Generation and characterization of human induced pluripotent stem cells (iPSCs) from hand osteoarthritis patient-derived fibroblasts.

Knowledge and research results about hand osteoarthritis (hOA) are limited due to the lack of samples and animal models of the disease. Here, we report the generation of two induced pluripotent stem cell (iPSC)-lines from patients with radiographic hOA. Furthermore, we wondered whether these iPSC-lines carried single nucleotide polymorphisms (SNPs) within genes that have been associated with hOA. Finally, we performed chondrogenic differentiation of the iPSCs in order to prove their usefulness as cellular models of the disease. We performed a non-integrative reprogramming of dermal fibroblasts obtained from two patients with radiographic rhizarthrosis and non-erosive hOA by introducing the transcriptional factors Oct4, Sox2, Klf4 and c-Myc using Sendai virus. After reprogramming, embryonic stem cell-like colonies emerged in culture, which fulfilled all the criteria to be considered iPSCs. Both iPSC-lines carried variants associated with hOA in the four studied genes and showed differences in their chondrogenic capacity when compared with a healthy control iPSC-line. To our knowledge this is the first time that the generation of iPSC-lines from patients with rhizarthrosis and non-erosive hOA is reported. The obtained iPSC-lines might enable us to model the disease in vitro, and to deeper study both the molecular and cellular mechanisms underlying hOA.

Generation of a human control iPS cell line (ESi080-A) from a donor with no rheumatic diseases.

Here, we report the establishment of the human iPS cell line N1-FiPS4F#7 generated from skin cells of a patient with no rheumatic diseases, thus obtaining an appropriate control iPS cell line for researchers working in the field of rheumatic diseases. The reprogramming factors Oct4, Sox2, Klf4 and c-Myc were introduced using a non-integrating reprogramming strategy involving Sendai Virus.

Faecal microbiota transplantation for recurrent Clostridioides difficile infection: experience with lyophilized oral capsules.

BACKGROUND: Faecal microbiota transplantation (FMT) is a highly effective approach for refractory and recurrent Clostridioides difficile infection (CDI). Despite its excellent efficacy, FMT is not yet a routine procedure in most centres. There is very little experience with FMT based on lyophilized capsules, and data from European institutions are lacking. This article describes our experience with FMT to treat recurrent CDI using lyophilized oral capsules. METHODS: A prospectively recorded single-centre case series of patients with recurrent CDI who underwent FMT between January 2018 and May 2019 were analysed. The primary outcome was defined as resolution of CDI without recurrences over a two-month period. Overall resolution was defined as resolution of diarrhoea without recurrence of CDI within two months after a further cycle of FMT. The FMT process involved oral ingestion of four or five lyophilized capsules in a single dose. All stool donors were rigorously screened. FINDINGS: FMT was performed in 32 patients. Primary cure was achieved in 81.3% of patients, and the overall cure rate was 87.5%. FMT via lyophilized capsules was well tolerated. No FMT procedure-related adverse events and no further complications were observed for lyophilized-capsule FMT. CONCLUSIONS: This initial clinical experience suggests that FMT based on oral lyophilized preparations is a safe, well-tolerated, and highly effective treatment for recurrent CDI. Administration of oral lyophilized capsules seems feasible in hospital routine and will enable FMT to be more widely used.

Usefulness of Mesenchymal Cell Lines for Bone and Cartilage Regeneration Research.

The unavailability of sufficient numbers of human primary cells is a major roadblock for in vitro repair of bone and/or cartilage, and for performing disease modelling experiments. Immortalized mesenchymal stromal cells (iMSCs) may be employed as a research tool for avoiding these problems. The purpose of this review was to revise the available literature on the characteristics of the iMSC lines, paying special attention to the maintenance of the phenotype of the primary cells from which they were derived, and whether they are effectively useful for in vitro disease modeling and cell therapy purposes. This review was performed by searching on Web of Science, Scopus, and PubMed databases from 1 January 2015 to 30 September 2019. The keywords used were ALL = (mesenchymal AND ("cell line" OR immortal*) AND (cartilage OR chondrogenesis OR bone OR osteogenesis) AND human). Only original research studies in which a human iMSC line was employed for osteogenesis or chondrogenesis experiments were included. After describing the success of the immortalization protocol, we focused on the iMSCs maintenance of the parental phenotype and multipotency. According to the literature revised, it seems that the maintenance of these characteristics is not guaranteed by immortalization, and that careful selection and validation of clones with particular characteristics is necessary for taking advantage of the full potential of iMSC to be employed in bone and cartilage-related research.

Risk factors for opportunistic infections in infliximab-treated patients: the importance of screening in prevention.

We sought to determine factors associated with opportunistic infections (OI) in infliximab-treated patients. A retrospective study cohort (1999-2004) was examined. Nine OI were diagnosed in 94 infliximab-treated patients: tuberculosis (four), visceral leishmaniasis (one), pyogenic muscular abscess (one Salmonella spp. and one Streptococcus pneumoniae), and two viral infections (hepatitis B virus [HBV] and zoster ophthalmicus). The risk for OI was significantly higher in the first year of treatment (odds ratio [OR] 8; 95% confidence interval [CI] 2-50). Previous treatment with more than two immunosuppressive drugs was the only factor related to OI (OR 8.686; 95% CI 1.889-39.943). We identified the subset of patients treated with infliximab who had a higher risk for OI. The screening of latent infections is key to diminishing the incidence of these infections.

[Prognostic significance of the implantation of a temporary pacemaker in patients with acute myocardial infarction]. / Significado pronóstico de la implantación de marcapasos transitorio en pacientes con infarto agudo de miocardio.

OBJECTIVE: Indication of temporary pacemakers in patients during acute myocardial infarction was widely studied in the pre-thrombolytic era without having determined whether the generalization of fibrinolysis might have changed the overall incidence and significance of temporary pacemakers. Our aim was to determine the incidence and the prognostic significance of insertion of temporary pacemakers in patients with acute myocardial infarction. PATIENTS AND METHODS: In a study involving 1,239 patients consecutively admitted to hospital with acute myocardial infarction we studied clinical characteristics and prognosis depending on temporary pacemaker insertion or not. We performed an univariate analysis on in-hospital mortality and those selected variables were introduced in to a logistic regression analysis. RESULTS: A temporary pacemaker was indicated in 55 patients (4.4%), prophylactically in 22% and therapeutically in 78%. Temporary pacemakers were inserted in 55% of the patients with advanced AV block and in the 10% of the patients with bundle-branch block. Pacemaker insertion was associated with higher number of affected leads in the ECG, and higher CK peak, regardless of the association with thrombolysis. The following complications were more often observed in patients with temporary pacemakers: atrial fibrillation, heart failure, right bundle-branch block, advanced atrioventricular block and in-hospital mortality (45.4 vs 10.2%; p < 0.001). Need for a temporary pacemaker was less frequent in patients treated with thrombolytics compared with those not treated (3.0 vs 6.1%; p < 0.02). Pacemaker insertion had an independent value for predicting in-hospital mortality (OR = 5.51; 95% CI, 2.71-11.19). CONCLUSION: The insertion of a temporary pacemaker in acute myocardial infarction is less frequent nowadays than on the pre-thrombolytic era. Pacemaker insertion is associated with higher indices of infarct extension and in-hospital mortality, having independent prognostic value on the in-hospital mortality.

[Incidence, clinical characteristics and prognostic significance of supraventricular tachyarrhythmias in acute myocardial infarction]. / Incidencia, características clínicas y significación pronóstica de las taquiarritmias supraventriculares en el infarto agudo de miocardio.

OBJECTIVES: The study of incidence and prognostic significance of supraventricular tachyarrhythmias in patients with acute myocardial infarction. PATIENTS AND METHODS: Prospective study on 1,239 patients consecutively admitted because of a diagnosis of acute myocardial infarction. Clinical characteristics, indexes of myocardial infarction and complications were analysed. RESULTS: Supraventricular tachyarrhythmias were observed in 116 (9.3%) cases: atrial fibrillation in 96 (7.7%); atrial tachycardia in 15 (1.2%); and atrial flutter in the remaining five cases (0.4%). Patients with supraventricular tachyarrhythmias were older, and presented higher heart rate, lower blood pressure, a higher number of affected leads in ECG, and higher Killip class. A higher creatine kinase peak and a lower left ventricular ejection fraction were associated with the presence of supraventricular tachyarrhythmias. Predictors of supraventricular tachyarrhythmias were: age, systolic blood pressure, number of affected leads in ECG, and congestive heart failure at admission. The following complications were found more frequently in patients with supraventricular tachyarrhythmias: bundle-branch block, complete A-V block, ventricular tachycardia, ventricular fibrillation; heart failure; stroke; and mortality, in-hospital 18.1% vs 11.1% (p < 0.05) and one-year, 38.7% vs 18.4% (p < 0.001). The logistic regression model showed that supraventricular tachyarrhythmias had no independent prognostic value on mortality. CONCLUSIONS: The appearance of supraventricular tachyarrhythmias during the acute phase of myocardial infarction is a relatively frequent finding, often associated with older age and larger infarctions. Supraventricular tachyarrhythmias are accompanied by higher short and long-term mortalities, although there is no independent prognostic significance.