Mouse genome-wide association study identifies polymorphisms on chromosomes 4, 11, and 15 for age-related cardiac fibrosis.

Dystrophic cardiac calcinosis (DCC), also called epicardial and myocardial fibrosis and mineralization, has been detected in mice of a number of laboratory inbred strains, most commonly C3H/HeJ and DBA/2J. In previous mouse breeding studies between these DCC susceptible and the DCC-resistant strain C57BL/6J, 4 genetic loci harboring genes involved in DCC inheritance were identified and subsequently termed Dyscalc loci 1 through 4. Here, we report susceptibility to cardiac fibrosis, a sub-phenotype of DCC, at 12 and 20 months of age and close to natural death in a survey of 28 inbred mouse strains. Eight strains showed cardiac fibrosis with highest frequency and severity in the moribund mice. Using genotype and phenotype information of the 28 investigated strains, we performed genome-wide association studies (GWAS) and identified the most significant associations on chromosome (Chr) 15 at 72 million base pairs (Mb) (P < 10(-13)) and Chr 4 at 122 Mb (P < 10(-11)) and 134 Mb (P < 10(-7)). At the Chr 15 locus, Col22a1 and Kcnk9 were identified. Both have been reported to be morphologically and functionally important in the heart muscle. The strongest Chr 4 associations were located approximately 6 Mb away from the Dyscalc 2 quantitative trait locus peak within the boundaries of the Extl1 gene and in close proximity to the Trim63 and Cap1 genes. In addition, a single-nucleotide polymorphism association was found on chromosome 11. This study provides evidence for more than the previously reported 4 genetic loci determining cardiac fibrosis and DCC. The study also highlights the power of GWAS in the mouse for dissecting complex genetic traits.

Functional reconstruction of large medial canthal defects.

The aim of this study is to describe a surgical technique for the reconstruction of large medial canthal defects involving the lacrimal apparatus following excision of medial canthal tumors. Many different techniques for constructing a neopassage from the lacrimal sac to the nasal sinuses have been investigated and described in the literature. However, there continues to be difficulty with successful functional reconstruction of the lacrimal outflow tract without the long-term use of an indwelling tube. We herein describe a technique utilizing a paramedian forehead flap combined with AlloDerm (LifeCell Corporation, Township of Branchburg, NJ) as the conduit for reconstruction of the medial canthus and lacrimal outflow tract. We present a case series of three patients successfully reconstructed with the above technique and describe their presentation, treatment, and postoperative course. We provide a detailed description of the surgical technique and document the success of the technique in regard to patency and postprocedure function of the lacrimal conduit.

Reconstruction of Full-Thickness Scalp Defects Using a Dermal Regeneration Template.

IMPORTANCE: Large full-thickness scalp defects pose a reconstructive problem and commonly require microvascular free flap reconstruction. OBJECTIVE: To describe a novel and effective reconstructive technique for full-thickness scalp defects that can be performed quickly without general anesthesia or free flap reconstruction. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of 10 patients at a single medical center who underwent surgical resection of a cutaneous lesion. Reconstruction of the large scalp defects included application of Integra bilayer wound matrix followed by delayed split-thickness skin grafting from January 1, 2008, to December 31, 2014. Patients ranged in age from 50 to 87 (mean, 71.5) years; 8 (80%) were men. Mean duration of follow-up was 481.1 days (range, 41-1199 days). MAIN OUTCOMES AND MEASURES: Skin graft viability and adherence to underlying tissue (take) and postoperative complications. RESULTS: The 10 patients in this study had excellent skin graft and wound closure outcomes. Nine patients showed a 100% initial take of the skin graft to the defect site. Only 1 patient showed a 95% to 100% initial take. Adequate coverage of the wound bed was achieved with acceptable cosmetic results. Two patients underwent postoperative intensity-modulated radiotherapy. One of these patients experienced radiotherapy-induced wound breakdown 3½ months after completion of therapy, which resolved completely after more than 6 months. CONCLUSIONS AND RELEVANCE: This novel technique for reconstruction of large full-thickness scalp defects has low morbidity and can be performed on an outpatient basis with minimal wound care. The technique provides the surgeon with an alternative to other reconstructive options, including microvascular free tissue transfer, for repair of large full-thickness scalp defects. The procedure has excellent results and can be performed under sedation and local anesthesia, which avoids the risks associated with general anesthesia. LEVEL OF EVIDENCE: 4.

Management of pediatric subglottic cysts using the Bugbee fulgurating electrode.

IMPORTANCE: Subglottic cysts are an important cause of pediatric airway obstruction. We describe the typical presentation and management of subglottic cysts, with historical recurrence rates between 12.5% and 71.0%, and treatment using the Bugbee fulgurating diathermy electrode as a technique to successfully manage subglottic cysts with a low recurrence rate. OBSERVATIONS: A retrospective review was performed on 16 consecutive patients treated for subglottic cysts at a single tertiary-care facility. The mean gestational age was 26.9 weeks, with a male to female ratio of 4.3:1. All patients had at least 1 prior intubation, with a mean of 1.8 prior intubations per patient. Biphasic stridor was the most common presenting symptom, occurring at a mean of 7.3 months after the last extubation. At the time of diagnosis, patients were found to have a mean of 1.6 cysts, and the left lateral subglottic wall was the most common location of unilateral cysts. Nine patients (56%) had an associated laryngeal pathologic condition. Symptomatic cyst recurrence occurred in only 6% of patients, and no major complications were reported. CONCLUSIONS AND RELEVANCE: This review presents a treatment method for subglottic cysts that is safe and effective and has a symptomatic recurrence rate lower than previously reported.