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Background Hepatosteatosis is the earliest stage in the pathogenesis of nonalcoholic fatty (NAFLD) and alcoholic liver disease (ALD). As NAFLD is affecting 10–24% of the general population and approximately 70% of obese patients, it carries a large economic burden and is becoming a major reason for liver transplantation worldwide. ALD is a major cause of morbidity and mortality causing 50% of liver cirrhosis and 10% of liver cancer related death. Increasing evidence has accumulated that gut-derived factors play a crucial role in the development and progression of chronic liver diseases. Methods A selective literature search was conducted in Medline and PubMed, using the terms “nonalcoholic fatty liver disease,” “alcoholic liver disease,” “lipopolysaccharide,” “gut barrier,” and “microbiome.” Results Gut dysbiosis and gut barrier dysfunction both contribute to chronic liver disease by abnormal regulation of the gut-liver axis. Thereby, gut-derived lipopolysaccharides (LPS) are a key factor in inducing the inflammatory response of liver tissue. The review further underlines that endotoxemia is observed in both NAFLD and ALD patients. LPS plays an important role in conducting liver damage through the LPS-TLR4 signaling pathway. Treatments targeting the gut microbiome and the gut barrier such as fecal microbiota transplantation (FMT), probiotics, prebiotics, synbiotics, and intestinal alkaline phosphatase (IAP) represent potential treatment modalities for NAFLD and ALD. Conclusions The gut-liver axis plays an important role in the development of liver disease. Treatments targeting the gut microbiome and the gut barrier have shown beneficial effects in attenuating liver inflammation and need to be further investigated.

Colorectal cancer (CRC) is one of the most common solid malignant burdens worldwide. Cancer immunology and immunotherapy have become fundamental areas in CRC research and treatment. Currently, the method of generating Immune-Related Gene Prognostic Indices (IRGPIs) has been found to predict patient prognosis as an immune-related prognostic biomarker in a variety of tumors. However, their role in patients with CRC remains mostly unknown. Therefore, we aimed to establish an IRGPI for prognosis evaluation in CRC. RNA-sequencing data and clinical information of CRC patients were retrieved from The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO) databases as training and validation sets, respectively. Immune-related gene data was obtained from the and databases. The weighted gene co-expression network analysis (WGCNA) was used to identify hub immune-related genes. An IRGPI was then constructed using Cox regression methods. Based on the median risk score of IRGPI, patients could be divided into high-risk and low-risk groups. To further investigate the immunologic differences, Gene set variation analysis (GSVA) studies were conducted. In addition, immune cell infiltration and related functional analysis were used to identify the differential immune cell subsets and related functional pathways. We identified 49 immune-related genes associated with the prognosis of CRC, 17 of which were selected for an IRGPI. The IRGPI model significantly differentiates the survival rates of CRC patients in the different groups. The IRGPI as an independent prognostic factor significantly correlates with clinico-pathological factors such as age and tumor stage. Furthermore, we developed a nomogram to improve the clinical utility of the IRGPI score. Immuno-correlation analysis in different IRGPI groups revealed distinct immune cell infiltration (CD4 T cells resting memory) and associated pathways (macrophages, Type I IFNs responses, iDCs.), providing new insights into the tumor microenvironment. At last, drug sensitivity analysis revealed that the high-risk IRGPI group was sensitive to 11 and resistant to 15 drugs. Our study established a promising immune-related risk model for predicting survival in CRC patients. This could help to better understand the correlation between immunity and the prognosis of CRC providing a new perspective for personalized treatment of CRC.

Liver transplantation as a treatment option for end-stage liver diseases is associated with a relevant risk for complications. On the one hand, immunological factors and associated chronic graft rejection are major causes of morbidity and carry an increased risk of mortality due to liver graft failure. On the other hand, infectious complications have a major impact on patient outcomes. In addition, abdominal or pulmonary infections, and biliary complications, including cholangitis, are common complications in patients after liver transplantation and can also be associated with a risk for mortality. Thereby, these patients already suffer from gut dysbiosis at the time of liver transplantation due to their severe underlying disease, causing end-stage liver failure. Despite an impaired gut-liver axis, repeated antibiotic therapies can cause major changes in the gut microbiome. Due to repeated biliary interventions, the biliary tract is often colonized by several bacteria with a high risk for multi-drug resistant germs causing local and systemic infections before and after liver transplantation. Growing evidence about the role of gut microbiota in the perioperative course and their impact on patient outcomes in liver transplantation is available. However, data about biliary microbiota and their impact on infectious and biliary complications are still sparse. In this comprehensive review, we compile the current evidence for the role of microbiome research in liver transplantation with a focus on biliary complications and infections due to multi-drug resistant germs.

Purposes Postoperative infections are the common cause of morbidity and mortality in colorectal surgery. Calprotectin, an S100 protein, may be a potential marker. The aim was to define the postoperative course (PC) of calprotectin in serum (CIS), compared to white blood cell (WBC), C-reactive protein (CRP), lactate and procalcitonin (PCT). Methods This prospective, single-center study measured all biomarkers preoperatively, on the first, third and fifth postoperative days (POD). The endpoint was the PC of CIS compared to the WBC, CRP, PCT, and lactate. CIS between benign and malignant disease and between patients with and without complications was compared. Also a correlation was carried out. Results 56 patients (14 rectum, 42 colon) were included. The postoperative CIS increased to preoperative values ( p  < 0.05). The preoperative CIS in malignant disease was higher ( p  < 0.05). CIS on the first and fifth POD was higher in the group with complications ( p  < 0.05). CIS and CRP, WBC and CRP on the third POD ( p  < 0.05) correlate in complications . Conclusion We present the normal course of CIS and its potential function as a marker for systemic inflammation. We showed that postoperative CIS were significantly higher in complications. Although our study has several limitations, - namely a small sample size and heterogeneous surgical procedures -, serum calprotectin may be an interesting biomarker for future larger studies, particularly due to its increased specificity for intestinal inflammation. Trial registration This study is prospectively registered in DRKS-ID (Deutsches Register Klinischer Studien, German WHO Register): DRKS00027142, data of registration 29.11.2021. This is a WHO-recognized primary registry that meets the requirements of the International Committee of Medical Journal Editors (ICMJE). We registered this study in the DKG (Deutsche Krebsgesellschaft) Sudybox ST-D512, data of registration 11.03.2022.

The incidence of early-onset colorectal cancer (EO-CRC, in patients younger than 50) is increasing worldwide. The specific gene signatures in EO-CRC patients are largely unknown. Since EO-CRC with microsatellite instability is frequently associated with Lynch syndrome, we aimed to comprehensively characterize the tumor microenvironment (TME) and gene expression profiles of EO-CRC with microsatellite stable (MSS-EO-CRC). Here, we demonstrated that MSS-EO-CRC has a similar pattern of tumor-infiltrating immune cells, immunotherapeutic responses, consensus molecular subtypes, and prognosis as late-onset CRC with MSS (MSS-LO-CRC). 133 differential expressed genes were identified as unique gene signatures of MSS-EO-CRC. Moreover, we established a risk score, which was positively associated with PD-L1 expression and could reflect both the level of tumor-infiltrating immune cells and the prognosis of MSS-EO-CRC patients. Application of this score on the anti-PD-L1 treatment cohort demonstrated that the low-risk score group has significant therapeutic advantages and clinical benefits. In addition, candidate driver genes were identified in the different-sidedness of MSS-EO-CRC patients. Altogether, MSS-EO-CRC exhibits distinct molecular profiles that differ from MSS-LO-CRC even though they have a similar TME characterization and survival pattern. Our risk score appears to be robust enough to predict prognosis and immunotherapeutic response and therefore could help to optimize the treatment of MSS-EO-CRC.

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disease, ranging from simple steatosis to hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Liver fibrosis, which portends a poor prognosis in NAFLD, is characterized by the excessive accumulation of extracellular matrix (ECM) proteins resulting from abnormal wound repair response and metabolic disorders. Various metabolic factors play crucial roles in the progression of NAFLD, including abnormal lipid, bile acid, and endotoxin metabolism, leading to chronic inflammation and hepatic stellate cell (HSC) activation. Autophagy is a conserved process within cells that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism. Accumulating evidence has shown the importance of autophagy in NAFLD and its close relation to NAFLD progression. Thus, regulation of autophagy appears to be beneficial in treating NAFLD and could become an important therapeutic target.

The development and progression of colorectal cancer (CRC) are known to be affected by the interplay between tumor and immune cells. However, the impact of CRC cells on the systemic immunity has yet to be elucidated. We aimed to comprehensively evaluate the circulating immune subsets and transcriptional profiles of CRC patients. In contrast to healthy controls (HCs), CRC patients had a lower percentage of B and T lymphocytes, T helper (Th) cells, non-classical monocytes, dendritic cells, and a higher proportion of polymorphonuclear myeloid-derived suppressor cells, as well as a reduced expression of CD69 on NK cells. Therefore, CRC patients exhibit a more evident systemic immune suppression than HCs. A diagnostic model integrating seven immune subsets was constructed to distinguish CRC patients from HCs with an AUC of 1.000. Moreover, NR3C2, CAMK4, and TRAT1 were identified as candidate genes regulating the number of Th cells in CRC patients. The altered composition of circulating immune cells in CRC could complement the regional immune status of the tumor microenvironment and contribute to the discovery of immune-related biomarkers for the diagnosis of CRC.

Purposes Postoperative bleeding remains a life-threatening complication in thyroid surgery. The aim was to assess the efficacy of four different hemostatic agents, Collagen-Fibrinogen-Thrombin Patch (CFTP) in two sizes (3 × 2.5 cm and 9.5 × 4.8 cm), polysaccharide particles (1 g) and Cellulose Gauze (2.5 × 5 cm) on postoperative drainage volume (DV) compared to a control group. Methods We included from October 2007 until Mai 2011, 150 patients (30 per group) for this monocentric, retrospective case-controlled study. Patients were scheduled for a hemithyroidectomy or thyroidectomy. The primary endpoint was the postoperative DV within the first 24 h, secondary the incidence of adverse events. Results There were no difference in demographic parameters. The mean DV (± SD) was 51.15 (± 36.86) ml in the control, 50.65 (± 42.79) ml in small (3 × 2.5 cm), 25.38 (± 23.99) ml in large CFTP (9.5 × 4.8 cm), 53.11 (± 39.48) ml in the polysaccharide particles and 48.94 (± 30.59) ml in the cellulose gauze group. DV was significantly reduced with the large CFTP ( p  < 0.05) compared to all other groups. There were no adverse events. Conclusions We were able to demonstrate a significant reduction in the DV for the large CFTP group compared to the other collectives. Although this as being associated with not inconsiderable costs and we would only recommend its use for high-risk patients only.

Background: mTOR-Is positively influence the occurrence and course of certain tumors after solid organ transplantation. mTOR-inhibitor (mTOR-I) treatment, either alone or in combination with Calcineurininhibitors (CNIs), significantly reduces the incidence of malignancies after organ transplantation. However, there is no information on which mTOR-I, Sirolimus (SIR) or Everolimus (ERL), has a stronger anti-tumoral effect. Methods: The current literature was searched for prospective randomized controlled trials in renal transplantation. There were 1.164 trials screened, of which 20 could be included (7465 patients). We performed a network meta-analysis to analyze the relative risk of different types of mTOR-I compared to CNI treatment on malignancies after transplantation. A minimum follow-up of 24 months was mandatory for inclusion. Results: Four different types of mTOR-I treatment were analyzed in network meta-analyses—SIR mono, ERL mono, SIR with CNI, and ERL with CNI. The average follow-up of all trials was 43.8 months. All four different mTOR-I regimes showed a significant reduced relative risk for malignancies compared to a regular CNI-treatment with the strongest effect under SIR in combination with a CNI (RR 0.23, CI 0.09–0.55, p = 0.001). This effect remained consistent for all tumor entities except non-melanoma skin cancer (RR 0.25, CI 0.07–0.90, p = 0.033). Conclusions: It is well known that an mTOR-I based treatment in transplant patients reduces the risk of tumor manifestation in comparison to CNI treatment. A combination of SIR and CNI seems to be the most potent mTOR-I therapy against malignancies.

Objectives Cold ischemia during kidney transplantation induces ischemia-reperfusion injury with endothelial dysfunction, capillary leak, and impaired perfusion. Its duration critically determines graft outcome. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables noninvasive assessment of renal microcirculation and may indicate ischemic injury. We evaluated the impact of ischemia duration on DCE-MRI-derived perfusion parameters in renal transplants in mice. Materials and methods Procedures were approved by the local institutional animal care and use committee. A total of 15 C57BL/6 mice underwent kidney transplantation and were assigned to a short or prolonged cold ischemia group. DCE-MRI was performed to assess renal perfusion. Imaging was conducted at a mean of 268 ± 30 days (mean ± standard deviation) after transplantation. Perfusion parameters were calculated using the Patlak model, which provides the plasma volume fraction (v p ), reflecting renal blood volume and perfusion, and the volume transfer constant (K trans ), characterizing the rate of contrast agent extravasation from capillaries into the extravascular extracellular space. Results Significant differences were observed in the K trans parameter of transplanted kidneys between groups. The median K trans (mL/100 mL/min) was significantly higher in the 16-h group (2.87, interquartile range 2.45–3.03) versus the 30-min group (0.91, 0.90–1.42; p  = 0.008). Median v p (mL/100 mL/min) was non-significantly lower in the 16-h group (21.89, 17.28–23.22) versus the 30-min group (29.02, 24.99–37.15; p  = 0.151). Conclusion Cold ischemia with 16-h duration was associated with significantly higher K trans values in kidney transplants, reflecting significantly increased vascular permeability. DCE-MRI provides a sensitive tool for detecting ischemia-induced microvascular dysfunction. Relevance statement Quantitative DCE-MRI detects microvascular injury after 16-h cold ischemia in kidney transplants in mice, supporting its potential as a noninvasive tool to assess graft integrity and guide interventions aimed at improving long-term transplant outcomes. Key Points The duration of ischemia critically affects endothelial integrity and perfusion characteristics in a mouse kidney transplant model. Prolonged 16-h ischemia leads to increased vascular permeability, indicating more severe endothelial and microcirculatory injury in transplanted kidneys. DCE-MRI enables sensitive detection of subtle ischemia-related microvascular alterations, supporting its value for noninvasive graft assessment. Graphical Abstract