Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

In vitro and in vivo evaluation of a new zirconia/niobium biocermet for hard tissue replacement

Metals and ceramics are commonly used in orthopaedics, dentistry and other load bearing applications. However, the use of ceramic matrix composites reinforced with biocompatible metals for heavy load-bearing hard tissue replacement applications has not previously been reported. In order to improve the reliability and the mechanical properties of biomedical implants, new zirconia-Nb composites have been recently developed. The aim of this study was to investigate the biological tolerance of these new zirconia/Nb biocermets implants with both in vitro and in vivo approaches. At first, human bone marrow derived mesenchymal stem cells were cultured on sintered biocermet discs with polished surfaces and were compared with responses to niobium metal. In vitro, the biocermets showed no deleterious effect on cell proliferation, extra-cellular matrix production or on cell morphology. Furthermore, the biocermet showed a higher percentage of cell proliferation than Nb metal. On the other hand, the bone response to these new zirconia/Nb biocermets was studied. Cylinders of biocermets, as well as commercially Nb rod were implanted in the tibiae of New Zealand white rabbits. All the animals were euthanatized after 6 months. The specimens were processed to obtain thin ground sections. The slides were observed in normal transmitted light microscope. A newly formed bone was observed in close contact with material surfaces. No inflamed or multinucleated cells were present. This study concluded that zirconia/Nb composites are biocompatible and osteoconductive. The ceramic-metal composite has even better osteointegration ability than pure Nb. In conclusion, zirconia-Nb biocermet is suitable for heavy load-bearing hard tissue replacement from the point of view of both mechanical properties and biocompatibility.This work was supported by the Spanish Ministry of Science and Innovation (MICINN) under the project MAT2012-38645.Peer Reviewe

Efficacy and safety of FOLFIRI/Aflibercept (FA) in an elderly population with metastatic colorectal cancer (mCRC) after the failure of an oxaliplatin-based regimen

Introduction: Aflibercept (ziv-aflibercept) significantly improves progression-free (PFS) and overall survival (OS) when added to FOLFIRI, compared with FOLFIRI alone, in the overall population of patients pretreated with oxaliplatin-based therapy. A subset analysis of elderly patients included in the registration VELOUR trial suggested that elderly (> 65 years) patients have a consistent, albeit small benefit in OS in PFS and a higher percentage of grade 3-4 toxicity. Our hypothesis was that selected patients with good PS could benefit from FOLFIRI-aflibercept (FA), provided they underwent careful monitoring of toxicity, and rapid intervention. Methods: We conducted a retrospective, multicentre, observational study of elderly patients (> 70 years) with mCRC treated with FOLFIRI-aflibercept after progression on an oxaliplatin-based regimen as part of routine clinical practice at seven hospitals from the Galician Research Group on Digestive Tumours (GITuD). Results: Of 315 patients treated with FA between June 2013 to November 2018, 71 elderly patients were recorded in this study. Median age was 72.7 years (range 70-84 years) and 33.4% were over 75 years (compared with only 14% in the VELOUR study subanalysis), 66.2 % were male, 83.1 % ECOG PS0-1, 43.7 % left-sided location, 76.1 % low grade, 63.4% RASmt and 2.8% BRAFmt, 66.2 % synchronous presentation and 77.5 % primary tumor resection. Prior therapy included bevacizumab (57.7%) and anti-EGFR agents (22.5%). Median of FA cycles was 9 (range 1-35 cycles). Overall Response Rate (ORR) and disease control rate (DCR) were 31.0 % and 63.4 %, respectively. With a median follow up of 27.1 months, median PFS was 6.6 months (95% CI, 5.0-8.3 months) and median OS was 15.1 months (95% CI, 12.1-18.1 months). The most common grade 3-4 toxicities were asthenia (18.3%), neutropenia (15.5%), diarrhoea (11.3%) and mucositis (9.9%). Aflibercept most common grade 3-4 related toxicities were hypertension (5.6%), dysphonia (5.6%), proteinuria (2.8%). Two patients experienced grade 5 toxicity (1 cerebrovascular event and 1 bowel perforation). This toxicity was managed with dose reduction of aflibercept in 39.4 % of cases, dose reduction of FOLFIRI on 57.7% and led to the discontinuation of aflibercept in 39.4%. Conclusion: Older patients with mCRC are underrepresented in clinical trials. The VELOUR study included only 6.4% patients over 65 years of age and only 14% of those over 65 were 75 years or older. Elderly patients treated with FA in the VELOUR trial experienced a higher rate of G3-4 adverse events (89.3% versus 80.5%) but this increase in toxicity was even more evident in the control arm (67.4% versus 59.4%). Our series confirms that with careful dose adjustment based on toxicity, including dose interruption if necessary elderly patients can be treated with FA with a 49.3% of grade 3-4 toxicity a PFS of 6.6 months and OS of 15.1 months, results that are comparable to those of younger patients