Developmental Considerations for the Use of Naltrexone in Children and Adolescents.

Naltrexone (NTX) is a well-tolerated drug with a wide safety margin and mechanism of action that affords use across a wide variety of indications in adults and children. By antagonizing the opioid reward system, NTX can modulate behaviors that involve compulsivity or impulsivity, such as substance use, obesity, and eating disorders. Evidence regarding the disposition and efficacy of NTX is mainly derived from adult studies of substance use disorders and considerable variability exists. Developmental changes, plausible disease-specific alterations and genetic polymorphisms in NTX disposition, and pharmacodynamic pathways should be taken into consideration when optimizing the use of NTX in the pediatric population. This review highlights the current state of the evidence and gaps in knowledge regarding NTX to facilitate evidence-based pharmacotherapy of mental health conditions, for which few pharmacologic options exist.

Infection rates following perioperative prophylactic antibiotics versus postoperative extended regimen prophylactic antibiotics in surgical management of mandibular fractures.

PURPOSE: To determine whether or not an extended regimen of prophylactic antibiotics following either open or closed reduction of mandibular fractures is beneficial in lowering the rate of infection in postoperative patients. PATIENTS AND METHODS: This study is a retrospective chart review of 150 patients treated operatively for both complicated and uncomplicated mandibular fractures at University of New Mexico Health Sciences Center in Albuquerque, NM, between January 1, 2000 and June 12, 2007. Treatment modalities used were closed reduction with maxillomandibular fixation or open reduction and internal fixation with either wire osteosynthesis or rigid internal fixation. Patients fell into 1 of 2 groups: the first group received antibiotics perioperatively, which consisted of no more than 24 hours of antibiotics in the postoperative period; the second group received extended regimen antibiotics, which consisted of anywhere from 24 hours to 10 days of antibiotics in the postoperative period. Seventy-five patients were included in each group. The type of antibiotic prescribed was at the discretion of the operating surgeon. This study was conducted using an intention-to-treat analysis. Postoperative infection was diagnosed either subjectively or objectively by the clinician evaluating the patient at follow-up appointments. RESULTS: In the extended antibiotic group, 8 out of 75 subjects (10.67%) developed infection. In the perioperative antibiotic group, 10 out of 75 subjects (13.33%) developed infection. Statistical analysis using chi(2) distribution showed that this difference in proportions was not significant (chi(2) = 0.06, P = 0.8). CONCLUSION: This study found that the use of postoperative prophylactic antibiotics does not have a statistically significant effect on postoperative infection rates in surgical management of complicated or uncomplicated mandibular fractures.

Biomechanical optimization of bone plates used in rigid fixation of mandibular fractures.

PURPOSE: To design and optimize a bone plate for fractures of the mandibular body that will provide maximum fracture stability with minimal implanted volume and patient intrusion. The design will be driven by the unique biomechanics specific to this fracture location. MATERIALS AND METHODS: A finite element model of a fractured human mandible was created using tomography scans. Material properties were assigned to the cortical bone, cancellous bone, and dental region. Boundary conditions included simulating a unilateral molar clench and incisal loading. The bone plate design process included a shape optimization routine and design parameter analysis using the model. The optimized bone plate design was finally compared with standard bone plate configurations based on stress and strain measures. RESULTS: For incisal loading, the newly designed InterFlex II plate has 69% of the fracture strain and only 34% of the plate stress of an 8-hole strut plate. For unilateral molar loading, those numbers improve even further to 59% and 27%, respectively. InterFlex II plate stresses are less than or equal to the paired plate configuration, and fracture strain is within 10% of the corresponding paired plate strain under both loading scenarios. In terms of mechanical performance, InterFlex II is in the same class as the commonly used paired plate configuration, despite having only 55% of the implanted volume. CONCLUSION: A design process focused on shape and design variable optimization can produce bone plates that provide maximum fracture stability with minimum implanted volume.

Mechanical design optimization of bioabsorbable fixation devices for bone fractures.

Bioabsorbable bone plates can eliminate the necessity for a permanent implant when used to fixate fractures of the human mandible. They are currently not in widespread use because of the low strength of the materials and the requisite large volume of the resulting bone plate. The aim of the current study was to discover a minimally invasive bioabsorbable bone plate design that can provide the same mechanical stability as a standard titanium bone plate. A finite element model of a mandible with a fracture in the body region is subjected to bite loads that are common to patients postsurgery. The model is used first to determine benchmark stress and strain values for a titanium plate. These values are then set as the limits within which the bioabsorbable bone plate must comply. The model is then modified to consider a bone plate made of the polymer poly-L/DL-lactide 70/30. An optimization routine is run to determine the smallest volume of bioabsorbable bone plate that can perform and a titanium bone plate when fixating fractures of this considered type. Two design parameters are varied for the bone plate design during the optimization analysis. The analysis determined that a strut style poly-L-lactide-co-DL-lactide plate of 690 mm2 can provide as much mechanical stability as a similar titanium design structure of 172 mm2. The model has determined a bioabsorbable bone plate design that is as strong as a titanium plate when fixating fractures of the load-bearing mandible. This is an intriguing outcome, considering that the polymer material has only 6% of the stiffness of titanium.

Perturbed myoepithelial cell differentiation in BRCA mutation carriers and in ductal carcinoma in situ.

Myoepithelial cells play key roles in normal mammary gland development and in limiting pre-invasive to invasive breast tumor progression, yet their differentiation and perturbation in ductal carcinoma in situ (DCIS) are poorly understood. Here, we investigated myoepithelial cells in normal breast tissues of BRCA1 and BRCA2 germline mutation carriers and in non-carrier controls, and in sporadic DCIS. We found that in the normal breast of non-carriers, myoepithelial cells frequently co-express the p63 and TCF7 transcription factors and that p63 and TCF7 show overlapping chromatin peaks associated with differentiated myoepithelium-specific genes. In contrast, in normal breast tissues of BRCA1 mutation carriers the frequency of p63+TCF7+ myoepithelial cells is significantly decreased and p63 and TCF7 chromatin peaks do not overlap. These myoepithelial perturbations in normal breast tissues of BRCA1 germline mutation carriers may play a role in their higher risk of breast cancer. The fraction of p63+TCF7+ myoepithelial cells is also significantly decreased in DCIS, which may be associated with invasive progression.

Immune Escape in Breast Cancer During In Situ to Invasive Carcinoma Transition.

To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma in situ (DCIS), and invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Gene expression profiling of CD45+CD3+ T cells demonstrated a decrease in CD8+ signatures in IDCs. Immunofluorescence analysis showed fewer activated GZMB+CD8+ T cells in IDC than in DCIS, including in matched DCIS and recurrent IDC. T-cell receptor clonotype diversity was significantly higher in DCIS than in IDCs. Immune checkpoint protein TIGIT-expressing T cells were more frequent in DCIS, whereas high PD-L1 expression and amplification of CD274 (encoding PD-L1) was only detected in triple-negative IDCs. Coamplification of a 17q12 chemokine cluster with ERBB2 subdivided HER2+ breast tumors into immunologically and clinically distinct subtypes. Our results show coevolution of cancer cells and the immune microenvironment during tumor progression.Significance: The design of effective cancer immunotherapies requires the understanding of mechanisms underlying immune escape during tumor progression. Here we demonstrate a switch to a less active tumor immune environment during the in situ to invasive breast carcinoma transition, and identify immune regulators and genomic alterations that shape tumor evolution. Cancer Discov; 7(10); 1098-115. ©2017 AACR.See related commentary by Speiser and Verdeil, p. 1062This article is highlighted in the In This Issue feature, p. 1047.

Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin.

OBJECTIVE: To evaluate the role of skin care products that contain a copper tripeptide complex, glycyl-l-histidyl-l-lysine-Cu(2+) (GHK-Cu), in treating carbon dioxide (CO(2)) laser-resurfaced skin. METHODS: Patients meeting the inclusion criteria underwent circumoral skin resurfacing using a CO(2) laser at standard settings. Patients were then randomized to receive posttreatment skin regimens with or without GHK-Cu. Evaluations for erythema throughout the posttreatment period were performed using computer software and blinded evaluators. In addition, overall improvement in wrinkles and overall improvement in skin appearance 12 weeks after treatment were assessed. Patients completed a validated questionnaire before and 12 weeks after treatment. RESULTS: Thirteen patients completed the study. Computer analysis and blinded evaluators found no statistically significant differences between groups for earlier resolution of erythema. All the patients experienced significant improvement in wrinkles and overall skin quality, but no differences were found between groups. The results of the questionnaire indicated a significant difference in the posttreatment improvement of overall skin quality for patients using GHK-Cu (P = .04). CONCLUSIONS: Copper tripeptide complex (GHK-Cu) skin care products placed on CO(2) laser-resurfaced skin offered no significant reduction or resolution of posttreatment erythema. Objective evaluation found no significant improvement in wrinkles or overall skin quality. However, patient satisfaction was significantly higher for those who used GHK-Cu skin care products after CO(2) laser skin resurfacing.

Dog bites of the scalp, face, and neck in children.

OBJECTIVE: To update the surgical management of injuries from dog bites of the scalp, face, and neck in children. STUDY DESIGN: Retrospective case review. METHODS: A retrospective review of 44 children with dog bites of the scalp, face, and neck was carried out at the University of New Mexico Health Sciences Center (Albuquerque, NM) between January 1, 1995, and December 31, 2000. Data on demographics, hospitalization, surgery, and outcome were collected and entered into an Access 2000 database. RESULTS: The children ranged in age from 1.0 to 12.1 years. The mean age of the study population was 5.2 years (+/-2.9 y standard deviation). Sixteen severely injured children (36%) were hospitalized to repair damage to the airway and blood vessels of the neck or to treat hemodynamic compromise. The length of stay in hospital ranged from 1 to 16 days. The most common injury in these children was a scalp laceration (57%). Twenty-six less severely injured children (64%) were not hospitalized. The most common surgery in these children (88%) was repair of multiple facial lacerations. Attention deficit hyperactivity disorder was noted in the medical records of 12 children (29%). Complications occurred in five children (31%) who were hospitalized and nine children (35%) who were not hospitalized. CONCLUSIONS: The injured child is typically a 5-year-old boy attacked by a familiar dog at home or in the local neighborhood. Children with the diagnosis of attention deficit hyperactivity disorder appear to be at a higher risk of dog bite injuries and should be monitored during interactions with dogs. The goal of surgical management for severely injured children is to avoid immediate mortality and to establish a schedule of multiple-staged procedures for revision surgeries. An optimal cosmetic result is the principal goal for less severely injured children.

Bilateral orbital complications of pediatric rhinosinusitis.

Orbital complications of pediatric rhinosinusitis are usually unilateral at presentation. We describe 3 children with bilateral orbital cellulitis that occurred as a complication of rhinosinusitis. The children ranged in age from 11 to 14 years, had prolonged hospital stays that ranged from 10 to 19 days, and underwent multiple surgical procedures to drain subperiosteal and intraorbital abscesses. They appeared to have direct spread of disease from the ethmoid sinuses to both orbits, without intracranial spread of infection. Therefore, the presence of bilateral orbital complications of rhinosinusitis does not necessarily imply spread of disease to the cavernous sinus. Children who present with bilateral orbital complications of rhinosinusitis should be treated aggressively from the outset, since they suffer from a more widespread form of the disease.

Salvage of partial facial soft tissue avulsions with medicinal leeches.

BACKGROUND: Medicinal leeches have been demonstrated to be extremely useful and safe in the salvage of venous outflow compromised tissue, particularly in digit replants and various forms of flaps. OBJECTIVE: To demonstrate the utility of medicinal leeches in the salvage of venous outflow-compromised traumatic soft tissue avulsions in key facial structures. METHODS: A retrospective review of 4 cases involving the external ear, nose, lip, and scalp in which apparent venous outflow compromise was present. Medicinal leeches were applied acutely in each of these 4 cases, salvaging each of the partially avulsed soft tissue segments. RESULTS: Complete or near complete salvage of each soft tissue segment after using medicinal leeches. CONCLUSIONS: Although it is unusual for a partial soft tissue avulsion of the face to require medicinal leech therapy, situations may occur in which there is adequate arterial inflow but inadequate venous outflow. In such cases, medicinal leeches may play a very important role in salvaging the soft tissue segment. This is particularly important in vital structures such as the ear, nose, lip, and eyelid in which acute or secondary reconstruction is complex. EBM RATING: C.

Comparison of plate-screw systems used in mandibular fracture reduction: finite element analysis.

A finite element model of the human dentate mandible has been developed to provide a comparison of fixation systems used currently for fracture reduction. Volume domains for cortical bone, cancellous bone, and teeth were created and meshed in ANSYS 8.0 based on IGES curves created from computerized tomography data. A unilateral molar clench was loaded on the model with a fracture gap simulated along the symphysis. Results based on Von Mises stress in cortical and cancellous bone surrounding the screws, and on fracture surface spatial fixation, show some relative differences between different screw-plate systems, yet all were judged to be appropriate in their reduction potential.

Silicone gel breast implant rupture presenting as a fluctuant back mass after latissimus dorsi breast reconstruction.

The authors describe a patient who presented with acute onset of a lower back fluctuant mass 12 years after breast reconstruction with a latissimus dorsi musculocutaneous flap and silicone gel implant. Aspiration and subsequent surgical exploration revealed this mass to be free-flowing silicone gel within a cavity that was confluent with the breast implant capsule through an axillary tunnel. Excision of the back cavity, explantation with subtotal capsulectomy, and implant replacement resolved the problem. Although distant migration of extracapsular silicone gel from the breast to the axilla, arm, abdomen, and groin has been described, the authors think this represents the first reported case of distant migration of silicone gel to the lower back.