Background
Although periacetabular osteotomy (PAO) for developmental dysplasia of the hip (DDH) provides conceptual advantages compared with other osteotomies and reportedly is associated with joint ...survivorship of 60% at 20 years, the beneficial effect of proper acetabular reorientation with concomitant arthrotomy and creation of femoral head-neck offset on 10-year hip survivorship remains unclear.
Questions/purposes
We asked the following questions: (1) Does the 10-year survivorship of the hip after PAO improve with proper acetabular reorientation and a spherical femoral head; (2) does the Merle d’Aubigné-Postel score improve; (3) can the progression of osteoarthritis (OA) be slowed; and (4) what factors predict conversion to THA, progression of OA, or a Merle d’Aubigné-Postel score less than 15 points?
Methods
We retrospectively reviewed 147 patients who underwent 165 PAOs for DDH with two matched groups: Group I (proper reorientation and spherical femoral head) and Group II (improper reorientation and aspherical femoral head). We compared the Kaplan-Meier survivorship, Merle d’Aubigné-Postel scores, and progression of OA in both groups. A Cox regression analysis (end points: THA, OA progression, or Merle d’Aubigné-Postel score less than 15) was performed to detect factors predicting failure. The minimum followup was 10 years (median, 11 years; range, 10–14 years).
Results
An increased survivorship was found in Group I. The Merle d’Aubigné-Postel score did not differ. Progression of OA in Group I was slower than in Group II. Factors predicting failure included greater age, lower preoperative Merle d’Aubigné-Postel score, and the presence of a Trendelenburg sign, aspherical head, OA, subluxation, postoperative acetabular retroversion, excessive acetabular anteversion, and undercoverage.
Conclusions
Proper acetabular reorientation and the creation of a spherical femoral head improve long-term survivorship and decelerate OA progression in patients with DDH.
Level of Evidence
Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
Purpose
(1) To determine the overall accuracy of synovial alpha-defensin, synovial C-reactive protein (sCRP), interleukin-6 (sIL-6), and leukocyte esterase (sLE) as diagnostic markers for ...periprosthetic joint infection (PJI) and (2) to independantly evaluate the accuracy of both the laboratory-based ELISA alpha-defensin test and the Synovasure™ alpha-defensin test kit.
Methods
An EMBASE and MEDLINE (PubMed) database search was performed using a set of professionally set search terms. Two independent reviewers rated eligible articles. Sensitivity and specificity were meta-analysed using a bivariate random-effects model.
Results
Accuracy values were extracted from 42 articles. Pooled sensitivity and specificity of the represented biomarkers were: alpha-defensin ELISA 0.97 (95% CI 0.91–0.99) and 0.97 (95% CI 0.94–0.98), respectively; Synovasure™ test kit assay 0.80 (95% CI 0.65–0.89) and 0.89 (95% CI 0.76–0.96), respectively; sLE 0.79 (95% CI 0.67–0.87) and 0.92 (95% CI 0.87–0.92), respectively; sIL-6 0.76 (95% CI 0.65–0.84) and 0.91 (95% CI 0.88–0.94), respectively; sCRP 0.86 (95% CI 0.81–0.91) and 0.90 (95% CI 0.86–0.93), respectively.
Conclusion
The labararory-based alpha-defensin ELISA test showed the highest ever reported accuracy for PJI diagnosis. However, this did not apply for the Synovasure™ alpha-defensin test, which was comparable in its overall diagnostic accuracy to sCRP, sIL-6 and sLE. The later biomarkers also did not yield an overall diagnostic accuracy higher than that previously reported for synovial white cell count (sWBC) or culture bacteriology. Based on current evidence, no synovial biomarker should be applied as a standalone diagnostic tool. Furthermore, the use of the laboratory-based alpha-defensin ELISA test should be encouraged, still, the Synovasure™ alpha-defensin test kit should be critically appreciated.
Lever of evidence
III.
Low back pain (LBP) has been among the leading causes of disability for the past 30 years. This highlights the need for improvement in LBP management. Many clinical trials focus on developing ...treatments against degenerative disc disease (DDD). The multifactorial etiology of DDD and associated risk factors lead to a heterogeneous patient population. It comes as no surprise that the outcomes of clinical trials on intradiscal mesenchymal stem cell (MSC) injections for patients with DDD are inconsistent. Intradiscal MSC injections have demonstrated substantial pain relief and significant disability-related improvements, yet they have failed to regenerate the intervertebral disc (IVD). Increasing evidence suggests that the positive outcomes in clinical trials might be attributed to the immunomodulatory potential of MSCs rather than to their regenerative properties. Therefore, patient stratification for inflammatory DDD phenotypes may (i) better serve the mechanisms of action of MSCs and (ii) increase the treatment effect. Modic type 1 changes-pathologic inflammatory, fibrotic changes in the vertebral bone marrow-are frequently observed adjacent to degenerated IVDs in chronic LBP patients and represent a clinically distinct subpopulation of patients with DDD. This review discusses whether degenerated IVDs of patients with Modic type 1 changes should be treated with an intradiscal MSC injection.
Abstract
Nanoparticulate silver coatings for orthopaedic implants promise to decrease postoperative infection rates. However, silver-induced cytotoxicity on bone cells has not been investigated in ...detail. This study investigated the cytotoxic effects of silver nano- and microparticles and Ag+ on osteoblasts (OBs) and osteoclasts (OCs) and correlated their effects with the antibacterial efficacy on Staphylococcus epidermidis. Silver nanoparticles (50 nm) exhibited strong cytotoxic effects on OBs and OCs. Weak cytotoxic effects were observed for silver microparticles (3 μm). The cytotoxicity was primarily mediated by a size-dependent release of Ag+. Antibacterial effects occurred at Ag+ concentrations that were 2-4 times higher than those inducing cytotoxic effects. Such adverse effects on OB and OC survival may have deleterious effects on the biocompatibility of orthopaedic implants. Our study represents an important step toward the detailed investigation of orthopaedic implant with nanoparticulate silver coatings prior to their widespread clinical usage.
Lower back pain is a leading cause of disability worldwide. The recovery of nucleus pulposus (NP) progenitor cells (NPPCs) from the intervertebral disc (IVD) holds high promise for future cell ...therapy. NPPCs are positive for the angiopoietin-1 receptor (Tie2) and possess stemness capacity. However, the limited Tie2+ NPC yield has been a challenge for their use in cell-based therapy for regenerative medicine. In this study, we attempted to expand NPPCs from the whole NP cell population by spheroid-formation assay. Flow cytometry was used to quantify the percentage of NPPCs with Tie2-antibody in human primary NP cells (NPCs). Cell proliferation was assessed using the population doublings level (PDL) measurement. Synthesis and presence of extracellular matrix (ECM) from NPC spheroids were confirmed by quantitative Polymerase Chain Reaction (qPCR), immunostaining, and microscopy. Compared with monolayer, the spheroid-formation assay enriched the percentage of Tie2+ in NPCs' population from ~10% to ~36%. Moreover, the spheroid-formation assay also inhibited the proliferation of the Tie2- NPCs with nearly no PDL. After one additional passage (P) using the spheroid-formation assay, NPC spheroids presented a Tie2+ percentage even further by ~10% in the NPC population. Our study concludes that the use of a spheroid culture system could be successfully applied to the culture and expansion of tissue-specific progenitors.
Intraluminal thrombus formation precipitates conditions such as acute myocardial infarction and disturbs local blood flow resulting in areas of rapidly changing blood flow velocities and steep ...gradients of blood shear rate. Shear rate gradients are known to be pro-thrombotic with an important role for the shear-sensitive plasma protein von Willebrand factor (VWF). Here, we developed a single-chain antibody (scFv) that targets a shear gradient specific conformation of VWF to specifically inhibit platelet adhesion at sites of shear rate gradients (SRG) but not in areas of constant shear. Microfluidic flow channels with stenotic segments were used to create SRG during blood perfusion. VWF-GPIbα interactions were increased at sites of SRG compared to constant shear rate of matched magnitude. The scFv-A1 specifically reduced VWF-GPIbα binding and thrombus formation at sites of SRG but did not block platelet deposition and aggregation under constant shear rate in upstream sections of the channels. Significantly, the scFv A1 attenuated platelet aggregation only in the later stages of thrombus formation. In the absence of shear, direct binding of scFv-A1 to VWF could not be detected and scFVA1 did not inhibit ristocetin induced platelet agglutination. We have exploited the pro-aggregatory effects of SRG on VWF dependent platelet aggregation and developed the shear gradient-sensitive scFv-A1 antibody that inhibits platelet aggregation exclusively at sites of SRG. The lack of VWF inhibition in non-stenosed vessel segments places scFV-A1 in an entirely new class of anti-platelet therapy for selective blockade of pathological thrombus formation while maintaining normal hemostasis.
Self-renewal is a key characteristic of leukemia stem cells (LSCs) responsible for the development and maintenance of leukemia. In this study, we identify CD93 as an important regulator of ...self-renewal and proliferation of murine and human LSCs, but not hematopoietic stem cells (HSCs). The intracellular domain of CD93 promotes gene transcription via the transcriptional regulator SCY1-like pseudokinase 1 independently of ligation of the extracellular domain. In a drug library screen, we identify the anti-emetic agent metoclopramide as an efficient blocker of CD93 signaling. Metoclopramide treatment reduces murine and human LSCs in vitro and prolongs survival of chronic myeloid leukemia (CML) mice through downregulation of pathways related to stemness and proliferation in LSCs. Overall, these results identify CD93 signaling as an LSC-specific regulator of self-renewal and proliferation and a targetable pathway to eliminate LSCs in CML.
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•CD93 is a marker for leukemia stem cells (LSCs) in CML•The intracellular domain of CD93 promotes stemness and self-renewal of CML LSCs•The anti-emetic drug metoclopramide blocks CD93 signaling in LSCs
CD93 is a marker for LSCs in CML, but its broad expression on normal tissue hinders the development of CD93-targeting therapies. Riether et al. show that signaling via the intracellular domain of CD93 selectively promotes self-renewal of LSCs and that this process can be inhibited with the anti-emetic drug metoclopramide.
Background
Acetabular retroversion can cause impaction-type femoroacetabular impingement leading to hip pain and osteoarthritis. It can be treated by anteverting periacetabular osteotomy (PAO) or ...acetabular rim trimming with refixation of the labrum. There is increasing evidence that acetabular retroversion is a rotational abnormality of the entire hemipelvis and not a focal overgrowth of the anterior acetabular wall, which favors an anteverting PAO. However, it is unknown if this larger procedure would be beneficial in terms of survivorship and Merle d’Aubigné scores in a midterm followup compared with rim trimming.
Questions/purposes
We asked if anteverting PAO results in increased survivorship of the hip compared with rim trimming through a surgical hip dislocation in patients with symptomatic acetabular retroversion.
Methods
We performed a retrospective, comparative study evaluating the midterm survivorship of two matched patient groups with symptomatic acetabular retroversion undergoing either anteverting PAO or acetabular rim trimming through a surgical hip dislocation. Acetabular retroversion was defined by a concomitantly present positive crossover, posterior wall, and ischial spine sign. A total of 279 hips underwent a surgical intervention for acetabular retroversion at our center between 1997 and 2012 (166 periacetabular osteotomies, 113 rim trimmings through surgical hip dislocation). A total of 99 patients (60%) were excluded from the PAO group and 56 patients (50%) from the rim trimming group because they had any of several prespecified conditions (eg, dysplasia or pediatric conditions 61 37% for the PAO group and two 2% for the rim trimming group), matching (10 6%/10 9% hips), deficient records (10 6%/13 12% hips), or the patient declined or was lost to followup (18 11%/31 27% hips). This left 67 hips (57 patients) that underwent anteverting PAO and 57 hips (52 patients) that had acetabular rim trimming. The two groups did not differ in terms of age, sex, body mass index, preoperative ROM, preoperative Merle d’Aubigné-Postel score, radiographic morphology of the acetabulum (except total and anterior acetabular coverage), alpha angle, Tönnis grade of osteoarthritis, and labral and chondral lesions on the preoperative MRI. During the period in question, we generally performed PAO from 1997 to 2003. With the availability of surgical hip dislocation and labral refixation, we generally performed rim trimming from 2004 to 2010. With growing knowledge of the underlying pathomorphology, anteverting PAOs became more common again around 2007 to 2008. A minimum followup of 2 years was required for this study. Failures were included at any time. The median followup for the anteverting PAO group was 9.5 years (range, 2–17.4 years) and 6.8 years (range, 2.2–10.5 years) for the rim trimming group (p < 0.001). Kaplan-Meier survivorship analysis was performed using the following endpoints at 5 and 10 years: THA, radiographic progression of osteoarthritis by one Tönnis grade, and/or Merle d’Aubigné-Postel score < 15 points.
Results
Although the 5-year survivorship of the two groups was not different with the numbers available (86% 95% confidence interval {CI}, 76%–94% for anteverting PAO versus 86% 95% CI, 76%–96% for acetabular rim trimming), we found increased survivorship at 10 years in hips undergoing anteverting PAO for acetabular retroversion (79% 95% CI, 68%–90%) compared with acetabular rim trimming (23% 95% CI, 6%–40%) at 10 years (p < 0.001). The drop in the survivorship curve for the acetabular rim trimming through surgical hip dislocation group started at Year 6. The main reason for failure was a decreased Merle d’Aubigné score.
Conclusions
Anteverting PAO may be the more appropriate treatment for hips with substantial acetabular retroversion. This may be the result of reduction of an already smaller lunate surface of hips with acetabular retroversion through rim trimming. However, rim trimming may still benefit hips with acetabular retroversion in which only one or two of the three signs are positive. Future randomized studies should compare these treatments.
Level of Evidence
Level III, therapeutic study.
Abstract
Objective
The present study aimed (1) to analyze the relative paraspinal autochthonous intramuscular fat volume before and after radiofrequency neurotomy (RFN) and (2) to compare it to the ...contralateral non-treated side.
Design
Retrospective cohort study.
Setting
Inselspital, University Hospital Bern, University of Bern.
Subjects
Twenty patients (59.60 ± 8.49 years; 55% female) with chronic low back pain, treated with RFN (L2/3—L5/S1) due to symptomatic facet joint syndrome (FCS) between 2008 and 2017 were included.
Methods
All patients received a magnetic resonance imaging (MRI) of the lumbar spine before and at a minimum of 6 months after RFN. The absolute (cm3) and relative (%) paraspinal muscle and fat volume was analyzed three-dimensionally on standard T2–MRI sequences using a newly developed software (iSix, Osiris plugin). Both sides were examined and allocated as treated or non-treated side.
Results
A total of 31 treated and 9 non-treated sides (Level L2/3–L5/S1) were examined. There were no differences in the relative paraspinal intramuscular fat volume before and at a median of 1.4 0.9 – 2.6 years after RFN (P = .726). We found no differences in the relative fat volume between the treated and non-treated side before (P = .481) and after (P = .578) RFN.
Conclusions
Our study shows that there are no differences in the paraspinal muscle/fat distribution after RFN. RFN of the medial branches for FCS does not seem to cause fatty degeneration of the lumbar paraspinal muscles as a sign of iatrogenic muscle denervation.
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