Surgery vs. radiotherapy in localized prostate cancer. Which is best?

Surgery and radiotherapy are currently accepted alternatives for the treatment of localized prostate cancer. In the absence of relevant randomized trials no decision regarding the superiority of any of the given approaches can be made. Up to now several cohort-based approaches indicate similar outcomes for both treatments. Based on a new population based approach, Merglen and co-workers recently concluded that surgery would offer the best chance of long-term control in terms of 10-year survival for T1–T3 prostate cancer patients. Unfortunately the strength of this trial is limited by several shortcomings. Most importantly, issues of radiation dosage have not been taken into account. In addition, several relevant parameters including Gleason score and PSA are not well balanced between the arms and the assignment to arbitrary risk groups does not reflect the real biological behaviour. Thus, the data provided do not support the strong conclusion issued by the authors. Based on the data available, surgery and radiotherapy still have to be considered as equally effective

ATG16L1 orchestrates interleukin-22 signaling in the intestinal epithelium via cGAS-STING.

A coding variant of the inflammatory bowel disease (IBD) risk gene ATG16L1 has been associated with defective autophagy and deregulation of endoplasmic reticulum (ER) function. IL-22 is a barrier protective cytokine by inducing regeneration and antimicrobial responses in the intestinal mucosa. We show that ATG16L1 critically orchestrates IL-22 signaling in the intestinal epithelium. IL-22 stimulation physiologically leads to transient ER stress and subsequent activation of STING-dependent type I interferon (IFN-I) signaling, which is augmented in Atg16l1 ΔIEC intestinal organoids. IFN-I signals amplify epithelial TNF production downstream of IL-22 and contribute to necroptotic cell death. In vivo, IL-22 treatment in Atg16l1 ΔIEC and Atg16l1 ΔIEC/Xbp1 ΔIEC mice potentiates endogenous ileal inflammation and causes widespread necroptotic epithelial cell death. Therapeutic blockade of IFN-I signaling ameliorates IL-22-induced ileal inflammation in Atg16l1 ΔIEC mice. Our data demonstrate an unexpected role of ATG16L1 in coordinating the outcome of IL-22 signaling in the intestinal epithelium

Engraftment of engineered ES cell–derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium

Cellular cardiomyoplasty is an attractive option for the treatment of severe heart failure. It is, however, still unclear and controversial which is the most promising cell source. Therefore, we investigated and examined the fate and functional impact of bone marrow (BM) cells and embryonic stem cell (ES cell)–derived cardiomyocytes after transplantation into the infarcted mouse heart. This proved particularly challenging for the ES cells, as their enrichment into cardiomyocytes and their long-term engraftment and tumorigenicity are still poorly understood. We generated transgenic ES cells expressing puromycin resistance and enhanced green fluorescent protein cassettes under control of a cardiac-specific promoter. Puromycin selection resulted in a highly purified (>99%) cardiomyocyte population, and the yield of cardiomyocytes increased 6–10-fold because of induction of proliferation on purification. Long-term engraftment (4–5 months) was observed when co-transplanting selected ES cell–derived cardiomyocytes and fibroblasts into the injured heart of syngeneic mice, and no teratoma formation was found (n = 60). Although transplantation of ES cell–derived cardiomyocytes improved heart function, BM cells had no positive effects. Furthermore, no contribution of BM cells to cardiac, endothelial, or smooth muscle neogenesis was detected. Hence, our results demonstrate that ES-based cell therapy is a promising approach for the treatment of impaired myocardial function and provides better results than BM-derived cells

Epithelial RNase H2 Maintains Genome Integrity and Prevents Intestinal Tumorigenesis in Mice

BACKGROUND & AIMS: RNase H2 is a holoenzyme, composed of 3 subunits (ribonuclease H2 subunits A, B, and C), that cleaves RNA:DNA hybrids and removes mis-incorporated ribonucleotides from genomic DNA through ribonucleotide excision repair. Ribonucleotide incorporation by eukaryotic DNA polymerases occurs during every round of genome duplication and produces the most frequent type of naturally occurring DNA lesion. We investigated whether intestinal epithelial proliferation requires RNase H2 function and whether RNase H2 activity is disrupted during intestinal carcinogenesis. METHODS: We generated mice with epithelial-specific deletion of ribonuclease H2 subunit B (H2bΔIEC) and mice that also had deletion of tumor-suppressor protein p53 (H2b/p53ΔIEC); we compared phenotypes with those of littermate H2bfl/fl or H2b/p53fl/fl (control) mice at young and old ages. Intestinal tissues were collected and analyzed by histology. We isolated epithelial cells, generated intestinal organoids, and performed RNA sequence analyses. Mutation signatures of spontaneous tumors from H2b/p53ΔIEC mice were characterized by exome sequencing. We collected colorectal tumor specimens from 467 patients, measured levels of ribonuclease H2 subunit B, and associated these with patient survival times and transcriptome data. RESULTS: The H2bΔIEC mice had DNA damage to intestinal epithelial cells and proliferative exhaustion of the intestinal stem cell compartment compared with controls and H2b/p53ΔIEC mice. However, H2b/p53ΔIEC mice spontaneously developed small intestine and colon carcinomas. DNA from these tumors contained T>G base substitutions at GTG trinucleotides. Analyses of transcriptomes of human colorectal tumors associated lower levels of RNase H2 with shorter survival times. CONCLUSIONS: In analyses of mice with disruption of the ribonuclease H2 subunit B gene and colorectal tumors from patients, we provide evidence that RNase H2 functions as a colorectal tumor suppressor. H2b/p53ΔIEC mice can be used to study the roles of RNase H2 in tissue-specific carcinogenesis

FDG-PET/CT zum Ausschluss von zervikalen Lymphknotenmetastasen bei Kopf-Hals-Tumoren in der klinischen N0-Situation

Background!#!In order to provide safe care to a patient in an emergency situation, it is useful to know something about the patient's previous medical conditions and medication. For this very reason smartphones have been equipped with so-called emergency apps (e.g. medical-ID, emergency-ID). The aim of our study was to find out whether the owners of smartphones are using the apps and whether medical professionals are trying to access this information.!##!Methods!#!We conducted a survey among patients in our outpatient clinic at a level one trauma center. We collected data over 3 months regarding the usage behavior of the aforementioned apps. We simultaneously asked emergency physicians at various hospitals about their experiences with these apps.!##!Results!#!We were able to interview 192 patients and 103 emergency physicians. The emergency apps were unknown to 45% (n = 79) of the respondents; only 10% (n = 19) of the respondents had the app with data stored. Furthermore, it was found that a total of 21% (n = 41) of the persons carried a note on themselves with previous illnesses and medication. Of the surveyed physicians, 42% (n = 44) stated that they had heard of the app before; however, only 6% (n = 5) routinely searched the smartphone for relevant information in the case of nonresponsive patients. Only 14% of physicians (n = 14) have successfully used the app so far.!##!Conclusion!#!The collected data show that the emergency apps are still unknown to many patients and emergency physicians alike. Due to the low distribution it does not seem to be recommendable to search the smartphone for the apps in time-critical situations after accidents. For patients over 55 years of age, it currently seems more promising to search their wallets for information regarding their previous illnesses