B cells in rheumatoid synovitis

In rheumatoid arthritis, T cells, B cells, macrophages, and dendritic cells invade the synovial membranes, establishing complex microstructures that promote inflammatory/tissue destructive lesions. B cell involvement has been considered to be limited to autoantibody production. However, recent studies suggest that B cells support rheumatoid disease through other mechanisms. A critical element of rheumatoid synovitis is the process of ectopic lymphoid neogenesis, with highly efficient lymphoid architectures established in a nonlymphoid tissue site. Rheumatoid synovitis recapitulates the pathways of lymph node formation, and B cells play a key role in this process. Furthermore, studies of rheumatoid lesions implanted in immunodeficient mice suggest that T cell activation in synovitis is B cell dependent, indicating the role played by B cells in presenting antigens and providing survival signals

Does commitment to rehabilitation influence clinical outcome of total hip resurfacing arthroplasty?

BACKGROUND: The purpose of this study was to evaluate whether compliance and rehabilitative efforts were predictors of early clinical outcome of total hip resurfacing arthroplasty. METHODS: A cross-sectional survey was utilized to collect information from 147 resurfacing patients, who were operated on by a single surgeon, regarding their level of commitment to rehabilitation following surgery. Patients were followed for a mean of 52 months (range, 24 to 90 months). Clinical outcomes and functional capabilities were assessed utilizing the Harris hip objective rating system, the SF-12 Health Survey, and an eleven-point satisfaction score. A linear regression analysis was used to determine whether there was any correlation between the rehabilitation commitment scores and any of the outcome measures, and a multivariate regression model was used to control for potentially confounding factors. RESULTS: Overall, an increased level of commitment to rehabilitation was positively correlated with each of the following outcome measures: SF-12 Mental Component Score, SF-12 Physical Component Score, Harris Hip score, and satisfaction scores. These correlations remained statistically significant in the multivariate regression model. CONCLUSIONS: Patients who were more committed to their therapy after hip resurfacing returned to higher levels of functionality and were more satisfied following their surgery

Mid-term results and factors affecting outcome of a metal-backed unicompartmental knee design: a case series

<p>Abstract</p> <p>Background</p> <p>Controversies exist regarding the indications for unicompartmental knee arthroplasty. The objective of this study is to report the mid-term results and examine predictors of failure in a metal-backed unicompartmental knee arthroplasty design.</p> <p>Methods</p> <p>At a mean follow-up of 60 months, 80 medial unicompartmental knee arthroplasties (68 patients) were evaluated. Implant survivorship was analyzed using Kaplan-Meier method. The Knee Society objective and functional scores and radiographic characteristics were compared before surgery and at final follow-up. A Cox proportional hazard model was used to examine the association of patient's age, gender, obesity (body mass index > 30 kg/m²), diagnosis, Knee Society scores and patella arthrosis with failure.</p> <p>Results</p> <p>There were 9 failures during the follow up. The mean Knee Society objective and functional scores were respectively 49 and 48 points preoperatively and 95 and 92 points postoperatively. The survival rate was 92% at 5 years and 84% at 10 years. The mean age was younger in the failure group than the non-failure group (p < 0.01). However, none of the factors assessed was independently associated with failure based on the results from the Cox proportional hazard model.</p> <p>Conclusion</p> <p>Gender, pre-operative diagnosis, preoperative objective and functional scores and patellar osteophytes were not independent predictors of failure of unicompartmental knee implants, although high body mass index trended toward significance. The findings suggest that the standard criteria for UKA may be expanded without compromising the outcomes, although caution may be warranted in patients with very high body mass index pending additional data to confirm our results.</p> <p><b>Level of Evidence</b>: IV</p

Botulinum toxin type A injections for the management of muscle tightness following total hip arthroplasty: a case series

<p>Abstract</p> <p>Background</p> <p>Development of hip adductor, tensor fascia lata, and rectus femoris muscle contractures following total hip arthroplasties are quite common, with some patients failing to improve despite treatment with a variety of non-operative modalities. The purpose of the present study was to describe the use of and patient outcomes of botulinum toxin injections as an adjunctive treatment for muscle tightness following total hip arthroplasty.</p> <p>Methods</p> <p>Ten patients (14 hips) who had hip adductor, abductor, and/or flexor muscle contractures following total arthroplasty and had been refractory to physical therapeutic efforts were treated with injection of botulinum toxin A. Eight limbs received injections into the adductor muscle, 8 limbs received injections into the tensor fascia lata muscle, and 2 limbs received injection into the rectus femoris muscle, followed by intensive physical therapy for 6 weeks.</p> <p>Results</p> <p>At a mean final follow-up of 20 months, all 14 hips had increased range in the affected arc of motion, with a mean improvement of 23 degrees (range, 10 to 45 degrees). Additionally all hips had an improvement in hip scores, with a significant increase in mean score from 74 points (range, 57 to 91 points) prior to injection to a mean of 96 points (range, 93 to 98) at final follow-up. There were no serious treatment-related adverse events.</p> <p>Conclusion</p> <p>Botulinum toxin A injections combined with intensive physical therapy may be considered as a potential treatment modality, especially in difficult cases of muscle tightness that are refractory to standard therapy.</p

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ABSTRACT. Objective. Bone scintigraphy has been advocated as a useful diagnostic tool for patients with suspected osteonecrosis or in screening for multifocal disease. We evaluated the sensitivity of bone scanning relative to magnetic resonance imaging (MRI) in the diagnosis of osteonecrosis. Methods. Forty-eight patients presented with suspected osteonecrosis of the shoulder, hip, knee, or ankle. All patients underwent simultaneous (&lt; 3 months apart) bone scans and MRI studies as part of diagnostic investigations. Histological confirmation of osteonecrosis was obtained for all suspected lesions. The diagnostic result for each imaging modality was then assessed and compared. Results. All 163 (100%) histologically confirmed lesions were identified by MRI, while only 91 lesions (56%) were identified by bone scan. There was complete congruency of bone scans with MR images in only 38% of patients (18/48). Bone scanning identified 72% of lesions (47/65) in oligofocal patients (≤ 2 joints involved) compared with 45% of the lesions (44/98) in multifocal patients (≥ 3 joints involved). Sensitivity of lesions was highest for the knee and hip and lower for the shoulder and ankle. Larger and later-stage lesions had a higher bone scan sensitivity. Conclusion. Our results demonstrated the low sensitivity of bone scintigraphy for diagnosing symptomatic osteonecrosis. It is least sensitive for early-stage lesions where it might be most useful to diagnose the disease. Our study also confirms that this test is less sensitive for joints other than the hip and is also not useful as a screening tool. Our study does not support the use of bone scans as a diagnostic or screening tool for osteonecrosis

Are component positioning and prosthesis size associated with hip resurfacing failure?

BACKGROUND: Recent studies suggest that there is a learning curve for metal-on-metal hip resurfacing. The purpose of this study was to assess whether implant positioning changed with surgeon experience and whether positioning and component sizing were associated with implant longevity. METHODS: We evaluated the first 361 consecutive hip resurfacings performed by a single surgeon, which had a mean follow-up of 59 months (range, 28 to 87 months). Pre and post-operative radiographs were assessed to determine the inclination of the acetabular component, as well as the sagittal and coronal femoral stem-neck angles. Changes in the precision of component placement were determined by assessing changes in the standard deviation of each measurement using variance ratio and linear regression analysis. Additionally, the cup and stem-shaft angles as well as component sizes were compared between the 31 hips that failed over the follow-up period and the surviving components to assess for any differences that might have been associated with an increased risk for failure. RESULTS: Surgeon experience was correlated with improved precision of the antero-posterior and lateral positioning of the femoral component. However, femoral and acetabular radiographic implant positioning angles were not different between the surviving hips and failures. The failures had smaller mean femoral component diameters as compared to the non-failure group (44 versus 47 millimeters). CONCLUSIONS: These results suggest that there may be differences in implant positioning in early versus late learning curve procedures, but that in the absence of recognized risk factors such as intra-operative notching of the femoral neck and cup inclination in excess of 50 degrees, component positioning does not appear to be associated with failure. Nevertheless, surgeons should exercise caution in operating patients with small femoral necks, especially when they are early in the learning curve

Fractures in myelomeningocele

BACKGROUND: In patients with myelomeningocele (MMC), a high number of fractures occur in the paralyzed extremities, affecting mobility and independence. The aims of this retrospective cross-sectional study are to determine the frequency of fractures in our patient cohort and to identify trends and risk factors relevant for such fractures. MATERIALS AND METHODS: Between March 1988 and June 2005, 862 patients with MMC were treated at our hospital. The medical records, surgery reports, and X-rays from these patients were evaluated. RESULTS: During the study period, 11% of the patients (n = 92) suffered one or more fractures. Risk analysis showed that patients with MMC and thoracic-level paralysis had a sixfold higher risk of fracture compared with those with sacral-level paralysis. Femoral-neck z-scores measured by dual-energy X-ray absorptiometry (DEXA) differed significantly according to the level of neurological impairment, with lower z-scores in children with a higher level of lesion. Furthermore, the rate of epiphyseal separation increased noticeably after cast immobilization. Mainly patients who could walk relatively well were affected. CONCLUSIONS: Patients with thoracic-level paralysis represent a group with high fracture risk. According to these results, fracture and epiphyseal injury in patients with MMC should be treated by plaster immobilization. The duration of immobilization should be kept to a minimum (<4 weeks) because of increased risk of secondary fractures. Alternatively, patients with refractures can be treated by surgery, when nonoperative treatment has failed

A New Promising Anti-Infective Agent Inhibits Biofilm Growth by Targeting Simultaneously a Conserved RNA Function That Controls Multiple Genes

Combating single and multi-drug-resistant infections in the form of biofilms is an immediate challenge. The challenge is to discover innovative targets and develop novel chemistries that combat biofilms and drug-resistant organisms, and thwart emergence of future resistant strains. An ideal novel target would control multiple genes, and can be inhibited by a single compound. We previously demonstrated success against Staphylococcus aureus biofilms by targeting the tRNA-dependent regulated T-box genes, not present in the human host. Present in Gram-positive bacteria, T-box genes attenuate transcription with a riboswitch-like element that regulates the expression of aminoacyl-tRNA synthetases and amino acid metabolism genes required for cell viability. PKZ18, the parent of a family of compounds selected in silico from 305,000 molecules, inhibits the function of the conserved T-box regulatory element and thus blocks growth of antibiotic-resistant S. aureus in biofilms. The PKZ18 analog PKZ18-22 was 10-fold more potent than vancomycin in inhibiting growth of S. aureus in biofilms. In addition, PKZ18-22 has a synergistic effect with existing antibiotics, e.g., gentamicin and rifampin. PKZ18-22 inhibits the T-box regulatory mechanism, halts the transcription of vital genes, and results in cell death. These effects are independent of the growth state, planktonic or biofilm, of the bacteria, and could inhibit emergent strains