Direct Conversion of Fibroblasts to Megakaryocyte Progenitors

Current sources of platelets for transfusion are insufficient and associated with risk of alloimmunization and blood-borne infection. These limitations could be addressed by the generation of autologous megakaryocytes (MKs) derived in vitro from somatic cells with the ability to engraft and differentiate in vivo. Here, we show that overexpression of a defined set of six transcription factors efficiently converts mouse and human fibroblasts into MK-like progenitors. The transdifferentiated cells are CD41+, display polylobulated nuclei, have ploidies higher than 4N, form MK colonies, and give rise to platelets in vitro. Moreover, transplantation of MK-like murine progenitor cells into NSG mice results in successful engraftment and further maturation in vivo. Similar results are obtained using disease-corrected fibroblasts from Fanconi anemia patients. Our results combined demonstrate that functional MK progenitors with clinical potential can be obtained in vitro, circumventing the use of hematopoietic progenitors or pluripotent stem cells

The impact of nutrition on the lives of patients with digestive cancers: a position paper

Nutritional intervention is an essential part of cancer treatments. Research and clinical evidence in cancer have shown that nutritional support can reduce length of hospitalisation, diminish treatment-related toxicity, and improve nutrient intake, quality of life, and physical function. Nutritional intervention can improve outcomes and help patients in the successful completion of oncological treatments by preventing malnutrition. Malnutrition is a very common hallmark in patients with cancers. Almost one-fourth of cancer patients are at risk of dying because of the consequences of malnutrition, rather than cancer itself. Patients with digestive cancers are at higher risk of suffering malnutrition due to the gastrointestinal impairment caused by their disease. They are at high nutritional risk by definition, yet the majority of them have insufficient or null access to nutritional intervention.Inadequate resources are dedicated to implementing nutritional services in Europe. Universal access to nutritional support for digestive cancer patients is not a reality in many European countries. To change this situation, health systems should invest in qualified staff to reinforce or create nutritional teams' experts in digestive cancer treatments. We aim to share the patient community's perspective on the status and the importance of nutritional intervention. This is an advocacy manuscript presenting data on the topic and analysing the current situations and the challenges for nutrition in digestive cancers. It highlights the importance of integrative nutrition in the treatment of digestive cancers and advocates for equitable and universal access to nutritional intervention for all patients.info:eu-repo/semantics/publishedVersio

Conversion of human fibroblasts into monocyte-like progenitor cells

International audienceReprogramming technologies have emerged as a promising approach for future regenerative medicine. Here, we report on the establishment of a novel methodology allowing for the conversion of human fibroblasts into hematopoietic progenitor-like cells with macrophage differentiation potential. SOX2 overexpression in human fibroblasts, a gene found to be upregulated during hematopoietic reconstitution in mice, induced the rapid appearance of CD34+ cells with a concomitant upregulation of mesoderm-related markers. Profiling of cord blood hematopoietic progenitor cell populations identified miR-125b as a factor facilitating commitment of SOX2-generated CD34+ cells to immature hematopoietic-like progenitor cells with grafting potential. Further differentiation toward the monocytic lineage resulted in the appearance of CD14+ cells with functional phagocytic capacity. In vivo transplantation of SOX2/miR-125b-generated CD34+ cells facilitated the maturation of the engrafted cells toward CD45+ cells and ultimately the monocytic/macrophage lineage. Altogether, our results indicate that strategies combining lineage conversion and further lineage specification by in vivo or in vitro approaches could help to circumvent long-standing obstacles for the reprogramming of human cells into hematopoietic cells with clinical potential

Risk of ischaemic stroke among new users of glucosamine and chondroitin sulphate: a nested case–control study

Background: Several studies have reported that the use of chondroitin sulphate (CS) and glucosamine may reduce the risk of acute myocardial infarction. Although it is thought that this potential benefit could be extended to ischaemic stroke (IS), the evidence is scarce. Objective: To test the hypothesis that the use of prescription glucosamine or CS reduces the risk of IS. Design: Case–control study nested in an open cohort. Methods: Patients aged 40–99 years registered in a Spanish primary healthcare database (BIFAP) during the 2002–2015 study period. From this cohort, we identified incident cases of IS, applying a case-finding algorithm and specific validation procedures, and randomly sampled five controls per case, individually matched with cases by exact age, gender and index date. Adjusted odds ratios (AORs) and 95% confidence interval (CI) were computed through a conditional logistic regression. Only new users of glucosamine or CS were considered. Results: A total of 13,952 incident cases of IS and 69,199 controls were included. Of them, 106 cases (0.76%) and 803 controls (1.16%) were current users of glucosamine or CS at index date, yielding an AOR of 0.66 (95% CI: 0.54–0.82) (for glucosamine, AOR: 0.55; 95% CI: 0.39–0.77; and for CS, AOR: 0.77; 95% CI: 0.60–0.99). The reduced risk among current users was observed in both sexes (men, AOR: 0.69; 95% CI: 0.49–0.98; women, AOR: 0.65; 95% CI: 0.50–0.85), in individuals above and below 70 years of age (AOR: 0.69; 95% CI: 0.53–0.89 and AOR: 0.59; 95% CI: 0.41–0.85, respectively), in individuals with vascular risk factors (AOR: 0.53; 95% CI: 0.39–0.74) and among current/recent users of nonsteroidal anti-inflammatory drugs (NSAIDs) (AOR: 0.71; 95% CI: 0.55–0.92). Regarding duration, the reduced risk was observed in short-term users (364 days AOR: 0.86; 95% CI: 0.57–1.31). Conclusions: Our results support a protective effect of prescription CS and glucosamine in IS, which was observed even in patients at vascular risk. Mini abstract Our aim was to analyse whether the use of glucosamine or chondroitin sulphate (CS) reduces the risk of ischaemic stroke (IS). We detected a significant decrease

Global management of patients with knee osteoarthritis begins with quality of life assessment: a systematic review

Background: Knee osteoarthritis (KOA) is a prevalent form of chronic joint disease associated with functional restrictions and pain. Activity limitations negatively impact social connectedness and psychological well-being, reducing the quality of life (QoL) of patients. The purpose of this review is to summarize the existing information on QoL in KOA patients and share the reported individual factors, which may influence it. Methods: We conducted a systematic review examining the literature up to JAN/2017 available at MEDLINE, EMBASE, Cochrane, and PsycINFO using KOA and QOL related keywords. Inclusion criteria were QOL compared to at least one demographic factor (e.g., age, gender), lifestyle factor (e.g., functional independence), or comorbidity factor (e.g., diabetes, obesity) and a control group. Analytical methods were not considered as part of the original design. Results: A total of 610 articles were reviewed, of which 62 met inclusion criteria. Instruments used to measure QoL included: SF-36, EQ-5D, KOOS, WHOQOL, HAS, AIMS, NHP and JKOM. All studies reported worse QoL in KOA patients when compared to a control group. When females were compared to males, females reported worse QOL. Obesity as well as lower level of physical activity were reported with lower QoL scores. Knee self-management programs delivered by healthcare professionals improved QoL in patients with KOA. Educational level and higher total mindfulness were reported to improve QoL whereas poverty, psychological distress, depression and lacking familial relationships reduce it. Surgical KOA interventions resulted in good to excellent outcomes generally; although, results varied by age, weight, and depression. Conclusion: KOA has a substantial impact on QoL. In KOA patients, QoL is also influenced by specific individual factors including gender, body weight, physical activity, mental health, and education. Importantly, education and management programs designed to support KOA patients report improved QoL. QoL data is a valuable tool providing health care professionals with a better comprehension of KOA disease to aid implementation of the most effective management plan

A patients' view of OA: the global osteoarthritis patient perception survey (GOAPPS), a pilot study

Background: Globally, osteoarthritis (OA) is the third condition associated with disability. There is still poor treatment in OA but science holds the key to finding better treatments and a cure. It is essential to learn what's important to patients from them to implement the most effective OA management. The OA Patients Task Force, conducted the Global OA Patient Perception Survey (GOAPPS)-the first global survey made by patients to analize the quality of life (QoL) & patient perceptions of care. The goal was to collect data on OA patients' perception of OA to understand patients' needs and expectations to improve OA management. Methods: Observational, cross-sectional study by online survey data collection from six countries, translated into three languages. The questionnaire was comprised of 3 sections: patient demographics and clinical symptomology characteristics; relationship with physicians: perception of attention, treatment, and information provided; and OA impact on daily activity and QoL. The results of the survey were evaluated using the Limited Data Set. The survey results were analyzed using descriptive statistics to characterize the patients' answers. Additionally, Cronbach's alpha was calculated to determine internal consistency validity. Results: A total of 1512 surveys were completed in 6 countries. 84.2% of respondents reported pain/tenderness and 91.1% experienced limitations to physical activities. 42.3% of patients were not satisfied with their current OA treatment. 86% had comorbidities, especially hypertension, and obesity. 51.3 and 78% would like access to additional drug or additional non-drug/non-surgical treatments respectively. 48.2% of patients perceived their QoL to be affected by OA. The Cronbach's alpha was 0.61. Conclusions: OA has a significant impact on patients' daily activities and their desire to play an active role in managing this disease. Patients are seeking additional treatments, especially no pharmacological/no surgical treatments stressing the need for investing in clinical research, implementing OA preventive measures, and managing interventions to improve the healthcare value chain in OA