Painless colonoscopy: fact or fiction?

Although colonoscopy is a routinely performed procedure, it is not devoid of challenges, such as the potential for perforation and considerable patient discomfort, leading to patients postponing the procedure with several healthcare risks. This review delves into preprocedural and procedural solutions, and emerging technologies aimed at addressing the drawbacks of colonoscopies. Insufflation and sedation techniques, together with various other methods, have been explored to increase patient satisfaction, and thereby, the quality of endoscopy. Recent advances in this field include the prevention of loop formation, encompassing the use of variable-stiffness endoscopes, computer-guided scopes, magnetic endoscopic imaging, robotics, and capsule endoscopy. An autonomous endoscope that relies on self-propulsion to completely avoid looping is a potentially groundbreaking technology for the next generation of endoscopes. Nevertheless, critical techniques need to be refined to ensure the development of effective and efficient endoscopes.

Development of muscle weakness in a mouse model of critical illness: does fibroblast growth factor 21 play a role?

BACKGROUND: Critical illness is hallmarked by severe stress and organ damage. Fibroblast growth factor 21 (FGF21) has been shown to rise during critical illness. FGF21 is a pleiotropic hormone that mediates adaptive responses to tissue injury and repair in various chronic pathological conditions. Animal studies have suggested that the critical illness-induced rise in FGF21 may to a certain extent protect against acute lung, liver, kidney and brain injury. However, FGF21 has also been shown to mediate fasting-induced loss of muscle mass and force. Such loss of muscle mass and force is a frequent problem of critically ill patients, associated with adverse outcome. In the present study, we therefore investigated whether the critical illness-induced acute rise in FGF21 is muscle-protective or rather contributes to the pathophysiology of critical illness-induced muscle weakness. METHODS: In a catheterised mouse model of critical illness induced by surgery and sepsis, we first assessed the effects of genetic FGF21 inactivation, and hence the inability to acutely increase FGF21, on survival, body weight, muscle wasting and weakness, and markers of muscle cellular stress and dysfunction in acute (30 h) and prolonged (5 days) critical illness. Secondly, we assessed whether any effects were mirrored by supplementing an FGF21 analogue (LY2405319) in prolonged critical illness. RESULTS: FGF21 was not required for survival of sepsis. Genetic FGF21 inactivation aggravated the critical illness-induced body weight loss (p = 0.0003), loss of muscle force (p = 0.03) and shift to smaller myofibers. This was accompanied by a more pronounced rise in markers of endoplasmic reticulum stress in muscle, without effects on impairments in mitochondrial respiratory chain enzyme activities or autophagy activation. Supplementing critically ill mice with LY2405319 did not affect survival, muscle force or weight, or markers of muscle cellular stress/dysfunction. CONCLUSIONS: Endogenous FGF21 is not required for sepsis survival, but may partially protect muscle force and may reduce cellular stress in muscle. Exogenous FGF21 supplementation failed to improve muscle force or cellular stress, not supporting the clinical applicability of FGF21 supplementation to protect against muscle weakness during critical illness.

Microgels as Platforms for Antibody-Mediated Cytokine Scavenging.

Therapeutic antibodies are the key treatment option for various cytokine-mediated diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. However, systemic injection of these antibodies can cause side effects and suppress the immune system. Moreover, clearance of therapeutic antibodies from the blood is limiting their efficacy. Here, water-swollen microgels are produced with a size of 25 µm using droplet-based microfluidics. The microgels are functionalized with TNFα antibodies to locally scavenge the pro-inflammatory cytokine TNFα. Homogeneous distribution of TNFα-antibodies is shown throughout the microgel network and demonstrates specific antibody-antigen binding using confocal microscopy and FLIM-FRET measurements. Due to the large internal accessibility of the microgel network, its capacity to bind TNFα is extremely high. At a TNFα concentration of 2.5 µg mL-1 , the microgels are able to scavenge 88% of the cytokine. Cell culture experiments reveal the therapeutic potential of these microgels by protecting HT29 colorectal adenocarcinoma cells from TNFα toxicity and resulting in a significant reduction of COX II and IL8 production of the cells. When the microgels are incubated with stimulated human macrophages, to mimic the in vivo situation of inflammatory bowel disease, the microgels scavenge almost all TNFα that is produced by the cells.

Evone® Flow-Controlled Ventilation During Upper Airway Surgery: A Clinical Feasibility Study and Safety Assessment.

Introduction: During upper airway surgery in a narrowed airway due to tumor or stenosis, safe ventilation, good laryngotracheal exposure, and preservation of an adequate surgical working space are of paramount importance. This can be achieved by small-lumen ventilation such as High Frequency Jet Ventilation (HFJV). However, this technique has major drawbacks, such as air-trapping and desaturation in patients with poor pulmonary reserve. Recently, an innovative ventilating system with flow-controlled ventilation (FCV) and a small-lumen endotracheal tube, the Evone® (Ventinova, Eindhoven, The Netherlands), was introduced, claiming to counter the drawbacks of HFJV. Objectives: To evaluate feasibility and safety of the Evone® FCV system in difficult upper airway surgery and to critically appraise this novel ventilation method. Patients and methods: Evone® is a FCV-device using a small-bore cuffed tube (Tritube®). This ventilator actively sucks air out of the lungs, rather than relying on the passive backflow of air like in HFJV. Data related to the medical history, surgery, and anesthesia of all consecutive patients undergoing upper airway surgery with Evone® FCV ventilation were included in a tertiary center retrospective observational study. Results: Fifteen Patients, with a median age of 54 years, were included. Surgical procedures and indications included laser-assisted endoscopic treatment of idiopathic subglottic stenosis (n = 3), tracheal stenosis (n = 1), and posterior glottic stenosis (n = 2), biopsy and/or Transoral Laser Microsurgery for laryngeal (pre)malignancy (n = 7) and resection of benign lesions with posterior (supra)glottic location (n = 2). Mean ventilation duration was 52.0 min (range 30-115 min, SD 19.6 min), mean surgery duration was 31.7 min (range 15-65 min, SD 13.2 min), mean minimal SaO2 was 96.3% (range 89-100%, SD 4.0%) and mean peak pCO2 was 41.4 mmHg (range 31-50 mmHg, SD = 5.5 mmHg). No anesthesia- or surgery-related complications, adverse events or intra-operative difficulties were reported during or after any of the 15 procedures. In all cases, compared to HFJV, Evone® FCV ventilation allowed a superior visualization and working space during the surgical procedure. Conclusion: The Evone® FCV ventilation system provides excellent conditions in patients undergoing upper airway surgery, as it combines excellent accessibility and visibility of the operation site with safe and stable ventilation.

Microgels Sopping Up Toxins-GM1a-Functionalized Microgels as Scavengers for Cholera Toxin.

Vibrio cholerae is a Gram-negative bacterium that causes secretory diarrhea and constitutes a major health threat in the industrialized world and even more in developing countries. Its main virulence factor is the cholera toxin, which is internalized by intestinal epithelial cells after binding to the glycosphingolipid receptor GM1a on their apical surface. A potential future solution to dampen complications of cholera infection is by scavenging the cholera toxin by presenting competitive binding motifs to diminish the in vivo toxicity of V. cholerae. Here, we generate GM1a-functionalized and biocompatible microgels with diameters of 20 µm using drop-based microfluidics. The microgels are designed to exhibit a mesoporous and widely meshed network structure, allowing diffusion of the toxin protein deep into the microgel scavengers. Flow cytometry demonstrates strong and multivalent binding at high capacity of these microgels to the binding domain of the cholera toxin. Cell culture-based assays reveal the ability of these microgels to scavenge and retain the cholera toxin in direct binding competition to colorectal cells. This ability is evidenced by suppressed cyclic adenosine monophosphate production as well as reduced vacuole formation in mucus-forming colorectal HT-29 cells. Therefore, glycan-functionalized microgels show great potential as a non-antibiotic treatment for toxin-mediated infectious disorders.

Cell Encapsulation in Soft, Anisometric Poly(ethylene) Glycol Microgels Using a Novel Radical-Free Microfluidic System.

Complex 3D artificial tissue constructs are extensively investigated for tissue regeneration. Frequently, materials and cells are delivered separately without benefitting from the synergistic effect of combined administration. Cell delivery inside a material construct provides the cells with a supportive environment by presenting biochemical, mechanical, and structural signals to direct cell behavior. Conversely, the cell/material interaction is poorly understood at the micron scale and new systems are required to investigate the effect of micron-scale features on cell functionality. Consequently, cells are encapsulated in microgels to avoid diffusion limitations of nutrients and waste and facilitate analysis techniques of single or collective cells. However, up to now, the production of soft cell-loaded microgels by microfluidics is limited to spherical microgels. Here, a novel method is presented to produce monodisperse, anisometric poly(ethylene) glycol microgels to study cells inside an anisometric architecture. These microgels can potentially direct cell growth and can be injected as rod-shaped mini-tissues that further assemble into organized macroscopic and macroporous structures post-injection. Their aspect ratios are adjusted with flow parameters, while mechanical and biochemical properties are altered by modifying the precursors. Encapsulated primary fibroblasts are viable and spread and migrate across the 3D microgel structure.