Effect of fine particulate matter exposure on gestational diabetes mellitus risk: a retrospective cohort study.

BACKGROUND: The literature on the association between fine particulate matter (PM2.5) exposure and gestational diabetes mellitus (GDM) risk has focused mainly on exposure during the first and second trimesters, and the research results are inconsistent. Therefore, this study aimed to investigate the associations between PM2.5 exposure during preconception, the first trimester and second trimester and GDM risk in pregnant women in Guangzhou. METHODS: A retrospective cohort study of 26 354 pregnant women was conducted, estimating PM2.5, particulate matter with a diameter >10 µm (PM10), sulphur dioxide (SO2), carbon monoxide (CO) and ozone (O3) exposure during preconception and the first and second trimesters. Analyses were performed using Cox proportional hazards models and nonlinear distributed lag models. RESULTS: The study found that exposure to PM2.5 or a combination of two pollutants (PM2.5+PM10, PM2.5+SO2, PM2.5+CO and PM2.5+O3) was found to be significantly associated with GDM risk (P < 0.05). In the second trimester, with significant interactions found for occupation and anaemia between PM2.5 and GDM. When the PM2.5 concentrations were ≥19.56, ≥25.69 and ≥23.87 µg/m3 during preconception and the first and second trimesters, respectively, the hazard ratio for GDM started to increase. The critical window for PM2.5 exposure was identified to be from 9 to 11 weeks before conception. CONCLUSIONS: Our study results suggest that PM2.5 exposure during preconception and the first and second trimesters increases the risk of GDM, with the preconception period appearing to be the critical window for PM2.5 exposure.

Efficacy of tyrosine kinase inhibitors in patients with advanced or metastatic sarcomas after prior chemotherapy: A meta-analysis.

BACKGROUND: Sarcoma is a heterogeneous malignancy arising from interstitial tissue. Anthracycline-based therapy is the first-line treatment recommended by guidelines for patients with locally advanced or metastatic unresectable sarcoma. Recently, targeted therapies, in particular tyrosine kinase inhibitors (TKIs), have made significant progress in the treatment of sarcoma, and their efficacy has been investigated in randomized controlled trials. The aim of this meta-analysis is to evaluate the efficacy of TKIs in patients with advanced or metastatic sarcoma who have previously received chemotherapy. METHODS: We completed a meta-analysis after conducting literature searches in PubMed, Embase, and Cochrane. The single-drug, placebo-controlled, randomized controlled clinical trials of TKIs in patients with advanced or progressive sarcoma who have previously received chemotherapy are available for inclusion in the study. The observation results were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). The subgroup analysis was performed according to histological subtypes of sarcoma. RESULTS: This study included 6 studies, including 1033 patients. The ORR (OR: 7.99, 95% CI: 3.62-19.61, P < .00001), DCR (OR: 2.54, 95% CI: 1.27-5.08, P = .009), PFS (HR: 0.46, 95% CI: 0.34-0.62, P < .00001), and OS (HR: 0.80, 95% CI: 0.67-0.96, P = .02) of patients treated with TKIs were better than those in the placebo group. CONCLUSIONS: In patients with advanced sarcoma, TKIs have been shown to have advantages in terms of ORR, DCR and PFS and OS. Multi-targeted TKIs may be considered as one of the second-line treatment options for sarcoma patients who have received prior chemotherapy.

Efficacy and safety of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy in locally advanced esophageal cancer: An updated meta-analysis.

BACKGROUND: Currently, the optimal treatment for neoadjuvant therapy for locally advanced esophageal cancer is not clear, and there is no evidence that neoadjuvant chemoradiotherapy (nCRT) is superior to neoadjuvant chemotherapy (nCT). Due to the publication of new clinical trials and defects in previous meta-analyses, we conducted an updated meta-analysis to evaluate the efficacy and safety of nCRT and nCT. METHODS: The following databases were searched for studies: PubMed, EMBASE, and Cochrane library (updated to April 22, 2023). All randomized trials comparing nCRT with nCT in locally advanced esophageal cancer met the inclusion criteria. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes assessed from the trials included overall survival (OS), progression-free survival (PFS), pathological complete response (pCR), R0 resection rate, postoperative complications, postoperative mortality, and grade 3 or higher adverse events (3 + AEs). RESULTS: This systematic review and meta-analysis included 7 randomized controlled studies involving 1372 patients (686 receiving nCRT and 686 receiving nCT). Compared with nCT, nCRT significantly improved OS (HR = 0.80; 95% CI: 0.68-0.94), PFS (HR = 0.78; 95% CI: 0.66-0.93), pCR (OR = 13.00; 95% CI: 7.82-21.61) and R0 resection (OR = 1.84; 95% CI: 1.32-2.57), but was associated with higher postoperative mortality (OR = 2.31; 95% CI: 1.26-4.25) and grade 3 + AEs (OR = 2.21; 95% CI: 1.36-3.58). There was no significant difference in postoperative complications between nCRT and nCT (OR = 1.15; 95% CI: 0.82-1.61). Subgroup analysis showed significant survival benefit in squamous cell carcinoma (HR = 0.80; 95% CI: 0.68-0.98), but not in adenocarcinoma (HR = 0.80; 95% CI: 0.63-1.08). CONCLUSIONS: Our meta-analysis found superior efficacy associated with nCRT compared with nCT in both tumor regression and prolonged survival, but increased the risk of postoperative mortality and grade 3 + AEs. Esophageal squamous cell carcinoma was more likely to benefit from nCRT than esophageal adenocarcinoma in the term of OS.

Efficacy and safety of zolbetuximab for first-line treatment of advanced Claudin 18. 2-positive gastric or gastro-esophageal junction adenocarcinoma: a systematic review and meta-analysis of randomized controlled trials.

Objective: Zolbetuximab is a "first-in-class" chimeric lgG1 monoclonal antibody targeting Claudin18.2 (CLDN 18.2). In recent years, several important trials have been published showing that zolbetuximab is associated with improved prognosis in patients with advanced gastric or gastro-esophageal junction (G/GEJ) adenocarcinoma. This promises great change to the current treatment landscape. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zolbetuximab for first-line treatment of advanced CLDN 18. 2-positive G/GEJ adenocarcinoma. Methods: The following databases were searched for relevant studies: PubMed, EMBASE, and Cochrane library (updated 10 June 2023). All randomized trials comparing zolbetuximab plus chemotherapy versus first-line chemotherapy alone for first-line treatment of advanced CLDN 18. 2-positive G/GEJ adenocarcinoma were eligible for inclusion. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes and measures included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Results: This systematic review and meta-analysis included three randomized controlled studies involving 1,402 patients (699 receiving zolbetuximab plus chemotherapy and 703 receiving chemotherapy alone). Compared with chemotherapy alone, zolbetuximab plus chemotherapy significantly improved OS (HR = 0.73; 95% CI: 0.68-0.84) and PFS (HR = 0.64; 95% CI: 0.50-0.82), but did not result in a higher ORR (RR = 0.92; 95% CI: 0.82-1.03). Further analysis of CLDN 18.2 expression showed a more significant benefit for OS (HR = 0.69; 95% CI: 0.55-0.87; p = 0.002) and PFS (HR = 0.61; 95% CI: 0.44-0.84; p = 0.003) from zolbetuximab in patients with high expression, while there was significant benefit in patients with lower expression. In terms of AEs, zolbetuximab plus chemotherapy was associated with higher risk of grade 3 and higher AEs, but increased risk of nausea and vomiting were more common. Conclusion: This systematic review and meta-analysis revealed that the effect of zolbetuximab plus chemotherapy was superior to that of chemotherapy alone for first-line treatment of advanced CLDN 18.2-positive G/GEJ adenocarcinoma. Thus, zolbetuximab plus chemotherapy represents a new first-line treatment for these patients. Zolbetuximab plus chemotherapy was associated with higher risk of grade 3 and higher AEs, but was generally manageable. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42023437126).

Major pathological remissions in a patient with stage IIIA nonsmall cell lung cancer after neoadjuvant tislelizumab combined with chemotherapy: a case report and literature review.

INTRODUCTION: Currently, there are few reports of patients with locally advanced lung cancer achieving a clinical complete response by medical treatment. Preoperative neoadjuvant immunotherapy combined with chemotherapy is an option for patients with unresectable, locally advanced nonsmall cell lung cancer (NSCLC) which is of great potential, and may change traditional treatment paradigms. There are relatively few large-scale, high-quality randomized-controlled trials yet, and limitations such as short postoperative follow-up period and immature disease-free survival and overall survival data still persist. Thus, evidence-based medical evidence is urgently needed. It is worthy to explore the further treatment of patients who achieved complete response after initial treatment, though lacking of evidence by now. CASE PRESENTATION: We report a stage IIIA lung squamous cell carcinoma case who achieved a major pathologic remission after neoadjuvant treatment with tislelizumab and chemotherapy. CONCLUSION: Our case study contributes to the existing evidence on the feasibility, efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC.

Case report: pathological complete response in an IIIB non-small cell lung cancer patient after preoperative neoadjuvant nivolumab therapy combined with chemotherapy.

RATIONALE: For locally advanced non-small cell lung cancer (NSCLC), the neoadjuvant therapy strategy of preoperative nivolumab combined with chemotherapy has great potential, especially for locally advanced NSCLC which are initially unresectable. They may be cured after neoadjuvant immunotherapy, and this may become a new direction of treatment. We hope that this representative medical record and literature review can provide some assistance for clinicians using immune checkpoint inhibitors to treat lung cancer. PATIENT CONCERNS: A 50-year-old male patient was admitted to Zhongshan Hospital of Traditional Chinese Medicine on April 27, 2020 due to "coughing for more than one month.". The patient had nothing of note in either his medical history or that of his family, and no history of smoking. DIAGNOSIS: The diagnosis was cT4N2M0IIIB stage right lower lung NSCLC with right hilar and mediastinal lymph node metastasis. The stage was inoperable stage IIIB NSCLC, but the patient had a strong willingness for doing surgery. INTERVENTIONS: The patient received 3 rounds of the neoadjuvant nivolumab therapy combined with TP (paclitaxel plus cisplatin) regimen, on 5-14-21, 06-07-21 and 07-07-21. OUTCOMES: The tumor's area shrunk. Then the patient underwent thoracoscopic radical resection of the cancer in the right upper lung and postoperative pathology achieved pathological complete response (pCR). LESSONS: In this case, combined with the wishes of the patient and the latest research results, we confirmed pCR by radical surgery after 3 rounds of the neoadjuvant nivolumab therapy combined with chemotherapy. This may be a modality to cure more lung cancer patients in the future.

Efficacy and safety of salvage radiotherapy combined with endocrine therapy in patients with biochemical recurrence after radical prostatectomy: A systematic review and meta-analysis of randomized controlled trials.

Background: The addition of endocrine therapy to salvage radiotherapy (SRT) is expected to further improve the prognosis of patients with biochemical recurrence of prostate cancer after radical prostatectomy (RP). The quantitative synthesis of clinical outcomes of SRT combined with endocrine therapy is limited. Whether salvage radiotherapy plus endocrine therapy remains inconclusive. We performed a systematic review and meta-analysis of existing randomized controlled trials to evaluate the efficacy and safety of salvage radiotherapy combined with endocrine therapy in patients with biochemical recurrence after radical prostatectomy. Methods: A systematic search of PubMed, EMBASE, and the Cochrane library was performed for articles published between January 1, 2012 and October 10, 2022. Data were analyzed using Review Manager 5.4.1 (Cochrane Collaboration Software). Main outcome and measures included biochemical progression-free survival (bPFS), metastasis free survival (MFS), overall survival (OS), and Grade 3 or higher adverse events (3+AEs), including acute and late adverse events. Results: In this systematic review and meta-analysis, 4 randomized controlled studies enrolling 2731 male (1374 of whom received SRT combined with endocrine therapy and 1357 controls) met the inclusion criteria. SRT combined with endocrine therapy were related to significantly improve bPFS (HR=0.52; 95% CI: 0.46 0.59; p<0.00001) and MFS (HR=0.75; 95% CI: 0.64 0.88; p<0.001). Compared with SRT alone, the combination therapy tended to be associated with prolong OS (HR=0.83; 95% CI: 0.69-1.01; p=0.06), but not statistically significant. At early follow-up, the risk of acute AEs was comparable in the two groups (RR=1.04; 95% CI: 0.22-4.85). However, the risk of late AEs was higher in the combination group at later follow-up (RR=1.33; 95% CI: 1.09-1.62). Conclusions: This systematic review and meta-analysis found superior efficacy associated with adding endocrine therapy to SRT compared with SRT alone in patients with biochemical recurrence after RP. Additional endocrine therapy is safe and feasible for patients with biochemical recurrence after RP. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42022365432).