3D bioprinting offers interesting opportunities for 3D tissue printing by providing living cells with appropriate scaffolds with a dedicated structure. Biological advances in bioinks are currently ...promising for cell encapsulation, particularly that of mesenchymal stem cells (MSCs). We present herein the development of cartilage implants by 3D bioprinting that deliver MSCs encapsulated in an original bioink at low concentration. 3D-bioprinted constructs (10×10×4 mm) were printed using alginate/gelatin/fibrinogen bioink mixed with human bone marrow MSCs. The influence of the bioprinting process and chondrogenic differentiation on MSC metabolism, gene profiles, and extracellular matrix (ECM) production at two different MSC concentrations (1 million or 2 million cells/mL) was assessed on day 28 (D28) by using MTT tests, real-time RT-PCR, and histology and immunohistochemistry, respectively. Then, the effect of the environment (growth factors such as TGF-β1/3 and/or BMP2 and oxygen tension) on chondrogenicity was evaluated at a 1 M cell/mL concentration on D28 and D56 by measuring mitochondrial activity, chondrogenic gene expression, and the quality of cartilaginous matrix synthesis. We confirmed the safety of bioextrusion and gelation at concentrations of 1 million and 2 million MSC/mL in terms of cellular metabolism. The chondrogenic effect of TGF-β1 was verified within the substitute on D28 by measuring chondrogenic gene expression and ECM synthesis (glycosaminoglycans and type II collagen) on D28. The 1 M concentration represented the best compromise. We then evaluated the influence of various environmental factors on the substitutes on D28 (differentiation) and D56 (synthesis). Chondrogenic gene expression was maximal on D28 under the influence of TGF-β1 or TGF-β3 either alone or in combination with BMP-2. Hypoxia suppressed the expression of hypertrophic and osteogenic genes. ECM synthesis was maximal on D56 for both glycosaminoglycans and type II collagen, particularly in the presence of a combination of TGF-β1 and BMP-2. Continuous hypoxia did not influence matrix synthesis but significantly reduced the appearance of microcalcifications within the extracellular matrix. The described strategy is very promising for 3D bioprinting by the bioextrusion of an original bioink containing a low concentration of MSCs followed by the culture of the substitutes in hypoxic conditions under the combined influence of TGF-β1 and BMP-2.
Key messages
No difference between both hands was observed for clinical and radiographical presentations in EHOA patients.
A bilateral and symmetrical relationship was found between hand joints.
...Highlights
EHOA have symmetrical distribution and specific association in structural lesions.
This study aims to analyse the preferential topographical distribution of clinical and structural lesions between the dominant and non-dominant hands in erosive hand osteoarthritis (EHOA) patients. Both hands were assessed via radiography in EHOA patients. A comparative analysis of the clinical features and structural lesions between the dominant and non-dominant hands was performed. The structural lesions were assessed according to the anatomical radiographic score of Verbruggen-Veys (VV). Next, a principal component analysis was performed to describe and highlight the relationships observed between the joints. Sixty patients were included in this study: there were 57 women, and the mean age was 66.1 (± 7.6) years. For the distal interphalangeal (DIP) joints, nodes were observed more frequently on the dominant hand (4 vs 3;
p
= 0.005). No difference in structural lesions was observed between the two hands except for the 2nd proximal interphalangeal (PIP) (
p
= 0.045). A principal component analysis with varimax rotation described relationships between the 2nd PIP, 3rd PIP, 4th PIP, 4th DIP and 5th DIP joints in both hands. No significant differences between dominant and non-dominant hands were observed for clinical and structural lesions in our sample of EHOA patients. A bilateral and symmetrical injury was observed in most EHOA joints.
Trial registration
Clinical trial registration number: NCT01068405.
The primary objective was to evaluate bone fragility on dual X-ray absorptiometry (DXA) in patients with obesity before and 2 years after bariatric surgery. The secondary objective was to identify ...risk factors for the development of a bone mineral density ≤ −2 SD at 2 years.
This descriptive study included patients with obesity who underwent DXA before and 2 years (±6 months) after bariatric surgery. The BMD and the T-score were assessed at the lumbar spine, femoral neck and total hip. Data on body composition on DXA were also collected. The diagnosis of osteoporosis was retained for a T-score ≤ − 2.5 SD at any measured location. Osteopenia, or low bone mass, was defined by −2.5 SD < T-score ≤ −1 SD.
Among the 675 included patients, 77.8 % were women, with a mean age of 49.5 years (±11.1). After bariatric surgery, there were significantly more patients with osteoporosis: 3.6 % vs. 0.9 % (p = 0.0001). Multivariate analysis revealed that the risk factors for developing a bone mineral density ≤ −2 SD 2 years after bariatric surgery in patients with normal BMD before surgery were age and lower lean and fat mass before the surgery (OR = 1.07, 95%CI = 1.03–1.12, OR = 0.83, 95%CI = 0.77–0.91, OR = 1.08, 95%CI = 1.02–1.15, respectively).
There was a significantly higher prevalence of osteoporosis and low bone mass 2 years after bariatric surgery. Older age and lower lean and fat mass at baseline were risk factors for the development of a BMD ≤ -2SD at 2 years.
•Higher prevalence of osteoporosis and low bone mass after bariatric surgery•Bone screening before and after bariatric surgery to diagnose osteoporosis•Especially in older patients with a lower lean and fat mass at baseline
Background and aims
Extraintestinal manifestations are common in inflammatory bowel disease patients, although there are few data available on their diagnosis, management and follow-up. We ...systematically reviewed the literature evidence to evaluate tools and investigations used for the diagnosis and for the assessment of the treatment response in inflammatory bowel disease patients with extraintestinal manifestations.
Methods
We searched in PubMed, Embase and Web of Science from January 1999–December 2019 for all interventional and non-interventional studies published in English assessing diagnostic tools and investigations used in inflammatory bowel disease patients with extraintestinal manifestations.
Results
Forty-five studies (16 interventional and 29 non-interventional) were included in our systematic review, enrolling 7994 inflammatory bowel disease patients. The diagnostic assessment of extraintestinal manifestations was performed by dedicated specialists in a percentage of cases ranging from 60–100% depending on the specific condition. The clinical examination was the most frequent diagnostic strategy, accounting for 35 studies (77.8%). In patients with primary sclerosing cholangitis or rheumatological symptoms, biochemical and imaging tests were also performed. Anti-TNF agents were the most used biological drugs for the treatment of extraintestinal manifestations (20 studies, 44.4%), and the treatment response varied from 59.1% in axial spondyloarthritis to 88.9% in ocular manifestations. No benefit was detected in primary sclerosing cholangitis patients after treatment with biologics.
Conclusions
In the clinical management of inflammatory bowel disease patients with extraintestinal manifestations the collaboration of dedicated specialists for diagnostic investigations and follow-up is key to ensure the best of care approach. However, international guidelines are needed to homogenise and standardise the assessment of extraintestinal manifestations.
To evaluate the short-term safety and outcome of 2 different experimental applications of rasburicase 0.2 mg/kg (monthly vs daily) in patients with tophaceous gout not treatable by allopurinol. ...Rasburicase could be useful for patients with gout that is unresponsive to allopurinol or who cannot tolerate the therapy.
Five patients received 6 monthly infusions of rasburicase (Group 1) and 5 received 5 daily infusions (Group 2).
In Group 1, serum uric acid (SUA) level decreased significantly, from 612.6 +/- 162.4 micromol/l at baseline to 341.2 +/- 91.8 micromol/l after 6 infusions (p = 0.001). Changes in tophus area were observed in 2 patients. In Group 2, daily infusions produced a rapid, marked decrease in SUA level during treatment. Yet SUA levels measured at 1 month (511.5 +/- 128.4 micromol/l) and 2 months (572 +/- 96.2 micromol/l) after treatment were not significantly lower than at baseline (573.6 +/- 48.2 micromol/l). No patient from Group 2 showed reduced tophus size. Eight of 10 patients experienced an adverse event, the most common being gout flare despite prophylactic treatment with colchicine.
Monthly infusions of rasburicase appear to be a possible therapy for severe gout not treatable by other means. Tolerance of rasburicase in gout appears to be diminished by frequent triggering of gout attacks, and hypersensitivity reactions might be an important limitation to longterm therapy.
Purpose To assess increased sacroiliac joint (SIJ) uptake on .sup.18F-NaF PET/CT and to compare with MRI for inflammation and with CT scan for structural damages in a population of 23 patients with ...spondyloarthritis (SpA). Methods Twenty-three patients with active SpA according to the Assessment of SpondyloArthritis international Society (ASAS) and/or modified NY criteria were included. All patients had a pelvic radiograph, MRI, and CT scan of the SIJ and .sup.18F-NaF PET/CT examinations within a month, analyzed by three blinded readers. MRIs were assessed according to the ASAS criteria and SPARCC method. On CT scans, erosion and ankylosis were quantified using the same methodology. On the .sup.18F-NaF PET, abnormal uptake was assessed using a qualitative method inspired by the ASAS criteria and two quantitative approaches (the PET-activity score according to the SPARCC method and Maximum Standardized Uptake Value (SUVmax)). Results Structural sacroiliitis was observed on 7 radiographs and 10 CT scans; 10 MRIs showed inflammatory sacroiliitis, and 20 patients had a positive PET. The inter-reader reliability was good for the PET activity score and good to excellent for the SUVmax. A positive PET was not correlated with a positive MRI or with a structural sacroiliitis on CT scan. The PET-activity score and SUVmax were correlated with the SPARCC inflammation score but not with erosion or ankylosis scores on CT scan. Conclusion Abnormal uptake by the SIJ on .sup.18F-NaF PET is more frequent than inflammatory and structural sacroiliitis in a population of SpA patients. The PET activity score and SUVmax had good correlations with inflammatory sacroiliitis but not with structural lesions on CT scan. Keywords: Spondyloarthritis, Sacroiliitis, Positron emission tomography, Inflammation
The primary objective was to evaluate bone fragility prevalence on dual X-ray absorptiometry (DXA) and computed tomography (CT) in patients with severe obesity. The secondary objective was to ...evaluate the risk factors for bone fragility. This monocentric study was conducted in patients with grade 2 and 3 obesity. Bone mineral density (BMD) and T-score were studied on DXA, and the scanographic bone attenuation coefficient of L1 (SBAC-L1) was measured on CT. Among the 1386 patients included, 1013 had undergone both DXA and CT within less than 2 years. The mean age was 48.4 (±11.4) years, 77.6% were women, and the mean BMI was 45.6 (±6.7) kg/m². Eight patients (0.8%) had osteoporosis in at least one site. The mean SBAC-L1 was 192.3 (±52.4) HU; 163 patients (16.1%) were under the threshold of 145 HU. Older age (ORCI95 = 1.1 1.08–1.16), lower BMD on the femoral neck and spine (ORCI95 = 0.040.005–0.33 and ORCI95 = 0.0010.0001–0.008, respectively), and higher lean mass (ORCI95 = 1.1 1.03–1.13) were significantly associated with an SBAC-L1 ≤ 145 HU in multivariate analysis. Approximately 16% of patients with severe obesity were under the SBAC-L1 threshold, while less than 1% were classified as osteoporotic on DXA.
As a wider variety of therapeutic options for osteoarthritis (OA) becomes available, there is an increasing need to objectively evaluate disease severity on magnetic resonance imaging (MRI). This is ...more technically challenging at the hip than at the knee, and as a result, few systematic scoring systems exist. The OMERACT (Outcome Measures in Rheumatology) filter of truth, discrimination, and feasibility can be used to validate image-based scoring systems. Our objective was (1) to review the imaging features relevant to the assessment of severity and progression of hip OA; and (2) to review currently used methods to grade these features in existing hip OA scoring systems.
A systematic literature review was conducted. MEDLINE keyword search was performed for features of arthropathy (such as hip + bone marrow edema or lesion, synovitis, cyst, effusion, cartilage, etc.) and scoring system (hip + OA + MRI + score or grade), with a secondary manual search for additional references in the retrieved publications.
Findings relevant to the severity of hip OA include imaging markers associated with inflammation (bone marrow lesion, synovitis, effusion), structural damage (cartilage loss, osteophytes, subchondral cysts, labral tears), and predisposing geometric factors (hip dysplasia, femoral-acetabular impingement). Two approaches to the semiquantitative assessment of hip OA are represented by Hip OA MRI Scoring System (HOAMS), a comprehensive whole organ assessment of nearly all findings, and the Hip Inflammation MRI Scoring System (HIMRISS), which selectively scores only active lesions (bone marrow lesion, synovitis/effusion). Validation is presently confined to limited assessment of reliability.
Two methods for semiquantitative assessment of hip OA on MRI have been described and validation according to the OMERACT Filter is limited to evaluation of reliability.
To investigate the influence of a calibrated exercise on the progression of structural lesions in an experimental model of osteoarthritis (OA) in the rat, and to explore the effect of exercise on the ...level of chondrocyte caspase-dependent apoptosis and of Hsp70.
The OA model was induced by anterior cruciate ligament transection (ACLT). Rats were placed in 4 experimental groups: operated (ACLT) free moving rats, and 3 exercise groups (slight, moderate and intense) subjected to running training. Rats were killed 14 and 28 days after surgery.
On D14 histological assessment demonstrated a beneficial influence of a slight and a moderate exercise vs control ACLT group. Hsp70 increased significantly in the moderate group vs controls. On D28, histological lesions strongly decreased in the slight and moderate exercise groups vs ACLT group, while an intense effort abolished this beneficial trend. Interestingly, the concomitant course of apoptotic events (caspase 3-positive cells) and the co-expression of Hsp70 in the various groups varied, when significant, in an inverse manner. In the intense group this overexpression was not noted, as a “burn out” appeared, thus leading to a loss of this protective effect.
This study shows that a calibrated slight or moderate exercise exerts a beneficial influence on the severity of chondral lesions in ACLT rats. Conversely, a strong effort abolishes this chondroprotective effect. This effect could be related to a reduced level of chondrocyte apoptosis through anti-apoptotic capacities of stress-induced Hsp70 overexpression.
To evaluate the reproducibility of clinical synovitis assessments in rheumatoid arthritis and the effect of variability on the Disease Activity Score-28 (DAS28).
Seven healthcare professionals from ...different cities examined the same patients with active non-early rheumatoid arthritis (RA; duration > 4 yrs), for whom a treatment change was being considered. There was no training session and the examination was to be performed as quickly as possible. The healthcare professionals assessed the 28 joints of the DAS28 in 7 patients (196 joints), then reexamined the same 28 joints in 4 of these 7 patients (112 joints), who had been rendered unrecognizable. Then 7 sonographers examined each of the 7 patients twice, using B-mode and power Doppler ultrasound (PD). The reference standards were presence of synovitis according to at least 50% of clinical examiners and 50% of sonographers. Agreement was assessed by Cohen's kappa statistic.
Intraobserver reliability ranged from 0.31 (least experienced research technician) to 0.77 (most experienced physician). Interobserver reliability ranged from 0.18 to 0.62. The largest difference between the lowest and the highest swollen joint counts in the same patient was 15, and the greatest variation in the DAS28 score was 0.92. Agreement between clinical and sonographic reference standards was 0.46, 0.37, and 0.36 for B-mode, PD, and both, respectively.
Clinical inter- and intraobserver reliability is highly dependent on the examiner. Consequences on the DAS28 score can be substantial. Agreement with sonography is poor when both B-mode and PD are used but seems better, although low, when B-mode is used alone.
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