Immune tolerance of allogeneic haematopoietic cell transplantation supports donor epidermal grafting of recessive dystrophic epidermolysis bullosa chronic wounds.

BACKGROUND: Chronic wounds, a common morbidity in recessive dystrophic epidermolysis bullosa (RDEB), lack definitive therapies. OBJECTIVES: To assess allogeneic epidermal skin grafts in terms of wound healing and durability over time. METHODS: In a prospective, open-label clinical trial for postallogeneic haematopoietic cell transplantation (post-alloHCT) patients with RDEB, up to nine chronic wounds per patient were grafted over 1 year. Epidermal grafts measuring 5 cm2 were obtained from related alloHCT donors in the outpatient setting using the CELLUTOMETM Epidermal Harvesting System. Wounds were photographed and symptom inventories completed at baseline and 6, 12 and 52 weeks after grafting. The trial was registered at ClinicalTrials.gov (NCT02670837). RESULTS: Between August 2016 and January 2019, eight patients with RDEB received a total of 35 epidermal allografts at a median of 1157 days (range 548-2884) post-alloHCT. The median (interquartile range) percentage reductions in wound surface area were 75% (52-94), 95% (72-100) and 100% (97-100) at 6, 12 and 52 weeks postgraft, respectively, each significantly reduced from baseline (P < 0·001). Donor harvest sites healed quickly without scarring. Biopsy evaluation at 1 year of an epidermal allograft site revealed wildtype type VII collagen (immunofluorescence), anchoring fibrils (electron microscopy), and full-thickness skin whole-DNA donor chimerism of 42% (compared with 16% in concurrently biopsied native skin). This strategy subsequently supported release of RDEB pseudosyndactyly. CONCLUSIONS: The immune tolerance established by alloHCT supports successful adoptive transfer of donor epidermal grafts. Persistence of donor grafts in a single patient beyond 1 year and observed migration of donor-grafted cells into adjacent wound suggest that epidermal allografts include nonterminally differentiated cells and/or trigger recruitment of donor bone-marrow-derived cells to mediate wound healing.

Analysis of factors affecting development of carpal tunnel syndrome in patients with Hurler syndrome after hematopoietic cell transplantation.

Children with Hurler syndrome (mucopolysaccharidosis type IH (MPSIH)) have skeletal, joint and soft tissue abnormalities that may persist or progress after hematopoietic stem cell transplantation (HSCT). We report our single center experience with development of carpal tunnel syndrome (CTS) in 43 children with MPSIH after HSCT. Twenty-three children (59%) developed CTS following HSCT; 19 of the 39 children with enzyme activity in the normal or heterozygous range developed CTS (49%), whereas all four children with low heterozygous or absent enzyme activity developed CTS after HSCT. Fourteen of 19 related donor marrow recipients, eight of 19 of those receiving an unrelated donor graft and one of five unrelated cord blood recipients developed CTS. The mean age at surgical release was 4.8 years. With each year increase in age at HSCT, there was a 55% increased risk. Age and enzyme activity after HSCT were significant factors in the development of CTS. Transplantation by 2 years of age reduced the risk of developing CTS by 46%; higher enzyme activity led to a 78% reduction in the risk of developing CTS. However, children transplanted for MPSIH remain at risk for the development of CTS, and should be monitored on an ongoing basis by nerve conduction velocity testing.

The supination effect of tendon transfer of the flexor carpi ulnaris to the extensor carpi radialis brevis or longus: a cadaveric study.

Flexor carpi ulnaris (FCU) transfer to the extensor carpi radialis brevis (ECRB) and/or the extensor carpi radialis longus (ECRL) has been commonly used to provide wrist extension. The ability of this wrist extension transfer to also provide forearm supination has been inferred but not formally investigated. This laboratory study investigated the forearm supination effect of FCU transfer to the ECRB and to the ECRL in a cadaveric model. Two vectors of pull were investigated: freeing either the distal one third or the distal two thirds of the FCU ulnar origin. Five fresh-frozen, above-elbow, non-matched cadaveric specimens placed in a mounting device that allowed the arm to rotate about its ulnar axis starting from a full pronated position were measured for resultant supination after tendon transfer and loading. This study showed that the transfer of the FCU into either the ECRB or the ECRL resulted in no significant difference in maximum supination. The vector of origin, however, did significantly affect the maximum supination obtained. Releasing the distal two thirds of the FCU ulnar origin resulted in a mean supination that was significantly greater than the mean supination achieved with releasing the distal one third of the FCU ulnar origin. We concluded that in the cadaveric model, transfer of the FCU into either the ECRB or ECRL provided similar resultant supination and that freeing the distal two thirds of the FCU ulnar origin provided significantly more supination than freeing only the distal one third. For the hand surgeon treating wrist flexion in combination with forearm pronation deformity, transfer of the FCU into the ECRB and/or the ECRL can be used to concomitantly provide wrist extension and forearm supination.

Cadaveric modeling of the pronator teres rerouting tendon transfer.

The purpose of this study is to report the biomechanics of the supination effect of the pronator teres rerouting procedure and to determine the optimum insertion point for the transfer using a cadaveric model. Pronator teres rerouting procedures were performed on 5 fresh-frozen above-elbow cadaver specimens mounted in a forearm rotation mounting frame. The pronator teres was detached from its native insertion and tested at 6 insertions on the radius. The amount of rotation of the forearm was measured after loading of the pronator teres muscle for each insertion site. The experiments were repeated by placing the pronator teres 1 cm proximal to the 6 experimental insertion sites for a total testing of 12 insertions. The results of this study show that placement of the pronator teres through the interosseous membrane, around the radius, with reinsertion onto the volar surface produced the greatest amount of forearm supination. Rerouting of the pronator teres tendon produces supination through a windlass effect when the tendon is rerouted through an interosseous window and reinserted onto its original insertion or onto the volar surface of the radius. Placement of the insertion 1 cm proximal on the radius did not affect the amount of forearm supination compared with 6 original insertion sites.

Upper extremity surgical treatment of cerebral palsy.

The purpose of this report is to review the surgical treatment of the upper extremity involved with cerebral palsy over a 25-year period and present our results with regard to changes in upper limb function. Surgical results were assessed by comparison of preoperative and postoperative levels of upper extremity functional use using a previously described 9-level scale. The effect of the following cofactors on surgical outcome were examined: type of cerebral palsy, age, voluntary control, mental impairment, sensibility, and type of surgical treatment. One hundred eighty operations representing 718 procedures in 134 patients were reviewed. Surgical treatment was based on the following principles: soft tissue releases of deforming spastic muscles, tendon transfers to augment antagonistic activity, and joint stabilization. Surgical planning was tailored to each child's particular needs. Comparison of the preoperative and postoperative 9-level functional use scores showed an average improvement of 2.6 functional levels for all patients. Patients with fair and good voluntary control had significantly greater improvement in functional use scores than those with poor voluntary control. No other statistically significant predictive cofactor was found. In selected patients with upper extremity dysfunction secondary to spastic cerebral palsy, surgical intervention improves function, as measured by the upper extremity functional use scale.

Biceps-to-triceps transfer in tetraplegic patients: report of the medial routing technique and follow-up of three cases.

We reviewed 4 biceps-to-triceps transfers for active elbow extension in 3 tetraplegic patients using a medial routing technique. The biceps-to-triceps transfer to regain active elbow extension in tetraplegic patients is an alternative to the more commonly described deltoid-to-triceps transfer. Before surgery, all 3 patients had absent triceps function and active biceps, brachialis, and supinator function. Postoperative results were assessed by a modified University of Minnesota Functional Improvement questionnaire and by follow-up evaluation of range of motion and muscle strength. All 3 patients had marked functional improvement in activities that involve active elbow extension, and no loss of function was noted in any activities. No patient achieved less than grade 4 extension strength; none had an extension lag greater than 8 degrees. Supination and flexion strength following transfer were rated as at least grade 4 in each limb. Based on the results of this study, we recommend the biceps-to-triceps transfer as an alternative to the deltoid-to-triceps transfer in spinal cord injury patients with active brachialis and supinator function. The medial routing technique has the advantage of avoiding the potentially devastating radial nerve injury that could occur with the previously described lateral routing.

Surgical treatment of carpal tunnel syndrome and trigger digits in children with mucopolysaccharide storage disorders.

The role of surgical intervention for carpal tunnel syndrome (CTS) and trigger digits in children with mucopolysaccharide storage disorders (MPSDs) has not been clearly defined, particularly as the treatment of the underlying disease has advanced to include bone marrow transplantation. This study reviews our experience in the treatment of CTS and trigger digits in 22 children with MPSDs who were evaluated for CTS by electromyographic (EMG)/nerve conduction velocity (NCV) testing. Seventeen children were diagnosed with CTS by EMG/NCV testing and were treated with bilateral open surgical release with or without flexor tenosynovectomy. The EMG/NCV testing revealed normal results in 5 patients who are subsequently being monitored. Forty-five digits in 8 children were diagnosed clinically with trigger digits. Nineteen digits were treated by annular pulley release alone. Twenty-six digits were treated by annular pulley release with partial flexor digitorum superficialis tendon resection. The average age at the time of hand surgery was 6.3 years, and at the time of follow-up, 9.6 years. Postoperative EMG/NCV testing in 7 children showed 1 with improvement and 6 with normalization. None of the patients undergoing carpal tunnel release went on to develop thenar atrophy or absent sensibility, as has been reported in untreated cases. Patients were evaluated for triggering digits both by preoperative tendon palpation and by intraoperative flexor tendon excursion at the time of open carpal tunnel release. All patients undergoing trigger release had improved active digital flexion seen at the final follow-up visit. Because of the very high incidence of CTS and trigger digits in this population, the authors currently recommend routine screening of EMG/NCV for all children with MPSDs. Early surgical intervention for nerve compression and stenosing flexor tenosynovitis can maximize hand function in these children.

Acute forearm lengthenings.

We describe our surgical technique of acute pediatric forearm lengthening and joint leveling for treatment of symptomatic forearm-length discrepancies. A retrospective clinical and radiographic analysis was performed of all patients undergoing acute forearm lengthenings of > 1.0 cm between 1983 and 1993. Twenty-four acute forearm lengthenings were reviewed with an average follow-up of 3 years. The diagnosis included osteochondromatosis in 17 patients, growth arrest in four patients, and skeletal dysplasia in three patients. Surgical indications included progressive forearm or wrist deformity, significantly limited or painful forearm rotation, or radial-head subluxation. The average lengthening was 1.5 cm (range, 1.0-2.3), which was 9% of total length (range, 3-20%). The goal for lengthening and wrist-joint leveling was near-neutral ulnar variance and was achieved in all cases. We conclude that the forearm can be lengthened acutely successfully to achieve near-neutral ulnar variance in children with forearm-length discrepancies caused by osteochondromas, growth arrests, or bone dysplasias. The surgical technique and the results are described in 24 forearm lengthenings.

A cadaveric anatomic study of radial artery pedicle grafts to the scaphoid and lunate.

This study was designed to determine the frequency of available radial styloid and metacarpal vascularized bone pedicle grafts and to determine the potential clinical availability (ie, sufficient length) of each pedicle graft for revascularization procedures to the dorsal and palmar scaphoid and dorsal lunate. Five vascularized bone pedicles (radial styloid 1, radial styloid 2, first metacarpal, second metacarpal, and third metacarpal) were evaluated in 20 fresh-frozen unpaired cadaveric forearms after methylene blue injection. For the dorsal approach to the scaphoid, radial styloid 2 bone graft was most reliable; for a palmar approach to the scaphoid, the first metacarpal graft was the most reliable; and for the dorsal approach to the lunate, the third metacarpal was the most reliable. Not all pedicles were available in all specimens; thus, versatility in using all five pedicles is recommended.

Two-stage reconstruction of apert acrosyndactyly.

This report retrospectively reviews presenting radiographs and surgical treatment of 28 hands in 14 children with Apert acrosyndactyly with the purpose of developing a classification system to describe the decision-making process used to determine the type and staging of hand reconstruction. The average patient age at last follow-up evaluation was 7 years (range, 3-17 years). Type I deformities (7 hands) had little or no angular deformity at the metacarpophalangeal (MP) joint; two-stage reconstruction created a four-fingered hand. Type IIA deformities (11 hands) had mild MP joint angular deformity and a more proximal complex syndactyly of the middle three digits; two-stage reconstruction created a three-fingered hand with ray resection of the third digit. Type IIB deformities (7 hands) had pronation of digit 2 superimposed on the thumb and radial angulation at the MP joint of digit 2; two-stage reconstruction created a three-fingered hand with ray resection of the second digit. Type IIC deformities (3 hands) had supination of digit 4 superimposed on digit 5 with ulnar angulation at the MP joint of digits 4 and 5; two-stage reconstruction created a three-fingered hand with ray resection of the fourth digit. This report presents a classification system and four different treatment strategies based on presenting radiographs.

Congenital disorders of the hand and upper extremity.

This article summarizes normal formation and growth of the upper limb as a basis for understanding malformation. Shoulder anomalies, including Sprengel's undescended scapula, clavicle pseudarthrosis, cleidocraniodystostosis, and Poland's syndrome, are presented. Classification and examples of limb malformations are discussed as well as neuromuscular disorders, such as obstetric brachial plexopathy, cerebral palsy, and arthrogryposis. The author hopes that this article provides a basic understanding of the evaluation necessary for appropriate counseling and referrals for treatment of the child with hand and upper extremity congenital deformities.

Wrist arthroscopy.

Major advancement in arthroscopic equipment and techniques has extended the ability of large joint arthroscopy to be performed in smaller joints. Although wrist arthroscopy is performed in small numbers, the same advantages are afforded as in large joint procedures. It provides important diagnostic information and therapeutic intervention, while avoiding the significant morbidity of open techniques. Patients with mechanical wrist pain are the best candidates for arthroscopy to evaluate ligamentous injuries or triangular fibrocartilage complex injuries. Arthroscopy is also an effective tool in the evaluation and treatment of intra-articular distal radius fractures and is particularly useful in radial styloid fractures. Wrist arthroscopy is a technically demanding procedure. However, it remains a safe and effective method for diagnosis and treatment if performed using a precise technique and if the surgeon has a precise understanding of the anatomy of the wrist.

Sensibility deficiencies in the hands of children with spastic hemiplegia.

We evaluated 40 children with spastic hemiplegia due to cerebral palsy for sensory function and relative limb size in the affected and unaffected upper extremities. Sensory function of each limb was evaluated with respect to stereognosis (12 objects), two-point discrimination, and proprioception. Four size measurements of each limb were made: arm and forearm circumference and forearm and forearm-hand length. This study showed that 97% of the spastic limbs had a stereognosis deficit, 90% had a two-point discrimination deficit, and 46% had a proprioception deficit. Thus sensory deficits are the rule rather than the exception in children with spastic hemiplegia. Those children with severe stereognosis deficits had significantly smaller limbs in all four measurement parameters than the children with mild or moderate stereognosis deficits. In the preoperative evaluation of children with spastic hemiplegia, severe size discrepancy is a physical examination tool that can be used as a predictor of severe sensory deficits. This information is helpful for the hand surgeon in establishing realistic surgical goals.