The endoscopic dual tracer method for SN biopsy was confirmed as safe and effective when applied to the superficial, relatively small gastric adenocarcinomas included in this study.
The outcome of sepsis and septic shock has not significantly improved in recent decades despite the development of numerous drugs and supportive care therapies. To reduce sepsis-related mortality, a better understanding of molecular mechanism(s) associated with the development of sepsis and sepsis-related organ injury is essential. There is increasing evidence that Toll-like receptors (TLRs) play a key role in the mediation of systemic responses to invading pathogens during sepsis. However, the role of TLRs in the development of sepsis and in sepsis-related organ injury remains debatable. In this review, we focus on the biological significance of TLRs during sepsis. Medline was searched for pertinent publications relating to TLRs, with emphasis on their clinical and pathophysiological importance in sepsis. In addition, a summary of the authors' own experimental data from this field was set in the context of current knowledge regarding TLRs. In both animal models and human sepsis, TLRs are highly expressed on monocytes/macrophages, and this TLR expression may not simply be a ligand-specific response in such an environment. The fact that TLR signaling enables TLRs to recognize harmful mediators induced by invading pathogens may be associated with a positive feedback loop for the inflammatory response among different cell populations. This mechanism(s) may contribute to the organ dysfunction and mortality that occurs in sepsis. A better understanding of TLR biology may unveil novel therapeutic approaches for sepsis.
Clinical and technological advances promoting early hemorrhage control and physiologic resuscitation as well as early diagnosis and optimal treatment of sepsis have significantly decreased in-hospital mortality for many critically ill patient populations. However, a substantial proportion of severe trauma and sepsis survivors will develop protracted organ dysfunction termed chronic critical illness (CCI), defined as ≥14 days requiring intensive care unit (ICU) resources with ongoing organ dysfunction. A subset of CCI patients will develop the persistent inflammation, immunosuppression, and catabolism syndrome (PICS), and these individuals are predisposed to a poor quality of life and indolent death. We propose that CCI and PICS after trauma or sepsis are the result of an inappropriate bone marrow response characterized by the generation of dysfunctional myeloid populations at the expense of lympho- and erythropoiesis. This review describes similarities among CCI/PICS phenotypes in sepsis, cancer, and aging and reviews the role of aberrant myelopoiesis in the pathophysiology of CCI and PICS. In addition, we characterize pathogen recognition, the interface between innate and adaptive immune systems, and therapeutic approaches including immune modulators, gut microbiota support, and nutritional and exercise therapy. Finally, we discuss the future of diagnostic and prognostic approaches guided by machine and deep-learning models trained and validated on big data to identify patients for whom these approaches will yield the greatest benefits. A deeper understanding of the pathophysiology of CCI and PICS and continued investigation into novel therapies harbor the potential to improve the current dismal long-term outcomes for critically ill post-injury and post-infection patients.
We focused on the impact of postoperative infection on long-term survival after potentially curative resection for gastric cancer. Postoperative surgical and medical complications have been implicated as a negative predictor of long-term outcome in various malignancies. However, there have been no published reports assessing the impact of complications arising from postoperative infection on survival in gastric cancer. We studied a population of 1,332 patients who underwent curative resection for gastric cancer. These patients were divided into two groups based on the occurrence (141 patients, 10.6%) or absence (1,191 patients, 89.4%) of postoperative complications due to infection. We investigated the demographic and clinicopathological features of each patient with and without postoperative complications from infection, and thereby the impact of postoperative infection on long-term survival. Patients with postoperative infection had significantly higher frequency of males, upper side tumor location, and total gastrectomy as a surgical procedure, more advanced stage of gastric cancer, and greater age compared with those without postoperative infection. Patients with complications due to postoperative infection had significantly more unfavorable outcome compared with those patients without postoperative infection. Multivariate analysis demonstrated that age, preoperative comorbidity, blood transfusion, tumor depth, nodal involvement, and postoperative infection correlated with overall survival. We conclude that postoperative complications from infection are a predictor of adverse clinical outcome in patients with gastric cancer. However, further immunological study and prospective trials are necessary to confirm the biological significance of these findings.
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