Subchondroplasty in the treatment of bone Marrow lesion in early Knee Osteoarthritis: A systematic review of clinical and radiological outcomes

BackgroundKnee osteoarthritis (KOA) is increasingly prevalent in North American society. The significant societal burden it represents makes it essential to promote and target new treatments in earlier phases of the disease. Among others, subchondroplasty is a newly documented technique using calcium phosphate injection targeting the osteochondral lesions preceding KOA, also known as Bone Marrow Lesions (BMLs). This article aimed to review the existing literature on clinical and radiological outcomes of subchondroplasty in the treatment of BMLs in KOA.MethodA systematic review was performed using PubMed, Embase, Medline and Cochrane Database of Systematic Reviews. Studies on calcium phosphate injections into BMLs for KOA and its clinical and radiological outcomes were screened and reviewed by independent evaluators.ResultsAfter screening, ten articles were included, totaling 540 patients. Follow-up ranged from 6 months to 7 years. Overall, the procedure showed significant functional and quality of life improvement, as well as pain relief, as shown by Patients-Reported Outcomes Measures (PROMs). There were very few complications reported, the most important being leakage of calcium phosphate outside the targeted site. Conversion rate to total knee arthroplasty (TKA) ranged from 14 % to 30 % at 2 years post-procedure. Long term radiological outcomes have been poorly documented.ConclusionsSubchondroplasty is a promising avenue for the treatment of KOA. However, quality evidence is still required before any real conclusions and practical management guidelines can be drawn. Prospective, randomized studies with a control group and a rigorous assessment of long-term clinical and radiological outcomes are recommended.     

八肽胆囊收缩素对TNF-α诱导的大鼠滑膜细胞株RSC-364 IL-6的作用及其可能的分子机制(英文)

目的: 观察硫酸化八肽胆囊收缩素（sCCK-8）对TNF-α诱导大鼠滑膜细胞株RSC-364 IL-6 mRNA 表达及核因子NF-κB的影响及其可能的受体机制。方法: 大鼠滑膜细胞株RSC-364经TNF-α(10　μg/L)、sCCK-8(10^-8-10^-6 mol/L)、CCK受体拮抗剂丙谷胺（2 mg/L）及溶剂单独或联合孵育3 h，用RT-PCR检测细胞IL-6、CCK-AR及CCK-BR mRNA的表达，孵育1 h，用电泳迁移率检测NF-κB活性，孵育30 min，用Western blotting检测胞浆IκB蛋白表达。结果: RSC-364细胞固有表达CCK-A/B受体，sCCK-8（10^-8-10^-6 mol/L）使IL-6、CCK-AR和CCK-BR mRNA表达进一步增高，明显增加TNF-α诱导的NF-κB活性，降低胞浆中IκB蛋白水平，并可被丙谷胺所拮抗。结论: sCCK-8通过NF-κB途径上调TNF-α诱导的大鼠滑膜细胞IL-6 mRNA表达，此作用可能通过滑膜细胞上的CCK受体实现，提示CCK-8在类风湿性关节炎（RA）发病过程中可能具有调控作用。     

Computed tomographic study of the posterior condylar angle in arthritic knees: its use in the rotational positioning of the femoral implant of total knee prostheses

The epicondylar axis is a reliable reference to check the rotation of the femoral implant in total knee prostheses (TKPs). However, during the operation it seems easier to use the posterior condylar axis as a landmark. The angle between these two axes is called the posterior condylar angle (PCA). The aim of this study was to measure the PCA in arthritic knees to assess the reliability of the posterior condylar axis as a reference for the control of the rotation of the femoral implant and to look for correlation with other radiological measurements. This prospective study consisted of 103 arthritic knees (81 varus, 22 valgus) before a TKP had been done in 103 patients (75 women, 28 men). The assessment of the PCA was made by computed tomographic scanning (CT). The HKA, HKS and HKT angles were measured on the pangonogram. The posterior condylar axis was internally rotated with respect to the epicondylar axis. The average value for all the patients was 2.65° degrees with a range from 0° to 7°. The PCA was significantly increased in the valgus knees. There was no correlation between the angles on the pangonogram and the posterior condylar axis. While the preoperative assessment of the PCA by CT scanning is reliable, the results obtained indicate the marked variability in its value. If one wishes to use the posterior condylar axis as a guide for rotation, it is therefore necessary to assess the PCA for each patient using adjustable jigs according to the value obtained. No measurement on standard radiographs allowed an extrapolation of the value of the PCA, and CT scanning seems to be the preferable radiological examination.

---

Electronic Supplementary Material The french version of this article is available in the form of electronic supplementary material and can be obtained by using the Springer Link server located at

---

Etude tomodensitométrique de l'angle condylien postérieur dans les genoux arthrosiques. Intérêt dans le positionnement en rotation de l'implant fémoral dans les prothèses totales de genou

Résumé L'axe épicondylien est une référence fiable pour le contrôle de la rotation de l'implant fémoral dans les prothèses totales de genou (PTG). Mais, lors de l'intervention, il semble plus facile d'utiliser l'axe condylien postérieur comme repère. L'angle entre ses deux axes est appelé angle condylien postérieur (ACP). Le but de cette étude était de mesurer l'ACP dans les genoux arthrosiques, d'évaluer la fiabilité de l'axe condylien postérieur comme référence pour le réglage de la rotation de l'implant fémoral, de rechercher une corrélation avec d'autres mesures radiologiques. Une étude prospective comportant 103 genoux arthrosiques (81 varus et 22 valgus), avant PTG a été effectuée, chez 103 patients (75 femmes et 28 hommes). L'évaluation de l'ACP a été faite par examen tomodensitométrique (TDM). Les angles HKA, HKS et HKT ont été mesurés sur le pangonogramme. L'axe condylien postérieur était en rotation interne par rapport à l'axe épicondylien. La valeur moyenne pour tous les patients était de 2.65°, avec des valeurs de 0 à 7°. La valeur de l'angle CP augmentait avec une différence significative dans le groupe des genu valgum. Il n'y avait pas de corrélation entre les angles du pangonogramme et l'ACP. Si l'évaluation pré-opératoire de l'ACP par TDM est fiable, les résultats obtenus mettent en évidence une variabilité importante de sa valeur. Il faut donc, si l'on veut utiliser l'axe condylien postérieur comme repère de rotation, évaluer pour chaque patient l'ACP, et utiliser un ancillaire réglable reportant la valeur obtenue. Aucune mesure sur des radiographies standard ne permettant d'extrapoler la valeur de l'ACP, la TDM semble l'examen radiologique de choix.

     

Local production of IgA- and IgM-rheumatoid factors in adult periodontal disease

The enzyme-linked immunospot assay was used to enumerate both the number and the frequency of spontaneous IgG, IgA, and IgM immunoglobulin-secreting cells and IgA- and IgM-rheumatoid factor (RF)-producing cells present in the gingivae and peripheral blood of adult periodontitis patients. Cells from 29 patients were incubated on plates coated with human IgG, Fc, or F(ab)₂ fragments and on plates coated with class-specific antihuman antibodies and secreted antibodies were subsequently visualized by means of an immunoenzymatic procedure. The data indicate that (1) IgA-RF- and IgM-RF-secreting cells are frequently present in the gingiva of adult periodontitis patients; (2) production of RF in gingivae of adult periodontitis patients occurs in the absence of demonstrable RF production by simultaneously obtained peripheral blood mononuclear cells, suggesting that local autoimmune reactions may occur in this disease; and (3) lack of correlation between IgA-RF and IgM-RF production in diseased gingiva suggests that the two RF isotypes are regulated independently of each other.     

Circulating interleukin 10 and interleukin-6 serum levels in rheumatoid arthritis patients treated with methotrexate or gold salts: Preliminary report

In order to evaluate the relationship between serum concentrations of interleukin-10 (IL-10), IL-6, and acute phase proteins in rheumatoid arthritis (RA) patients treated with methotrexate (MTX) or intramuscular gold (IMG) we determined IL-10, IL-6, C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP) and alpha-1-antichymotrypsin (ACT) in the sera of 35 RA patients. IL-10 and IL-6 levels were evaluated using an enzyme-linked immunoassay (ELISA). AGP and ACT level were measured using rocket immunoelectrophoresis. IL-10 serum level was not increased in RA patients as compared to controls (58.7 ± 18.1 pg/ml vs. 57.2 ± 11.9 pg/ml). IL-6 level was significantly elevated (91.6 ± 46.9 pg/ml vs. 45 ± 19 pg/ml, p < 0.05). CRP was significantly increased as compared to healthy controls (35 ± 19 mg/l vs. 3 ± 2 mg/l, p < 0.05). Patients treated with MTX or IMG presented an increased level of IL-10 and decreased amounts of IL-6, as compared to those treated with NSAID only. However, only changes between patients treated with IMG and NSAID were found to be statistically significant. A good negative correlation between IL-10 and IL-6 serum level was found (r = –0.75, p < 0.05). A positive significant correlation between IL-6 serum level and CRP (r = 0.62, p < 0.05), AGP (r = 0.78, p < 0.05) and ACT (r = 0.45, p < 0.05) was established. On the other hand, a negative correlation between IL-10 and serum level of CRP (r = –0.76, p < 0.05), AGP (r = –0.64, p < 0.05) and ACT (r = –0.38, p < 0.05) was also observed. Moreover, these relationships were maintained when patients treated with MTX, IMG, or NSAID were analyzed independently. According to the data thus far obtained, it seems that IL-10 decreases IL-6 production, and thereby indirectly affects the acute phase response, decreasing CRP, AGP, and ACT concentration in RA patients.Abbreviations ACT -1-antichymotrypsin - AGP ₁-acid glycoprotein - APP acute phase protein - CRP C-reactive protein - CSF colony stimulating factor - IFN interferon - IL interleukin - IMG intramuscular gold - MTX methotrexate - NSAID non-steroidal anti-inflammatory drug - RA rheumatoid arthritis     

Muscle spindles in rheumatoid arthritis

Summary Ultrastructural features of muscle spindles were studied in biopsy material from 100 patients suffering from classical rheumatoid arthritis. Thickening of the outer capsule, increased amount of extracellular ground substance within the inner capsule, and marked thickening of the basement membrane of capillary blood vessels supplying the muscle spindles were observed. Chronic inflammatory cells and macrophages were present within the spindles. Changes affecting the intrafusal muscle fibres were also seen. They were manifest as atrophy and degeneration of the intrafusal muscle fibres, absence of the specialised junctional complexes, and of the intercellular bridges, microladders and satellite cells. It is suggested that the changes affecting the intrafusal muscle fibres are probably secondary. Damage to the myelinated nerves was present, while the sensory and motor nerve endings were well preserved.Temporary Research Fellow the Rotterdam Centre for Rheumatic Disease Present address: Division of Pathology, Department of Obstetrics and Gynaecology, University of Chicago, Chicago, Illinois 60637, USA     

Autoimmune diseases in myelodysplastic syndrome favors patients survival: A case control study and literature review

Background

We conducted a monocentric retrospective study of patients with myelodysplastic syndromes (MDS) and autoimmune or inflammatory disorders (AIMs) and a literature review. We analyzed the association with subgroups of the WHO 2016 MDS classification and patient's survival in a case control study. Risk factors associated with survival were analyzed by uni- and multivariate analysis.

Does Hemopoietic Stem Cell Transplantation Have a Role in Treatment of Severe Rheumatoid Arthritis?

Based on animal models and limited clinical experience, there is considerable interest in use of high-dose immunosuppression followed by hemopoietic stem cell transplantation as treatment for severe rheumatoid arthritis. Because of its relatively low treatment-related mortality and morbidity, autologous transplantation is a more attractive option than allogeneic transplantation for initial clinical trials, even though anecdotal reports suggest that allogeneic transplantation has a greater likelihood of bringing about long-term disease control. The approach remains experimental with many unanswered questions such as the value and safety of high-dose therapy without transplantation, the need for T cell purging, the possible deleterious effects of post-transplant hemopoietic growth factors and the potential of mini allogeneic transplantation (a process whereby intense immunosuppression is combined with less intense myelosuppression). To achieve quick progress it is essential that clinical trials be carefully designed with all cases being reported to the Autoimmune Disease Stem Cell Project Database.     

<Emphasis Type="Italic">Demodex folliculorum</Emphasis> in patients with rheumatoid arthritis

The objective of this study was to investigate the incidence and density of Demodex folliculorum in the patients with rheumatoid arthritis (RA). Forty-one patients with RA and twenty-seven age and sex matched healthy controls were enrolled in this study. Disease Activity Score (DAS 28) was used for the assessment of disease activity. Out of 41 patients, 33 were females and 8 males. The mean disease duration was 10.9 ± 8.2 years. The mean DAS 28 was 3.8 ± 1.2. No statistically significant differences in the incidence and density of Demodex mites were found between patients with RA and controls. Although immunosuppression is thought to be a risk factor for the D. folliculorum infestation no such correlations could be found in the 41 immunosuppressed patients with RA, therefore, further studies with larger groups are needed.     

A Morphological and Immunohistochemical Study of Lymphoid Germinal Centers in Synovial and Lymph Node Tissues from Rheumatoid Arthritis Patients with Special Reference to Complement Components and Their Receptors

Rheumatoid arthritis (RA) is one of the immune complex (IC) diseases in which lymphoid germinal centers (GCs) are found in the synovial tissue. Simultaneously, patients with RA often show swelling of lymph nodes. The morphology and function of the lymph node GCs in patients with RA is not clear. The aim of this study was to evaluate the differences in morphology and immunoreactions to complement (C) components, their receptors, and lgM-rheumatoid factor (RF) between synovial GCs and lymph-node GCs in RA. Furthermore, the relationship between these immuno-reactive substances and follicular dendritic cells (FDCs) in GCs was investigated. The tissues examined were 41 RA synovial specimens, seven RA lymph nodes with massive lymphadenopathy, and 10 non-RA lymph nodes. The number of synovial GCs was relatively decreased in comparison with lymph-node GCs in RA, and the diameter of each synovial GC was smaller than that of each lymph-node GC. The synovial GCs were edematous and less cellular, and moreover, those from RF-seronegative cases were smaller than those from RF seropositive cases. On the other hand, the lymph-node GCs in RA were larger, more cellular and hyperplastic, but contained more tingible-body macro-phages (TBMs) and neutrophils. In the GCs of both synovial tissues and lymph nodes in RA, early C components (C1q, C4, C3c, C3d), IgM RF, and C3b receptor (C3bR) and C3d receptor (C3dR) were expressed as a lacy network by light microscopy, and were demonstrated on the surfaces of FDCs and lymphocytes, and in the intercellular spaces by electron microscopy. Furthermore, immuno-staining for dendritic reticulum cells (DRC, DAKO DRC1) was observed in a lacy pattern by light microscopy and on the cell surface of FDCs by electron microscopy. In the GCs of non-RA lymph nodes, early C components, C3bR, C3dR, and DRC showed a similar reaction pattern, but IgMRF did not. Consequently, no marked difference in immunoreactions in the GCs, except for the immunoreactions of late C components, was found between synovial tissues and lymph nodes in RA. On the basis of these findings, we discuss the possibility of the presence of a RF-IC.