Dermal Regenerative Template as a Cost-Effective Alternative for Complex Scalp Reconstruction.

BACKGROUND: Use of dermal regeneration template (DRT) is well documented in the literature for complex wounds ranging from the scalp, trunk, and lower extremity. METHODS: A retrospective cohort study was performed of the use of dermal regeneration template and skin grafting. A literature review was performed of all studies where DRT was used for scalp reconstruction. RESULTS: Patients in the DRT cohort had an average age of 70, with wounds averaging 108 cm in size. These patients also had a relatively low rate of complications (0.4), a short hospital stay (average 2 days), and a relatively short operating room time (114 minutes). CONCLUSION: This study demonstrates dermal regeneration template to be an effective and reliable option for soft tissue reconstruction with minimal morbidity and complications in patients with extensive medical comorbidities. Emerging applications include radiation exposure and hypercoaguable states.

A breast prosthesis infection update: Two-year incidence, risk factors and management at single institution.

BACKGROUND: Infection following augmentation and prosthetic-based breast reconstruction can cause significant physical and psychological distress for patients. It may delay adjuvant therapies and compromise aesthetic outcomes. The aim of this study is to identify modifiable risk factors for infection and identify common bacterial isolates to achieve optimal outcomes for patients. METHODS: A retrospective cohort study was performed for patients undergoing implant-based breast reconstruction over a 2-year period. In each case, we documented demographics, co-morbidities, complications and antibiotic use. We reviewed treatments, infectious species cultured where applicable and all outcomes. RESULTS: A total of 292 patients met the inclusion criteria. Fifty-five patients (19%) developed an infection. Univariate analysis showed a significantly increased infection rate with longer operative times (P = 0.001) and use of tissue expanders (P = 0.001). Multiple logistic regression analysis confirmed drain use and elevated body mass index (BMI) as risk factors (odds ratio [OR] 2.427 and 1.061, respectively). After controlling for BMI, smoking status and radiation, we found an increased odd of infection with allograft use (OR 1.838) and a decreased odd with skin preparation using 2% chlorhexidine gluconate in 70% isopropyl (OR 0.554), though not statistically significant. Forty of 55 patients with infections had cultures, with 62.5% of isolates being Gram-positive species and 30% Gram-negative species. The median time to clinical infection was 25 days. Implant salvage with surgical interventions was achieved in 61.5% of patients. CONCLUSIONS: This study identified judicious use of drains and efficiency in the operating room as modifiable risk factors for infections following implant-based breast reconstruction. Prospective trials to analyse techniques for infection prevention are warranted. Implant salvage following infection is a possible end-point in the appropriate patient.

Diabetic Mastopathy: A Systematic Review of Surgical Management of a Rare Breast Disease.

Diabetic mastopathy is a benign condition of the breast that typically manifests in patients with diabetes mellitus. Lymphocytic mastopathy is the term used to describe this condition in patients without diabetes mellitus. Most patients undergo excisional biopsy, but the use of mastectomy, even in cases of diffuse, bilateral disease, is rarely reported. We present a 32-year-old female patient with type 1 diabetes and bilateral diabetic mastopathy. Because of pain, and concern for limitations in future cancer detection, she underwent bilateral nipple-sparing mastectomies with immediate direct-to-implant reconstruction. A systematic literature review was performed to examine the treatment options for this disease, particularly from a plastic surgery perspective. Sixty articles were reviewed which contained information regarding 313 patients. Of these patients, only 4 underwent mastectomy. This case is the first report of bilateral nipple sparing mastectomy and immediate implant reconstruction for a patient with bilateral, symptomatic diabetic mastopathy.

Symptomatic Nonsyndromic Pancarpal Coalition: Report of a Rare Case and Review of the Literature.

Carpal coalition, the union of 2 or more carpal bones, can be congenital or acquired. Congenital, nonsyndromic carpal coalition usually presents in otherwise healthy individuals. The most common coalition is between the lunate and the triquetrum, followed by the capitate and the hamate. Pancarpal coalition, or coalition of all or most of the bones of the carpus, is an extremely rare finding and usually occurs as part of a syndrome. We present a nonsyndromic case of this rare entity, in a 28-year-old woman of West African descent, with symptoms of left hand and wrist pain. Our literature review revealed only 1 other reported case of isolated, nonsyndromic symptomatic pancarpal coalition.

Executive Function and Adaptive Behavior in Muenke Syndrome.

OBJECTIVE: To investigate executive function and adaptive behavior in individuals with Muenke syndrome using validated instruments with a normative population and unaffected siblings as controls. STUDY DESIGN: Participants in this cross-sectional study included individuals with Muenke syndrome (P250R mutation in FGFR3) and their mutation-negative siblings. Participants completed validated assessments of executive functioning (Behavior Rating Inventory of Executive Function [BRIEF]) and adaptive behavior skills (Adaptive Behavior Assessment System, Second Edition [ABAS-II]). RESULTS: Forty-four with a positive FGFR3 mutation, median age 9 years, range 7 months to 52 years were enrolled. In addition, 10 unaffected siblings served as controls (5 males, 5 females; median age, 13 years; range, 3-18 years). For the General Executive Composite scale of the BRIEF, 32.1% of the cohort had scores greater than +1.5 SD, signifying potential clinical significance. For the General Adaptive Composite of the ABAS-II, 28.2% of affected individuals scored in the 3rd-8th percentile of the normative population, and 56.4% were below the average category (<25th percentile). Multiple regression analysis did not identify craniosynostosis as a predictor of BRIEF (P = .70) or ABAS-II scores (P = .70). In the sibling pair analysis, affected siblings performed significantly poorer on the BRIEF General Executive Composite and the ABAS-II General Adaptive Composite. CONCLUSION: Individuals with Muenke syndrome are at an increased risk for developing adaptive and executive function behavioral changes compared with a normative population and unaffected siblings.

Talocalcaneal coalition in Muenke syndrome: report of a patient, review of the literature in FGFR-related craniosynostoses, and consideration of mechanism.

Muenke syndrome is an autosomal dominant craniosynostosis syndrome resulting from a defining point mutation in the Fibroblast Growth Factor Receptor3 (FGFR3) gene. Muenke syndrome is characterized by coronal craniosynostosis (bilateral more often than unilateral), hearing loss, developmental delay, and carpal and/or tarsal bone coalition. Tarsal coalition is a distinct feature of Muenke syndrome and has been reported since the initial description of the disorder in the 1990s. Although talocalcaneal coalition is the most common tarsal coalition in the general population, it has never previously been reported in a patient with Muenke syndrome. We present a 7-year-old female patient with Muenke syndrome and symptomatic talocalcaneal coalition. She presented at the age of 7 with limping, tenderness and pain in her right foot following a fall and strain of her right foot. She was treated with ibuprofen, shoe inserts, a CAM walker boot, and stretching exercises without much improvement in symptoms. A computed tomography (CT) scan revealed bilateral talocalcaneal coalitions involving the middle facet. She underwent resection of the talocalcaneal coalitions, remaining pain-free post-operatively with an improvement in her range of motion, gait, and mobility. This report expands the phenotype of tarsal coalition in Muenke syndrome to include talocalcaneal coalition. A literature review revealed a high incidence of tarsal coalition in all FGFR related craniosynostosis syndromes when compared to the general population, a difference that is statistically significant. The most common articulation involved in all syndromic craniosynostoses associated with FGFR mutations is the calcaneocuboid articulation.

Impact of genetics on the diagnosis and clinical management of syndromic craniosynostoses.

PURPOSE: More than 60 different mutations have been identified to be causal in syndromic forms of craniosynostosis. The majority of these mutations occur in the fibroblast growth factor receptor 2 gene (FGFR2). The clinical management of syndromic craniosynostosis varies based on the particular causal mutation. Additionally, the diagnosis of a patient with syndromic craniosynostosis is based on the clinical presentation, signs, and symptoms. The understanding of the hallmark features of particular syndromic forms of craniosynostosis leads to efficient diagnosis, management, and long-term prognosis of patients with syndromic craniosynostoses. METHODS: A comprehensive literature review was done with respect to the major forms of syndromic craniosynostosis and additional less common FGFR-related forms of syndromic craniosynostosis. Additionally, information and data gathered from studies performed in our own investigative lab (lab of Dr. Muenke) were further analyzed and reviewed. A literature review was also performed with regard to the genetic workup and diagnosis of patients with craniosynostosis. RESULTS: Patients with Apert syndrome (craniosynostosis syndrome due to mutations in FGFR2) are most severely affected in terms of intellectual disability, developmental delay, central nervous system anomalies, and limb anomalies. All patients with FGFR-related syndromic craniosynostosis have some degree of hearing loss that requires thorough initial evaluations and subsequent follow-up. CONCLUSIONS: Patients with syndromic craniosynostosis require management and treatment of issues involving multiple organ systems which span beyond craniosynostosis. Thus, effective care of these patients requires a multidisciplinary approach.

Phenotype profile of a genetic mouse model for Muenke syndrome.

PURPOSE: The Muenke syndrome mutation (FGFR3 (P250R)), which was discovered 15 years ago, represents the single most common craniosynostosis mutation. Muenke syndrome is characterized by coronal suture synostosis, midface hypoplasia, subtle limb anomalies, and hearing loss. However, the spectrum of clinical presentation continues to expand. To better understand the pathophysiology of the Muenke syndrome, we present collective findings from several recent studies that have characterized a genetically equivalent mouse model for Muenke syndrome (FgfR3 (P244R)) and compare them with human phenotypes. CONCLUSIONS: FgfR3 (P244R) mutant mice show premature fusion of facial sutures, premaxillary and/or zygomatic sutures, but rarely the coronal suture. The mice also lack the typical limb phenotype. On the other hand, the mutant mice display maxillary retrusion in association with a shortening of the anterior cranial base and a premature closure of intersphenoidal and spheno-occipital synchondroses, resembling human midface hypoplasia. In addition, sensorineural hearing loss is detected in all FgfR3 (P244R) mutant mice as in the majority of Muenke syndrome patients. It is caused by a defect in the mechanism of cell fate determination in the organ of Corti. The mice also express phenotypes that have not been previously described in humans, such as reduced cortical bone thickness, hypoplastic trabecular bone, and defective temporomandibular joint structure. Therefore, the FgfR3 (P244R) mouse provides an excellent opportunity to study disease mechanisms of some classical phenotypes of Muenke syndrome and to test novel therapeutic strategies. The mouse model can also be further explored to discover previously unreported yet potentially significant phenotypes of Muenke syndrome.

Palatal and oral manifestations of Muenke syndrome (FGFR3-related craniosynostosis).

Although Muenke syndrome is the most common syndromic form of craniosynostosis, the frequency of oral and palatal anomalies including high-arched palate, cleft lip with or without cleft palate has not been documented in a patient series of Muenke syndrome to date. Further, to our knowledge, cleft lip and palate has not been reported yet in a patient with Muenke syndrome (a previous patient with isolated cleft palate has been reported). This study sought to evaluate the frequency of palatal anomalies in patients with Muenke syndrome through both a retrospective investigation and literature review. A total of 21 patients who met criteria for this study were included in the retrospective review. Fifteen patients (71%) had a structural anomaly of the palate. Cleft lip and palate was present in 1 patient (5%). Other palatal findings included high-arched hard palate in 14 patients (67%). Individuals with Muenke syndrome have the lowest incidence of cleft palate among the most common craniosynostosis syndromes. However, high-arched palate in Muenke syndrome is common and may warrant clinical attention, as these individuals are more susceptible to recurrent chronic otitis media with effusion, dental malocclusion, and hearing loss.

De novo deletion of chromosome 20q13.33 in a patient with tracheo-esophageal fistula, cardiac defects and genitourinary anomalies implicates GTPBP5 as a candidate gene.

BACKGROUND: Tracheo-esophageal fistula (TEF) with/or without esophageal atresia (EA) is a common congenital malformation that is often accompanied by other anomalies. The causes of this condition are thought to be heterogeneous but are overall not well understood. CASE REPORT: We identified a patient with a TEF/EA, as well as cardiac and genitourinary anomalies, who was found to have a 0.7 Mb de novo deletion of chromosome 20q13.33. One gene within the deleted interval, GTPBP5, is of particular interest as a candidate gene. CONCLUSIONS: GTPBP5 bears further study as a cause of TEF/EA accompanied by other malformations.

Noncontact speckle contrast diffuse correlation tomography of blood flow distributions in tissues with arbitrary geometries.

A noncontact electron multiplying charge-coupled-device (EMCCD)-based speckle contrast diffuse correlation tomography (scDCT) technology has been recently developed in our laboratory, allowing for noninvasive three-dimensional measurement of tissue blood flow distributions. One major remaining constraint in the scDCT is the assumption of a semi-infinite tissue volume with a flat surface, which affects the image reconstruction accuracy for tissues with irregular geometries. An advanced photometric stereo technique (PST) was integrated into the scDCT system to obtain the surface geometry in real time for image reconstruction. Computer simulations demonstrated that a priori knowledge of tissue surface geometry is crucial for precisely reconstructing the anomaly with blood flow contrast. Importantly, the innovative integration design with one single-EMCCD camera for both PST and scDCT data collection obviates the need for offline alignment of sources and detectors on the tissue boundary. The in vivo imaging capability of the updated scDCT is demonstrated by imaging dynamic changes in forearm blood flow distribution during a cuff-occlusion procedure. The feasibility and safety in clinical use are evidenced by intraoperative imaging of mastectomy skin flaps and comparison with fluorescence angiography.

Laparoscopic Harvest of the Rectus Abdominis for Perineal Reconstruction.

The rectus abdominis is a workhorse flap for perineal reconstruction, in particular after abdominoperineal resection (APR). Laparoscopic and robotic techniques for abdominoperineal surgery are becoming more common. The open harvest of the rectus abdominis negates the advantages of these minimally invasive approaches. (Sentence relating to advantages of laparoscopic rectus deleted here.) We present our early experience with laparoscopic harvest of the rectus muscle for perineal reconstruction. Three laparoscopic unilateral rectus abdominis muscle harvests were performed for perineal reconstruction following minimally invasive colorectal and urological procedures. The 2 patients who underwent APR also had planned external perineal skin reconstruction with local flaps. (Sentence deleted here to shorten abstract.) All rectus muscle harvests were performed laparoscopically. Two were for perineal reconstruction following laparoscopic APR, and 1 was for anterior vaginal wall reconstruction. This was done with 4 ports positioned on the contralateral abdomen. The average laparoscopic harvest time was 60-90 minutes. The rectus muscle remained viable in all cases. One patient developed partial necrosis of a posterior thigh fasciocutaneous flap after cancer recurrence. There were no pelvic abscesses, or abdominal wall hernias. Laparoscopic harvest of the rectus appears to be a cost-effective, reliable, and reproducible procedure for perineal with minimal donor-site morbidity. Larger clinical studies are needed to further establish the efficacy and advantages of the laparoscopic rectus for perineal reconstruction.

Noncontact 3-D Speckle Contrast Diffuse Correlation Tomography of Tissue Blood Flow Distribution.

Recent advancements in near-infrared diffuse correlation techniques and instrumentation have opened the path for versatile deep tissue microvasculature blood flow imaging systems. Despite this progress there remains a need for a completely noncontact, noninvasive device with high translatability from small/testing (animal) to large/target (human) subjects with trivial application on both. Accordingly, we discuss our newly developed setup which meets this demand, termed noncontact speckle contrast diffuse correlation tomography (nc_scDCT). The nc_scDCT provides fast, continuous, portable, noninvasive, and inexpensive acquisition of 3-D tomographic deep (up to 10 mm) tissue blood flow distributions with straightforward design and customization. The features presented include a finite-element-method implementation for incorporating complex tissue boundaries, fully noncontact hardware for avoiding tissue compression and interactions, rapid data collection with a diffuse speckle contrast method, reflectance-based design promoting experimental translation, extensibility to related techniques, and robust adjustable source and detector patterns and density for high resolution measurement with flexible regions of interest enabling unique application-specific setups. Validation is shown in the detection and characterization of both high and low contrasts in flow relative to the background using tissue phantoms with a pump-connected tube (high) and phantom spheres (low). Furthermore, in vivo validation of extracting spatiotemporal 3-D blood flow distributions and hyperemic response during forearm cuff occlusion is demonstrated. Finally, the success of instrument feasibility in clinical use is examined through the intraoperative imaging of mastectomy skin flap.

A Novel Noncontact Diffuse Correlation Spectroscopy Device for Assessing Blood Flow in Mastectomy Skin Flaps: A Prospective Study in Patients Undergoing Prosthesis-Based Reconstruction.

A new advanced technology, noncontact diffuse correlation spectroscopy, has been recently developed for the measurement of tissue blood flow through analyzing the motions of red blood cells in deep tissues. This technology is portable, inexpensive, and noninvasive, and can measure up to 1.5-cm tissue depth. In this prospective study, the authors aimed to explore the use of this novel device in the prediction of mastectomy skin flap necrosis. The noncontact diffuse correlation spectroscopy device was used to measure mastectomy skin flap flow in patients undergoing mastectomy and immediate implant-based breast reconstruction before and immediately after mastectomy, and after placement of the prosthesis. Patients were tracked for the development of complications, including skin necrosis and the need for further surgery. Nineteen patients were enrolled in the study. Four patients (21 percent) developed skin necrosis, one of which required additional surgery. The difference in relative blood flow levels immediately after mastectomy in patients with or without necrosis was statistically significant, with values of 0.27 ± 0.11 and 0.66 ± 0.22, respectively (p = 0.0005). Relative blood flow measurements immediately after mastectomy show a significant high accuracy in prediction of skin flap necrosis, with an area under the receiver operating characteristic curve of 0.95 (95 percent confidence interval, 0.81 to 1). The noncontact diffuse correlation spectroscopy device is a promising tool that provides objective information regarding mastectomy skin flap viability intraoperatively, allowing surgeons early identification of those compromised and ischemic flaps with the hope of potentially salvaging them. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.

Multiple bromodomain genes are involved in restricting the spread of heterochromatic silencing at the Saccharomyces cerevisiae HMR-tRNA boundary.

The transfer RNA gene downstream from the HMR locus in S. cerevisiae functions as part of a boundary (barrier) element that restricts the spread of heterochromatic gene silencing into the downstream region of chromosome III. A genetic screen for identifying additional genes that, when mutated, allow inappropriate spreading of silencing from HMR through the tRNA gene was performed. YTA7, a gene containing bromodomain and ATPase homologies, was identified multiple times. Previously, others had shown that the bromodomain protein Bdf1p functions to restrict silencing at yeast euchromatin-heterochromatin boundaries; therefore we deleted nonessential bromodomain-containing genes to test their effects on heterochromatin spreading. Deletion of RSC2, coding for a component of the RSC chromatin-remodeling complex, resulted in a significant spread of silencing at HMR. Since the bromodomain of YTA7 lacks a key tyrosine residue shown to be important for acetyllysine binding in other bromodomains, we confirmed that a GST-Yta7p bromodomain fusion was capable of binding to histones in vitro. Epistasis analysis suggests that YTA7 and the HMR-tRNA function independently to restrict the spread of silencing, while RSC2 may function through the tRNA element. Our results suggest that multiple bromodomain proteins are involved in restricting the propagation of heterochromatin at HMR.

Hearing loss in syndromic craniosynostoses: otologic manifestations and clinical findings.

OBJECTIVE: This review addresses hearing loss as it occurs and has been reported in Muenke syndrome as well as six additional FGFR related craniosynostosis syndromes (Apert syndrome, Pfeiffer syndrome, Crouzon syndrome, Beare-Stevenson syndrome, Crouzon syndrome with acanthosis nigricans, and Jackson-Weiss syndrome. DATA SOURCES: Pub-Med, Medline, Cochrane Database, Science Direct, NLM Catalog. REVIEW METHODS: A Medline search was conducted to find all reported cases of the 7 FGFR related syndromic craniosynostosis. Special attention was paid to literature that reported hearing findings and the audiology literature. RESULTS: Hearing loss occurs in variable percentage as a component part of all FGFR related craniosynostosis syndromes. Our literature review revealed the following incidences of hearing loss in FGFR craniosynostoses: 61% in Muenke syndrome, 80% in Apert Syndrome, 92% in Pfeiffer syndrome, 74% in Crouzon syndrome, 68% in Jackson Weiss syndrome, 4% in Beare Stevenson syndrome and 14% in Crouzon syndrome with Acanthosis Nigricans. The majority of the hearing loss is a conductive hearing loss, with the exception of Muenke syndrome where the majority of patients have a sensorineural hearing loss and Crouzon syndrome where almost half of patients have a pure or component of sensorineural hearing loss. CONCLUSION: This manuscript presents a diagnostic and management algorithm for patients with syndromic craniosynostosis. It will aid clinicians in treating these patients and further, the recognition of a possible syndrome in patients with hearing loss who also have syndromic features.

Hearing loss in syndromic craniosynostoses: introduction and consideration of mechanisms.

PURPOSE: There are a number of craniosynostosis syndromes with hearing loss-including Muenke, Apert, Pfeiffer, Crouzon, Beare-Stevenson, Crouzon with acanthosis nigricans, and Jackson-Weiss syndromes-that result from mutations in the fibroblast growth factor receptor (FGFR) genes. Studies of FGFRs and their ligands, fibroblast growth factors (FGFs), have revealed clues to the precise contribution of aberrant FGFR signaling to inner ear morphogenesis and the hearing loss encountered in craniosynostoses. The purpose of this article is to review basic studies of FGFRs with emphasis on their function and expression in the inner ear and surrounding structures. METHOD: A Medline search was performed to find basic science articles regarding FGFR, their ligands, and their expression and relevant mouse models. Additional items searched included clinical descriptions and studies of individuals with FGFR-related craniosynostosis syndromes. RESULTS: The FGF signaling pathway is essential for the morphogensis and proper function of the inner ear and auditory sensory epithelium. CONCLUSION: The variable auditory phenotypes seen in individuals with Muenke syndrome may have a genetic basis, likely due to multiple interacting factors in the genetic environment or modifying factors. Further analysis and studies of mouse models of Muenke syndrome, in particular, may provide clues to the specific effects of the defining mutation in FGFR3 in the inner ear not only at birth but also into adulthood. In particular, investigations into these models may give insight into the variable expression and incomplete penetrance of this phenotype.

Epilepsy in Muenke syndrome: FGFR3-related craniosynostosis.

Epilepsy, a neurologic disorder characterized by the predisposition to recurrent unprovoked seizures, is reported in more than 300 genetic syndromes. Muenke syndrome is an autosomal-dominant craniosynostosis syndrome characterized by unilateral or bilateral coronal craniosynostosis, hearing loss, intellectual disability, and relatively subtle limb findings such as carpal bone fusion and tarsal bone fusion. Muenke syndrome is caused by a single defining point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. Epilepsy rarely occurs in individuals with Muenke syndrome, and little detail is reported on types of epilepsy, patient characteristics, and long-term outcomes. We present seven patients with Muenke syndrome and seizures. A review of 789 published cases of Muenke syndrome, with a focus on epilepsy and intracranial anomalies in Muenke syndrome, revealed epilepsy in six patients, with intracranial anomalies in five. The occurrence of epilepsy in Muenke syndrome within our cohort of 58 patients, of whom seven manifested epilepsy, and the intracranial anomalies and epilepsy reported in the literature, suggest that patients with Muenke syndrome may be at risk for epilepsy and intracranial anomalies. Furthermore, the impact of Muenke syndrome on the central nervous system may be greater than previously thought.