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Free functional muscle transfer is a reconstructive strategy for the reconstruction of lost muscle units in the lower extremity after oncologic resection, trauma, compartment syndrome, or severe nerve injuries. Under appropriate circumstances, free functional muscle transfer may be the only suitable reconstructive option. This article reviews the underlying principles of free functional muscle transfer, its application to lower extremity reconstruction, appropriate patient selection, and surgical techniques. The underlying principles of free functional muscle transfer, its application to lower extremity reconstruction, appropriate patient selection, and surgical techniques are presented. Commonly used donor muscles appropriate for each type of functional defect are discussed. A review of recent publications on free functional muscle transfer in the lower extremity was also performed. Good functional recovery with a Medical Research Council grade of up to 4/5 and full range of motion can be attained with free functional muscle transfer. Clinical outcomes and specific parameters for published case series in lower extremity free functional muscle transfer are presented and an illustrative case. Free functional muscle transfer is a suitable treatment for the appropriate patient to restore essential functions and potentially regain ambulation. However, additional published clinical outcomes are needed and represent a major area for further investigation. [ABSTRACT FROM AUTHOR]

Summary Complex pelvic reconstruction is challenging for plastic and reconstructive surgeons following surgical resection of the lower gastrointestinal or genitourinary tract. Complication rates and hospital costs are variable and may be linked to the hospital case volume of pelvic reconstructions performed. A comprehensive examination of these factors has yet to be performed. Data were retrieved for patients undergoing pedicled flap reconstruction after pelvic resections in the American National Inpatient Sample database between 2010 and 2014. Patients were then separated into three groups based on hospital case volume for pelvic reconstruction. Multivariate logistic regression and gamma regression with log-link function were used to analyze associations between hospital case volume, surgical outcomes, and cost. In total, 2,942 patients underwent pelvic flap reconstruction with surgical complications occurring in 1,466 patients (49.8%). Total median cost was $38,469.40. Pelvic reconstructions performed at high-volume hospitals were significantly associated with fewer surgical complications (low: 51.4%, medium: 52.8%, high: 34.8%; p < 0.001) and increased costs (low: $35,645.14, medium: $38,714.92, high: $44,967.29; p < 0.001). After regression adjustment, high hospital volume was the strongest independently associated factor for decreased surgical complications (Exp[β], 0.454; 95% Confidence Interval, 0.346–0.596; p < 0.001) and increased hospital cost (Exp[β], 1.351; 95% Confidence Interval, 1.285–1.421; p < 0.001). Patients undergoing pelvic flap reconstruction after oncologic resections experience high complication rates. High case volume hospitals were independently associated with significantly fewer surgical complications but increased hospital costs. Reconstructive surgeons may approach these challenging patients with greater awareness of these associations to improve outcomes and address cost drivers. [ABSTRACT FROM AUTHOR]

Nanotechnology, in conjunction with convection-enhanced delivery (CED), has gained traction as a promising method to treat many debilitating neurological diseases, including gliomas. One of the key parameters to evaluate the effectiveness of delivery is the volume of distribution (V d ) of nanoparticles within the brain parenchyma. Measurements of V d are commonly made using fluorescent reporter systems. However, reported analyses lack accurate and robust methods for determining V d . Current methods face the problems of varying background intensities between images, high intensity aggregates that can shift intensity distributions, and faint residual backgrounds that can occur as artifacts of fluorescent imaging. These problems can cause inaccurate results to be reported when a percentage of the maximum intensity is set as the threshold value. Here we show an implementation of Otsu’s method more reliably selects accurate threshold values than the fixed-threshold method. We also introduce a goodness of fit value η that quantifies the appropriateness of using Otsu’s method to calculate V d . Adoption of Otsu’s method and reporting of η may help standardize fluorescent image analysis of nanoparticles administered by convection-enhanced delivery. [ABSTRACT FROM AUTHOR]

Summary While the multiple endocrine neoplasia type 1 ( MEN1 ) gene functions as a tumor suppressor in a variety of cancer types, we explored its oncogenic role in breast tumorigenesis. The MEN1 gene product menin is involved in H3K4 trimethylation and co-activates transcription. We integrated ChIP-seq and RNA-seq data to identify menin target genes. Our analysis revealed that menin-dependent target gene promoters display looping to distal enhancers that are bound by menin, FOXA1 and GATA3. In this fashion, MEN1 co-regulates a proliferative breast cancer-specific gene expression program in ER + cells. In primary mammary cells, MEN1 exerts an anti-proliferative function by regulating a distinct expression signature. Our findings clarify the cell-type-specific functions of MEN1 and inform the development of menin-directed treatments for breast cancer. [ABSTRACT FROM AUTHOR]

Summary Although poly(ADP-ribose) polymerase (PARP) inhibitors are active in homologous recombination (HR)-deficient cancers, their utility is limited by acquired resistance after restoration of HR. Here, we report that dinaciclib, an inhibitor of cyclin-dependent kinases (CDKs) 1, 2, 5, and 9, additionally has potent activity against CDK12, a transcriptional regulator of HR. In BRCA- mutated triple-negative breast cancer (TNBC) cells and patient-derived xenografts (PDXs), dinaciclib ablates restored HR and reverses PARP inhibitor resistance. Additionally, we show that de novo resistance to PARP inhibition in BRCA1 -mutated cell lines and a PDX derived from a PARP-inhibitor-naive BRCA1 carrier is mediated by residual HR and is reversed by CDK12 inhibition. Finally, dinaciclib augments the degree of response in a PARP-inhibitor-sensitive model, converting tumor growth inhibition to durable regression. These results highlight the significance of HR disruption as a therapeutic strategy and support the broad use of combined CDK12 and PARP inhibition in TNBC. [ABSTRACT FROM AUTHOR]

Objectives 1. To report our experience in children with sudden-onset sensorineural hearing loss (SSNHL). 2. To describe the etiology and management of children with SSNHL. Methods Retrospective review of 20 children with SSNHL, from 2000 to 2013 at a tertiary pediatric facility. Patients had the following inclusion criteria: history of normal hearing, hearing loss occurring in less than 3 days, and audiogram documentation. Results The average age of patients presenting with SSNHL is 11 years 3 months (22months-18years). Only 6 (30%) children presented prior to 2 weeks. Tinnitus (55%) was the most common associated symptoms followed by otalgia (25%), and vertigo (20%). Eight patients had bilateral hearing loss, 6 only right and 6 only left. Hearing loss severity ranged from profound (45%) being most common to mild. Etiology was unknown (30%), viral (25%), anatomic abnormality (25%), Meniere's disease (5%), autoimmune (5%), perilymphatic fistula (5%), and suppurative labyrinthitis (5%). Eight patients had initial treatment with oral steroids of which 50% had improvement on audiograms. Two patients underwent intratympanic injections, both showed improvement. Of the 12 patients with no treatment, only 1 had improved hearing. Conclusions The true incidence of pediatric SSNHL is not well established in our literature. Unique aspects of pediatric SSNHL are delayed presentation and higher percent of anatomic findings. In our study 70% presented more than 2 weeks after experiencing symptoms. Anatomic abnormalities are in 40% of patients. Hearing improvement occurred in 50% of children treated with oral steroids. Intratympanic steroid treatment is another option but may have practical limitation in the pediatric population. [ABSTRACT FROM AUTHOR]

Abstract: Background: Neck trauma in the pediatric population is relatively rare with limited discussion in the literature describing the injury patterns and outcomes of all neck trauma victims. This study characterizes pediatric neck trauma both inside and outside the context of injuries requiring otolaryngology (ENT) intervention. Methods: Patients sustaining neck trauma presenting to a single tertiary care hospital between January 2001 and June 2010 were included. Demographic information was obtained in addition to information regarding the initial hospital stay and follow up visits related to the initial trauma. Results: Seventy-four patients were included. Blunt injuries were found in 44 children with 30 sustaining penetrating injuries. Twenty-eight percent of patients had an ENT consultation. Those patients with injuries warranting ENT consultation were nearly 3 times more likely to require intubation than those without an ENT consultation (p =0.009). Laryngotracheal injuries were documented in 11 patients with 6 of these characterized as major injuries and 5 minor injuries. Conclusion: Pediatric neck trauma represents a spectrum of injuries from ecchymosis to major laryngotracheal injury. Otolaryngology involvement is not necessary in all cases; however, one must be aware of the risk of laryngotracheal injury, particularly with blunt trauma and there should be a low threshold for Otolaryngology consultation and endoscopy. [Copyright &y& Elsevier]

Abstract: The organization of developing auditory circuits depends on the elimination of aberrant connections and strengthening of appropriate ones. Endocannabinoid mediated plasticity is a proposed mechanism for this refinement. Here we investigated for the anatomical presence of cannabinoid receptors (CB1R) in the lateral superior olive (LSO) and medial nucleus of the trapezoid body (MNTB) of developing rats. We found that CB1R is present within the LSO and that it colocalized with vesicular glutamate transporter (VGLUT3), a presynaptic marker for MTNB terminals. Both before (P5) and around hearing onset (P12), the expression levels of CB1R were higher in the lateral limb of the LSO than in the medial limb. These results suggest that endocannabinoid signaling can modulate the strength of the developing MNTB-LSO synapse. [Copyright &y& Elsevier]

Abstract: The purpose is to describe the presentation and management of a tracheo-innominate artery fistula in a tracheostomy-dependent child. The study design is case report and the method is retrospective chart review. 7-Year-old female with a history of anoxia at birth, seizure disorder, tracheostomy and ventilator dependency since infancy presented to community hospital after one episode of spontaneous bleeding around and through the tracheostomy tube. The patient was transported to a tertiary pediatric teaching hospital and had more profuse bleeding upon arrival. She was taken emergently to the Operating Room (OR) where the cuff of a 5.0 endotracheal tube (ETT) placed through the existing stoma was used to tamponade the bleeding. The airway was secured proximally with a rigid bronchoscope which also provided photodocumentation during the procedure. The cardiothoracic surgery service performed ligation of the innominate artery and repair of the anterior tracheal wall defect through a midline sternotomy approach. The patient was monitored for 7 days in the ICU sedated and paralyzed and returned the OR for a new airway endoscopy and replacement of the ETT with a 5.0 tracheostomy tube. The patient was discharged after 12 days of hospitalization. Subsequent interval endoscopies revealed well-healed fistulous site and no further complications after 12 months of follow-up. Tracheo-innominate artery fistulae can be successfully managed if recognized and treated early. Special attention should be given to “sentinel events” that often precede more catastrophic bleeds. [Copyright &y& Elsevier]

Objectives: 1) Demonstrate the surgical anatomy of a fourth branchial cleft sinus relative to the superior and recurrent laryngeal nerves. 2) Review the diagnosis and management of a fourth branchial cleft sinus. Design: Case Study. Setting: Tertiary Children's Hospital. Patient: Three year old female who presented with a fever and painful right neck mass. CT scan demonstrated a right neck abscess containing air adjacent to the thyroid. Intervention: Two months after initial drainage, the patient underwent enbloc excision of the sinus including the thyroid lobe with closure of the piriform sinus defect. Main Outcome Measure: Intraoperative photo documentation of the anatomic relationship between the fourth branchial sinus and surrounding neural structures. Results: The sinus tract was shown to terminate in the piriform sinus inferior to the superior laryngeal nerve. [ABSTRACT FROM AUTHOR]

This study was done to define the mechanical and histological properties of tissue-engineered cartilage (TEC) derived from human chondrocytes and to compare these findings with those of native cartilage. Chondrocytes were obtained from 10 human auricular cartilages and seeded onto a biodegradable template of polyglycolic acid and poly l-lactic acid. Each template was shaped into a 1 cm×2 cm rectangle. The templates were implanted in athymic mice for 8 weeks. Eight human auricular cartilages were used for comparison. Mechanical analysis with a tensile testing device provided values of ultimate tensile strength (UTS), stiffness, and resilience. Statistical analysis was performed with the Student''s t-test. Histological assessment was done with hematoxylin-eosin staining along with other special stains. The TEC had UTS of 2.07 MPa, stiffness of 3.7 MPa, and resilience of 0.37 J/m3. The control specimens had UTS of 2.18 MPa, stiffness of 5.11 MPa, and resilience of 0.42 J/m3. No statistical difference was found between the experimental and control groups for each of the three parameters. Histological analysis showed mature cartilage with characteristic collagen, glycosaminoglycans, and elastin in the TEC. The neo-cartilage showed slightly smaller size and more irregular distribution of chondrocytes and unique fibrous capsule formation with peripheral infiltration of fibrous tissue. This study showed that the mechanical qualities of TEC from human chondrocytes are similar to those of native auricular cartilage. It suggests that the engineered cartilage from human chondrocytes may have sufficient strength and durability for clinical uses. The histological findings revealed some differences with neo-cartilage. [Copyright &y& Elsevier]

• Violent and self-inflicted injuries occur in dissimilar populations and result in distinctive patterns of injury. • Violently inflicted UE GSWs occur in young, black men; self-inflicted gunshot wounds more often occur in older, comorbid, Caucasian men. • Violent injuries exhibit a bimodal distribution at the shoulder/arm level and again at the hand level. • Accidental, self-inflicted GSWs most often occur distally at the hand or wrist. • There is a trend that more distal injuries of the hand and wrist, particularly bony injuries, are more likely to require operative management. Upper Extremity gunshot wounds represent a significant strain on community and hospital resources, and reports of their epidemiology are varied. We hypothesized that demographic and socioeconomic variables would be associated with variable injury patterns and management, and that two distinct populations would be affected by upper extremity ballistic injury based on violent versus accidental, self-inflicted mechanism. Retrospective review of all adult patients sustaining ballistic injury to the upper extremity at a single urban Level I trauma center over 10 years (n = 797). Demographic, injury pattern, treatment, and outcomes data were collected. Comparisons between groups were conducted with unpaired t-tests and chi-square testing where appropriate. Most patients were male (89.1%) and mean age was 30.1 years (18-83). Violence accounted for 89.1% of injuries. Black individuals were disproportionately affected at 87% of patients. Shoulder injuries were most common (34%), and wrist least common (7%). Demographics and injury pattern varied significantly between patients sustaining violent injury and those with self-inflicted mechanisms. Patients sustaining violent injury were most often young, Black men more likely to be injured proximally, whereas patients with self-inflicted injuries were more likely to be older, Caucasian men with more comorbidities injured distally. Cumulatively, 35.3% of patients required operative intervention. Distal injuries were more likely operative. The most commonly injured structure across all levels was bone (53%), and 54.3% of fractures required operation. Median follow-up was 24.5 months. Complication rate was 13.6%. Gunshot wounds of the upper extremity create complex patterns of injury which vary based on level of injury and mechanism. Violent and self-inflicted injuries occur in dissimilar populations and result in distinctive injury patterns. [ABSTRACT FROM AUTHOR]

Objective To review all cases intratemporal and intracranial complications of acute otitis media (AOM) in infants and children from 1998 to 2013. Methods Retrospective chart review of 109 consecutive patients admitted for complications of AOM during a 15-year period at a tertiary-care children's hospital. The main outcomes are: (1) complications of AOM, (2) bacteriology, (3) management strategies. Results In our population, complications included mastoiditis (86.1%), subperiosteal abscess (38%), facial nerve palsy (16.7%), sigmoid sinus thrombosis (8.3%) and epidural abscess (7.4%). Other complications included post-auricular cellulitis, otic hydrocephalus and elevated intracranial pressure, internal jugular thrombosis, cranial nerve VI palsy and Gradenigo's syndrome, labyrinthine fistula, sensorineural hearing loss, and cerebellar infarct. Sixty-one patients (56%) received antibiotics prior to presentation. Cultures revealed Streptococcus pneumoniae in 36 patients (33.3%), other bacteria in 30 patients (27.8%), and “no growth” in 33 patients (30.5%). Nine patients (8.3%) did not undergo culture. Of the patients with S. pneumoniae , 20 cultures (55%) were found to be multidrug-resistant. Eleven patients (10.2%) were treated non-surgically, 31 (31%) were treated with myringotomy and intravenous antibiotics. Forty patients (97.5%) presenting with subperiosteal abscess required mastoid surgery. Thirteen of 18 (72.2%) patients with facial paralysis had full recovery. Eight of 10 (80%) patients with epidural abscess empyema required mastoid surgery and incision and drainage of the abscess. Conclusion Complications of AOM are uncommon, yet continue to have potentially serious consequences. The bacteriology in this population reveals an increasing trend of multi-drug resistant S. pneumoniae as the causative organism. [ABSTRACT FROM AUTHOR]

Summary: Breast cancer is a heterogeneous disease and can be classified based on gene expression profiles that reflect distinct epithelial subtypes. We identify prostate-derived ETS factor (PDEF) as a mediator of mammary luminal epithelial lineage-specific gene expression and as a factor required for tumorigenesis in a subset of breast cancers. PDEF levels strongly correlate with estrogen receptor (ER)-positive luminal breast cancer, and PDEF transcription is inversely regulated by ER and GATA3. Furthermore, PDEF is essential for luminal breast cancer cell survival and is required in models of endocrine resistance. These results offer insights into the function of this ETS factor that are clinically relevant and may be of therapeutic value for patients with breast cancer treated with endocrine therapy. [Copyright &y& Elsevier]

Children with Down syndrome (DS) have a higher incidence of tympanostomy tube insertion (TTI) than children in the general population. As there were no studies investigating factors that are associated with multiple TTIs in children with DS, we sought to determine what factors increase or decrease the likelihood of repeat TTI in children with DS. A retrospective case-control study was performed on consecutive children with DS from 2007 to 2018 with first TTI at a large tertiary children's hospital and follow-up duration at least 27 months since first TTI. 277 patients met the inclusion criteria. Repeat TTI rate was 61.4%. Having an indication of chronic otitis media with effusion (COME) at first TTI was an adjusted risk factor for increased rate of repeat TTI (OR: 2.01, 95%CI: 1.15–3.51, p =.014), while being older at first TTI was an adjusted protective factor for decreased rate of repeat TTI (OR: 0.84, 95%CI: 0.74–0.95, p =.004). Adenotonsillectomy at or before first TTI was not an adjusted protective factor for decreased rate of repeat TTI (OR: 0.915, 95%CI: 0.448–1.872, p =.809) and bilateral intra-operative fluid was not an adjusted risk factor for repeat TTI (OR: 1.97, 95%CI: 0.99–3.90, p =.054). Children with DS were more likely to undergo repeat TTI if they were of younger age and if the indication for surgery was COME. The repeat TTI rate for children with DS was high at 61.4%. Prospective studies are warranted to more precisely investigate factors associated with repeat TTIs in this unique patient population. [ABSTRACT FROM AUTHOR]

Objectives As data continue to emerge demonstrating improved hearing outcomes associated with younger age at time of cochlear implantation, more children aged 12 months or younger are undergoing this procedure. Drilling a well to house the cochlear implant receiver/stimulator (R/S) may carry an increased risk in this group of patients as the calvarium is thin and drilling an adequate well may require exposure of the underlying dura. Our group has employed a technique in this age group which involves securing the R/S in a subperiosteal pocket without creating a bony well. We report our experience with six infants 12 months of age or younger undergoing cochlear implantation with the subperiosteal pocket technique. Methods Cases were identified by searching an IRB approved research registry. Charts were reviewed for demographics, surgical technique, and clinical outcomes. Descriptive statistics were calculated. Results Six patients 12 months of age or younger underwent cochlear implantation over a one year period. Simultaneous bilateral implantation was performed in all cases, for a total of 12 implanted ears. The average age at time of implantation was 9.8 months (SD 2.1 months). There were no postoperative wound complications. No evidence of device migration was noted in any patient as of the most recent follow-up appointment. There was one device hard failure at 32 months. Average length of follow-up was 28.4 months (SD 13.8 months). Conclusions No wound complications or device migrations occurred in 12 cochlear implantations in six children aged 12 months or younger. Advantages of this technique include no risk to the dura in this location, smaller incisions, and shorter surgical time. A potential disadvantage is the increased device profile from the lack of a well. New thinner implant designs may minimize this concern. Further prospective study is justified to confirm our initial experience in this small group. [ABSTRACT FROM AUTHOR]

Recent cochlear implant (CI) electrodes are designed to be atraumatic to inner ear structures. Studies in adults have demonstrated improved hearing preservation rates with the CI532/632 electrode, but none have examined this in children. Our objective is to describe the hearing preservation rate with CI532/632 in pediatric patients and determine factors that influence hearing preservation. We conducted a retrospective cohort study of children undergoing CI over a three-year period. Inclusion criteria were: CI with the 532/632 electrode, presence of pre-operative low frequency hearing defined by pure tone average (PTA) of ≤80 dB at 250 Hz or at the average of 250 and 500 Hz, and post-operative unaided audiometry. Other data collected included demographics, otologic history, imaging, and surgical details. A total of 13 patients and 15 ears were included. Hearing was preserved in 10/15 (66%) ears at an average follow-up of 6 months, similar to that reported in the adult literature. Patients with preserved hearing post-operatively were more likely to have a positive family history of hearing loss. There was a trend towards patients with anatomic inner ear abnormalities being more likely to lose hearing after CI, but this was not statistically significant. Pre-operative thresholds were not predictive of hearing preservation. Patients with preserved hearing had a significantly smaller shift in thresholds after cochlear implantation. Therefore, hearing preserved and non-preserved groups differed more by the magnitude of change in threshold, rather than their preoperative threshold. Other factors such as age, sex, surgeon, and surgery duration were not associated with hearing preservation. This study describes low frequency hearing preservation after pediatric CI532/632 implantation. The hearing preservation rate in our cohort was consistent with that reported in the adult literature. Our data suggest that preoperative thresholds do not solely determine which patients will go on to experience hearing preservation. We believe this will aid surgeons with patient-specific device selection and counseling potential pediatric CI recipients with preserved hearing. • Hearing preservation rate in this pediatric cohort was 66% with CI532/632. • Comparable to reports in adults with perimodiolar and lateral wall implants. • Anatomic inner ear abnormalities may confer higher risk of residual hearing loss. • Pre-operative thresholds are not strongly associated with hearing preservation. [ABSTRACT FROM AUTHOR]