Donald S. Bae

CRH and the immune system

Inflammatory cytokines released during immune system activation can stimulate the hypothalamic-pituitary-adrenal axis and cause increased secretion of corticotropin-releasing hormone (CRH), adrenocorticotropin and glucocorticoids. Identification of CRH peptide and mRNA, as well as its receptors in immune tissues, suggested a role for this peptide as a mediator of the neuroendocrine-immune interactions. Experimental evidence suggests that CRH may modulate the immune and inflammatory responses via two pathways: an antiinflammatory one operated by centrally released CRH, most likely through stimulation of glucocorticoid and catecholamine release, and one proinflammatory, through direct action of peripherally released CRH. This review highlights these concepts. In addition preliminary data on immune activation and inflammatory response in CRH-deficient mice created in our laboratory are discussed.

Effect of Tendon Transfers and Extra-articular Soft-tissue Balancing on Glenohumeral Development in Brachial Plexus Birth Palsy

BACKGROUND Persistent muscle imbalance and soft-tissue contractures can lead to progressive glenohumeral joint deformity in patients with brachial plexus birth palsy. The objective of this investigation was to determine the effects of correction of external rotation weakness and internal rotation contractures with tendon transfers and extra-articular soft-tissue releases on glenohumeral development in patients with brachial plexus birth palsy. METHODS Twenty-five patients with brachial plexus birth palsy who underwent latissimus dorsi and teres major tendon transfers to the rotator cuff-with or without concomitant musculotendinous lengthenings-were evaluated clinically and radiographically before the operation and at a minimum of two years (average, forty-three months) postoperatively. Shoulder function was prospectively assessed with use of the modified Mallet classification system, in which aggregate shoulder function is assigned a score of 5 to 25 points. Glenoid version and humeral head subluxation were quantified with magnetic resonance imaging or computed tomography, and glenohumeral deformity was graded. RESULTS Clinically, all patients demonstrated improved global shoulder function, with the mean aggregate Mallet score improving from 13 points preoperatively to 18 points postoperatively (p < 0.01). As seen radiographically, the mean glenoid retroversion improved from 22 degrees preoperatively to 16.5 degrees postoperatively (p = 0.012). The mean posterior humeral head subluxation improved from 30% to 37% (p = 0.03). No patient had progressive worsening of the glenohumeral deformity. CONCLUSIONS Latissimus dorsi and teres major tendon transfers to the rotator cuff, combined with appropriate extraarticular musculotendinous lengthenings, significantly improved global shoulder function but led to only modest improvements in glenoid retroversion and humeral head subluxation. No profound glenohumeral remodeling occurs after these extra-articular rebalancing procedures, even when they are performed in patients of a young age. While the long-term clinical and radiographically apparent effects at skeletal maturity are uncertain, soft-tissue rebalancing procedures alone were found to have halted the progression of, but not to have markedly decreased, glenohumeral dysplasia at the time of a two to five-year follow-up.

Lateral entry compared with medial and lateral entry pin fixation for completely displaced supracondylar humeral fractures in children. A randomized clinical trial.

BACKGROUND Closed reduction and percutaneous pin fixation is the treatment of choice for completely displaced (type-III) extension supracondylar fractures of the humerus in children, although controversy persists regarding the optimal pin-fixation technique. The purpose of this study was to compare the efficacy of lateral entry pin fixation with that of medial and lateral entry pin fixation for the operative treatment of completely displaced extension supracondylar fractures of the humerus in children. METHODS This prospective, randomized clinical trial had sufficient power to detect a 10% difference in the rate of loss of reduction between the two groups. The techniques of lateral entry and medial and lateral entry pin fixation were standardized in terms of the pin location, the pin size, the incision and position of the elbow used for medial pin placement, and the postoperative course. The primary study end points were a major loss of reduction and iatrogenic ulnar nerve injury. Secondary study end points included radiographic measurements, clinical alignment, Flynn grade, elbow range of motion, function, and complications. RESULTS The lateral entry group (twenty-eight patients) and the medial and lateral entry group (twenty-four patients) were similar in terms of mean age, sex distribution, and preoperative displacement, comminution, and associated neurovascular status. No patient in either group had a major loss of reduction. There was no significant difference between the rates of mild loss of reduction, which occurred in six of the twenty-eight patients treated with lateral entry and one of the twenty-four treated with medial and lateral entry (p = 0.107). There were no cases of iatrogenic ulnar nerve injury in either group. There were also no significant differences (p > 0.05) between groups with respect to the Baumann angle, change in the Baumann angle, humerocapitellar angle, change in the humerocapitellar angle, Flynn grade, carrying angle, elbow flexion, elbow extension, total elbow range of motion, return to function, or complications. CONCLUSIONS With use of the specific techniques employed in this study, both lateral entry pin fixation and medial and lateral entry pin fixation are effective in the treatment of completely displaced (type-III) extension supracondylar fractures of the humerus in children. LEVEL OF EVIDENCE Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.

Reliability of Three Classification Systems Measuring Active Motion in Brachial Plexus Birth Palsy

BACKGROUND Several classification systems for the categorization of function in patients with brachial plexus birth palsy have been proposed. The purpose of this investigation was to determine the intraobserver and interobserver reliability of the modified Mallet Classification, Toronto Test Score, and Hospital for Sick Children Active Movement Scale in the evaluation of these patients. METHODS Eighty children with brachial plexus birth palsy were evaluated by two trained examiners on two different occasions. Intraobserver and interobserver reliability was determined with use of the kappa statistic. RESULTS On the basis of the kappa statistic, intraobserver reliability was good to excellent for individual elements of the modified Mallet Classification, Toronto Test Score, and Active Movement Scale in all age-groups. Interobserver reliability for individual elements of these three systems ranged from fair to excellent. When aggregate Toronto Test and modified Mallet scores were assessed, positive intraobserver and interobserver correlations were noted (Pearson r = 0.70 to 0.98, p < 0.001). Internal consistency (test-retest reliability) as determined by the Cronbach alpha for the aggregate Toronto Test and modified Mallet scores was excellent for each age-group (alpha > 0.90, p < 0.001). CONCLUSIONS The modified Mallet Classification, Toronto Test Score, and Active Movement Scale are reliable instruments for assessing upper-extremity function in patients with brachial plexus birth palsy. The natural history and surgical outcomes of these patients can now be conducted with use of these reliable outcomes instruments.

A systematic review of medial and lateral entry pinning versus lateral entry pinning for supracondylar fractures of the humerus.

The supracondylar fracture of the distal humerus is the most common pediatric fracture in the elbow. This systematic review summarizes the existing data about the effect of medial and lateral (medial/lateral) entry pins versus only lateral entry pin fixation on the risk of iatrogenic nerve injury and deformity or loss of reduction. A literature search identified clinical trials and observational studies presenting the probability of nerve injury and/or deformity or loss of reduction associated with closed reduction and either medial/lateral entry or lateral entry pinning of supracondylar fractures in pediatric patients. Data from 2054 children were identified from 35 studies; 2 randomized trials, 6 cohort studies, and 25 case series. For operative fixation with medial/lateral entry pins, the probability of ulnar nerve injury is 5.04 times higher than with lateral entry pins. When all documented operative nerve injuries are included, the probability of iatrogenic nerve injury is 1.84 times higher with medial/lateral entry pins than with isolated lateral pins. Medial/lateral pin entry provides a more stable configuration, and the probability of deformity or loss of reduction is 0.58 times lower than with isolated lateral pin entry. When the prospective studies alone were analyzed, there were no significant difference in the probability of iatrogenic nerve injury or deformity and displacement, although the confidence intervals were wide. This systematic review indicates that medial/lateral entry pinning, of pediatric supracondylar fractures, remains the most stable configuration and that care needs to be taken regardless of technique to avoid iatrogenic nerve injury and loss of reduction.

Current Concepts in the Management of Brachial Plexus Birth Palsy

Brachial plexus birth palsy, although rare, may result in substantial and chronic impairment. Physiotherapy, microsurgical nerve reconstruction, secondary joint corrections, and muscle transpositions are employed to help the child maximize function in the affected upper extremity. Many present controversies regarding natural history, microsurgical treatment, and secondary shoulder reconstructive surgery remain unresolved in infants with brachial plexus birth palsies. Recent literature has enhanced our understanding of the pathoanatomy and natural history of the injury as well as the surgical indications, expected outcomes, and complications; this literature has led to improved care of these patients. Based on the present evidence, recommendations for both microsurgery and shoulder reconstruction with tendon transfer and arthroscopic and open reductions are presented.

Impaired diurnal adrenal rhythmicity restored by constant infusion of corticotropin-releasing hormone in corticotropin-releasing hormone-deficient mice.

The normal pattern of daily glucocorticoid production in mammals requires circadian modulation of hypothalamicpituitary-adrenal axis activity. To assess both the factors responsible for imparting this diurnal profile and its physiologic importance, we have exploited corticotropin-releasing hormone (CRH)-deficient mice generated by homologous recombination in embryonic stem cells. CRH-deficient mice have lost normal circadian variations in plasma ACTH and glucocorticoid while maintaining normal circadian locomotor activity. Constant peripheral infusion of CRH produced marked diurnal excursions of plasma glucocorticoid, indicating that CRH acts in part as a permissive factor for other circadian modulators of adrenocortical activity. The presence of atrophic adrenals in CRH-deficient mice without an overt deficit in basal plasma ACTH concentration suggests that the diurnal increase in ACTH is essential to maintain normal adrenal function.

The Effect of Derotational Humeral Osteotomy on Global Shoulder Function in Brachial Plexus Birth Palsy

BACKGROUND Derotational humeral osteotomies have been used in older children with brachial plexus birth palsy and glenohumeral joint deformity to place the upper extremity in a more functional position. The purpose of this study was to determine the effects of these procedures on shoulder function and joint morphology. METHODS Forty-three patients underwent a derotational humeral osteotomy for functional impairment in the setting of internal rotation contracture and/or glenohumeral joint deformity at our institution from 1996 to 2004. Osteotomies were performed proximal to the deltoid insertion and were stabilized with plate-and-screw fixation. The average age of the patients at the time of surgery was 7.6 years (range, 2.3 to 17.0 years). Shoulder function was graded according to the modified Mallet classification system. Glenohumeral deformity was graded according to the classification scheme of Waters et al. The results for twenty-seven patients who were followed for a minimum of two years (average, 3.7 years) are reported. RESULTS The average amount of external rotation achieved with osteotomy was 64 degrees (range, 35 degrees to 90 degrees). The mean aggregate Mallet classification score improved from 13 to 18 points (p < 0.01). The mean Mallet classification scores for the individual elements similarly demonstrated improvement following osteotomy, with the greatest gains in hand-to-mouth, hand-to-neck, and external rotation motions. The mean classification of the glenohumeral deformity was type IV preoperatively and postoperatively, signifying the persistence of glenohumeral dysplasia. There were no nonunions. One patient required a revision osteotomy for inadequate initial correction. One patient sustained a humeral fracture distal to the plate fixation because of sports-related trauma. CONCLUSIONS Derotational humeral osteotomy improves shoulder function in patients with brachial plexus birth palsy, internal rotation contracture, and/or advanced glenohumeral joint deformity. This osteotomy provides an attractive treatment option for patients with brachial plexus birth palsy who have advanced glenohumeral dysplasia precluding soft-tissue releases and tendon transfers.

Cast immobilization versus percutaneous pin fixation of displaced distal radius fractures in children: a prospective, randomized study.

Thirty-four patients were enrolled in a prospective randomized study comparing cast immobilization alone versus percutaneous pin fixation following closed reduction of distal radial metaphyseal fractures. Patients older than 10 years of age with greater than 30 degrees of dorsal angulation or with complete fracture displacement were eligible for enrollment. Average follow-up was 10.5 weeks. All fractures healed uneventfully without deformity, growth arrest, or functional limitations. Overall complication rates were similar between groups. Thirty-nine percent of patients treated with casting had subsequent loss of reduction requiring remanipulation; there were no cases of loss of reduction in patients treated with pin fixation. Thirty-eight percent of patients treated with pin fixation had pin-related complications; all resolved following pin removal without long-term sequelae. Cost analysis showed no significant difference in treatment charges between groups. Treating surgeons should be aware of the potential short-term complications of each treatment method and adjust their postoperative care appropriately.

The Early Effects of Tendon Transfers and Open Capsulorrhaphy on Glenohumeral Deformity in Brachial Plexus Birth Palsy

BACKGROUND Persistent muscle imbalance and soft-tissue contractures can lead to progressive glenohumeral joint dysplasia in patients with brachial plexus birth palsy. The objective of the present investigation was to determine the effects of tendon transfers and open glenohumeral reduction on shoulder function and dysplasia in patients with preexisting joint deformity secondary to brachial plexus birth palsy. METHODS Twenty-three patients with preexisting glenohumeral deformity underwent latissimus dorsi and teres major tendon transfers to the rotator cuff with concomitant musculotendinous lengthening of the pectoralis major and/or subscapularis and open glenohumeral joint reduction for the treatment of internal rotation contracture and external rotation weakness. Shoulder function was assessed with use of the modified Mallet classification system and the Active Movement Scale. Glenoid version and humeral head subluxation were quantified radiographically, and glenohumeral deformity was appropriately graded. The mean duration of clinical and radiographic follow-up was thirty-one and twenty-five months, respectively. RESULTS Clinically, all patients demonstrated improved global shoulder function, with the mean aggregate Mallet score improving from 10 points preoperatively to 18 points postoperatively (p < 0.01). The mean modified Mallet score for external rotation improved from 2 to 4 (p < 0.01). Similarly, the mean Active Movement Scale score for external rotation improved from 3 to 6 (p < 0.01). The mean Mallet hand-to-spine score improved from 1 to 2 (p < 0.01). The mean Active Movement Scale score for internal rotation remained constant at 6. Radiographically, the mean glenoid version improved from -39 degrees preoperatively to -18 degrees postoperatively (p < 0.01). The mean percentage of the humeral head anterior to the middle of the glenoid similarly improved from 13% to 38% (p < 0.01). The mean glenohumeral deformity score improved from 3 to 2 (p < 0.01). Nineteen (83%) of the twenty-three patients demonstrated glenohumeral remodeling; one patient had progressive worsening of glenohumeral deformity. CONCLUSIONS Tendon transfers to the rotator cuff, combined with musculotendinous lengthenings and open reduction of the glenohumeral joint, improve global shoulder function and lead to glenohumeral joint remodeling in the majority of selected patients with mild-to-moderate preexisting glenohumeral dysplasia secondary to brachial plexus birth palsy. Future study of the long-term outcomes of these procedures will help to clarify the ultimate effect on glenohumeral joint function. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.