Major depressive disorder (MDD) is a prevalent disease, in which one third of sufferers do not respond to antidepressants. Probiotics have the potential to be well-tolerated and cost-efficient treatment options. However, the molecular pathways of their effects are not fully elucidated yet. Based on previous literature, we assume that probiotics can positively influence inflammatory mechanisms. We aimed at analyzing the effects of probiotics on gene expression of inflammation genes as part of the randomized, placebo-controlled, multispecies probiotics PROVIT study in Graz, Austria. Fasting blood of 61 inpatients with MDD was collected before and after four weeks of probiotic intake or placebo. We analyzed the effects on gene expression of tumor necrosis factor (TNF), nuclear factor kappa B subunit 1 (NFKB1) and interleukin-6 (IL-6). In IL-6 we found no significant main effects for group (F(1,44) = 1.33, p = ns) nor time (F(1,44) = 0.00, p = ns), but interaction was significant (F(1,44) = 5.67, p < 0.05). The intervention group showed decreasing IL-6 gene expression levels while the placebo group showed increasing gene expression levels of IL-6. Probiotics could be a useful additional treatment in MDD, due to their anti-inflammatory effects. Results of the current study are promising, but further studies are required to investigate the beneficial effects of probiotic interventions in depressed individuals.

Enthusiasm has emerged for the potential of liquid biopsies to provide easily accessible genetic biomarkers for early diagnosis and mutational cancer characterization. We here systematically investigated the suitability of circulating cell‐free DNA (cfDNA) analysis for mutation detection in colorectal cancer (CRC) patients with respect to clinicopathological disease stage. Droplet Digital PCR (ddPCR) was performed to detect common point mutations in the KRAS and BRAF oncogenes in cfDNA from 65 patients and compared to mutations in tumor tissue. Stage of disease was classified according to UICC (Union for International Cancer Control) criteria. In tumor tissue, KRAS or BRAF mutations were present in 35 of 65 cases (44% UICC stage I, 50% stage II, 47% stage III, and 62% stage IV). Although cfDNA was detected in 100% of patients, ddPCR displayed the tumor tissue mutation in only 1 of 6 (17%) stage II patients, whereas 10 of 18 (56%) reported variants were verified in cfDNA samples of the stage IV cohort. No BRAF or KRAS mutation was detected in cfDNA from patients with wild‐type tumor tissue. In one case of mutant stage II colon cancer ( KRAS ‐G12C), the G12D variant was detected in cfDNA instead. Further workup revealed that circulating tumor‐derived DNA and liver metastases originated from a synchronous KRAS ‐mutated cancer of the pancreas. Our results demonstrate that ddPCR‐based analysis is highly specific and useful for mutation monitoring, but the sensitivity limits its usefulness for early cancer detection.

ZusammenfassungChordome sind maligne Knochentumoren, die mit einer jährlichen Inzidenz von 0,08 pro 100.000 Personen auftreten. Sie zeigen eine notochordale Differenzierung mit einer nukleären Expression von Brachyury (TBXT). Hauptlokalisation ist das axiale Skelett vom Clivus bis zum Sakrum und dem Os coccygis. Chordome wachsen langsam und lange nur lokal destruierend. Sie werden daher oft erst spät diagnostiziert. Putative Vorläuferläsionen sind Chordareste und der benigne notochordale Zelltumor. Dabei handelt es sich um zumeist mikroskopisch kleine, intraossäre Läsionen. Bei Chordomen werden unterschiedliche histologische Subtypen differenziert, welche sich prognostisch unterscheiden. Wiederkehrende genetische Veränderungen als Tumorauslöser sind nicht bekannt. Brachyury scheint eine noch nicht im Detail geklärte Schlüsselfunktion in der Entstehung von Chordomen zu besitzen. Die chirurgische En-bloc-Resektion mit negativen Resektionsrändern ist die einzige kurative Behandlungsoption. Die Hochdosisbestrahlung, speziell mit Protonen und Carbonionen, ist eine therapeutische Alternative in inoperablen Fällen. Medikamentöse Therapien sind für Chordome derzeit nicht zugelassen. Erste klinische Studien zu neuen Therapiemodalitäten laufen.