Does Gastroesophageal Reflux Disease Increase the Risk of Sepsis and Its 28-day Mortality? A Causal Study Using a Mendelian Randomization Approach.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder. Recent studies indicate that GERD may exert systemic effects, potentially elevating the risk of severe infections, including sepsis. Nevertheless, the causal relationship between GERD and sepsis, as well as sepsis-related 28-day mortality, remains uncertain. AIM: The aim of this study is to investigate the causal relationship between GERD and the risk of sepsis, including 28-day mortality of sepsis. METHODS: This study utilized a two-sample Mendelian Randomization (MR) approach to analyze data from publicly available genome-wide association studies (GWAS) databases ( https://gwas.mrcieu.ac.uk/ ). The analysis comprised 129,080 cases and 473,524 controls for GERD; 11,643 patients and 474,841 controls for sepsis; and 1,896 patients and 484,588 controls for 28-day mortality from sepsis. The objective was to evaluate the causal impact of GERD on the risk of sepsis and 28-day sepsis mortality. Genetic variation data pertinent to GERD were obtained from the most recent genome-wide association studies (GWAS). The primary analysis employed the Inverse Variance Weighted (IVW) method. Sensitivity and pleiotropy analyses were performed to validate the robustness of the findings. RESULTS: MR analysis revealed a notable link between genetically predicted GERD and increased sepsis risk (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.24-1.52; p = 2.79 × 10-9). Moreover, GERD correlated with elevated 28-day mortality of sepsis (OR 1.44, 95% CI 1.11-1.85; p = 5.34 × 10-3). These results remained consistent throughout various sensitivity analyses, indicating their resilience against potential pleiotropy and other biases. CONCLUSION: This study indicates that genetic predisposition to GERD may be linked to an elevated risk of sepsis and its associated 28-day mortality. However, the study does not establish a direct causal relationship for GERD itself, nor does it assess the impact of GERD treatment. Further research is needed to explore the underlying mechanisms and potential therapeutic interventions involved.

Complete response to first-line osimertinib monotherapy in a complex epidermal growth factor receptor mutant ( L833V / H835L ) lung adenocarcinoma patient: a case report.

Although uncommon epidermal growth factor receptor (EGFR) mutations account for 10-15% EGFR mutant non-small cell lung cancer (NSCLC) patients, clinical evidence for uncommon EGFR mutations, such as complex mutations remain limited. In this study, we reported a NSCLC patient harboring complex EGFR L833V / H835L mutation in exon 21, who had a complete response to first-line osimertinib monotherapy. The patient admitted to our hospital for space-occupying lesions of right lower lung during an annual health checkup, and was diagnosed as stage IIIA lung adenocarcinoma. Targeted next-generation sequencing (NGS) on tumor samples showed a complex EGFR mutation: L833V / H835L in exon 21. Therefore, she was treated with osimertinib monotherapy and complete remission achieved soon. During follow-up period, no metastasis was found and serum carcinoembryonic antigen returned to normal. In addition, NGS monitoring of mutations in circulating tumor DNA maintained negative. The patient remain benefitted for osimertinib monotherapy over 22 months with no disease progression. Our case firstly provided clinical evidences of first-line osimertinib therapy in lung cancer patients with rare L833V / H835L EGFR mutation.

Molecular characteristics of multiple primary pulmonary nodules under a three-dimensional reconstruction model and relevant multi-omics analyses: a case report.

Background: In addition to CT images and pathological features, many other molecular characteristics remain unknown about multiple primary lung cancer (MPLC) from intrapulmonary metastatic lung cancer. Case presentation: In this study, we reported a patient with an early-stage MPLC with both adenocarcinoma in situ (AIS) subtype and minimally invasive adenocarcinoma (MIA) subtype. The patient was diagnosed with more than 10 nodules and underwent precise surgery assisted by three-dimensional (3D) reconstruction at the left upper lung lobe. Whole-exome sequencing (WES) and multiple immunohistochemistry (mIHC) were performed to reveal the genomic profiling and tumor microenvironments of multiple nodules in this patient with MPLC. Based on 3D reconstruction location information, we found that the genomic and pathological results of adjacent lymph nodes were quite different. On the other hand, PD-L1 expression and the proportion of infiltrating lymphocytes in tumor microenvironments were all at a low status and did not vary in adjacent lymph nodes. Additionally, maximum diameter and tumor mutational burden levels were found to be significantly associated with CD8+ T cell proportion (p<0.05). Besides, CD163+ macrophages and CD4+ T cell proportion were higher in MIA nodules than in AIS nodules (p<0.05). This patient reached a recurrence-free survival of 39 months. Conclusion: Generally, in addition to CT imaging and pathological results, genomic profiling and tumor microenvironments may facilitate identifying the potential molecular mechanisms and clinical outcomes in patients with early-stage MPLC.

The Association between the Risk of Esophageal Cancer and Type 2 Diabetes Mellitus: An Updated Meta-Analysis.

Background: A large amount of publications had reported the association between incidence of esophageal cancer (EC) and type 2 diabetes mellitus (T2DM) in the past decade. However, those papers' results are inconsistent on relationships between T2DM the incidence of EC. Therefore, the objective of this meta-analysis was to determine the relationship between T2DM and the risk of EC (including 2 histological types, esophageal adenocarcinoma [EADC] and esophageal squamous cell carcinoma [ESCC]). Method: We finally extracted 19 articles though Pubmed, Embased, and Cochrane library. Those identify extraction date including 14,312 cases and 24,959,067 control records and then mixed the relative risks (RRs) and corresponding 95% confidence intervals (95%CIs) through STATA. Results: We observed that there are significantly positive correlation between T2DM and EC risk (RR = 1.28, 95% CI: 1.05-1.57, P = 0.015).Also, our study showed positive correlation between T2DM and EADC (esophageal adenocarcinoma) risk (RR = 1.28, 95% CI: 1.05-1.57, P < 0.001). What's more, subgroup analysis based on ethnicity represented the Caucasian is more susceptible to EC (RR = 1.28 ,95% CI: 1.10-1.49, P = 0.001). Conclusion: Those results offer a recent epidemiological and integrated evidence to ascertain the correlations between T2DM and incidence of EC. Those results take public health implications on preventing T2DM and then depress the occurrence of EC. Our study also provides referenced information for the prevention. However, some data is still insufficient, and more research should be carried out.