Jon-Michael Caldwell

Gremlin 1 Identifies a Skeletal Stem Cell with Bone, Cartilage, and Reticular Stromal Potential

The stem cells that maintain and repair the postnatal skeleton remain undefined. One model suggests that perisinusoidal mesenchymal stem cells (MSCs) give rise to osteoblasts, chondrocytes, marrow stromal cells, and adipocytes, although the existence of these cells has not been proven through fate-mapping experiments. We demonstrate here that expression of the bone morphogenetic protein (BMP) antagonist gremlin 1 defines a population of osteochondroreticular (OCR) stem cells in the bone marrow. OCR stem cells self-renew and generate osteoblasts, chondrocytes, and reticular marrow stromal cells, but not adipocytes. OCR stem cells are concentrated within the metaphysis of long bones not in the perisinusoidal space and are needed for bone development, bone remodeling, and fracture repair. Grem1 expression also identifies intestinal reticular stem cells (iRSCs) that are cells of origin for the periepithelial intestinal mesenchymal sheath. Grem1 expression identifies distinct connective tissue stem cells in both the bone (OCR stem cells) and the intestine (iRSCs).

Radial nerve injury associated with application of a hinged elbow external fixator: a report of 2 cases

involving open reduction and internal fixation of the distal humerus with an iliac crest autograft for the missing trochlea, open reduction and internal fixation of the proximal ulna, and external fixation followed by a staged proximal ulnar allograft reconstruction. In the first stage of the procedure, a posterior extensile approach of the elbow was used. The elbow was found to be unstable even after completion of fracture reduction and fixation. A DJD II external fixator (Stryker Trauma) was applied according to the manufacturer’s instructions. 1 Following the insertion of the central axis pin through the distal humerus, the posterior skin incision was approximatedusingafewnylonsutures.Thiswasdonetolocatethe appropriate skin incision sites for the humeral half pins. The rods, hinge, and drill guide were mounted over the axis pin, and the proximal humeral half-pin site was determined. A 1.5-cm skin incisionwas madeon thelateralaspect of the armapproximately 10 cmproximalfromthejoint,andastraightclampwasusedtobluntly dissect to the lateral aspect of the humerus. A self-drilling 4.0-mm humeral half-pin was then drilled into the humerus making the proximal humeral half-pin (Fig. 2). The drill guide was applied to the rodonce againto locatethedistalhumeralhalf-pinsite.Another 1.5-cm skin incision was made 80 mm proximal to the joint, and blunt dissection was carriedout down to the humerus.Upon drilling the distal humeral half-pin, it became obvious that the half-pin had engagedtheradialnerve.Thenervewascarefullyremovedfromthe pin and inspected for the extent of damage. The nerve was found to have severe avulsion at a more proximal location from the fast spinning half-pin. A small portion of the fascicle bundle was found to maintain the continuity. The fascicles from the both ends were repairedinanend-to-endfashionandthenwrappedinaNeuroflexII (Stryker Trauma) collagen conduit.The distal humeral half-pin was thenplacedwhiletheradialnervewasprotectedunderdirectvision. Two 3.0-mm ulnar half-pins were placed. The external fixator was immobilizedat90 flexionusingabarattachedtoboththerods.The wound was closed and a posterior long-arm splint was applied. Postoperatively, the patient was found to be unable to extend her wrist or fingers and have decreased sensation on the dorsum of the

Optimal internal fixation of anatomically shaped synthetic bone grafts for massive segmental defects of long bones

BACKGROUND Large segmental bone defects following tumor resection, high-energy civilian trauma, and military blast injuries present significant clinical challenges. Tissue engineering strategies using scaffolds are being considered as a treatment, but there is little research into optimal fixation of such scaffolds. METHODS Twelve fresh-frozen paired cadaveric legs were utilized to simulate a critical sized intercalary defect in the tibia. Poly-ε-caprolactone and hydroxyapatite composite scaffolds 5 cm in length with a geometry representative of the mid-diaphysis of an adult human tibia were fabricated, inserted into a tibial mid-diaphyseal intercalary defect, and fixed with a 14-hole large fragment plate. Optimal screw fixation comparing non-locking and locking screws was tested in axial compression, bending, and torsion in a non-destructive manner. A cyclic torsional test to failure under torque control was then performed. FINDINGS Biomechanical testing showed no significant difference for bending or axial stiffness with non-locking vs. locking fixation. Torsional stiffness was significantly higher (P=0.002) with the scaffold present for both non-locking and locking compared to the scaffold absent. In testing to failure, angular rotation was greater for the non-locking compared to locking constructs at each torque level up to 40 N-m (P<0.05). The locking constructs survived a significantly higher number of loading cycles before reaching clinical failure at 30 degrees of angular rotation (P<0.02). INTERPRETATION The presence of the scaffold increased the torsional stiffness of the construct. Locking fixation resulted in a stronger construct with increased cycles to failure compared to non-locking fixation.

The medicolegal landscape of spine surgery: how do surgeons fare?

BACKGROUND CONTEXT Because of the limited and confidential nature of most legal data, scarce literature is available to physicians about reasons for litigation in spine surgery. To optimally compensate patients while protecting physicians, further understanding of the medicolegal landscape is needed for high-risk procedures such as spine surgery. Based on these, surgeons can explore ways to better protect both their patients and themselves. PURPOSE To characterize the current medicolegal environment of spine surgery by analyzing a recent dataset of malpractice litigation. STUDY DESIGN A retrospective study. PATIENT SAMPLE All malpractice cases involving spine surgery available to public query between the years of 2010 and 2014. OUTCOME MEASURES Case outcome for spine surgery malpractice cases between the years of 2010 and 2014. METHODS WestlawNext was used to analyze spine surgery malpractice cases at the state and federal level between the years 2010 and 2014. WestlawNext is a subscription-based, legal search engine that contains publicly available federal and state court records. All monetary values were inflation adjusted for 2016. One hundred three malpractice cases were categorized by case descriptors and outcome measures. Claims were categorized as either intraoperative complaints or preoperative complaints. RESULTS Rulings in favor of the defendant (surgeon) were noted in 75% (77 of 103) of the cases. Lack of informed consent was cited in 34% of cases. For the 26 cases won by the plaintiff, the average amount in settlement was

Tissue engineering advances in spine surgery

2,384,775 versus

CA‐074Me compound inhibits osteoclastogenesis via suppression of the NFATc1 and c‐Fos signaling pathways

3,945,456 in cases brought before a jury. Cases involving consent averaged a compensation of

Integrating soft and hard tissues via interface tissue engineering: INTEGRATING SOFT AND HARD TISSUES

2,029,884, whereas cases involving only intraoperative complaints averaged a compensation of

Evaluation of common elbow pathologies: a focus on physical examination

3,667,530. A significant correlation was seen between increased compensation for plaintiffs and cases involving orthopedic surgeons (p=.020) or nerve injury (p=.005). Wrong-level surgery may be associated with lower plaintiff compensation (p=.055). The length of cases resulting in defense verdicts averaged 5.51 years, which was significantly longer than the 4.34 years average length of settlements or verdicts in favor of plaintiffs (p=.016). CONCLUSIONS Spine surgeons successfully defended themselves in 75% of lawsuits, although the cases won by physicians lingered significantly longer than those settled. Better understanding of these cases may help surgeons to minimize litigation. More than one third of cases involved a claim of insufficient informed consent. Surgeons can protect themselves and optimize care of patients through clear and documented patient communication, education, and intraoperative vigilance to avoid preventable complications.

Biologic Augmentation of Rotator Cuff Repair

Autograft, while currently the gold standard for bone grafting, has several significant disadvantages including limited supply, donor site pain, hematoma formation, nerve and vascular injury, and fracture. Bone allografts have their own disadvantages including reduced osteoinductive capability, lack of osteoprogenitor cells, immunogenicity and risk of disease transmission. Thus demand exists for tissue-engineered constructs that can produce viable bone while avoiding the complications associated with human tissue grafts. This review will focus on recent advancements in tissue-engineered bone graft substitutes utilizing nanoscale technology in spine surgery applications. An evaluation will be performed of bone graft substitutes, biomimetic 3D scaffolds, bone morphogenetic protein, mesenchymal stem cells and intervertebral disc regeneration strategies.

Effects of Hormone Therapy on Regional Surface Strain as a Function of Applied Strain in the Macaque Inferior Glenohumeral Ligament

The osteoclast is an integral cell of bone resorption. Since osteolytic disorders hinge on the function and dysfunction of the osteoclast, understanding osteoclast biology is fundamental to designing new therapies that curb osteolytic disorders. The identification and study of lysosomal proteases, such as cathepsins, have shed light on mechanisms of bone resorption. For example, Cathepsin K has already been identified as a collagen degradation protease produced by mature osteoclasts with high activity in the acidic osteoclast resorption pits. Delving into the mechanisms of cathepsins and other osteoclast related compounds provides new targets to explore in osteoclast biology. Through our anti‐osteoclastogenic compound screening experiments we encountered a modified version of the Cathepsin B inhibitor CA‐074: the cell membrane‐permeable CA‐074Me (L‐3‐trans‐(Propylcarbamoyl) oxirane‐2‐carbonyl]‐L‐isoleucyl‐L‐proline Methyl Ester). Here we confirm that CA‐074Me inhibits osteoclastogenesis in vivo and in vitro in a dose‐dependent manner. However, Cathepsin B knockout mice exhibited unaltered osteoclastogenesis, suggesting a more complicated mechanism of action than Cathepsin B inhibition. We found that CA‐074Me exerts its osteoclastogenic effect within 24 h of osteoclastogenesis stimulation by suppression of c‐FOS and NFATc1 pathways.