Systematic evaluation of clinical predictors of aggressive ulcerative colitis

Background: Studies evaluating risk factors associated with an "aggressive" disease course in ulcerative colitis (UC) are scarce. A recent definition of "aggressive" UC incorporated the following characteristics: 1) high relapse rate, 2) need for surgery, 3) development of colorectal cancer, and 4) presence of extraintestinal manifestations (EIM). The following factors for an aggressive / disabling disease course in UC have been identified so far: age < 40 years at S140 Poster presentations UC diagnosis, pancolitis, concomitant primary sclerosing cholangitis, and deep ulcerations of the colonic mucosa. We aimed to evaluate risk factors for an "aggressive" disease course in UC patients. Methods: Data from the Swiss IBD cohort study were analyzed. Patients were recruited from university centers (80%), regional hospitals (19%), and private practices (1%). We applied the following definition for "aggressive" UC: 1) patients ever treated with TNFantagonists or calcineurin inhibitors (tacrolimus / cyclosporine), and 2) need for (procto)-colectomy. Non-normal data are presented as median and interquartile range [IQR]

Cell therapies for skin regeneration: an overview of 40 years of experience in burn units.

The earliest attempts at cell therapy can be attributed to Charles-Edward Brown-Séquard (1817–1894), who sought to treat senescence and aging by injecting animal gonad shreds into his contemporaries, a practice that was widespread in late 19th century. Since then, advances in science have enabled the development of biological substitutes to restore the function of various tissues. Skin was one of the first tissues to be regenerated. For severe burns, patient survival depends on the restoration of skin function as a barrier against pathogens and control of body temperature and fluid loss. We aim here to overview the different cell therapy techniques implemented at the University Hospital of Lausanne (CHUV), one of the two Swiss national centres of highly specialised medicine for burn care. In particular, we will describe the specific indications for each of the different therapies as well as future perspectives

CD200 as a Potential New Player in Inflammation during Rotator Cuff Tendon Injury/Repair: An In Vitro Model

Rotator cuff tendon (RCT) disease results from multifactorial mechanisms, in which inflammation plays a key role. Pro-inflammatory cytokines and tendon stem cell/progenitor cells (TSPCs) have been shown to participate in the inflammatory response. However, the underlying molecular mechanism is still not clear. In this study, flow cytometry analyses of different subpopulations of RCT-derived TSPCs demonstrate that after three days of administration, TNFα alone or in combination with IFNγ significantly decreases the percentage of CD146+CD49d+ and CD146+CD49f+ but not CD146+CD109+ TSPCs populations. In parallel, the same pro-inflammatory cytokines upregulate the expression of CD200 in the CD146+ TSPCs population. Additionally, the TNFα/IFNγ combination modulates the protein expression of STAT1, STAT3, and MMP9, but not fibromodulin. At the gene level, IRF1, CAAT (CAAT/EBPbeta), and DOK2 but not NF-κb, TGRF2 (TGFBR2), and RAS-GAP are modulated. In conclusion, although our study has several important limitations, the results highlight a new potential role of CD200 in regulating inflammation during tendon injuries. In addition, the genes analyzed here might be new potential players in the inflammatory response of TSPCs

Características morfológicas de avena blanca y raigrás en sistema silvopastoril y al pleno sol.

Resúmene

Optimized Manufacture of Lyophilized Dermal Fibroblasts for Next-Generation Off-the-Shelf Progenitor Biological Bandages in Topical Post-Burn Regenerative Medicine.

Cultured fibroblast progenitor cells (FPC) have been studied in Swiss translational regenerative medicine for over two decades, wherein clinical experience was gathered for safely managing burns and refractory cutaneous ulcers. Inherent FPC advantages include high robustness, optimal adaptability to industrial manufacture, and potential for effective repair stimulation of wounded tissues. Major technical bottlenecks in cell therapy development comprise sustainability, stability, and logistics of biological material sources. Herein, we report stringently optimized and up-scaled processing (i.e., cell biobanking and stabilization by lyophilization) of dermal FPCs, with the objective of addressing potential cell source sustainability and stability issues with regard to active substance manufacturing in cutaneous regenerative medicine. Firstly, multi-tiered FPC banking was optimized in terms of overall quality and efficiency by benchmarking key reagents (e.g., medium supplement source, dissociation reagent), consumables (e.g., culture vessels), and technical specifications. Therein, fetal bovine serum batch identity and culture vessel surface were confirmed, among other parameters, to largely impact harvest cell yields. Secondly, FPC stabilization by lyophilization was undertaken and shown to maintain critical functions for devitalized cells in vitro, potentially enabling high logistical gains. Overall, this study provides the technical basis for the elaboration of next-generation off-the-shelf topical regenerative medicine therapeutic products for wound healing and post-burn care

Prevalence of extraintestinal manifestations in paediatric patients with Inflammatory Bowel Disease : results from the Swiss IBD Cohort Study

Background: There is a paucity of data from large cohort studies on the prevalence and type of extraintestinal manifestations in pediatric patients with Crohn's disease (CD) and ulcerative colitis (UC). We aimed to assess the prevalence and type of EIM in pediatric patients with inflammatory bowel disease (IBD). Methods: Data from patients enrolled in the Pediatric Swiss IBD Cohort Study (P-SIBDCS) were analyzed. Since 2008 the P-SIBDCS collects data on patients aged 2-17 from hospitals and private practices across Switzerland. Results of continuous data are reported as median and interquartile range

The PRRT2 knockout mouse recapitulates the neurological diseases associated with PRRT2 mutations.

Heterozygous and rare homozygous mutations in PRoline-Rich Transmembrane protein 2 (PRRT2) underlie a group of paroxysmal disorders including epilepsy, kinesigenic dyskinesia episodic ataxia and migraine. Most of the mutations lead to impaired PRRT2 expression and/or function. Recently, an important role for PRTT2 in the neurotransmitter release machinery, brain development and synapse formation has been uncovered. In this work, we have characterized the phenotype of a mouse in which the PRRT2 gene has been constitutively inactivated (PRRT2 KO)beta-galactosidase staining allowed to map the regional expression of PRRT2 that was more intense in the cerebellum, hindbrain and spinal cord, while it was localized to restricted areas in the fore-brain. PRRT2 KO mice are normal at birth, but display paroxysmal movements at the onset of locomotion that persist in the adulthood. In addition, adult PRRT2 KO mice present abnormal motor behaviors characterized by wild running and jumping in response to audiogenic stimuli that are ineffective in wild type mice and an increased sensitivity to the convulsive effects of pentylentetrazol. Patch-clamp electrophysiology in hippocampal and cerebellar slices revealed specific effects in the cerebellum, where PRRT2 is highly expressed, consisting in a higher excitatory strength at parallel fiber-Purkinje cell synapses during high frequency stimulation. The results show that the PRRT2 KO mouse reproduces the motor paroxysms present in the human PRRT2-linked pathology and can be proposed as an experimental model for the study of the pathogenesis of the disease as well as for testing personalized therapeutic approaches

Fluid balance and urine volume are independent predictors of mortality in acute kidney injury.

INTRODUCTION: In ICUs, both fluid overload and oliguria are common complications associated with increased mortality among critically ill patients, particularly in acute kidney injury (AKI). Although fluid overload is an expected complication of oliguria, it remains unclear whether their effects on mortality are independent of each other. The aim of this study is to evaluate the impact of both fluid balance and urine volume on outcomes and determine whether they behave as independent predictors of mortality in adult ICU patients with AKI. METHODS: We performed a secondary analysis of data from a multicenter, prospective cohort study in 10 Italian ICUs. AKI was defined by renal sequential organ failure assessment (SOFA) score (creatinine >3.5 mg/dL or urine output (UO) <500 mL/d). Oliguria was defined as a UO <500 mL/d. Mean fluid balance (MFB) and mean urine volume (MUV) were calculated as the arithmetic mean of all daily values. Use of diuretics was noted daily. To assess the impact of MFB and MUV on mortality of AKI patients, multivariate analysis was performed by Cox regression. RESULTS: Of the 601 included patients, 132 had AKI during their ICU stay and the mortality in this group was 50\%. Non-surviving AKI patients had higher MFB (1.31 ± 1.24 versus 0.17 ± 0.72 L/day; P <0.001) and lower MUV (1.28 ± 0.90 versus 2.35 ± 0.98 L/day; P <0.001) as compared to survivors. In the multivariate analysis, MFB (adjusted hazard ratio (HR) 1.67 per L/day, 95\%CI 1.33 to 2.09; <0.001) and MUV (adjusted HR 0.47 per L/day, 95\%CI 0.33 to 0.67; <0.001) remained independent risk factors for 28-day mortality after adjustment for age, gender, diabetes, hypertension, diuretic use, non-renal SOFA and sepsis. Diuretic use was associated with better survival in this population (adjusted HR 0.25, 95\%CI 0.12 to 0.52; <0.001). CONCLUSIONS: In this multicenter ICU study, a higher fluid balance and a lower urine volume were both important factors associated with 28-day mortality of AKI patients

Burn Center Organization and Cellular Therapy Integration: Managing Risks and Costs.

The complex management of severe burn victims requires an integrative collaboration of multidisciplinary specialists in order to ensure quality and excellence in healthcare. This multidisciplinary care has quickly led to the integration of cell therapies in clinical care of burn patients. Specific advances in cellular therapy together with medical care have allowed for rapid treatment, shorter residence in hospitals and intensive care units, shorter durations of mechanical ventilation, lower complications and surgery interventions, and decreasing mortality rates. However, naturally fluctuating patient admission rates increase pressure toward optimized resource utilization. Besides, European translational developments of cellular therapies currently face potentially jeopardizing challenges on the policy front. The aim of the present work is to provide key considerations in burn care with focus on architectural and organizational aspects of burn centers, management of cellular therapy products, and guidelines in evolving restrictive regulations relative to standardized cell therapies. Thus, based on our experience, we present herein integrated management of risks and costs for preserving and optimizing clinical care and cellular therapies for patients in dire need