A combined biomaterial and cellular approach for annulus fibrosus rupture repair

Recurrent intervertebral disc (IVD) herniation and degenerative disc disease have been identified as the most important factors contributing to persistent pain and disability after surgical discectomy. An annulus fibrosus (AF) closure device that provides immediate closure of the AF rupture, restores disc height, reduces further disc degeneration and enhances self-repair capacities is an unmet clinical need. In this study, a poly(trimethylene carbonate) (PTMC) scaffold seeded with human bone marrow derived mesenchymal stromal cells (MSCs) and covered with a poly(ester-urethane) (PU) membrane was assessed for AF rupture repair in a bovine organ culture annulotomy model under dynamic load for 14 days. PTMC scaffolds combined with the sutured PU membrane restored disc height of annulotomized discs and prevented herniation of nucleus pulposus (NP) tissue. Implanted MSCs showed an up-regulated gene expression of type V collagen, a potential AF marker, indicating in situ differentiation capability. Furthermore, MSCs delivered within PTMC scaffolds induced an up-regulation of anabolic gene expression and down-regulation of catabolic gene expression in adjacent native disc tissue. In conclusion, the combined biomaterial and cellular approach has the potential to hinder herniation of NP tissue, stabilize disc height, and positively modulate cell phenotype of native disc tissue.

Spine radiography in the evaluation of back and neck pain in an orthopaedic emergency clinic

BACKGROUND AND OBJECTIVES Despite the recommendations of national and international societies for the treatment of patients with acute neck and back pain, still too many radiologic examinations were performed. The purpose of this study was to analyze and optimize diagnostics and treatment of patients with acute back pain. METHODS The medical records of 484 patients presented to the emergency clinic with acute neck or back pain were analyzed for clinical history, physical examination, radiographic findings and therapy. RESULTS Radiographs of the lumbar, cervical, or thoracic spine were performed in 338 cases (70%). Radiographs were normal in 142 patients (42%) and degenerative changes were identified in 123 patients (36%). Only 2 patients (0.4%) had radiographic findings that had direct therapeutic relevance: 1 patient with metastatic disease and 1 patient with posttraumatic C1-C2 instability. For most patients without sensorimotor deficits and absent specific indications for radiography (“red flags”), therapy was not affected by the results of radiography. CONCLUSIONS Plain radiography of the spine was unnecessary in most patients initially evaluated with non-specific acute back pain and does not improve the clinical outcome. The implementation of national and international guidelines is a slow process, but helps to reduce costs and to protect patients from unnecessary ionizing radiation exposure.

Glenohumeral dislocation. Injury patterns and combination injuries

Hintergrund Begleitverletzungen können in bis zu 90 % der Fälle nach erstmaliger Schulterluxation auftreten. Auch wenn sie nicht immer einen Einfluss auf die Therapiewahl haben, so ist eine sorgfältige Diagnostik entscheidend. Einteilung In der Akutsituation ist eine konventionelle Bildgebung in mindestens 2 Ebenen (a.-p./Neer/evtl. axial) vor und nach Reposition zwingend. Luxationsfrakturen dürfen nicht übersehen bzw. durch das Manöver der geschlossenen Reposition sekundär disloziert werden. Bestehen ossäre glenoidale, humerale oder kombinierte Verletzungen, sollten sie gemäß Stabilitätskriterien versorgt werden. Dies kann umgehend, nach manifester Dezentrierung oder Instabilität entweder mittels Osteosythese oder als glenohumerale Stabilisation im Verlauf erfolgen. Bei einer Instabilität ist prinzipiell zur Bilanzierung einer ossären Ursache das Arthro-CT die Untersuchung der Wahl, welche auch eine Beurteilung der kapsulolabroligamentären Verletzung sowie einer traumatischen Rotatorenmanschettenläsion ermöglicht. Letztere ist jedoch besser mittels Arthro-MRT zu beurteilen. Diskussion Eine signifikante frische, meist größere oder massive, Rotatorenmanschettenläsion sollte rasch operativ angegangen werden. Medial reichende „off the track“ Hill-Sachs-Läsionen können mittels einer Hill-Sachs-Remplissage oder, wie auch glenoidale Defekte, mittels einer Kochenaugmentation versorgt werden. Langzeitresultate des Latarjet-Verfahrens zeigen 25 Jahre nach dem Eingriff die niedrigste Reluxationsrate < 4 %, eine gute Außenrotation, eine sehr hohe Patientenzufriedenheit und degenerative Veränderungen, welche vergleichbar mit der natürlichen Entwicklung nach erstmaliger Schulterluxation ohne Rezidiv sind.

RASSF7 expression and its regulatory roles on apoptosis in human intervertebral disc degeneration

Apoptosis plays an important role in intervertebral disc degeneration (IDD). Overwhelming evidence indicates that RASSF7 is essential for cell growth and apoptosis. Recently, it has been noted that the JNK signaling can be negatively regulated by suppressing phosphorylated-MKK7 activation during pro-apoptosis. We aimed to investigate the RASSF7 expression level in human degenerative nucleus pulposus (NP) cells and non-degenerative NP cells and the link between RASSF7-JNK with NP cells apoptosis. We harvested NP tissues from 20 IDD patients as disease group and 8 cadaveric donors as normal controls. We detected RASSF7 expression by Real-time-PCR and western blotting. Consequently, we found that the expression of RASSF7 was higher in non-degenerative group than in degenerative group (P<0.05). Overexpression of RASSF7 in degenerative NP cells led to decreased apoptosis rate than that in scramble group (P<0.05). Collectively, our findings suggest that RASSF7 plays an important role in human IDD and RASSF7 might be potentially developed as a curative agent.

Characterization of fetal antigen 1/delta-like 1 homologue expressing cells in the rat nigrostriatal system: effects of a unilateral 6-hydroxydopamine lesion.

Fetal antigen 1/delta-like 1 homologue (FA1/dlk1) belongs to the epidermal growth factor superfamily and is considered to be a non-canonical ligand for the Notch receptor. Interactions between Notch and its ligands are crucial for the development of various tissues. Moreover, FA1/dlk1 has been suggested as a potential supplementary marker of dopaminergic neurons. The present study aimed at investigating the distribution of FA1/dlk1-immunoreactive (-ir) cells in the early postnatal and adult midbrain as well as in the nigrostriatal system of 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian adult rats. FA1/dlk1-ir cells were predominantly distributed in the substantia nigra (SN) pars compacta (SNc) and in the ventral tegmental area. Interestingly, the expression of FA1/dlk1 significantly increased in tyrosine hydroxylase (TH)-ir cells during early postnatal development. Co-localization and tracing studies demonstrated that FA1/dlk1-ir cells in the SNc were nigrostriatal dopaminergic neurons, and unilateral 6-OHDA lesions resulted in loss of both FA1/dlk1-ir and TH-ir cells in the SNc. Surprisingly, increased numbers of FA1/dlk1-ir cells (by 70%) were detected in dopamine-depleted striata as compared to unlesioned controls. The higher number of FA1/dlk1-ir cells was likely not due to neurogenesis as colocalization studies for proliferation markers were negative. This suggests that FA1/dlk1 was up-regulated in intrinsic cells in response to the 6-OHDA-mediated loss of FA1/dlk1-expressing SNc dopaminergic neurons and/or due to the stab wound. Our findings hint to a significant role of FA1/dlk1 in the SNc during early postnatal development. The differential expression of FA1/dlk1 in the SNc and the striatum of dopamine-depleted rats could indicate a potential involvement of FA1/dlk1 in the cellular response to the degenerative processes.

Is the sedimentation sign associated with spinal stenosis surgical treatment effect in SPORT?

STUDY DESIGN Subgroup analysis of the lumbar spinal stenosis (LSS) without degenerative spondylolisthesis diagnostic cohort of the Spine Patient Outcomes Research Trial multicenter randomized clinical trial with a concurrent observational cohort. OBJECTIVE To determine if sedimentation sign on magnetic resonance image can help with LSS treatment decisions. SUMMARY OF BACKGROUND DATA LSS is one of the most common reasons for surgery in the US elderly, but there is a dearth of reliable diagnostic tools that give a clear indication for surgery. Recent studies have suggested that positive sedimentation sign on magnetic resonance image may be a possible prognostic indicator. METHODS All patients with LSS in both the randomized and observational cohorts had imaging-confirmed stenosis, were surgical candidates, and had neurogenic claudication for at least 12 weeks prior to enrollment. Patients were categorized as "mild," "moderate," or "severe" according to stenosis severity. Of the 654 patients with LSS enrolled in Spine Patient Outcomes Research Trial, complete T2-weighted axial and sagittal digitized images of 115 patients were available for retrospective review. An independent orthopedic spine surgeon evaluated these deidentified Digital Imaging and Communications in Medicine files for the sedimentation sign. RESULTS Sixty-six percent (76/115) of patients were found to have a positive sedimentation sign. Those with a positive sedimentation sign were more likely to have stenosis at L2-L3 (33% vs. 10% P=0.016) or L3-L4 76% vs. 51%, P=0.012), and to have severe (72% vs. 33%, P<0.0001) central stenosis (93% vs. 67% P<0.001) at 2 or more concurrent levels (57% vs. 18%, P=0.01). In multivariate models, the surgical treatment effect was significantly larger in the positive sedimentation sign group for Oswestry Disability Index (-16 vs. -7; P=0.02). CONCLUSION A positive sedimentation sign was associated with a small but significantly greater surgical treatment effect for Oswestry Disability Index in patients with symptomatic LSS, after adjusting for other demographic and imaging features. These findings suggest that positive sedimentation sign may potentially be a useful adjunct to help guide an informed treatment choice regarding surgery for LSS. LEVEL OF EVIDENCE 2.

Total disc arthroplasty versus anterior cervical interbody fusion: use of the Spine Tango registry to supplement the evidence from randomized control trials.

BACKGROUND CONTEXT Several randomized controlled trials (RCTs) have compared patient outcomes of anterior (cervical) interbody fusion (AIF) with those of total disc arthroplasty (TDA). Because RCTs have known limitations with regard to their external validity, the comparative effectiveness of the two therapies in daily practice remains unknown. PURPOSE This study aimed to compare patient-reported outcomes after TDA versus AIF based on data from an international spine registry. STUDY DESIGN AND SETTING A retrospective analysis of registry data was carried out. PATIENT SAMPLE Inclusion criteria were degenerative disc or disc herniation of the cervical spine treated by single-level TDA or AIF, no previous surgery, and a Core Outcome Measures Index (COMI) completed at baseline and at least 3 months' follow-up. Overall, 987 patients were identified. OUTCOME MEASURES Neck and arm pain relief and COMI score improvement were the outcome measures. METHODS Three separate analyses were performed to compare TDA and AIF surgical outcomes: (1) mimicking an RCT setting, with admission criteria typical of those in published RCTs, a 1:1 matched analysis was carried out in 739 patients; (2) an analysis was performed on 248 patients outside the classic RCT spectrum, that is, with one or more typical RCT exclusion criteria; (3) a subgroup analysis of all patients with additional follow-up longer than 2 years (n=149). RESULTS Matching resulted in 190 pairs with an average follow-up of 17 months that had no residual significant differences for any patient characteristics. Small but statistically significant differences in outcome were observed in favor of TDA, which are potentially clinically relevant. Subgroup analyses of atypical patients and of patients with longer-term follow-up showed no significant differences in outcome between the treatments. CONCLUSIONS The results of this observational study were in accordance with those of the published RCTs, suggesting substantial pain reduction both after AIF and TDA, with slightly greater benefit after arthroplasty. The analysis of atypical patients suggested that, in patients outside the spectrum of clinical trials, both surgical interventions appeared to work to a similar extent to that shown for the cohort in the matched study. Also, in the longer-term perspective, both therapies resulted in similar benefits to the patients.

Clinicopathological Phenotype of Autosomal Recessive Cholesterol Deficiency in Holstein Cattle.

BACKGROUND Cholesterol deficiency (CD), a newly identified autosomal recessive genetic defect in Holstein cattle, is associated with clinical signs of diarrhea, failure to thrive, and hypocholesterolemia. HYPOTHESIS/OBJECTIVES The objective is to describe the clinicopathological phenotype of affected Holstein cattle homozygous for the causative apolipoprotein B gene (APOB) mutation. ANIMALS Six Holstein cattle, 5 calves with a clinical history of chronic diarrhea, and 1 heifer with erosions in the buccal cavity and neurologic symptoms were admitted to the Clinic for Ruminants. METHODS This case review included a full clinical examination, a complete blood count, blood chemistry, and measurements of cholesterol and triglycerides. The animals were euthanized and necropsied. A PCR-based direct gene test was applied to determine the APOB genotype. RESULTS All 6 animals were inbred, could be traced back to the sire Maughlin Storm, and were confirmed homozygous for the APOB mutation. The clinical phenotype included poor development, underweight, and intermittent diarrhea in the calves, and neurologic signs in the heifer included hypermetria and pacing. Hypocholesterolemia and low triglycerides concentrations were present in all animals. The pathological phenotype of all animals was steatorrhea with enterocytes of the small intestine containing intracytoplasmic lipid vacuoles. The peripheral nervous system of the heifer displayed degenerative changes. CONCLUSIONS AND CLINICAL IMPORTANCE Suspicion of CD in Holstein cattle is based on the presence of chronic diarrhea with no evidence of primary infections. Confirmation of the associated APOB gene mutation is needed. Additionally, the heifer demonstrated primarily signs of neurologic disease providing an unexpected phenotype of CD.