Selective but not pan-CDK inhibition abrogates 5-FU-driven tissue factor upregulation in colon cancer.

Thromboembolic events are complications in cancer patients and hypercoagulability has been linked to the tissue factor (TF) pathway, making this an attractive target. Here, we investigated the effects of chemotherapeutics and CDK inhibitors (CDKI) abemaciclib/palbociclib (CDK4/6), THZ-1 (CDK7/12/13), and dinaciclib (CDK1/2/5/9) alone and in combination regimens on TF abundance and coagulation. The human colorectal cancer (CRC) cell line HROC173 was treated with 5-FU or gemcitabine to stimulate TF expression.

Urinary acid-base excretion deciphers high acid load from colonic bicarbonate loss in intestinal failure patients with ileocolonic anastomosis - Guidance for composition of parenteral support.

Background & Aims: Acid-base disturbances are common in short bowel (SB) patients due to increased intestinal bicarbonate loss. However, the resulting systemic acid load has not been quantified. Base excess is used to monitor metabolic acid-base disturbances but inadequately reflects the acid load.

Orally compensated short bowel patients are thin, potentially malnourished but rarely sarcopenic.

Background And Aim: In short bowel syndrome, insufficient absorptive capacity of the remnant bowel may lead to metabolic and nutritional consequences including electrolyte disturbances, severe diarrhea and malnutrition. While intestinal failure requires parenteral nutrition, short bowel patients with intestinal insufficiency (SB/II) have achieved oral autonomy. The aim of this exploratory study was to assess the nutritional, muscular and functional status of orally compensated SB/II patients.

Ileocolonic Healing after Small Ileocecal Resection in Mice: NOD2 Deficiency Impairs Anastomotic Healing by Local Mechanisms.

Ileocecal resection (ICR) is frequently performed in Crohn's disease (CD). mutations are risk factors for CD. knockout (ko) mice show impaired anastomotic healing after extended ICR.

Validation of the Readiness for End-of-Life Conversations (REOLC) scale in a German hospital setting.

Objective: For every health behavior, readiness to engage is a necessary and crucial foundation for following conversations, interventions or behavior changes. The present study aims to support a one-factor structure for the Readiness for End-of-Life Conversations (REOLC) scale (Berlin et al., 2021) in a population of cancer patients ( = 295).

Dysbiosis and reduced small intestinal function are required to induce intestinal insufficiency in mice.

Extensive bowel resection can lead to short bowel syndrome and intestinal failure. Resection-induced dysbiosis may be related to the specific anatomic site of resection and influences the disease progression. Although patients with end-jejunostomy are at high risk for intestinal failure, preservation of the ileocecal valve and colon counteracts this risk.

Effects of Bile Duct Ligation and Ghrelin Treatment on the Colonic Barrier and Microbiome of Mice.

Introduction: Cholestatic liver disease (CLD) is associated with intestinal barrier dysfunction. The peptide hormone ghrelin may exert both hepatoprotective and barrier-strengthening effects. Here, we have evaluated these effects under the conditions of experimental cholestasis.

Developing a care pathway for hospital-based advance care planning for cancer patients: A modified Delphi study.

Objectives: The objective of this study is to develop a care pathway for a hospital-based advance care planning service for cancer patients.

Methods: A web-based modified Delphi study consulted an expert panel consisting of a convenience sample of stakeholders including professionals with a special interest in advance care planning as well as a 'public and patient involvement group'. After generating ideas for core elements of a care pathway in the first round, numerical ratings and rankings informed the multi-professional research steering group's decision process eventually resulting in a final pathway.

Death anxiety as general factor to fear of cancer recurrence.

Objective: Fear of cancer recurrence or progress is strongly related to death anxiety (DA) in cancer patients, but due to lack of conceptualization and measurement methods, the relationship was not analyzed quantitatively before. The aim of the present study was to investigate the conceptual relationship of both constructs, with DA expected to be the general construct.

Methods: Cancer patients (N = 121) participated in an online study.

The dual GLP-1 and GLP-2 receptor agonist dapiglutide promotes barrier function in murine short bowel.

Short bowel syndrome can occur after extensive intestinal resection, causing intestinal insufficiency or intestinal failure, which requires long-term parenteral nutrition. Glucagon-like peptide-2 (GLP-2) pharmacotherapy is now clinically used to reduce the disease burden of intestinal failure. However, many patients still cannot be weaned off from parenteral nutrition completely.

The versatile role of the contact system in cardiovascular disease, inflammation, sepsis and cancer.

The human contact system consists of plasma proteins, which - after contact to foreign surfaces - are bound to them, thereby activating the zymogens of the system into enzymes. This activation mechanism gave the system its name - contact system. It is considered as a procoagulant and proinflammatory response mechanism, as activation finally leads to the generation of fibrin and bradykinin.

Dapiglutide, a novel dual GLP-1 and GLP-2 receptor agonist, attenuates intestinal insufficiency in a murine model of short bowel.

Background: Extensive intestinal resection may lead to short bowel (SB) syndrome, resulting in intestinal insufficiency or intestinal failure (IF). Intestinal insufficiency and IF involve deficiency of the proglucagon-derived hormones glucagon-like peptide-1 (GLP-1) and GLP-2. Two major problems of SB are epithelial surface loss and accelerated transit.

Combined Gemcitabine and Immune-Checkpoint Inhibition Conquers Anti-PD-L1 Resistance in Low-Immunogenic Mismatch Repair-Deficient Tumors.

Tumors arising in the context of Lynch Syndrome or constitutional mismatch repair deficiency are hypermutated and have a good response towards immune-checkpoint inhibitors (ICIs), including α-PD-L1 antibodies. However, in most cases, resistance mechanisms evolve. To improve outcomes and prevent resistance development, combination approaches are warranted.

Development and Validation of the Readiness for End-of-Life Conversations (REOLC) Scale.

Engaging in end-of-life care considerations is beneficial when the time is right. The purpose of this study is to provide a valid instrument to assess peoples readiness for end-of-life conversations before they are initiated. A community sample was recruited in study one for exploratory factor analysis of a 13-item questionnaire.

Ileocolonic Healing After Extended Small Bowel Resection in Mice: NOD2 Deficiency Impairs Anastomotic Healing and Postoperative Outcome.

Background: Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) mutations are a genetic risk factor for Crohn disease. Ileocecal resection is the most often performed surgery in Crohn disease. We investigated the effect of Nod2 knockout (KO) status on anastomotic healing after extended ileocecal resection (ICR) in mice.

Nutritional management of chronic pancreatitis: A systematic review and meta-analysis of randomized controlled trials.

Background And Aim: Malnutrition is a frequent complication of chronic pancreatitis. Adequate nutritional support is imperative, but there is still uncertainty about the optimal nutritional treatment. This work systematically compiles evidence from randomized controlled trials investigating dietary interventions in chronic pancreatitis and, in a further step, contrasts those findings with existing dietary recommendations.

Preclinical insights into the gut-skeletal muscle axis in chronic gastrointestinal diseases.

Muscle wasting represents a constant pathological feature of common chronic gastrointestinal diseases, including liver cirrhosis (LC), inflammatory bowel diseases (IBD), chronic pancreatitis (CP) and pancreatic cancer (PC), and is associated with increased morbidity and mortality. Recent clinical and experimental studies point to the existence of a gut-skeletal muscle axis that is constituted by specific gut-derived mediators which activate pro- and anti-sarcopenic signalling pathways in skeletal muscle cells. A pathophysiological link between both organs is also provided by low-grade systemic inflammation.

SNX27 regulates DRA activity and mediates its direct recycling by PDZ-interaction in early endosomes at the apical pole of Caco2 cells.

DRA (downregulated in adenoma, SLC26A3) and NHE3 (Na/H exchanger 3, SLC9A3) together mediate intestinal electroneutral NaCl absorption. Both transporters contain PDZ (postsynaptic density 95, disc large, zonula occludens 1) binding motifs and interact with PDZ adaptor proteins regulating their activity and recycling. SNX27 (sorting nexin 27) contains a PDZ domain and is involved in the recycling of cargo proteins including NHE3.

Teduglutide Promotes Epithelial Tight Junction Pore Function in Murine Short Bowel Syndrome to Alleviate Intestinal Insufficiency.

Background: In short bowel syndrome, epithelial surface loss results in impaired nutrient absorption and may lead to intestinal insufficiency or intestinal failure. Nucleotide oligomerization domain 2 (Nod2) dysfunction predisposes to the development of intestinal failure after intestinal resection and is associated with intestinal barrier defects. Epithelial barrier function is crucial for intestinal absorption and for intestinal adaptation in the short bowel situation.

deficiency functionally impairs adaptation to short bowel syndrome via alterations of the epithelial barrier function.

Nucleotide-binding oligomerization domain-containing protein 2 () gene mutations are a risk factor for Crohn's disease and also associated with worse outcome in short bowel syndrome (SBS) patients independent of the underlying disease. The aim of this study was to analyze the effect of deficiency on barrier function and stool microbiome after extensive ileocecal resection in mice. Male C57BL6/J wild-type (WT) and -knockout (KO) mice underwent 40% ileocecal resection.

Villus Growth, Increased Intestinal Epithelial Sodium Selectivity, and Hyperaldosteronism Are Mechanisms of Adaptation in a Murine Model of Short Bowel Syndrome.

Background: Short bowel syndrome results from extensive small bowel resection and induces adaptation of the remaining intestine. Ileocecal resection (ICR) is the most frequent situation in humans. Villus hypertrophy is one hallmark of mucosal adaptation, but the functional mechanisms of mucosal adaptation are incompletely understood.

Vitamin D administration leads to a shift of the intestinal bacterial composition in Crohn's disease patients, but not in healthy controls.

Objective: Dysbiosis is a common feature in the pathogenesis of inflammatory bowel diseases (IBD). Environmental factors, such as vitamin D deficiency, seem to play a role in the intestinal inflammation of IBD. The aim of this study was to investigate whether vitamin D administration has an impact on the bacterial composition in Crohn's disease (CD) compared to healthy controls (HC).

Triathlon Medical Coverage: A Guide for Medical Directors.

Interest and participation in triathlon has grown rapidly over the past 20 yr and with this growth, there has been an increase in the number of new events. To maximize the safety of participation, triathlons require medical directors to plan and oversee medical care associated with event participation. Provision of proper medical care requires knowledge of staffing requirements, common triathlon medical conditions, impact of course design, communication skill, and a familiarity of administrative requirements.

Biofunctional Materials Based on Amino Cellulose Derivatives--A Nanobiotechnological Concept.

This feature article summarizes recent developments in the field of so-called aminodeoxy cellulose derivatives ("amino celluloses") that are applied for functional surface coating of biofunctional materials. After introducing common manufacturing methods for nanostructurized substrates (material surfaces and nanoparticles) biorelevant amino celluloses are described. It could be demonstrated that cellulose is a unique starting material for chemical modification of hydroxyl groups and the adjacent carbon atom.