Biomarker zu Sepsisdiagnose und -therapiesteuerung – Nicht mehr als ein Puzzleteil

Die Anaesthesiologie -     

Helicobacter pylori infection,chronic atrophic gastritis and risk of stomach and esophagus cancer: Results from the prospective population-based ESTHER cohort study

Helicobacter pylori (H. pylori) infection is considered as principal cause of gastric cancer. It is further associated with a reduced risk of esophageal adenocarcinomas. In a large prospective population-based cohort study including 9,949 subjects with average observation time of 13.8 years, we assessed the risk of invasive gastric and esophageal cancer according to H. pylori infection and presence of chronic atrophic gastritis (CAG). Incidence rates and hazard ratios (HR) derived by Cox proportional hazards models and adjusted for relevant confounders were derived by seroprevalence of H. pylori and cytotoxin-associated gene A (CagA) antibodies and presence of CAG based on serological markers at baseline, respectively. During follow-up, 30 cases of noncardia gastric cancer and 33 cases of esophageal cancer were observed. Infection by H. pylori without and with expression of CagA was associated with a 5.2-fold (95% confidence interval 1.00–27.1) and an 18.2-fold (4.3–77.4) increase of noncardia gastric cancer incidence. A 0.65-fold decreased risk of esophageal adenocarcinomas (HR 0.35, 0.12–0.97) was observed among H. pylori-infected individuals. In participants infected with CagA expressed H. pylori, the presence of mild/moderate and severe CAG was associated with a 6.4-fold (1.3–31.0) and an 11.8-fold (3.1–45.4) increase of gastric cancer incidence, respectively. The results of this prospective population-based cohort study may contribute relevant evidence to the ongoing research of H. pylori-related cancers. The results may furthermore enhance the empirical basis for risk stratification among H. pylori-infected people and for recommendations regarding H. pylori screening and treatment among older adults in a Western population.     

PELP1 signaling contributes to medulloblastoma progression by regulating the NF-κB pathway

Medulloblastoma (MB) is the most common and deadliest brain tumor in children. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a scaffolding protein and its oncogenic signaling is implicated in the progression of several cancers. However, the role of PELP1 in the progression of MB remains unknown. The objective of this study is to examine the role of PELP1 in the progression of MB. Immunohistochemical analysis of MB tissue microarrays revealed that PELP1 is overexpressed in the MB specimens compared to normal brain. Knockdown of PELP1 reduced cell proliferation, cell survival, and cell invasion of MB cell lines. The RNA-sequencing analysis revealed that PELP1 knockdown significantly downregulated the pathways related to inflammation and extracellular matrix. Gene set enrichment analysis confirmed that the PELP1-regulated genes were negatively correlated with nuclear factor-κB (NF-κB), extracellular matrix, and angiogenesis gene sets. Interestingly, PELP1 knockdown reduced the expression of NF-κB target genes, NF-κB reporter activity, and inhibited the nuclear translocation of p65. Importantly, the knockdown of PELP1 significantly reduced in vivo MB progression in orthotopic models and improved the overall mice survival. Collectively, these results suggest that PELP1 could be a novel target for therapeutic intervention in MB.     

Mailed fecal immunochemical test outreach for colorectal cancer screening: Summary of a Centers for Disease Control and Prevention–sponsored Summit

Uptake of colorectal cancer screening remains suboptimal. Mailed fecal immunochemical testing (FIT) offers promise for increasing screening rates, but optimal strategies for implementation have not been well synthesized. In June 2019, the Centers for Disease Control and Prevention convened a meeting of subject matter experts and stakeholders to answer key questions regarding mailed FIT implementation in the United States. Points of agreement included: 1) primers, such as texts, telephone calls, and printed mailings before mailed FIT, appear to contribute to effectiveness; 2) invitation letters should be brief and easy to read, and the signatory should be tailored based on setting; 3) instructions for FIT completion should be simple and address challenges that may lead to failed laboratory processing, such as notation of collection date; 4) reminders delivered to initial noncompleters should be used to increase the FIT return rate; 5) data infrastructure should identify eligible patients and track each step in the outreach process, from primer delivery through abnormal FIT follow-up; 6) protocols and procedures such as navigation should be in place to promote colonoscopy after abnormal FIT; 7) a high-quality, 1-sample FIT should be used; 8) sustainability requires a program champion and organizational support for the work, including sufficient funding and external policies (such as quality reporting requirements) to drive commitment to program investment; and 9) the cost effectiveness of mailed FIT has been established. Participants concluded that mailed FIT is an effective and efficient strategy with great potential for increasing colorectal cancer screening in diverse health care settings if more widely implemented.     

Survival of malignant mesothelioma and other rare thoracic cancers in Germany and the United States: A population-based study

Evidence on survival of malignant mesothelioma (MM) and other rare thoracic cancers is limited due to the rarity of these cancer sites. Here, we provide a comprehensive overview of MM incidence and survival after MM and other rare thoracic cancers in Germany and the United States (US). Incidence was estimated from a German National Cancer Database and from the Surveillance, Epidemiology and End Results (SEER) 18 database for 2000–2014. Patients diagnosed in 1997–2013 with malignant epithelial tumors of the trachea (Etra), epithelial tumors of the thymus (Ethy) and MM were extracted from a German cancer survival database and from the SEER 13 database. Period analysis was employed to compute 5-year relative survival (RS). During 2000–2014, an annual average of 0.9 and 0.6 MM cases per 100,000 person-years was diagnosed in Germany and the US. Rates decreased in Germany and in the US. Patients with Ethy had highest 5-year RS with US patients surviving longer (69.1% compared to 63.7%, p = 0.02). Survival after Etra was comparable in both countries (Germany 33.6%, US 34.4%, p = 0.07). Survival in MM patients was poor overall (Germany 11.8%, US 12.1%, p < 0.01). Survival improvements were only observed in MM patients in Germany (10.8% [2002–2007] vs. 13.0% [2008–2013], p < 0.01). The lack of progress in survival for Etra and Ethy patients underlines the need of novel preventive, therapeutic and diagnostic approaches. MM incidence significantly decreased in Germany and in the US. Further monitoring of MM incidence is warranted given that a peak in incidence is expected in 2020–2030 in Western countries.