Vertebral osteomyelitis caused by non-tuberculous mycobacteria is a rare disease, with only 31 cases and one nosocomial outbreak reported in the literature (MedLine review between 1965 and December 2003). The clinical features are often indistinguishable from those of pyogenic osteomyelitis. Early diagnosis of such infections is a major challenge because of the slow growth of these microorganisms. No consensus guidelines for the treatment of these infections exist. Prolonged anti-mycobacterial therapy in combination with surgical debridement is recommended.

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The field of regenerative medicine has increasingly recognized the importance to be inspired by developmental processes to identify signaling pathways crucial for 3D organogenesis and tissue regeneration. Here, we aimed at recapitulating the first events occurring during limb development (ie, cell condensation and expansion of an undifferentiated mesenchymal cell population) to prime 3D cultures of human bone marrow-derived mesenchymal stromal/stem cells (hBM-MSC) toward the chondrogenic route. Based on embryonic development studies, we hypothesized that Wnt3a and fibroblast growth factor 2 (FGF2) induce hBM-MSC to proliferate in 3D culture as an undifferentiated pool of progenitors (defined by clonogenic capacity and expression of typical markers), retaining chondrogenic potential upon induction by suitable morphogens. hBM-MSC were responsive to Wnt signaling in 3D pellet culture, as assessed by significant upregulation of main target genes and increase of unphosphorylated b-catenin levels. Wnt3a was able to induce a five-fold increase in the number of proliferating hBM-MSC (6.4% vs. 1.3% in the vehicle condition), although total DNA content of the 3D construct was decreasing over time. Preconditioning with Wnt3a improved transforming growth factor-b1 mediated chondrogenesis (30% more glycosaminoglycans/cell in average). In contrast to developmental and 2D MSC culture models, FGF2 antagonized the Wnt-mediated effects. Interestingly, the CD146 + subpopulation was found to be more responsive to Wnt3a. The presented data indicate a possible strategy to prime 3D cultures of hBM-MSC by invoking a ''developmental engineering'' approach. The study also identifies some opportunities and challenges to cross-fertilize skeletal development models and 3D hBM-MSC culture systems.

Osteoarthritis of the knee and spine is highly prevalent in modern society, yet a disease-modifying pharmacological treatment remains an unmet clinical need. A major challenge for drug development includes selection of appropriate preclinical models that accurately reflect clinical phenotypes of human disease. The aim of this study was to establish an ex vivo explant model of human knee and spine osteoarthritis that enables assessment of osteochondral tissue responses to inflammation and drug treatment. Equal-sized osteochondral fragments from knee and facet joints (both n = 6) were subjected to explant culture for 7 days in the presence of a toll-like receptor 4 (TLR4) agonist and an inhibitor of transforming growth factor-beta (TGF-β) receptor type I signaling. Markers of inflammation, interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), but not bone metabolism (pro-collagen-I) were significantly increased by treatment with TLR4 agonist. Targeting of TGF-β signaling resulted in a strong reduction of pro-collagen-I and significantly decreased IL-6 levels. MCP-1 secretion was increased, revealing a regulatory feedback mechanism between TGF-β and MCP-1 in joint tissues. These findings demonstrate proof-of-concept and feasibility of explant culture of human osteochondral specimens as a preclinical disease model, which might aid in definition and validation of disease-modifying drug targets.

Background  Perioperative myocardial infarction/injury (PMI) diagnosed by high-sensitivity troponin (hs-cTn) T is frequent and a prognostically important complication of non-cardiac surgery. We aimed to evaluate the incidence and outcome of PMI diagnosed using hs-cTnI, and compare it to PMI diagnosed using hs-cTnT. Methods We prospectively included 2455 patients at high cardiovascular risk undergoing 3111 non-cardiac surgeries, for whom hs-cTnI and hs-cTnT concentrations were measured before surgery and on postoperative days 1 and 2. PMI was defined as a composite of perioperative myocardial infarction (PMIInfarct) and perioperative myocardial injury (PMIInjury), according to the Fourth Universal Definition of Myocardial Infarction. All-cause mortality was the primary endpoint. Results Using hs-cTnI, the incidence of overall PMI was 9% (95% confidence interval [CI] 8–10%), including PMIInfarct 2.6% (95% CI 2.0–3.2) and PMIInjury 6.1% (95% CI 5.3–6.9%), which was lower versus using hs-cTnT: overall PMI 15% (95% CI 14–16%), PMIInfarct 3.7% (95% CI 3.0–4.4) and PMIInjury 11.3% (95% CI 10.2–12.4%). All-cause mortality occurred in 52 (2%) patients within 30 days and 217 (9%) within 1 year. Using hs-cTnI, both PMIInfarct and PMIInjury were independent predictors of 30-day all-cause mortality (adjusted hazard ratio [aHR] 2.5 [95% CI 1.1–6.0], and aHR 2.8 [95% CI 1.4–5.5], respectively) and, 1-year all-cause mortality (aHR 2.0 [95% CI 1.2–3.3], and aHR 1.8 [95% CI 1.2–2.7], respectively). Overall, the prognostic impact of PMI diagnosed by hs-cTnI was comparable to the prognostic impact of PMI using hs-cTnT. Conclusions Using hs-cTnI, PMI is less common versus using hs-cTnT. Using hs-cTnI, both PMIInfarct and PMIInjury remain independent predictors of 30-day and 1-year mortality. Graphic abstract

BackgroundVertebral osteomyelitis (VO) may lead to disabling neurologic complications. Little evidence exists on optimal antibiotic management.MethodsAll patients with primary, non-implant VO, admitted from 2000–2010 were retrospectively analyzed. Patients with endocarditis, immunodeficiency, vertebral implants and surgical site infection following spine surgery were excluded. Persistence of clinical or laboratory signs of inflammation at 1 year were defined as treatment failure. Logistic regression was used to estimate the odds ratios (OR) of switch to an oral regimen after 2 weeks.ResultsMedian antibiotic treatment was 8.1 weeks in 61 identified patients. Switch to oral antibiotics was performed in 72% of patients after a median intravenous therapy of 2.7 weeks. Switch to oral therapy was already performed after two weeks in 34% of the patients. A lower CRP at 2 weeks was the only independent predictor for switch to oral therapy (OR 0.7, 95% confidence interval 0.5-0.9, p = 0.041, per 10 mg/l increase). Staphylococcus aureus was the most frequently isolated microorganism (21%). Indications for surgery, other than biopsy, included debridement with drainage of epidural or paravertebral abscess (26 patients; 42%), and CT - guided drainage (3 patients).During the follow-up, no recurrences were observed but 2 patients died of other reasons than VO, i.e. the 1 year intention to treat success rate was 97%.ConclusionsCure rates for non-implant VO were very high with partly short intravenous and overall antibiotic therapy. Switching to an oral antibiotic regimen after two weeks intravenous treatment may be safe, provided that CRP has decreased and epidural or paravertebral abscesses of significant size have been drained.

Facet joint osteoarthritis may be a cause of low back pain in degenerative spine diseases including lumbar spinal stenosis. Subchondral bone is regarded as a potential therapeutic target for osteoarthritis treatment. The goal of this study was to characterize subchondral bone histopathology in osteoarthritic facet joints from lumbar spinal stenosis patients. Fifteen patients with degenerative spinal stenosis scheduled for transforaminal lumbar interbody fusion surgery were recruited for this study. Osteoarthritis severity was graded on T1- and T2-weighted MRI images using Weishaupt scoring system. Dissected osteoarthritic facet joints were subjected to histological and immunohistochemistry analyses to study relative abundance of osteoblast, osteoclasts, and macrophages using van Gieson's, tartrate-resistant acid phosphatase and CD68-antibody staining, respectively. Presence of nerve fibers was evaluated by PGP9.5-antibody staining. Differential bone histopathology, independent from radiological osteoarthritis grade, was observed in facet joints. Extensive de novo bone formation was found in subchondral bone tissues of eight of fifteen specimens. Regions of bone formation showed high abundance of blood vessels and CD68-positive macrophages, but were devoid of multinucleated osteoclasts. Additional pathological changes in subchondral marrow spaces, including inflammatory infiltration and enhanced osteoclast activity, were characterized by macrophage-rich tissues. PGP9.5-positive nerve fibers were detected near arterioles, but not in regions displaying bone pathology. Individual histopathological parameters did not associate with clinical features or radiological osteoarthritis severity. Subchondral bone histopathology of facet joint osteoarthritis in lumbar spinal stenosis is characterized by marrow infiltration by macrophage-rich tissues and enhanced de novo bone formation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1475-1480, 2016.

Fractures of the atlas account for 1-2% of all vertebral fractures. We divide atlas fractures into 5 groups: isolated fractures of the anterior arch of the atlas, isolated fractures of the posterior arch, combined fractures of the anterior and posterior arch (so-called Jefferson fractures), isolated fractures of the lateral mass and fractures of the transverse process. Isolated fractures of the anterior or posterior arch are benign and are treated conservatively with a soft collar until the neck pain has disappeared. Jefferson fractures are divided into stable and unstable fracture depending on the integrity of the transverse ligament. Stable Jefferson fractures are treated conservatively with good outcome while unstable Jefferson fractures are probably best treated operatively with a posterior atlanto-axial or occipito-axial stabilization and fusion. The authors preferred treatment modality is the immediate open reduction of the dislocated lateral masses combined with a stabilization in the reduced position using a transarticular screw fixation C1/C2 according to Magerl. This has the advantage of saving the atlanto-occipital joints and offering an immediate stability which makes immobilization in an halo or Minerva cast superfluous. In late instabilities C1/2 with incongruency of the lateral masses occurring after primary conservative treatment, an occipito-cervical fusion is indicated. Isolated fractures of the lateral masses are very rare and may, if the lateral mass is totally destroyed, be a reason for an occipito-cervical fusion. Fractures of the transverse processes may be the cause for a thrombosis of the vertebral artery. No treatment is necessary for the fracture itself.