Kevin J. Little

Hypoxia: a critical regulator of early human tendinopathy

Objectives To seek evidence for the role of hypoxia in early human tendinopathy, and thereafter to explore mechanisms whereby tissue hypoxia may regulate apoptosis, inflammatory mediator expression and matrix regulation in human tenocytes. Methods Fifteen torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing ‘early pathology’) biopsies were collected from patients undergoing arthroscopic shoulder surgery. Control samples of the subscapularis tendon were collected from 10 patients undergoing arthroscopic stabilisation surgery. Markers of hypoxia were quantified by immunohistochemical methods. Human tendon-derived primary cells were derived from hamstring tendon tissue obtained during hamstring tendon anterior cruciate ligament reconstruction. The impact of hypoxia upon tenocyte biology ex vivo was measured using quantitative real-time PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V fluorescence-activated cell sorter staining. Results Increased expression of hypoxia-inducible factor 1α, Bcl-2 and clusterin was detected in subscapularis tendon samples compared with both matched torn samples and non-matched control samples (p<0.01). Hypoxic tenocytes exhibited increased production of proinflammatory cytokines (p<0.001), altered matrix regulation (p<0.01) with increased production of collagen type III operating through a mitogen-activated protein kinase-dependent pathway. Finally, hypoxia increased the expression of several mediators of apoptosis and thereby promoted tenocyte apoptosis. Conclusion Hypoxia promotes the expression of proinflammatory cytokines, key apoptotic mediators and drives matrix component synthesis towards a collagen type III profile by human tenocytes. The authors propose hypoxic cell injury as a critical pathophysiological mechanism in early tendinopathy offering novel therapeutic opportunities in the management of tendon disorders.

Early Functional Recovery of Elbow Flexion and Supination Following Median and/or Ulnar Nerve Fascicle Transfer in Upper Neonatal Brachial Plexus Palsy

BACKGROUND Nerve transfers using ulnar and/or median nerve fascicles to restore elbow flexion have been widely used following traumatic brachial plexus injury, but their utility following neonatal brachial plexus palsy remains unclear. The present multicenter study tested the hypothesis that these transfers can restore elbow flexion and supination in infants with neonatal brachial plexus palsy. METHODS We retrospectively reviewed the cases of thirty-one patients at three institutions who had undergone ulnar and/or median nerve fascicle transfer to the biceps and/or brachialis branches of the musculocutaneous nerve after neonatal brachial plexus palsy. The primary outcome measures were postoperative elbow flexion and supination as measured with the Active Movement Scale (AMS). Patients were followed for at least eighteen months postoperatively unless they obtained full elbow flexion or supination (AMS = 7) prior to eighteen months of follow-up. RESULTS Twenty-seven (87%) of the thirty-one patients obtained functional elbow flexion (AMS ≥ 6), and twenty-four (77%) obtained full recovery of elbow flexion against gravity (AMS = 7). Of the twenty-four patients for whom recovery of supination was recorded, five (21%) obtained functional recovery. Combined ulnar and median nerve fascicle transfers were performed in five patients and resulted in full recovery of elbow flexion against gravity and supination of AMS ≥ 5 for all five. Single-fascicle transfer was performed in twenty-six patients and resulted in functional flexion in 85% (twenty-two of twenty-six) and functional supination in 15% (three of twenty). Patients with nerve root avulsion were treated at a younger age (p < 0.01), had poorer preoperative elbow flexion (p < 0.01), and recovered greater supination (p < 0.01) compared with patients with dissociative recovery. Younger patients (p < 0.01) and patients with C5-C6 avulsion (p < 0.02) recovered the greatest supination. One patient sustained a transient anterior interosseous nerve palsy after median nerve fascicle transfer. CONCLUSIONS Ulnar and/or median nerve fascicle transfers were able to effectively restore functional elbow flexion in patients with nerve root avulsion, dissociative recovery, or late presentation following neonatal brachial plexus palsy. Recovery of supination was less, with greater success noted in younger patients with nerve root avulsion.

Context-Dependent Effects of Ranaviral Infection on Northern Leopard Frog Life History Traits

Pathogens have important effects on host life-history traits, but the magnitude of these effects is often strongly context-dependent. The outcome of an interaction between a host and an infectious agent is often associated with the level of stress experienced by the host. Ranavirus causes disease and mortality in amphibian populations in various locations around the world, but most known cases of ranaviral infection have occurred in North America and the United Kingdom. While Ranavirus virulence has been investigated, the outcome of Ranavirus infection has seldom been related to the host environment. In a factorial experiment, we exposed Northern leopard frog (Lithobates pipiens, formerly Rana pipiens) tadpoles to different concentrations of Ranavirus and investigated the effect of host density on certain life-history traits, namely survival, growth rate, developmental stage and number of days from virus exposure to death. Our results suggest a prominent role of density in driving the direction of the interaction between L. pipiens tadpoles and Ranavirus. We showed that increasing animal holding density is detrimental for host fitness as mortality rate is higher, day of death earlier, development longer and growth rate significantly lower in high-density tanks. We observed a linear increase of detrimental effects when Ranavirus doses increased in low-density conditions, with control tadpoles having a significantly higher overall relative fitness. However, this pattern was no longer observed in high-density conditions, where the effects of increasing Ranavirus dose were limited. Infected and control animals fitness were consequently similar. We speculate that the host may eventually diverts the energy required for a metabolic/immune response triggered by the infection (i.e., direct costs of the infection) to better cope with the increase in environmental “stress” associated with high density (i.e., indirect benefits of the infection). Our results illustrate how the net fitness of organisms may be shaped by ecological context and emphasize the necessity of examining the direct/indirect costs and benefits balance to fully understand host-pathogen interactions.

Physeal arrest of the distal radius.

Fractures of the distal radius are among the most common pediatric fractures. Although most of these fractures heal without complication, some result in partial or complete physeal arrest. The risk of physeal arrest can be reduced by avoiding known risk factors during fracture management, including multiple attempts at fracture reduction. Athletes may place substantial compressive and shear forces across the distal radial physes, making them prone to growth arrest. Timely recognition of physeal arrest can allow for more predictable procedures to be performed, such as distal ulnar epiphysiodesis. In cases of partial arrest, physeal bar excision with interposition grafting can be performed. Once ulnar abutment is present, more invasive procedures may be required, including ulnar shortening osteotomy or radial lengthening.

Limitations of the radiocapitellar line for assessment of pediatric elbow radiographs.

Background The radiocapitellar line (RCL) is recommended for evaluating radiocapitellar alignment in skeletally immature elbows, yet its parameters have not been clearly defined. This study systematically assesses the RCL relationship in normal elbows, investigating the impacts of radiographic view, choice of anatomic landmarks, patient age, forearm position, and observer bias on the manner in which the RCL intersects the capitellum. Methods On radiographs of 20 normal elbows (age range, 1 to 8 y), 3 pediatric orthopaedic surgeons, blinded to clinical history, drew lines (RCLs) on anteroposterior and lateral projections, along the radial shaft and neck, and with and without the capitellum visible. Line placement was repeated 2 weeks later. The relationship of each RCL to the capitellum was assessed continuously using the perpendicular distance to the center of the capitellum, normalized to capitellar width [line-capitellar distance (LCD)], and categorically as passing through the middle third, outer two-thirds, or outside the capitellum. Results Of the 480 RCLs drawn, 23 (5%) missed the capitellum and 224 (47%) missed the middle third. More radial neck than shaft lines intersected the middle third on both anteroposterior and lateral views (P<0.05, Fisher exact test), with the lowest LCD values for neck lines on the lateral view (P<0.05, analysis of variance (ANOVA)). More RCLs intersected the middle third when the capitellum was visible than when it was obscured (P=0.03, Fisher exact test), suggesting an effect of observer bias. Patient age correlated inversely with LCD (P<0.001). The angle between the neck and shaft lines correlated positively with LCD (P<0.001), suggesting an impact of forearm rotation position. Intraobserver and interobserver reliability was moderate-to-substantial (&kgr;=0.40-0.75). Conclusions The RCL best defines normal radiocapitellar alignment when the line is drawn along the radial neck on the lateral view, although this relationship is affected by bias, patient age, and forearm rotation position. The RCL does not reliably intersect the middle third of the capitellum, arguing against its sufficiency for assessing precise radiocapitellar alignment. Level of Evidence Diagnostic Level 3.

Elbow Fractures and Dislocations

Elbow fractures are common in pediatric patients. Most injuries to the pediatric elbow are stable and require simple immobilization; however, more severe fractures can occur, often requiring operative stabilization and/or close monitoring. This article highlights the common fractures and dislocations about the pediatric elbow and discusses the history, evaluation, and treatment options for specific injuries.

Glenohumeral Abduction Contracture in Children with Unresolved Neonatal Brachial Plexus Palsy

BACKGROUND Following neonatal brachial plexus palsy, the Putti sign-obligatory tilt of the scapula with brachiothoracic adduction-suggests the presence of glenohumeral abduction contracture. In the present study, we utilized magnetic resonance imaging (MRI) to quantify this glenohumeral abduction contracture and evaluate its relationship to shoulder joint deformity, muscle atrophy, and function. METHODS We retrospectively reviewed MRIs of the thorax and shoulders obtained before and after shoulder rebalancing surgery (internal rotation contracture release and external rotation tendon transfer) for twenty-eight children with unresolved neonatal brachial plexus palsy. Two raters measured the coronal positions of the scapula, thoracic spine, and humeral shaft bilaterally on coronal images, correcting trigonometrically for scapular protraction on axial images. Supraspinatus, deltoid, and latissimus dorsi muscle atrophy was assessed, blinded to other measures. Correlations between glenohumeral abduction contracture and glenoid version, humeral head subluxation, passive external rotation, and Mallet shoulder function before and after surgery were performed. RESULTS MRI measurements were highly reliable between raters. Glenohumeral abduction contractures were present in twenty-five of twenty-eight patients, averaging 33° (range, 10° to 65°). Among those patients, abductor atrophy was present in twenty-three of twenty-five, with adductor atrophy in twelve of twenty-five. Preoperatively, greater abduction contracture severity correlated with greater Mallet global abduction and hand-to-neck function. Abduction contracture severity did not correlate preoperatively with axial measurements of glenohumeral dysplasia, but greater glenoid retroversion was associated with worse abduction contractures postoperatively. Surgery improved passive external rotation, active abduction, and hand-to-neck function, but did not change the abduction contracture. CONCLUSIONS A majority of patients with persistent shoulder weakness following neonatal brachial plexus palsy have glenohumeral abduction deformities, with contractures as severe as 65°. The abduction contracture occurs with abductor atrophy, with or without associated adductor atrophy. This contracture may improve global shoulder abduction by positioning the glenohumeral joint in abduction. Glenohumeral and scapulothoracic kinematics and muscle pathology must be further elucidated to advance an understanding of the etiology and the prevention and treatment of the complex shoulder deformity following neonatal brachial plexus palsy. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Combining micro-computed tomography with histology to analyze biomedical implants for peripheral nerve repair ☆

BACKGROUND Biomedical implants used in tissue engineering repairs, such as scaffolds to repair peripheral nerves, can be too large to examine completely with histological analyses. Micro-computed tomography (micro-CT) with contrast agents allows ex vivo visualization of entire biomaterial implants and their interactions with tissues, but contrast agents can interfere with histological analyses of the tissues or cause shrinkage or loss of antigenicity. NEW METHOD Soft tissue, ex vivo micro-CT imaging using Lugols iodine was compatible with histology after using a rapid (48 h) method of removing iodine. RESULTS Adult normal and repaired rat sciatic nerves were infiltrated ex vivo with iodine, imaged with micro-CT and then the iodine was removed by incubating tissues in sodium thiosulfate. Subsequent paraffin sections of normal nerve tissues showed no differences in staining with hematoxylin and eosin or immunostaining with multiple antibodies. Iodine treatment and removal did not alter axonal diameter, nuclear size or relative area covered by immunostained axons (p>0.05). Combining imaging modalities allowed comparisons of macroscopic and microscopic features of nerve tissues regenerating through simple nerve conduits or nerve conduits containing a titanium wire for guidance. COMPARISON WITH EXISTING METHODS Quantification showed that treatment with iodine and sodium thiosulfate did not result in tissue shrinkage or loss of antigenicity. CONCLUSIONS Because this combination of treatments is rapid and does not alter tissue morphology, this expands the ex vivo methods available to examine the success of biomaterial implants used for tissue engineering repairs.

Local Anaesthetic Infusion with Elastomeric Pump After Arthroscopic Subacromial Decompression

INTRODUCTION The use of extended local anaesthesia for postoperative pain has previously been reported, and has several advantages over other methods, including ease of placement, safety, reliability, lower cost and effective analgesia. We present our experience with a portable elastomeric infusion device in patients undergoing arthroscopic subacromial decompression, and make a case for its potential to allow same-day discharge. PATIENTS AND METHODS Forty patients undergoing arthroscopic subacromial decompression were followed-up. At the end of the procedure, an epidural catheter connected to a portable elastomeric local anaesthetic infusion system was inserted into the subacromial space. All patients were electively admitted for overnight stay postoperatively and assessed using a visual analogue scale (VAS) to evaluate their level of pain. RESULTS No patient reported severe pain at any stage. None of the patients required any parenteral opiate analgesia with the pump in situ. CONCLUSIONS These findings suggest that the use of this elastomeric infusion device following shoulder surgery allows safe and early discharge of patients with decreased need for parenteral opiate analgesia.

Congenital Anomalies of the Hand—Principles of Management

Physicians who specialize in pediatric orthopedics and hand surgery frequently encounter congenital hand abnormalities, despite their relative rarity. The treating physician should be aware of the associated syndromes and malformations that may, in some cases, be fatal if not recognized and treated appropriately. Although these congenital disorders have a wide variability, their treatment principles are similar in that the physician should promote functional use and cosmesis for the hand. This article discusses syndactyly, preaxial polydactyly and post-axial polydactyly, and the hypoplastic thumb.