Integrin-modulating therapy prevents fibrosis and autoimmunity in mouse models of scleroderma.

In systemic sclerosis (SSc), a common and aetiologically mysterious form of scleroderma (defined as pathological fibrosis of the skin), previously healthy adults acquire fibrosis of the skin and viscera in association with autoantibodies. Familial recurrence is extremely rare and causal genes have not been identified. Although the onset of fibrosis in SSc typically correlates with the production of autoantibodies, whether they contribute to disease pathogenesis or simply serve as a marker of disease remains controversial and the mechanism for their induction is largely unknown. The study of SSc is hindered by a lack of animal models that recapitulate the aetiology of this complex disease. To gain a foothold in the pathogenesis of pathological skin fibrosis, we studied stiff skin syndrome (SSS), a rare but tractable Mendelian disorder leading to childhood onset of diffuse skin fibrosis with autosomal dominant inheritance and complete penetrance. We showed previously that SSS is caused by heterozygous missense mutations in the gene (FBN1) encoding fibrillin-1, the main constituent of extracellular microfibrils. SSS mutations all localize to the only domain in fibrillin-1 that harbours an Arg-Gly-Asp (RGD) motif needed to mediate cell-matrix interactions by binding to cell-surface integrins. Here we show that mouse lines harbouring analogous amino acid substitutions in fibrillin-1 recapitulate aggressive skin fibrosis that is prevented by integrin-modulating therapies and reversed by antagonism of the pro-fibrotic cytokine transforming growth factor ß (TGF-ß). Mutant mice show skin infiltration of pro-inflammatory immune cells including plasmacytoid dendritic cells, T helper cells and plasma cells, and also autoantibody production; these findings are normalized by integrin-modulating therapies or TGF-ß antagonism. These results show that alterations in cell-matrix interactions are sufficient to initiate and sustain inflammatory and pro-fibrotic programmes and highlight new therapeutic strategies.

Longitudinal Assessment of Developmental Outcomes in Infants Undergoing Late Craniosynostosis Repair.

Evaluation of infants with craniosynostosis for surgical intervention, as opposed to conservative management, remains a challenge within the field of craniofacial surgery. Studies have consistently demonstrated that surgical repair of craniosynostosis is ideally performed between 3 and 12 months of age. As such, there is limited data regarding neurocognitive development in infants who initially present with uncorrected craniosynostosis after 12 months of age. Moreover, the impact of cranial vault surgery on neurocognitive development at all ages remains under investigation. A prospective, nonrandomized study was performed. All children with nonsyndromic craniosynostosis who presented for initial evaluation after 12 months of age were enrolled. The Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) was utilized to assess pre- and postoperative cognitive development and comparisons were made to normative values. Developmental delay is defined as scoring < 85. Five infants, average age 26 months (13-43 months) at initial presentation, underwent cranial vault remodeling and developmental testing. Fused cranial sutures involved: metopic (n = 4), and right coronal (n = 1). Cognitive testing demonstrated that 4 of 5 infants (80%) were developmentally delayed at presentation (scores: 60, 70, 72, and 80), and 1 infant was within normal limits (score: 100). Postoperative testing was performed between 2 and 12 months postoperatively. Universal improvement was observed in infants who were delayed prior to surgery (80, 80, 75, and 90, respectively). The infant who was not delayed prior to surgery remained within normal limits after surgery. This study demonstrates an association between cranial vault surgery and cognitive improvement in infants presenting late with developmental delay.

Biomechanical assessment of fixation methods for segmental mandible reconstruction with fibula in the polyurethane model.

BACKGROUND: A variety of plating techniques are employed by microsurgeons to provide rigid fixation for vascularized bone constructs of the mandible. The aim of this study was to biomechanically compare three commonly utilized plating techniques for rigid fixation of fibula bone flaps in reconstructing lateral segmental mandibular defects. MATERIALS AND METHODS: Polyurethane mandibles with 3-cm segmental defects were reconstructed using polyurethane fibula models. Three fixation techniques were compared (n = 5 models per group): Group 1 used two 2.0-mm miniplates at each osteotomy site, Group 2 used a single 2.3-mm plate, and Group 3 used a single 2.7-mm plate. Biomechanical testing of maximum force and displacement at failure for each plating technique was assessed and statistical comparison performed. RESULTS: The average displacement for Group 1 was 14.08 ± 1.42 mm, Group 2 was 5.79 ± 0.89 mm, and Group 3 was 6.03 ± 1.59 mm. Group 1 had significantly greater (P < 0.05) displacement when compared with Group 2 and 3. Analysis of variance demonstrated the three groups varied significantly in mean displacement (0 < 0.01). The average force before failure for Group 1 was 616.4 ± 33.83N, Group 2 was 737.8 ± 72.57N, and Group 3 was 681.0 ± 67.98N. Group 2 withstood significantly greater force than Group 1 (P < 0.05), and withstood greater force than Group 3, although the difference was not significant. Analysis of variance showed the three groups varied significantly in mean force at failure (P < 0.05). CONCLUSION: Reconstruction using a single 2.3-mm plate provided the best rigid fixation for lateral segmental defects of the mandible. © 2016 Wiley Periodicals, Inc. Microsurgery 36:330-333, 2016.

Assessment of Deformational Plagiocephaly Severity and Neonatal Developmental Delay.

Deformational plagiocephaly (DP) in infants has been associated with developmental delay that can last until adolescence. Despite this association and a 5-fold increase in incidence of DP over the past 2 decades, there are currently no guidelines regarding screening for developmental delay or identification of which infants with DP are at the greatest risk of delay. A prospective, nonrandomized study was performed. Infants diagnosed with DP who had no prior intervention were eligible for enrollment. Cranial deformity was measured by cross-cranial measurements using calipers, and developmental delay was measured using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Correlation between cranial deformity and developmental delay was analyzed using a linear regression. Twenty-seven infants, ages 4.0 to 11.0 months (mean = 6.61 months) diagnosed with DP were studied. Developmental delay was observed on the composite language (n = 3 of 27, 11%), and composite motor (n = 5 of 23, 22%) scales, but not the cognitive scale. Severity of cranial deformity did not correlate with scores on any Bayley-III scales (cognitive R = 0.058, P = 0.238; composite language R = 0.03, P = 0.399; composite motor R = 0.0195, P = 0.536). This study demonstrates that severity of cranial deformity cannot be used to predict presence or degree of developmental delay. Craniofacial surgeons should be aware of this risk and consider developmental screening based on clinical suspicion.

For What It's Worth: Medical School Reputation in The Integrated Plastic Surgery Match.

Integrated Plastic and Reconstructive Surgery residency programs may use medical school reputation to help fill the gap of a pass/fail USMLE Step 1 in the match. The main objective of this manuscript was to consider if this shifting emphasis is warranted. Herein, a cross-sectional analysis of academic plastic surgeons found that medical school reputation did not predict career achievement. In the absence of evidence demonstrating its worth, residency programs should exercise caution in using medical school reputation in the match.

Correlative vs. Causative Relationship between Neonatal Cranial Head Shape Anomalies and Early Developmental Delays.

Deformational plagiocephaly and craniosynostosis are two of the most common neonatal cranial head shape anomalies. Traditionally, both entities were thought to cause aesthetic concerns solely. Recently, many groups have demonstrated that both conditions are strongly associated with developmental delays. The relationship between the abnormal neonatal cranial shape and early developmental delays manifested in both conditions remains poorly understood.

Angiolymphoid Hyperplasia With Eosinophilia Within a Vascular Malformation: Case Report and Review of the Literature.

OBJECTIVES: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare, benign microvascular proliferation tumor. The etiology of ALHE is unknown, though some hypothesize it occurs in reaction to focal trauma. This study presents a case of AHLE within a vascular malformation, its treatment, and a review of the literature. METHODS: A retrospective case report was performed with a 4-year follow-up. Medical records including clinic notes, radiography, operative reports, pathology, and long-term follow-up were reviewed. RESULTS: Radiologic imaging revealed a vascular malformation with highly tortuous, corkscrew-shaped arterial vessels. Histology revealed midsized vessels with plump, epithelialized endothelium and focal areas of lymphocytic infiltrate punctuated with eosinophils, consistent with ALHE. CONCLUSION: This case demonstrates a unique presentation of ALHE in association with vascular malformation. Initial physical exam lacked the classic dermatologic presentation of clusters of red-to-brown nodules; however, the corkscrew vessels lined by epithelized endothelial cells and eosinophilic infiltrate were pathognomonic for ALHE.