Prognostic relevance of immune-related adverse events in lung cancer patients undergoing immune checkpoint inhibitor therapy: a systematic review and meta-analysis.

Background: Immune checkpoint inhibitors (ICIs) work by activating the immune system, a mechanism that may also cause immune-related adverse events (irAEs). This study seeks to investigate on how different irAEs impact prognosis of advanced lung cancer (LC) patients and identify useful approaches to manage irAEs. Methods: A thorough literature search of PubMed, Embase, the Cochrane Library and manual searches up to January 2024 were undertaken. Treatment outcomes including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were obtained. Meta-analysis was conducted using R software (version 4.3.1). Results: There were 106 studies with 41,050 advanced or recurrent LC patients included. The occurrence of irAEs was correlated with better PFS [hazard ratio (HR) =0.54; 95% confidence interval (CI): 0.49-0.59], OS (HR =0.57; 0.51-0.63), ORR [risk ratio (RR) =2.03; 95% CI: 1.81-2.28] and DCR (RR =1.55; 95% CI: 1.40-1.72) and remained significant after adjusting programmed death-ligand 1 (PD-L1) level. IrAEs affecting skin (OS: HR =0.45; 95% CI: 0.38-0.53) and endocrine system (OS: HR =0.51; 95% CI: 0.41-0.62), of mild severity (OS: HR =0.52; 95% CI: 0.35-0.79), arising in multiple sites (OS: HR =0.47; 95% CI: 0.38-0.59), induced by monotherapy (OS: HR =0.58; 95% CI: 0.52-0.65), with a delayed onset (cutoff: 3 months; OS: HR =0.37; 95% CI: 0.19-0.71) were identified as positive prognostic markers. In contrast, though pulmonary irAEs were found to be corelated with enhanced treatment response (ORR: RR =1.75; 95% CI: 1.37-2.25), they may harm survival, especially those with grade ≥3 (OS: HR =2.40; 95% CI: 1.39-4.14). Treatment resumption tended to improve PFS but might not reduce the risk of death compared to permanent discontinuation. Conclusions: IrAEs suggest better treatment outcomes generally, yet severe pneumonia could increase mortality risk. Close supervision and appropriate handling protocols are warranted to weigh treatment benefit against risk.

Large-scale analysis reveals splicing biomarkers for tuberculosis progression and prognosis.

BACKGROUND: Emerging evidence suggests that aberrant alternative splicing (AS) may play an important role in tuberculosis (TB). However, current knowledge regarding the value of AS in TB progression and prognosis remains unclear. METHOD: Public RNA-seq datasets related to TB progression and prognosis were searched and AS analyses were conducted based on SUPPA2. Percent spliced in (PSI) was used for quantifying AS events and multiple machine learning (ML) methods were employed to construct predictive models. Area under curve (AUC), sensitivity and specificity were calculated to evaluate the model performance. RESULTS: A total of 1587 samples from 7 datasets were included. Among 923 TB-progression related differential AS events (DASEs), 3 events (GET1-skipping exon (SE), TPD52-alternative first exons (AF) and TIMM10-alternative 5' splice site (A5)) were selected as candidate biomarkers; however, their predictive performance was limited. For TB prognosis, 5 events (PHF23-AF, KIF1B-SE, MACROD2-alternative 3' splice site (A3), CD55-retained intron (RI) and GALNT11-AF) were selected as candidates from the 1282 DASEs. Six ML methods were used to integrate these 5 events and XGBoost outperformed than others. AUC, sensitivity and specificity of XGBoost model were 0.875, 81.1% and 83.5% in training set, while they were 0.805, 68.4% and 73.2% in test set. CONCLUSION: GET1-SE, TPD52-AF and TIMM10-A5 showed limited role in predicting TB progression, while PHF23-AF, KIF1B-SE, MACROD2-A3, CD55-RI and GALNT11-AF could well predict TB prognosis and work as candidate biomarkers. This work preliminarily explored the value of AS in predicting TB progression and prognosis and offered potential targets for further research.

Prognostic value of cross-lineage expression of the myeloid-associated antigens CD13 and CD33 in adult B-lymphoblastic leukemia: A large real-world study of 1005 patients.

BACKGROUND: Cross-lineage expression of the myeloid-associated antigens CD13/CD33 is common in adult B-lymphoblastic leukemia (B-ALL) patients, yet its prognostic value is still controversial. METHODS: We conducted a retrospective study of 1005 de novo adult B-ALL patients from January 2009 to December 2019 in our hospital. Logistic and Cox regression were used to analyze the prognostic value of CD13/CD33 expression in B-ALL. A Cox regression model was established to predict overall survival (OS) for B-ALL patients. RESULTS: Of the 1005 B-ALL patients, 53.7% (n = 540) aberrantly expressed CD13/CD33 (CD13/CD33+ ). Patients in the CD13/CD33+ group showed a higher incidence of BCR::ABL1 rearrangement and minimal/measurable residual disease (MRD) positivity but similar complete remission rate, relapse-free survival, mortality, and OS with CD13/CD33- . CD13/CD33+ patients had a higher risk of MRD positivity than CD13/CD33- patients. Notably, CD13/CD33+ patients who underwent tyrosine kinase inhibitor (TKI) therapy had a better long-term prognosis than those without TKI experience. Sex, group based on CD13/CD33 expression and TKI experience and white blood cell count were variables independently associated with OS. The Cox regression model integrating these three variables showed a moderate performance for OS prediction (C-index: 0.724). CONCLUSIONS: In real-world practice, CD13/CD33 expression can predict the risk of MRD in patients without TKI experience, but has no adverse effect on the prognosis of adult B-ALL patients. Incorporating CD13/CD33 into the standard antibody panels of B-ALL diagnosis and MRD measurements can help predict relapse risk and decisions on therapy options.

From tuberculosis bedside to bench: UBE2B splicing as a potential biomarker and its regulatory mechanism.

Alternative splicing (AS) is an important approach for pathogens and hosts to remodel transcriptome. However, tuberculosis (TB)-related AS has not been sufficiently explored. Here we presented the first landscape of TB-related AS by long-read sequencing, and screened four AS events (S100A8-intron1-retention intron, RPS20-exon1-alternaitve promoter, KIF13B-exon4-skipping exon (SE) and UBE2B-exon7-SE) as potential biomarkers in an in-house cohort-1. The validations in an in-house cohort-2 (2274 samples) and public datasets (1557 samples) indicated that the latter three AS events are potential promising biomarkers for TB diagnosis, but not for TB progression and prognosis. The excellent performance of classifiers further underscored the diagnostic value of these three biomarkers. Subgroup analyses indicated that UBE2B-exon7-SE splicing was not affected by confounding factors and thus had relatively stable performance. The splicing of UBE2B-exon7-SE can be changed by heat-killed mycobacterium tuberculosis through inhibiting SRSF1 expression. After heat-killed mycobacterium tuberculosis stimulation, 231 ubiquitination proteins in macrophages were differentially expressed, and most of them are apoptosis-related proteins. Taken together, we depicted a global TB-associated splicing profile, developed TB-related AS biomarkers, demonstrated an optimal application scope of target biomarkers and preliminarily elucidated mycobacterium tuberculosis-host interaction from the perspective of splicing, offering a novel insight into the pathophysiology of TB.

Metformin promotes smear conversion in tuberculosis-diabetes comorbidity and construction of prediction models.

BACKGROUND: The comorbidity of tuberculosis (TB) and diabetes mellitus (DM) is a global health concern. Metformin is commonly used in DM but the potential effectiveness in comorbid patients is uncertain. This retrospective study aims to investigate the effect of metformin on TB-DM comorbidity and construct prediction models. METHODS: Patients diagnosed with TB-DM in West China Hospital were retrospectively enrolled from Nov 2013 to Sep 2019. Electronic health records of patients were extracted. Two-month smear conversion (2SC) was considered an outcome indicator of TB. Univariate and multivariate logistic regression (LR) were used to assess the role of metformin and other independent predictors. Meanwhile, prediction models were built by LR, elastic net regression, support vector machine, k-nearest neighbors, and random forest. RESULTS: A total of 927 individuals were recruited, among which 408 (44.01%) were metformin-exposed patients. A higher 2SC rate was observed in the metformin users. Other impact factors such as smoking, glucose, and creatinine levels were also identified. Multivariable models were then constructed using filtered variables. The support vector machine model yields the highest AUC (0.808, 95% CI: 0.767-0.849) and specificity (83.24%). LR model outperformed others in terms of sensitivity (69.71%). CONCLUSION: This retrospective study of a large population from southwestern China provides strong clinical evidence for the positive effects of metformin in TB-DM. Metformin is associated with a better therapeutic outcome and promising for the adjuvant therapy of TB-DM. Furthermore, a combination of support vector machine and LR models is recommended to discriminate the patients with poor treatment outcomes.

Risk factors for prolonged air leak after pulmonary surgery: A systematic review and meta-analysis.

This study aimed to comprehensively identify risk factors for the occurrence of prolonged air leak (PAL) in patients undergoing pulmonary surgery. Studies were retrieved from 3 databases, including PubMed, Web of Science, and EmBase up to 13 May 2020. We performed meta-analysis using Bayesian random effect models through divergence restricting conditional tessellation (DIRECT) algorithm. The effect size was expressed as odds ratio (OR) or mean difference (MD), each with 95% credible interval (CrI). The evidence quality was evaluated. Subgroup analyses and sensitivity analyses were conducted. Thirty-nine studies with 89006 patients were finally included. Pooled PAL incidence was 15%. Of 30 risk factors, 22 were significantly associated with increased PAL incidence. Five risk factors were ultimately selected with high evidence quality: smoking history (OR 1.84, 95%CrI 1.45 to 2.31, P<0.001), preoperative steroid use (OR 1.51, 95%CrI 0.87 to 2.65, P = 0.031), lower ratio of forced expiratory volume in 1 s and forced vital capacity (OR 1.99, 95%CrI 1.22 to 3.33, P = 0.005), non-fissureless technique (OR 2.14, 95%CrI 1.31 to 3.66, P = 0.003), and pathological TNM stage III/IV (OR 1.50, 95%CrI 1.07 to 2.12, P = 0.003). Regarding the negative impact of PAL on the personal cost and postoperative recovery, the verification of previous proposed factors and investigation of recently discovered ones both implied directions for risk stratification and the establishment of an applicable prediction model.

Suction Versus Nonsuction Drainage After Uniportal Video-Assisted Thoracoscopic Surgery: A Propensity Score-Matched Study.

BACKGROUND: Uniportal video-assisted thoracoscopic surgery (UniVATS) was utilized with a rapid growth. The evidence is sparse, however, on whether to add external suction to water-seal drainage for chest drainage after UniVATS. This retrospective propensity score-matched study aimed to identify the necessity of adding external suction to chest drainage after UniVATS. METHODS: Patients with lung cancer who underwent UniVATS were included from our prospectively maintained database. Patients were divided into two cohorts based on the addition of external suction to postoperative water-seal drainage or not. Propensity score-matched analysis was performed to identify the impact of suction on chest tube duration, incidence of persistent air leak, hospital stay, and hospitalization cost. Multivariable model with interaction terms was constructed to identify impact of covariables on effect of suction. RESULTS: The two cohorts matched well on baseline characteristics (nonsuction: 173; suction: 96). Compared with nonsuction group, suction group showed longer median chest tube duration (3 vs. 2 days, p = 0.003), higher incidences of persistent air leak (9.4% vs. 1.2%, p = 0.003), persistent drainage (16.8% vs. 5.8%, p = 0.007), and reduced drainage volume within first 3 postoperative days (386.90 vs. 504.78 ml, p = 0.011). Resection extent was identified to mediate the relationship between suction and chest tube drainage. CONCLUSIONS: These findings discouraged adding external suction to water-seal drainage after UniVATS regarding longer chest tube duration and more persistent air leak. Patients undergoing lobectomy would benefit more from water-seal drainage without external suction compared with those doing sublobectomy.

Comparison of the clinical benefits for non-small cell lung cancer patients between different volume of pleural lavage fluid following video-assisted thoracoscopic lobectomy and systematic mediastinal lymph node dissection: study protocol for a randomized controlled trial.

BACKGROUND: Pleural lavage is regularly performed before closing the chest wall in pulmonary surgeries to prevent pleural implantation of tumor cells and postoperative infection. However, scant data could be found in the literature regarding the optimal regimen for performing pleural lavage. To establish a proper volume of pleural lavage, we herein designed a protocol for a randomized controlled trial. METHODS: A total of 400 participants with non-small cell lung cancer undergoing video-assisted thoracoscopic surgery (VATS) lobectomy and systematic mediastinal lymph node dissection (MLND) will be randomly assigned to one of two groups: group A (500 mL pleural lavage fluid) and group B (3000 mL pleural lavage fluid). The primary outcomes include the levels of leukocytes, neutrophils, and inflammatory factors on the first postoperative day. The secondary outcomes include (i) the levels of leukocytes, neutrophils, and inflammatory factors on the second and third postoperative days; (ii) the incidence of postoperative fever on the first, second, and third postoperative days; (iii) the volumes of chest drainage within the first 3 operative days, the duration of drainage, and postoperative hospitalization; and (iv) the incidence of postoperative complications (incision infection, pain, atelectasis, hemorrhage, etc.) and the incidence of pleural effusion requiring thoracic puncture or drainage within 30 days after surgery. The main content of the analysis includes effectiveness and safety analysis. We will perform subgroup analyses to identify potential influence factors. DISCUSSION: As far as we know, this will be the first randomized controlled trial to compare the clinical outcomes between different volumes of pleural lavage fluid following VATS and MLND. Findings from this trial will determine the appropriate amount of pleural lavage before chest wall closure. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry ( on 17 March 2019. ChiCTR 1900021950).

Prognostic value of lymph node ratio in non-small-cell lung cancer: a meta-analysis.

BACKGROUND: This meta-analysis aimed to investigate the prognostic value of lymph node ratio in non-small-cell lung cancer. METHODS: We searched systematically for eligible studies in PubMed, Web of Science, Medline (via Ovid) and Cochrane library through 6 November 2018. The primary outcome was overall survival. Disease-free survival and cancer-specific survival were considered as secondary outcomes. Hazard ratio with corresponding 95% confidence interval were pooled. Quality assessment of included studies was conducted. Subgroup analyses were performed based on N descriptors, types of tumor resection, types of lymphadenectomy and study areas. Sensitivity analysis and evaluation of publication bias were also performed. RESULTS: Altogether, 20 cohorts enrolling 76 929 patients were included. Mean Newcastle-Ottawa Scale was 7.65 ± 0.59, indicating the studies' quality was high. The overall result showed non-small-cell lung cancer patients with lower lymph node ratio was associated with better overall survival (HR: 1.946; 95% CI: 1.746-2.169; P < 0.001), disease-free survival (HR: 2.058; 95% CI: 1.717-2.467; P < 0.001) and cancer-specific survival (HR: 2.149; 95% CI: 1.864-2.477; P < 0.001). Subgroup analysis prompted types of lymphadenectomy and the station of positive lymph node have an important effect on the prognosis. No significant discovery was found in sensitivity analysis. CONCLUSION: Patients with lower lymph node ratio was associated with better survival, indicating that lymph node ratio may be a promising prognostic predictor in non-small-cell lung cancer. The type of lymphadenectomy, an adequate examined number and the removed stations should be considered for more accurate prognosis assessment.

The prognosis predictive value of FMS-like tyrosine kinase 3-internal tandem duplications mutant allelic ratio (FLT3-ITD MR) in patients with acute myeloid leukemia detected by GeneScan.

INTRODUCTION: This study aimed to explore the significance and cut-off values of FMS-like tyrosine kinase 3-internal tandem duplications mutant allelic ratio (FLT3-ITD MR) in prognostic evaluation of acute myeloid leukemia (AML) patients. METHODS: This study enrolled 249 Chinese AML patients. The exons 14 and 15 of FLT3 gene were amplified by genomic polymerase chain reaction. GeneScan and single nucleotide sequencing were also performed. Participants were grouped into high- and low-ratio FLT3-ITD MR (FLT3-ITD MRhigh and FLT3-ITD MRlow) applying the median of FLT3-ITD MR as the cut-off ratio, and patients without FLT3-ITD were grouped as FLT3-wild type (wt). Duration of complete remission (CR), relapsed remission and overall survival (OS) were examined. RESULTS: FLT3-ITD was detected in 58 patients. The medians of FLT3-ITD MR were 0.31 and 0.29 for all AML and non-M3 patients, respectively. For all patients, FLT3-ITD MRhigh group had the lowest CR rate among these 3 groups (p < 0.001). The FLT3-wt group, FLT3-ITD MRlow and FLT3-ITD MRhigh group had the median OS of 36.00 months (range: 2.00-92.00 months), 12.00 months (range: 1.00-78.00 months) and 14.00 months (range: 0.00-79.00 months), respectively. Subjects in FLT3-ITD MRhigh group had 2.675 times (95% CI: 1.726-4.146; p < 0.001) and 1.879 times (95% CI: 1.061-3.328; p = 0.031) higher death risk than those in FLT3-wt group and FLT3-ITD MRlow group, respectively. For non-M3 patients, the median OS was 35.00 months (range: 2.00-92.00 months), 9.5 months (range: 1.00-74.00 months) and 10.00 months (range: 1.00-38.00 months) in the FLT3-wt group, FLT3-ITD MRlow group and FLT3-ITD MRhigh group, respectively. Non-M3 patients in FLT3-ITD MRhigh group had 3.301 times (95% CI: 1.423-7.661; p = 0.005) higher death risk than those in FLT3-wt group. CONCLUSION: The present study found that FLT3-ITD MR is closely related to CR and OS in AML patients. Furthermore, FLT3-ITD MR may serve as an independent prognostic factor for OS in non-M3 AML patients. Classifying risk grades based on FLT3-ITD MR is crucial for individualized treatment and prognostic evaluation.

Do genetic polymorphisms of B-cell CLL/lymphoma 2 confer susceptibility to anti-tuberculous therapy-associated drug-induced liver injury?

OBJECTIVES: The aim of this study was to identify the relationship between B-cell CLL/lymphoma 2 (BCL2) polymorphisms and susceptibility to anti-tuberculous therapy-associated drug-induced liver injury (ATT-DILI). METHODS: A total of 746 tuberculosis (TB) patients were enrolled in this study. Twenty-one selected single nucleotide polymorphisms in BCL2 were analyzed by custom-by-design 2×48-Plex SNPscan kit. The allele and genotype frequencies between patients with and without ATT-DILI were compared using three different genetic models. RESULTS: A total of 727/746 participants were successfully genotyped, and 112 of them were diagnosed with ATT-DILI. The A allele of rs8085707, G allele of rs76986960, and A allele of rs949037 conferred an increased risk of ATT-DILI, with estimated odd ratios (ORs) of 2.181 (95% confidence interval (CI) 1.345-3.536, p=0.001), 1.983 (95% CI 1.060-3.709, p=0.029), and 1.390 (95% CI 1.032-1.873, p=0.03), respectively. Bonferroni correction indicated that the A allele of rs8085707 was a risk factor for ATT-DILI (Bonferroni correction: p=0.026). The additive model suggested that patients with the AA genotype of rs8085707 had a significantly higher risk of ATT-DILI compared with those with the GG genotype (Bonferroni correction: p=0.036). The influence of BCL2 polymorphisms on clinical characteristics (clinical symptoms, disease subtypes, and laboratory indicators) was also identified. CONCLUSIONS: This study is novel in suggesting an association between BCL2 polymorphisms and the risk of ATT-DILI.

Efficacy of Transcutaneous Electronic Nerve Stimulation in Postoperative Analgesia After Pulmonary Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of the study was to identify the analgesic efficacy and safety of transcutaneous electronic nerve stimulation in postoperative pain after pulmonary surgery. DESIGN: Electronic databases (PubMed, Embase, Web of Science, and CENTRAL) were systematically searched from their inception to June 2019. The continuous variables were pooled as the weighted mean difference with correlated 95% confidence interval. Results were recognized as significant when a P value is less than 0.05. Subgroup analyses, sensitivity analyses, and quality assessment were performed. RESULTS: Altogether, 10 studies were included. The pooled results indicated that transcutaneous electronic nerve stimulation group conferred lower pain intensity score on the first postoperative day (weighted mean difference = -0.93, 95% confidence interval = -1.56 to -0.30, P = 0.004), postoperative day 2 (weighted mean difference = -1.00, 95% confidence interval = -1.64 to -0.35, P = 0.002), postoperative day 3 (weighted mean difference = -0.92, 95% confidence interval = -1.76 to -0.09, P = 0.03), postoperative day 4 (weighted mean difference = -0.90, 95% confidence interval = -1.24 to -0.56, P < 0.001), and postoperative day 5 (weighted mean difference = -1.39, 95% confidence interval = -2.20 to -0.57, P < 0.001) compared with the placebo transcutaneous electronic nerve stimulation group. No publication bias was found. No significant discovery was obtained in sensitivity analyses. CONCLUSIONS: Transcutaneous electronic nerve stimulation might be an effective supplementary analgesic regimen in multimodal analgesia to decrease pain intensity after pulmonary surgery.

The genetic variants in calcium signaling related genes influence anti-tuberculosis drug induced liver injury: A prospective study.

Although many genetic variants related to anti-tuberculosis drug induced liver injury (ATDILI) have been identified, the prediction and personalized treatment of ATDILI have failed to achieve, indicating there remains an area for further exploration. This study aimed to explore the influence of single nucleotide polymorphisms (SNPs) in Bradykinin receptor B2 (BDKRB2), Teneurin transmembrane protein 2 (TENM2), transforming growth factor beta 2 (TGFB2), and solute carrier family 2 member 13 (SLC2A13) on the risk of ATDILI.The subjects comprised 746 Chinese tuberculosis (TB) patients. Custom-by-design 2x48-Plex SNPscanTM kit was employed to genotype 28 selected SNPs. The associations of SNPs with ATDILI risk and clinical phenotypes were analyzed according to the distributions of allelic and genotypic frequencies and different genetic models. The odds ratio (OR) with corresponding 95% confidence interval (CI) was calculated.Among subjects with successfully genotyped, 107 participants suffered from ATDILI during follow-up. In BDKRB2, patients with rs79280755 G allele or rs117806152 C allele were more vulnerable to ATDILI (PBonferronicorrection = .002 and .03, respectively). Rs79280755 increased the risk of ATDILI significantly whether in additive (OR = 3.218, 95% CI: 1.686-6.139, PBonferroni correction = .003) or dominant model (PBonferroni correction = .003), as well as rs117806152 (Additive model: PBonferroni correction = .05; dominant model: PBonferroni correction = .03). For TENM2, rs80003210 G allele contributed to the decreased risk of ATDILI (PBonferroni correction = .02), while rs2617972 A allele conferred susceptibility to ATDILI (PBonferroni correction = .01). Regarding rs2617972, significant findings were also observed in both additive (OR = 3.203, 95% CI: 1.487-6.896, PBonferroni correction = .02) and dominant model (PBonferroni correction = .02). Moreover, rs79280755 and rs117806152 in BDKRB2 significantly affected some laboratory indicators. However, no meaningful SNPs were observed in TGFB2 and SLC2A13.Our study revealed that both BDKRB2 and TENM2 genetic polymorphisms were interrogated in relation to ATDILI susceptibility and some laboratory indicators in the Western Chinese Han population, shedding a new light on exploring novel biomarkers and targets for ATDILI.

Efficiency and safety of TachoSil® in the treatment of postoperative air leakage following pulmonary surgery: a meta-analysis of randomized controlled trials.

OBJECTIVE: There has been still no consensus whether to apply TachoSil® to reduce the incidence of air leakage after pulmonary surgery. We conducted this meta-analysis of randomized controlled trials (RCTs) to identify the efficiency and safety of TachoSil® applied in the prevention of postoperative air leakage following pulmonary surgery. METHODS: We performed a systematic electronic search through EMABSE, PubMed and Web of Science up to March 2018. Summary risk ratio (RR) and weight mean difference (WMD) with corresponding 95% confidence intervals (CI) were calculated to analyze the outcomes. Fixed effect or random effect model was used to pool the estimates. Two independent reviewers assessed the quality of included studies using Cochrane risk-of-bias tool for RCTs. RESULTS: We included six RCTs with a total of 921 patients. Compared with standard treatment (suturing, stapling techniques or electrocautery), TachoSil® was associated with the decreased air leak duration (WMD: -3.32 days; 95% CI: -5.34--1.31; P = 0.001), chest tube duration (WMD: -1.99 days; 95% CI: -3.14--0.84; P = 0.0007), hospital stay (WMD: -1.89 days; 95% CI: -2.42--1.35; P < 0.0001), and incidence of prolonged air leak (RR: 0.57; 95% CI: 0.35-0.92; P = 0.02). No significant difference was found between the two groups regarding the incidence of postoperative complications (RR: 0.86; 95% CI: 0.69-1.06; P = 0.16). CONCLUSIONS: TachoSil® was safe, cost-effective and superior over standard treatment for patients who underwent pulmonary surgery in decreasing incidence of postoperative air leak, air leak duration, chest tube duration and the length of hospital stay.

The diagnostic value of circulating tumor cells and ctDNA for gene mutations in lung cancer.

PURPOSE: Detecting gene mutations by two competing biomarkers, circulating tumor cells (CTCs) and ctDNA has gradually paved a new diagnostic avenue for personalized medicine. We performed a comprehensive analysis to compare the diagnostic value of CTCs and ctDNA for gene mutations in lung cancer. METHODS: Publications were electronically searched in PubMed, Embase, and Web of Science as of July 2018. Pooled sensitivity, specificity, and AUC, each with a 95% CI, were yielded. Subgroup analyses and sensitivity analyses were conducted. Quality assessment of included studies was also performed. RESULTS: From 4,283 candidate articles, we identified 47 articles with a total of 7,244 patients for qualitative review and meta-analysis. When detecting EGFR, the CTC and ctDNA groups had pooled sensitivity of 75.4% (95% CI 0.683-0.817) and 67.1% (95% CI 0.647-0.695), respectively. When testing KRAS, pooled sensitivity was 38.7% (95% CI 0.266-0.519) in the CTC group and 65.1% (95% CI 0.558-0.736) in the ctDNA group. The diagnostic performance of ctDNA in testing ALK and BRAF was also evaluated. Heterogeneity among the 47 articles was acceptable. CONCLUSION: ctDNA might be a more promising biomarker with equivalent performance to CTCs when detecting EGFR and its detailed subtypes, and superior diagnostic capacity when testing KRAS and ALK. In addition, the diagnostic performance of ctDNA and CTCs depends on the detection methods greatly, and this warrants further studies to explore more sensitive methods.

A surgical case of ciliated muconodular papillary tumor.

Ciliated muconodular papillary tumor (CMPT) is a rare type of pulmonary tumor with mucoid features. Only a few cases confirmed by surgery have been reported worldwide. We report a case of CMPT following sublobectomy, with no recurrence detected in 10 months of follow-up. The accumulation of similar cases is essential for pathologists and surgeons to improve their understanding of such tumors.

External suction versus simple water-seal on chest drainage following pulmonary surgery: an updated meta-analysis.

OBJECTIVES: The decision to apply simple water-seal drainage or the addition of an external suction to the simple water-seal drainage following pulmonary surgery is made based on the surgeon's experience or preference and has remained controversial. This meta-analysis aimed to assess the effects of the addition of suction to simple water-seal on the postoperative outcomes. METHODS: PubMed, EMBASE and Web of Science were searched from their inception to 30 August 2017. The risk ratio and the weight mean difference were calculated for dichotomous and continuous outcomes, respectively, each with 95% confidence intervals (CIs). The heterogeneity and risk of bias were also assessed. RESULTS: A total of 10 randomized controlled trials enrolling 1601 patients were included. Overall, compared with simple water-seal, the addition of external suction reduced the occurrence of postoperative pneumothorax (risk ratio 0.35, 95% CI 0.13-0.93; P = 0.04) and other cardiopulmonary complications (risk ratio 0.65, 95% CI 0.48-0.89; P = 0.008), and increased the duration of chest tube drainage (weight mean difference 0.92 days, 95% CI 0.04-1.81, P = 0.04). However, the effect difference between the 2 groups was not significant regarding air leak duration, length of hospital stay and the occurrence of prolonged air leak. The stability of these studies was strong. No evidence of publication bias was detected. CONCLUSIONS: The addition of suction to simple water-seal made no difference to air leak duration, hospital stay or the occurrence of prolonged air leak following pulmonary surgery. In patients where there is concern about a residual or increasing pneumothorax, the addition of suction may be applied selectively.

Digital chest drainage is better than traditional chest drainage following pulmonary surgery: a meta-analysis.

In this systematic review with meta-analysis, we sought to determine the current strength of evidence for or against digital and traditional chest drainage systems following pulmonary surgery with regards to hard clinical end points and cost-effectiveness. PubMed, EMBASE and Web of Science were searched from their inception to 31 July 2017. The weighted mean difference (WMD) and the risk ratio were used for continuous and dichotomous outcomes, respectively, each with 95% confidence intervals (CIs). The heterogeneity and risk of bias were also assessed. A total of 10 randomized controlled trials enrolling 1268 patients were included in this study. Overall, digital chest drainage reduced the duration of chest tube placement (WMD -0.72 days; 95% CI -1.03 to -0.40; P < 0.001), length of hospital stay (WMD -0.97 days; 95% CI -1.46 to -0.48; P < 0.001), air leak duration (WMD -0.95 days; 95% CI -1.51 to 0.39; P < 0.001), and postoperative cost (WMD -443.16 euros; 95% CI -747.60 to -138.73; P = 0.004). However, the effect differences between the 2 groups were not significant for the duration of a prolonged air leak and the percentage of patients discharged home on a device. The stability of these studies was strong. No publication bias was detected. It may be necessary to use a digital chest drainage system for patients who underwent pulmonary surgery to reduce the duration of chest tube placement, length of hospital stay and air leak duration.