounding factors to enhance the quality of evidence.

Correlation Between Proprioceptive Impairment and Motor Deficits After Stroke: A Meta-Analysis Review

Introduction: Proprioceptive impairment is a common symptom after stroke. Clarifying how proprioception correlates with motor function after stroke may be helpful in optimizing proprioception-augmented movement training. Previous studies have shown inconsistent findings. A meta-analysis is an optimal method to explore the correlation and identify the factors contributing to these inconsistencies.Objective: To explore the correlation between proprioception and motor function after stroke through a meta-analysis, taking into account characteristics of the measurements used in these studies.Methods: We searched multiple databases until November 2021 for eligible studies that measured both proprioception and motor functions in persons with stroke and reported their correlation or data for correlation analysis. A meta-analysis of the correlations was performed. The subgroup analysis and meta-regression were further conducted to investigate potential factors contributing to the heterogeneity of correlation strength, based on the participants' characteristics, proprioception, and motor function measures.Results: In total, 28 studies comprising of 1,829 participants with stroke were included in the meta-analysis. The overall correlation between proprioception and motor function was significant (r = 0.267, p &lt; 0.05), but there was heterogeneity across studies (I2 = 45%, p &lt; 0.05). The results of the subgroup analysis showed proprioception of the axial segment in weight-bearing conditions (r = 0.443, p &lt; 0.05) and upper limb without weight-bearing (r = 0.292, p &lt; 0.05) had a stronger correlation with motor function than proprioception of the lower limb without weight-bearing. The proprioception measured through ipsilateral matching (r = 0.412, p &lt; 0.05) showed a stronger correlation with motor function than through contralateral matching. The International Classification of Functioning, Disability, and Health (ICF) domains of motor function, movement function (r = 0.338, p &lt; 0.05), activity performance (r = 0.239, p &lt; 0.05), and independence (r = 0.319, p &lt; 0.05) showed a stronger correlation with proprioception than with other domains.Conclusion: There is a significant correlation between proprioception and motor dysfunction after stroke. The proprioception measured in the axial segment under weight-bearing conditions or measured with ipsilateral matching, and motor function, specifically in the ICF domains of movement function, activity performance, and independence showed a positive contribution to the association between proprioception and motor function. The correlation does not imply causation and might be underestimated by attributes of current tests for proprioception and motor function. Further studies are needed to clarify the cause-effect relationship.