Functional outcomes and clinical strength assessment after infraspinatus-sparing surgical approach to scapular fracture: Does it really make a difference?

Background: Surgical treatment of scapular fractures with posterior approach is frequently associated with postoperative infraspinatus hypotrophy and weakness. The aim of this retrospective study is to compare infraspinatus strength and functional outcomes in patients treated with the classic Judet versus modified Judet approach for scapular fracture. Patients and methods: 20 cases with scapular neck and body fracture treated with posterior approach for lateral border plate fixation were reviewed. In 11 of 20 cases, we used the modified Judet approach (MJ group), and in 9 cases we used the classic Judet approach (CJ group). All fractures were classified according to the AO classification system. At follow-up examinations, patients had X-ray assessment with acromiohumeral distance (AHD) measurement, clinical evaluation, active range of motion (ROM) examination, Constant Shoulder Score, and Disability of the Arm, Shoulder and Hand (DASH) Score. Infraspinatus strength assessment was measured using a dynamometer during infraspinatus strength test (IST) and infraspinatus scapular retraction test (ISRT). Results: Demographic data did not significantly differ between the CJ group and MJ group, except for mean follow-up, which was 4.15\ua0years in the CJ group and 2.33 in the MJ group (p\ua0<\ua00.001). All X-ray examinations showed fracture healing. AHD was significantly decreased in the CJ group (p\ua0=\ua00.006). We did not find significant differences in active ROM between the MJ and CJ groups in the injured arm (p\ua0<\ua00.05). The Constant Score was 75.83 (\ub114.03) in the CJ group and 82.75 (\ub110.72) in the MJ group (p\ua0=\ua00.31); DASH Score was 10.16 in the CJ group and 6.25 in the MJ group (p\ua0=\ua00.49). IST showed mean strength of 8.38\ua0kg (\ub11.75) in the MJ group and 4.61\ua0kg (\ub11.98) in the CJ group (p\ua0=\ua00.002), ISRT test was 8.7 (\ub11.64) in the MJ group and 4.95 (\ub12.1) in the CJ group (p\ua0=\ua00.002). Infraspinatus hypotrophy was detected during inspection in six patients (five in the CJ group and one in the MJ group); it was related to infraspinatus strength weakness in IST and ISRT (p\ua0<\ua00.001). Conclusions: Infraspinatus-sparing surgical approach for scapular fracture avoids infraspinatus hypotrophy and external-rotation strength weakness. We suggest use of the modified Judet approach for scapular fracture and to restrict the classic Judet approach to only when the surgeon believes that the fracture is not easily reducible with a narrower exposure. Level of evidence: Level\ua0IV

Expression analysis of HLA-E and NKG2A and NKG2C receptors points at a role for natural killer function in ankylosing spondylitis

Background. Ankylosing Spondylitis (AS) is a complex chronic inflammatory disease strongly associated with the majority of HLA-B27 alleles. HLA-E are non-classical MHC class I molecules that specifically interact with the natural killer receptors NKG2A (inhibitory) and NKG2C (activating), and have been recently proposed to be involved in AS pathogenesis. Objectives: To analyze the expression of HLA-E and the CD94/NKG2 pair of receptors in HLA-B27 positive AS patients and healthy controls (HC) bearing the AS-associated, B*2705 and the non-AS-associated, B*2709 allele. Methods: The level of surface expression of HLA-E molecules on CD14 positive peripheral blood mononuclear cell was evaluated in 21 HLA-B*2705 patients with AS, 12 HLA-B*2705 HC, 12 HLA-B*2709 HC and 6 HLA-B27 negative HC, using the monoclonal antibody MEM-E/08 by quantitative cytofluorimetric analysis. The percentage and density of expression of HLA-E ligands NKG2A and NKG2C were also measured on CD3-CD56+ NK cells. Results. HLA-E expression in CD14 positive cells was significantly higher in AS patients (587.0 IQR 424-830) compared to B*2705 HC (389 IQR 251.3-440.5, p=0.0007), B*2709 HC (294.5 IQR 209.5-422, p=0.0004) and HLA-B27 negative HC (380 IQR 197.3-515.0, p=0.01). A higher number of NK cells expressing NKG2A compared to NKG2C was found in all cohort analysed as well as a higher cell surface density. Conclusion: The higher surface level of HLA-E molecules in AS patients compared to HC, concurrently with a prevalent expression of NKG2A, suggests that the crosstalk between these two molecules might play a role in AS pathogenesis accounting for the previously reported association between HLA-E and AS

Gene expression profiling of monozygotic twins affected by psoriatic arthritis

Introduction: Psoriatic Arthritis (PsA) is a multifactorial disease, where the relative burden of genetic, epigenetic and environmental factors in clinical course and damage accrual is not yet definitively clarified. In clinical practice, there is a real need for useful candidate biomarkers in PsA diagnosis and disease progression, by exploring its underlying transcrip-tomic and epigenomic mechanisms. This work aims to profile the transcriptome in mono-zygotic (MZ) twins with psoriatic arthritis (PsA) highly concordant for clinical presentation, but discordant for the radiographic outcomes’ severity. Methods: We describe i) the clinical case of two MZ twins; ii) their comparative gene expression profiling (HTA 2.0 Affymetrix) and iii) signal pathways and pathophysiological processes in which differentially expressed genes are involved (in silico analysis by the IPA software, QIAGEN). Results: One hundred sixty-three transcripts and 36 coding genes (28 up and 8 down) were differentially expressed between twins, and in the brother with the most erosive form, the transcriptomic profiling highlights the overexpression of genes known to be involved in immunomodulatory processes and on a broad spectrum of PsA manifestations. Discussion: Twins’ clinical cases are still a gold mine in medical research: twin brothers are ideal experimental models in estimating the relative importance of genetic versus nongenetic components as determinants of complex phenotypes, non-Mendelian and multifactorial diseases as PsA

Juvenile hemochromatosis associated with heterozygosity for novel hemojuvelin mutations and with unknown cofactors

Background & Aims. Juvenile hemochromatosis (JH) is a rare autosomal recessive disorder characterized by severe early-onset iron overload, caused by mutations in hemojuvelin (HJV), hepcidin (HAMP), or a combination of genes regulating iron metabolism. Here we describe two JH cases associated with simple heterozygosity for novel HJV mutations and unknown genetic factors. Case 1: A 12 year-old male from Central Italy with beta-thalassemia trait, increased aminotransferases, ferritin 9035 ng/ml and transferrin saturation 84%, massive hepatocellular siderosis and hepatic bridging fibrosis. Case 2: A 12 year-old female from Northern Italy with ferritin 467 ng/ml, transferrin saturation 87-95%, and moderate hepatic iron overload. Material and methods. Direct sequencing of hemochromatosis genes (HFE-TfR2-HJV-HAMP-FPN-1) was performed in the children and siblings. Results. In case 1, we detected heterozygosity for a novel HJV mutation (g.3659_3660insG), which was inherited together with the beta thalassemia trait from the father, who (as well as the mother) had normal iron parameters. In case 2, we detected another novel HJV mutation (g.2297delC) in heterozygosity, which was inherited from the mother, affected by mild iron deficiency. The father had normal iron stores. Both mutations are frameshifts determining premature stop codons. No other disease causing variant was detected. Conclusion. Although beta-thalassemia trait was a possible cofactor of iron overload in case 1, iron overload cannot be explained by simple heterozygosity for HJV mutations in both cases. Other genetic factors should be investigated, and further studies are needed to understand genotype-phenotype correlations in JH

Analysis and Evaluation of Service-Oriented Architectures for Digital Libraries

The Service Oriented Architecture (SOA) that underlies the Web Services paradigm of computing is widely regarded as the future of distributed computing. The applicability of such an architecture for digital library systems is still uncertain, as evidenced by the fact that virtually none of the large open source projects (e.g., Greenstone, EPrints, DSpace) have adopted it for internal component structuring. In contrast, the Open Archives Initiative (OAI) has received much support in the DL community for its Protocol for Metadata Harvesting, one that in principle falls within the scope of SOA. As a natural extension, the Open Digital Library project carried the principles of the OAI forward into a set of experimental derived and related protocols to create a testbed for component-based digital library experiments. This paper discusses a series of experiments with these components to confirm that SOA and a service-oriented component architecture is indeed applicable to digital library systems, by evaluating issues of simplicity and understandability, reusability, extensibility and performance

Combined microwave ablation and osteosynthesis for long bone metastases

Background and Objectives: The purpose of this study was to evaluate the feasibility, safety and efficacy of microwave ablation (MWA) in combination with open surgery nail positioning for the treatment of fractures or impending fractures of long bone metastases. Material and Methods: Eleven patients (four men, seven women) with painful bone metastases of the humerus, femur or tibia with non-displaced fractures (one case) or impending fractures (10 cases) underwent open MWA in combination with osteosynthesis by locked nail positioning. Pain intensity was measured using a VAS score before and after treatment. CT or MRI were acquired at one month before and 1, 3, 6, 12 and 18 months after treatment. Results: All procedures were successfully completed without major complications. The level of pain was significantly reduced one month after treatment. For the patients with humerus metastases, the complete recovery of arm use took 8 weeks, while for the patients with femoral metastases the complete recovery of walking capacity took 11 weeks. The VAS score ranged from 7 (4–9) before treatment to 1.5 (0–2.5) after treatment. During a mid-term follow-up of 18 months (range 4–29 months), none of the patients showed tumor relapse or new fractures in the treated site. Two patients died due to tumor disease progression. Conclusion: Results of this preliminary study suggest that combined MWA and surgical osteosynthesis with locked nails is a safe and effective treatment for pathological fractures or malignant impending fractures of long bone metastases of the humerus, femur and tibia. Further analyses with larger cohorts are warranted to confirm these findings

Toward the renal vesicle: Ultrastructural investigation of the cap mesenchyme splitting process in the developing kidney

Background: A complex sequence of morphogenetic events leads to the development of the adult mouse kidney. In the present study, we investigated the morphological events that characterize the early stages of the mesenchymal-to-epithelial transition of cap mesenchymal cells, analyzing in depth the relationship between cap mesenchymal induction and ureteric bud (UB) branching. Design and methods: Normal kidneys of newborn non-obese diabetic (NOD) mice were excised and prepared for light and electron microscopic examination. Results: Nephrogenesis was evident in the outer portion of the renal cortex of all examined samples. This process was mainly due to the interaction of two primordial derivatives, the ureteric bud and the metanephric mesenchyme. Early renal developmental stages were initially characterized by the formation of a continuous layer of condensed mesenchymal cells around the tips of the ureteric buds. These caps of mesenchymal cells affected the epithelial cells of the underlying ureteric bud, possibly inducing their growth and branching. Conclusions: The present study provides morphological evidence of the reciprocal induction between the ureteric bud and the metanephric mesenchyme showing that the ureteric buds convert mesenchyme to epithelium that in turn stimulates the growth and the branching of the ureteric bud

Stratification of biological therapies by pathobiology in biologic-naive patients with rheumatoid arthritis (STRAP and STRAP-EU): two parallel, open-label, biopsy-driven, randomised trials

BACKGROUND: Despite highly effective targeted therapies for rheumatoid arthritis, about 40% of patients respond poorly, and predictive biomarkers for treatment choices are lacking. We did a biopsy-driven trial to compare the response to rituximab, etanercept, and tocilizumab in biologic-naive patients with rheumatoid arthritis stratified for synovial B cell status. METHODS: STRAP and STRAP-EU were two parallel, open-label, biopsy-driven, stratified, randomised, phase 3 trials done across 26 university centres in the UK and Europe. Biologic-naive patients aged 18 years or older with rheumatoid arthritis based on American College of Rheumatology (ACR)–European League Against Rheumatism classification criteria and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs) were included. Following ultrasound-guided synovial biopsy, patients were classified as B cell poor or B cell rich according to synovial B cell signatures and randomly assigned (1:1:1) to intravenous rituximab (1000 mg at week 0 and week 2), subcutaneous tocilizumab (162 mg per week), or subcutaneous etanercept (50 mg per week). The primary outcome was the 16-week ACR20 response in the B cell-poor, intention-to-treat population (defined as all randomly assigned patients), with data pooled from the two trials, comparing etanercept and tocilizumab (grouped) versus rituximab. Safety was assessed in all patients who received at least one dose of study drug. These trials are registered with the EU Clinical Trials Register, 2014-003529-16 (STRAP) and 2017-004079-30 (STRAP-EU). FINDINGS: Between June 8, 2015, and July 4, 2019, 226 patients were randomly assigned to etanercept (n=73), tocilizumab (n=74), and rituximab (n=79). Three patients (one in each group) were excluded after randomisation because they received parenteral steroids in the 4 weeks before recruitment. 168 (75%) of 223 patients in the intention-to-treat population were women and 170 (76%) were White. In the B cell-poor population, ACR20 response at 16 weeks (primary endpoint) showed no significant differences between etanercept and tocilizumab grouped together and rituximab (46 [60%] of 77 patients vs 26 [59%] of 44; odds ratio 1·02 [95% CI 0·47–2·17], p=0·97). No differences were observed for adverse events, including serious adverse events, which occurred in six (6%) of 102 patients in the rituximab group, nine (6%) of 108 patients in the etanercept group, and three (4%) of 73 patients in the tocilizumab group (p=0·53). INTERPRETATION: In this biologic-naive population of patients with rheumatoid arthrtitis, the dichotomic classification into synovial B cell poor versus rich did not predict treatment response to B cell depletion with rituximab compared with alternative treatment strategies. However, the lack of response to rituximab in patients with a pauci-immune pathotype and the higher risk of structural damage progression in B cell-rich patients treated with rituximab warrant further investigations into the ability of synovial tissue analyses to inform disease pathogenesis and treatment response. FUNDING: UK Medical Research Council and Versus Arthritis