A Novel Operation Technique for Forearm Deformities in Patients with Brachial Plexus Birth Injury: Retrospective Analysis of 14 Patients.

Background: We aimed to evaluate the effectiveness of our novel operation technique that included radial shaft shortening plus supination producing osteotomy and transfer of the biceps brachii tendon to the brachialis tendon in patients with chronic radial head dislocation secondary to brachial plexus birth injury (BPBI). Methods: Fourteen patients with chronic radial head dislocation resulting from BPBI were included in this study, with a minimum 1-year postoperative follow-up period. All patients underwent the same surgical procedure. The range of motion of affected elbow was measured with a standard goniometer. The Mayo Elbow Performance Score (MEPS) was used to measure for evaluation of functional result of these patients. The affected elbow radiograph also obtained in the last visit for evaluation of compatibility of the radiocapitellar joint. Results: Fourteen patients (10 males and 4 females) were included in the study. The average age at the time of surgery was 7.2 (5-8) years and average follow-up was 73.2 ± 19 (36-131) months. Although the forearm active-passive pronation decreased, active-passive supination significantly improved postoperatively (p < 0.001). Ten patients had excellent MEPS results (90 and above), two patients with good results (75 and 80), one patient with fair (65) and one patient with poor result (55). Radiocapitellar reduction was achieved in 78.5% (11/14) of the patients. Conclusions: The novel surgical techniques that included radial shaft shortening plus supination producing osteotomy and transfer of the biceps brachii tendon to the brachialis tendon improved the functional outcomes of patients with chronic radial head dislocation secondary to BPBI. Level of Evidence: Level IV (Therapeutic).

ADAM19 cleaves the PTH receptor and associates with brachydactyly type E.

Brachydactyly type E (BDE), shortened metacarpals, metatarsals, cone-shaped epiphyses, and short stature commonly occurs as a sole phenotype. Parathyroid hormone-like protein (PTHrP) has been shown to be responsible in all forms to date, either directly or indirectly. We used linkage and then whole genome sequencing in a small pedigree, to elucidate BDE and identified a truncated disintegrin-and-metalloproteinase-19 (ADAM19) allele in all affected family members, but not in nonaffected persons. Since we had shown earlier that the extracellular domain of the parathyroid hormone receptor (PTHR1) is subject to an unidentified metalloproteinase cleavage, we tested the hypothesis that ADAM19 is a sheddase for PTHR1. WT ADAM19 cleaved PTHR1, while mutated ADAM-19 did not. We mapped the cleavage site that we verified with mass spectrometry between amino acids 64-65. ADAM-19 cleavage increased Gq and decreased Gs activation. Moreover, perturbed PTHR1 cleavage by ADAM19 increased ß-arrestin2 recruitment, while cAMP accumulation was not altered. We suggest that ADAM19 serves as a regulatory element for PTHR1 and could be responsible for BDE. This sheddase may affect other PTHrP or PTH-related functions.

An unusual cause of posterior interosseous nerve palsy and contribution of ultrasonography to electromyography in a patient with neurofibroma.

Neurofibroma, a benign peripheral nerve sheath tumor, represents a rare cause of posterior interosseous nerve syndrome. Electrodiagnostic studies may not identify the exact site of nerve compression, a possible lesion that compresses the nerve and do not provide information about the morphological changes. Ultrasound is a cost-effective, practical modality that provides the opportunity for dynamic tracking in the peripheral nerves, and it is widely considered as the initial imaging modality for peripheral nerves. Herein, we report a case of posterior interosseous nerve palsy in a 13-year-old boy with neurofibroma of posterior interosseous nerve diagnosed with ultrasound. The benefit of ultrasound in localizing and determining the etiology of the posterior interosseous nerve palsy is emphasized in this case report. A meticulous ultrasound examination is recommended in suspected peripheral nerve lesions, regardless of the results of electrophysiological and imaging modalities.

The effect of botulinum toxin application on latissimus dorsi and teres major muscles in patients with brachial plexus birth palsy: An electron microscopic and clinical study.

BACKGROUND: In brachial plexus birth palsy (BPBP), botulinum toxin may be utilized to prevent glenohumeral dysplasia and to maintain the stable growth of the glenohumeral joint. Repeated injections may cause muscular atrophy and their functional effects are uncertain. The aim of this study was to compare the microstructure and the function of the muscles that received two injections before transfer with the muscles that were not injected. METHODS: BPBP patients that were operated between January 2013 and December 2015 were included in the study. Latissimus dorsi and teres major muscles were transferred to humerus in standard fashion. Patients were divided in two groups according to bo-tulinum toxin status. Group 1 was toxin negative whereas Group 2 was toxin positive. For each patient, mean latissimus dorsi myocyte thickness (LDMT) was measured with electron microscopy and pre-operative and post-operative active shoulder abduction, flexion, external and internal rotation, and Mallet scores were evaluated with goniometry. RESULTS: Fourteen patients (seven patients per group) were evaluated. Five patients were female whereas nine were male. Mean LDMT was not affected significantly (p>0.05). The operation improved shoulder abduction, flexion, and external rotation significantly (p<0.05), independent of the toxin status. The internal rotation decreased significantly only in Group 2 (p<0.05). The Mallet score increased in both groups, but it was not significant (p>0.05), independent of the toxin status. CONCLUSION: Botulinum toxin that was applied twice prevented glenohumeral dysplasia and it did not cause permanent latissimus dorsi muscle atropy and function loss in late period. It augmented upper extremity functions by alleviating internal rotation contracture.

Reorganization of inter-chromosomal interactions in the 2q37-deletion syndrome.

Chromosomes occupy distinct interphase territories in the three-dimensional nucleus. However, how these chromosome territories are arranged relative to one another is poorly understood. Here, we investigated the inter-chromosomal interactions between chromosomes 2q, 12, and 17 in human mesenchymal stem cells (MSCs) and MSC-derived cell types by DNA-FISH We compared our findings in normal karyotypes with a three-generation family harboring a 2q37-deletion syndrome, featuring a heterozygous partial deletion of histone deacetylase 4 (HDAC4) on chr2q37. In normal karyotypes, we detected stable, recurring arrangements and interactions between the three chromosomal territories with a tissue-specific interaction bias at certain loci. These inter-chromosomal interactions were confirmed by Hi-C. Interestingly, the disease-related HDAC4 deletion resulted in displaced inter-chromosomal arrangements and altered interactions between the deletion-affected chromosome 2 and chromosome 12 and/or 17 in 2q37-deletion syndrome patients. Our findings provide evidence for a direct link between a structural chromosomal aberration and altered interphase architecture that results in a nuclear configuration, supporting a possible molecular pathogenesis.

Distally based subcutaneous veins for venous insufficiency of the reverse posterior interosseous artery flap.

BACKGROUND: The reverse posterior interosseous artery flap (PIAF) provides soft, thin, and pliable tissue for upper extremity reconstruction without sacrificing any major arteries of the hand. The authors performed a new technique that included one extra distally based subcutaneous vein within the pedicle to diminish venous insufficiency and they aimed to present the results of reconstruction with this technique. PATIENTS AND METHODS: Twelve patients with a mean age of 30 years (range 5-52 years) underwent reverse PIAF surgery. The defects were located on the hand and wrist, with a mean area of 57.8 cm2 (range 20-99 cm2) . After the skin between the distal edge and the pivot point of the flap was elevated, the most reliable subcutaneous vein was chosen, chased, and included within the flap. RESULTS: The average size of the PIAF was 6 × 5 cm to 12 × 9 cm (mean area: 64.4 cm2 ) and the median follow-up time was 13 months (range 4-16 months). The mean quick Disabilities of the Arm, Shoulder and Hand (DASH) score was 21.4, indicating a low degree of disability. Of the 12 patients, ten were very satisfied and two were satisfied with the result of the reconstruction. All but one flap survived completely. One flap was nearly totally lost due to arterial insufficiency after hemodialysis. We observed no venous congestion or insufficiency in the patients. CONCLUSIONS: Subcutaneous veins may be reliable and useful for overcoming major drawbacks associated with reverse flow posterior interosseous artery flap and for diminishing flap loss due to venous insufficiency. © 2016 Wiley Periodicals, Inc. Microsurgery 36:384-390, 2016.

PDE3A mutations cause autosomal dominant hypertension with brachydactyly.

Cardiovascular disease is the most common cause of death worldwide, and hypertension is the major risk factor. Mendelian hypertension elucidates mechanisms of blood pressure regulation. Here we report six missense mutations in PDE3A (encoding phosphodiesterase 3A) in six unrelated families with mendelian hypertension and brachydactyly type E (HTNB). The syndrome features brachydactyly type E (BDE), severe salt-independent but age-dependent hypertension, an increased fibroblast growth rate, neurovascular contact at the rostral-ventrolateral medulla, altered baroreflex blood pressure regulation and death from stroke before age 50 years when untreated. In vitro analyses of mesenchymal stem cell-derived vascular smooth muscle cells (VSMCs) and chondrocytes provided insights into molecular pathogenesis. The mutations increased protein kinase A-mediated PDE3A phosphorylation and resulted in gain of function, with increased cAMP-hydrolytic activity and enhanced cell proliferation. Levels of phosphorylated VASP were diminished, and PTHrP levels were dysregulated. We suggest that the identified PDE3A mutations cause the syndrome. VSMC-expressed PDE3A deserves scrutiny as a therapeutic target for the treatment of hypertension.

Digital artery perforator flaps: an easy and reliable choice for fingertip amputation reconstruction.

OBJECTIVE: The aim of this study was to evaluate the use and efficacy of digital artery perforator (DAP) flaps in fingertip reconstruction. METHODS: From 2007 to 2011, 7 fingers of 5 patients (4 male, 1 female) underwent fingertip reconstruction with extended DAP flaps following traumatic fingertip amputation. Average flap size was 4.25 cm². RESULTS: All flaps survived except one case in which partial skin necrosis was observed and treated with wet-dressing. Donor sites were closed with full-thickness skin grafting in 5 and primarily in 2 fingers. We did not observe hypersensitivity or cold intolerance in repaired fingers. CONCLUSION: The DAP flap is a reliable, free-style perforator flap that can be used for all types of fingertip injuries.

Cosmetic closure of pilonidal sinus defects with bilateral transpositional adipofascial flaps.

The optimal treatment of the pilonidal sinus has not currently been defined. This study described the use of a modified bilateral transpositional adipofascial flap technique that effectively serves to flatten the deep natal cleft while keeping the scar limited to the intergluteal fold for good cosmesis. Between June 2007 and September 2011, 83 patients (61 men, 22 women) were included in the study. Duration of pilonidal sinus symptoms ranged from 1-15 (median 5) years; 15 patients had recurrent disease. Before the operation, perforating branches of the four pairs of lateral sacral arteries were identified with a Doppler audioscope. After complete excision of the sinus cavity and adequate undermining of the skin, bilateral adipofascial flaps were raised in order to realise a Yin-Yang pattern, with the lateral sacral artery perforators at the base of each flap. Complementary flaps were then transposed into the defect and inset to completely obliterate dead space. Skin was closed primarily in two layers. The median (range) defect size after total excision of the sinus cavity was 38 (19-60) cm2. All flaps survived. There was no wound infection or dehiscense. Median (range) follow-up was 26 (6-52) months. No recurrences were observed. Extensive scarring or asymmetry in the gluteal prominences was not observed. Transient paraesthesia over the flap donor region occurred in 14 cases (16%) and resolved completely within 6 months. The bilateral adipofascial transpositional flap method is an alternative to previously described treatment options in pilonidal sinus surgery. It is a safe, reliable, and easily applicable method, which provides cosmetically acceptable coverage of pilonidal sinus defects of moderate size.

Psychological adjustment, maternal distress, and family functioning in children with obstetrical brachial plexus palsy.

PURPOSE: To examine emotional and behavioral characteristics of children with obstetrical brachial plexus palsy (OBPP), psychological distress of their mothers and their family functioning, and compare them with healthy peers. METHODS: Participants included 42 children with OBPP (22 boys, 20 girls; age range, 4-16 y; mean, 7 y 0 mo; SD, 3 y 3 mo) and 43 healthy controls (24 boys, 19 girls; age range, 4-15 y; mean, 8 y 0 m; SD, 3 y 0 mo). Childhood Behavior Checklist, Symptom Checklist 90, and Family Assessment Device were filled in by the mothers. RESULTS: Participants with OBPP displayed higher problem scores than the comparison children in most of the domains, including internalizing and externalizing problems. Maternal distress was higher in the OBPP group, and few differences in family functioning were noted. Maternal distress and having the diagnosis of OBPP were the strongest predictors of children's total problem scores and explained 26% of the variance when the effect of age, sex, and family functioning were controlled. CONCLUSIONS: Children with OBPP and their mothers are at increased risk for a variety of psychological problems. Professionals should be aware of these children's and their caregivers' psychological adjustment and refer them for further psychological support when needed. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

A misplaced lncRNA causes brachydactyly in humans.

Translocations are chromosomal rearrangements that are frequently associated with a variety of disease states and developmental disorders. We identified 2 families with brachydactyly type E (BDE) resulting from different translocations affecting chromosome 12p. Both translocations caused downregulation of the parathyroid hormone-like hormone (PTHLH) gene by disrupting the cis-regulatory landscape. Using chromosome conformation capturing, we identified a regulator on chromosome 12q that interacts in cis with PTHLH over a 24.4-megabase distance and in trans with the sex-determining region Y-box 9 (SOX9) gene on chromosome 17q. The element also harbored a long noncoding RNA (lncRNA). Silencing of the lncRNA, PTHLH, or SOX9 revealed a feedback mechanism involving an expression-dependent network in humans. In the BDE patients, the human lncRNA was upregulated by the disrupted chromosomal association. Moreover, the lncRNA occupancy at the PTHLH locus was reduced. Our results document what we believe to be a novel in cis- and in trans-acting DNA and lncRNA regulatory feedback element that is reciprocally regulated by coding genes. Furthermore, our findings provide a systematic and combinatorial view of how enhancers encoding lncRNAs may affect gene expression in normal development.

Quadruple salivary duct diversion for drooling in cerebral palsy.

Drooling complicates many neurologic disorders including cerebral palsy. It is socially debilitating for the patient and very tedious for the caregiver. Surgical treatment consists mainly of ablative (excision/ligation) or physiological (diversion) methods; combined techniques have also been proposed. We have applied bilateral diversion of both submandibular and parotid ducts in 12 cerebral palsy patients (age range, 7-15 years). Preoperative drooling severity was grade 4/5 in 10 cases and grade 5/5 in 2 of the cases. All patients underwent physiotherapy for a minimum of 6 months and were consulted with a dentist, otolaryngologist, and a speech therapist before surgery. No bleeding, hematoma, or infection has been observed in any of the patients. Two patients had early postoperative tongue edema that regressed with conservative treatment. All patients except one regressed to grade 2/5 drooling by the first postoperative month. In 1 patient who had previously been classified as grade 5/5, surgery provided limited improvement with only 1 grade of step-down. Satisfactory results for the patients and their families could be achieved and sustained for a median 18 months (7-20 months) of follow-up. In conclusion, the quadruple duct diversion method is an effective physiological surgical method in the control of drooling in cerebral palsy.

Does primary brachial plexus surgery alter palliative tendon transfer surgery outcomes in children with obstetric paralysis?

BACKGROUND: The surgical management of obstetrical brachial plexus palsy can generally be divided into two groups; early reconstructions in which the plexus or affected nerves are addressed and late or palliative reconstructions in which the residual deformities are addressed. Tendon transfers are the mainstay of palliative surgery. Occasionally, surgeons are required to utilise already denervated and subsequently reinnervated muscles as motors. This study aimed to compare the outcomes of tendon transfers for residual shoulder dysfunction in patients who had undergone early nerve surgery to the outcomes in patients who had not. METHODS: A total of 91 patients with obstetric paralysis-related shoulder abduction and external rotation deficits who underwent a modified Hoffer transfer of the latissimus dorsi/teres major to the greater tubercle of the humerus tendon between 2002 and 2009 were retrospectively analysed. The patients who had undergone neural surgery during infancy were compared to those who had not in terms of their preoperative and postoperative shoulder abduction and external rotation active ranges of motion. RESULTS: In the early surgery groups, only the postoperative external rotation angles showed statistically significant differences (25 degrees and 75 degrees for total and upper type palsies, respectively). Within the palliative surgery-only groups, there were no significant differences between the preoperative and postoperative abduction and external rotation angles. The significant differences between the early surgery groups and the palliative surgery groups with total palsy during the preoperative period diminished postoperatively (p < 0.05 and p > 0.05, respectively) for abduction but not for external rotation. Within the upper type palsy groups, there were no significant differences between the preoperative and postoperative abduction and external rotation angles. CONCLUSIONS: In this study, it was found that in patients with total paralysis, satisfactory shoulder abduction values can be achieved with tendon transfers regardless of a previous history of neural surgery even if the preoperative values differ.

Olecranon bone graft: revisited.

Autogenous bone grafts are frequently in use in the field of reconstructive upper extremity surgery. Cancellous bone grafts are applied to traumatic osseous defects, nonunions, defects after the resection of benign bone tumors, arthrodesis, and osteotomy procedures. Cancellous bone grafts do not only have benefits such as rapid revascularization, but they also have mechanical advantages. Despite the proximity to the primary surgical field, cancellous olecranon grafts have not gained the popularity they deserve in the field of reconstructive hand surgery. In this study, the properties, advantages, and technical details of harvesting cancellous olecranon grafts are discussed.

The results of surgical repair of sciatic nerve injuries.

OBJECTIVES: The aim of this study was to evaluate surgical treatment and follow-up results of patients who presented to our department with sciatic nerve injuries. METHODS: The study included 13 patients (12 males, 1 female; mean age 23 years; range 11 to 35 years) who underwent surgical treatment for sciatic nerve injuries. The etiologies of sciatic nerve injuries were penetrating trauma in five patients, firearm injuries in four patients, and motor vehicle accidents in four patients. Injuries involved the knee level in five patients, and above-the-knee level in eight patients. Peroneal nerve involvement was seen in all the patients, and the tibial nerve was involved in 11 patients. Primary repair was performed in six patients, neurolysis in three patients, and nerve grafting in three patients. One patient underwent neurolysis for the peroneal portion, and nerve grafting for the tibial portion. Muscle strength and reflex changes were recorded at every stage of the treatment. Muscle strength was assessed according to the British Medical Research Council scale. The Semmes-Weinstein monofilament test was used for sensory evaluation. The mean follow-up period was 4 years (range 1 to 6 years). RESULTS: In 11 patients with tibial nerve injuries, the soleus/gastrocnemius strength was measured as follows: M1 in one patient, M3 in four patients, M4 in four patients, and M5 in two patients. Plantar sensation was absent in four patients, while seven patients had at least adequate protective sensation. In 13 patients with a peroneal nerve injury, the strength of the anterior tibial muscle was measured as follows: M0 in three patients, M2 in three patients, M3 in one patient, M4 in three patients, and M5 in three patients. Of these, four patients had persistent insensitivity in the dorsum of the foot, while six patients had protective sensation, and three patients had normal sensation. Two patients with inadequate anterior tibial muscle strength following nerve repair underwent posterior tibial tendon transfer for restoration of foot dorsiflexion. The greatest functional improvement was obtained in cases in which neurolysis was performed; patients undergoing primary repair had better outcomes compared to those where nerve grafts were used. The results were better in thigh level injuries than those in the gluteal region. CONCLUSION: Low expectations after sciatic nerve repair in the past are now being rapidly replaced by a more optimistic approach. Advances in microsurgery and use of treatment algorithms based on scientific research account for this significant improvement in outcomes after sciatic nerve surgery. Tendon transfers can enhance the success rate and be combined with nerve repair in selected cases.

Sensory recovery of the reverse homodigital island flap in fingertip reconstruction: a review of 66 cases.

OBJECTIVES: The location of the fingertip entitles it to have significant cosmetic and functional values, but also places it at high risk for injury. During repair, finger length and function should be maintained, and stiffness and neuroma should be avoided. Various flaps have been described for reconstruction of distal finger defects with bone, tendon, or joint exposures, including reverse flow homodigital island flap. In this study, we present our experience of reverse flow homodigital island flap in terms of sensory recovery. METHODS: Sixty-six patients (70 fingers) with fingertip amputations were included in the study. Patients were treated with homodigital island flaps. All patients underwent sensitivity assessment by 2-point discrimination and Semmes-Weinstein monofilament tests at 6, 12, and 18 months during follow-up, and complications were recorded. RESULTS: Monofilament testing results were normal in 64 fingers (91.4%), and diminished light touch was found in six fingers. Two-point discrimination results were normal (<6 mm) in 40 fingers and fair (6-10 mm) in 30 fingers (mean 5.7 mm, range 4-9 mm). Complications included one partial flap necrosis, three flexion contractures, and two neuromas. CONCLUSION: In repair of injuries to areas in which sensory feedback is critical, such as the index finger, the homodigital flap may be the treatment of choice.

A cis-regulatory site downregulates PTHLH in translocation t(8;12)(q13;p11.2) and leads to Brachydactyly Type E.

Parathyroid hormone-like hormone (PTHLH) is an important chondrogenic regulator; however, the gene has not been directly linked to human disease. We studied a family with autosomal-dominant Brachydactyly Type E (BDE) and identified a t(8;12)(q13;p11.2) translocation with breakpoints (BPs) upstream of PTHLH on chromosome 12p11.2 and a disrupted KCNB2 on 8q13. We sequenced the BPs and identified a highly conserved Activator protein 1 (AP-1) motif on 12p11.2, together with a C-ets-1 motif translocated from 8q13. AP-1 and C-ets-1 bound in vitro and in vivo at the derivative chromosome 8 breakpoint [der(8) BP], but were differently enriched between the wild-type and BP allele. We differentiated fibroblasts from BDE patients into chondrogenic cells and found that PTHLH and its targets, ADAMTS-7 and ADAMTS-12 were downregulated along with impaired chondrogenic differentiation. We next used human and murine chondrocytes and observed that the AP-1 motif stimulated, whereas der(8) BP or C-ets-1 decreased, PTHLH promoter activity. These results are the first to identify a cis-directed PTHLH downregulation as primary cause of human chondrodysplasia.

[Reconstruction of the head and neck with free osteoseptocutaneous flap in elderly heavy smokers]. / Agir sigara içici yasli hastalarin bas-boyun rekonstrüksiyonunda serbest osteoseptokutan flep uygulamalari.

OBJECTIVES: We evaluated complications of free flap reconstruction following oncological head and neck surgery in elderly patients who smoked heavily. PATIENTS AND METHODS: The study included eight patients (2 females, 6 males; mean age 68.5 years; range 65 to 74 years) over 65 years of age, who smoked heavily (at least 1 pack/day). All cases but one with mandibular ameloblastoma had intraoral squamous cell carcinoma. Two patients underwent reconstruction with free radial forearm osteoseptocutaneous flap following bilateral maxillary resection, and six patients with free fibular osteoseptocutaneous flap following mandibular resection. Postoperative complications, in particular those associated with the donor and recipient sites were evaluated. RESULTS: No partial or total flap loss was observed. Wound healing problems were seen in three patients (37%), which were at the donor site in two patients, and at the recipient site in one patient. Psychogenic disorders were observed in two patients (25%). No other complications were encountered. CONCLUSION: Aside from some recipient- and donor-site-related healing problems, heavy smoking and advanced age cannot be regarded as contraindications for free flap reconstruction.