Reconstruction of oral cavity defects using myogenous-only scapular tip free-flaps.

Background: Oral cavity reconstruction is very challenging anatomical subsite to reconstruct. Large defects often require free tissue reconstruction to provide the best chance of form and function. Additionally, free tissue reconstruction aids to prevent fistula formation. We aimed to determine outcomes of oral cavity defect reconstruction using scapular tip free flaps with a myogenous intraoral component. Methods: All patients with a mandibular or maxillary bony defect that included a disruption of the intraoral mucosa component between 07/1/14 and 07/31/17. Patients were reconstructed with a scapular tip free flap, which included a muscular component that was used to recreate the oral mucosa. The primary study outcomes were flap success rates, development of orocutaneous or oronasal fistula, rate of resuming oral diet as well as the occurrence of medical and surgical complications in the first month following surgery. The tested hypothesis was formulated before data collection began. Results: Twenty-five patients were identified by the study criteria. There was one (4%) flap that failed, while orocutaneous fistula occurred in two patients (8%). Prior history of osteoradionecrosis was a statistically significant predictor of overall complication (p < .05). Conclusions: Intraoral myogenous reconstruction allows for re-mucosalization of the oral cavity defect and is associated with high viability and low-complication rates. In patients with amenable oral mucosal defects, a myogenous scapular tip free flap is a suitable reconstructive option.

Sinus Development and Pneumatization in a Primary Ciliary Dyskinesia Cohort.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a genetically diverse disease which causes impaired mucociliary clearance, and results in pulmonary, otologic, and rhinologic disease in affected patients. Genetic mutations in multiple genes impair the ability of patients to clear mucous from the lungs, middle ear, and sinonasal cavity and lead to chronic pulmonary and sinonasal symptoms. METHODS: We identified 17 PCD patients who had available CT scans. Volumes for bilateral maxillary, sphenoid, and frontal sinuses were calculated. A control population of patients who had preoperative CT scans for endoscopic endonasal resection of skull base pathology without sinonasal cavity involvement was also identified. RESULTS: The mean age of PCD was 33 and ranged from 13 to 54 years. Patients were age- and gender-matched to a control group that underwent resection of anterior skull-base tumors and had a mean age of 35 that ranged between 17-53 years old. The volumes for all thee sinus cavities were significantly smaller (p < 0.007) compared to the control population. The average Lund-Mackay score was 10.6 in the PCD cohort (range 6-16) in comparison to an average of 0.7 in the control cohort (range 0-2). CONCLUSIONS: Overall sinus volumes were smaller in patients with PCD compared to our control population. Future studies will be aimed at understanding defects in sinus development as a function of specific genetic mutations in PCD patients. Ultimately, a better understanding of the underlying pathophysiology of PCD will allow us to identify the optimal treatment practices for this unique patient group.

Radiologic Analysis of Balloon Sinuplasty in a Human Cadaver Model: Observed Effects on Sinonasal Anatomy.

BACKGROUND: Balloon sinuplasty is increasingly used in the outpatient clinic for treatment of chronic rhinosinusitis, but radiologic analysis of its effects on sinonasal anatomy is largely uncharacterized in the known literature. OBJECTIVE: The purpose of this study is to examine the anatomic effects of balloon sinuplasty in a cadaveric model. METHODS: Five fresh cadaver heads underwent sequential endoscopic balloon dilation of maxillary ostia, frontal recess outflow tracts, and sphenoid ostia bilaterally by fellowship-trained rhinologists. Pre- and post-procedural CT imaging was obtained. CT scans were imported into Mimics™ software and sinonasal anatomy was analyzed systematically. RESULTS: Visual confirmation of balloon dilation was achieved in all 3 sites bilaterally in each cadaver. Radiologic analysis demonstrated that the frontal sinus outflow tract was appropriately dilated 60% (6/10 sites) of the time while the agger was inadvertently dilated 30% of the time (3/10). The sphenoid os was successfully dilated 70% (7/10 sites) of the time. In two cases, a posterior sphenoethmoid (Onodi) cell was dilated instead of the sphenoid. Successful dilation of maxillary os was noted 60% of the time (6/10 sites). No significant change in maxillary os was noted after balloon dilation. Normal middle turbinates were significantly medialized following balloon dilation 75% (6/8 sites) of the time. CONCLUSIONS: While the goal of balloon sinuplasty is to improve natural sinonasal drainage by dilating existing outflow tracts, as evidenced by radiologic evaluation the procedure appears not to achieve this in all cases, while occasionally creating unintended changes in sinonasal anatomy as well. These unrecognized changes in anatomy may be responsible for the post-procedure change in symptomatology that some patients experience.

Hair cell and neural contributions to the cochlear summating potential.

The cochlear summating potential (SP) to a tone is a baseline shift that persists for the duration of the burst. It is often considered the most enigmatic of cochlear potentials because its magnitude and polarity vary across frequency and level and its origins are uncertain. In this study, we used pharmacology to isolate sources of the SP originating from the gerbil cochlea. Animals either had the full complement of outer and inner hair cells (OHCs and IHCs) and an intact auditory nerve or had systemic treatment with furosemide and kanamycin (FK) to remove the outer hair cells. Responses to tone bursts were recorded from the round window before and after the neurotoxin kainic acid (KA) was applied. IHC responses were then isolated from the post-KA responses in FK animals, neural responses were isolated from the subtraction of post-KA from pre-KA responses in NH animals, and OHC responses were isolated by subtraction of post-KA responses in FK animals from post-KA responses in normal hearing (NH) animals. All three sources contributed to the SP; OHCs with a negative polarity and IHCs and the auditory nerve with positive polarity. Thus the recorded SP in NH animals is a sum of contributions from different sources, contributing to the variety of magnitudes and polarities seen across frequency and intensity. When this information was applied to observations of the SP recorded from the round window in human cochlear implant subjects, a strong neural contribution to the SP was confirmed in humans as well as gerbils. NEW & NOTEWORTHY Of the various potentials produced by the cochlea, the summating potential (SP) is typically described as the most enigmatic. Using combinations of ototoxins and neurotoxins, we show contributions to the SP from the auditory nerve and from inner and outer hair cells, which differ in polarity and vary in size across frequency and level. This complexity of sources helps to explain the enigmatic nature of the SP.

How Much Blood Could a JP Suck If a JP Could Suck Blood?

OBJECTIVE: Active surgical drains minimize fluid accumulation in the postoperative period. The Jackson-Pratt (JP) system consists of a silicone drain connected by flexible tubing to a bulb. When air in the bulb is evacuated, negative pressure is applied at the surgical site to aspirate fluid. The objective of this study was to determine if the evacuation method and volume of accumulated fluid affect the pressure generated by the bulb. METHODS: Bulbs were connected to a digital manometer under various experimental conditions. A random number generator determined the initial evacuation method for each bulb, either side-in or bottom-up. Subsequent evacuations were alternated until data was collected in triplicate for each method. Predetermined amounts of water were placed into the bulb; air was evacuated; and pressure was recorded. The digital manometer was allowed to equilibrate for 1 minute prior to data acquisition. RESULTS: The average amount of pressure after a side-in evacuation of a JP bulb was 87.4 cm H2 O compared to 17.7 cm H2 O for a bottom-up evacuation (P < 0.0001). When the drain contained 25 mL, 50 mL, 75 mL, and 100 mL of fluid, the pressure applied dropped to 72.6, 41.3, 37.0, and 35.6 cm H2 O, respectively. CONCLUSIONS: JP drains generate negative pressure in order to reduce fluid accumulation at surgical sites. Although its function is frequently taken for granted, this study demonstrates that both the specific method for evacuating the bulb as well as the amount of fluid in the bulb significantly affect the performance of this device. LEVEL OF EVIDENCE: NA Laryngoscope, 129:1806-1809, 2019.

Predictors of Adverse Outcomes in Free Flap Reconstruction: A Single-Institution Experience.

OBJECTIVE: Understanding the independent predictors of poor outcomes in free flap surgery is essential for patient selection. We aim to determine the independent predictors of major complications, flap survival, and extended hospital stays. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary medical center. SUBJECTS AND METHODS: We reviewed medical records from all vascularized tissue transfers in the head and neck between 2007 and 2014 at our institution. We recorded demographics, medical comorbidities, disease characteristics, flap characteristics, and intraoperative events. We defined outcomes as major complications in the 30-day postoperative period, flap death or partial flap survival, and a length of stay ≥14 days. We used bivariate and multivariate methods to test for associations. RESULTS: Of 170 free flap operations, 44% had major complications; 11% fully or partially failed; and 27% required an extended hospital stay. Independent predictors of major complications were age ≥60 years (odds ratio [OR], 3.7; P = .001), revision surgery (OR, 3.5; P = .004), and a prior neck dissection (OR, 3.5; P = .004). Independent predictors of flap failure were revision surgery (OR, 4.1, P = .01) and the use of a plate (OR, 3.7; P = .03). Revision surgery was independently associated with a longer stay (OR, 3.0; P = .01), and the use of a radial forearm flap was associated with a shorter stay (OR, 0.3, P = .047). CONCLUSION: These results underscore that caution is warranted in revision flap surgery, patients with prior neck operations, and patients aged ≥60 years.

A pilot study comparing mechanical properties of tissue-engineered cartilages and various endogenous cartilages.

BACKGROUND: Mechanical properties of tissue-engineered cartilage and a variety of endogenous cartilage were measured. The main goal was to evaluate if the tissue-engineered cartilage have similar mechanical characteristics to be replaced with rib cartilage in microtia reconstruction. Such study lays the foundation for future human clinical trials for microtia reconstruction. METHOD: Atomic force microscopy and compression testing were used to measure the viscoelasticity of tissue-engineered cartilage (stem cell seeded on Poly lactic co-glycolytic acid nanofibers and Pellet) and endogenous cartilage: conchal bowl, microtic ears, preauricular remnants, and rib. Atomic force microscopy, calculates biomaterial elasticity through force-deformation measurement and Hertz model. Compression testing determines the stress relaxation by measuring slope of stress reduction at 10% strain. FINDING: Tissue-engineered cartilage demonstrated elasticity (4.6kPa for pellet and 6.6kPa for PLGA) and stress relaxation properties (7.6 (SD 1.1) kPa/s for pellet) most similar to those of native conchal bowl cartilage (31.8 (SD 18) kPa for the elasticity and 15.1 (SD 2.1) kPa/s for stress relaxation factor). Rib cartilage was most dissimilar from the mechanical characteristics of conchal cartilage and demonstrated the highest elastic modulus (361 (SD 372) kPa). Moreover, except preauricular cartilage samples, the level of elastic modulus increased with age. INTERPRETATION: The use of tissue-engineered cartilage developed via PLGA and Pellet methods, may be an appropriate substitute for rib cartilage in the reconstruction of microtic ears, however their mechanical characteristics still need to be improved and require further validation in animal studies.

The Compound Action Potential in Subjects Receiving a Cochlear Implant.

HYPOTHESIS: The compound action potential (CAP) is a purely neural component of the cochlea's response to sound, and may provide information regarding the existing neural substrate in cochlear implant (CI) subjects that can help account for variance in speech perception outcomes. BACKGROUND: Measurement of the "total response" (TR), or sum of the magnitudes of spectral components in the ongoing responses to tone bursts across frequencies, has been shown to account for 40 to 50% of variance in speech perception outcomes. The ongoing response is composed of both hair cell and neural components. This correlation may be improved with the addition of the CAP. METHODS: Intraoperative round window electrocochleography (ECochG) was performed in adult and pediatric CI subjects (n = 238). Stimuli were tones of different frequencies (250 Hz-4 kHz) at 90 dB nHL. The CAP was assessed in two ways, as an amplitude and with a scaling factor derived from a function fitted to the response. The results were correlated with consonant-nucleus-consonant (CNC) word scores at 6 months post-implantation (n = 51). RESULTS: Only about half of the subjects had a measurable CAP at any frequency. The CNC word scores correlated weakly with both amplitude (r = 0.20, p < 0.001) and scaling factor (r = 0.25, p < 0.01). In contrast, the TR alone accounted for 43% of the variance, and addition of either CAP measurement in multiple regression did not account for additional variance. CONCLUSIONS: The underlying pathology in CI patients causes the CAP to be often absent and highly variable when present. The TR is a better predictor of speech perception outcomes than the CAP.

Osteoinduction of umbilical cord and palate periosteum-derived mesenchymal stem cells on poly(lactic-co-glycolic) acid nanomicrofibers.

The need for tissue-engineered bone to treat complex craniofacial bone defects secondary to congenital anomalies, trauma, and cancer extirpation is sizeable. Traditional strategies for treatment have focused on autologous bone in younger patients and bone substitutes in older patients. However, the capacity for merging new technologies, including the creation of nanofiber and microfiber scaffolds with advances in natal sources of stem cells, is crucial to improving our treatment options. The advantages of using smaller diameter fibers for scaffolding are 2-fold: the similar fiber diameters mimic the in vivo extracellular matrix construct and smaller fibers also provide a dramatically increased surface area for cell-scaffold interactions. In this study, we compare the capacity for a polymer with Federal Drug Administration approval for use in humans, poly(lactic-co-glycolic) acid (PLGA) from Delta polymer, to support osteoinduction of mesenchymal stem cells (MSCs) harvested from the umbilical cord (UC) and palate periosteum (PP). Proliferation of both UC- and PP-derived MSCs was improved on PLGA scaffolds. The PLGA scaffolds promoted UC MSC differentiation (indicated by earlier gene expression and higher calcium deposition), but not in PP-derived MSCs. Umbilical cord-derived MSCs on the PLGA nanomicrofiber scaffolds have potential clinical utility in providing solutions for craniofacial bone defects, with the added benefit of earlier availability.

Biochemical properties of tissue-engineered cartilage.

OBJECTIVE: Microtia is treated with rib cartilage sculpting and staged procedures; though aesthetically pleasing, these constructs lack native ear flexibility. Tissue-engineered (TE) elastic cartilage may bridge this gap; however, TE cartilage implants lead to hypertrophic changes with calcification and loss of flexibility. Retaining flexibility in TE cartilage must focus on increased elastin, maintained collagen II, decreased collagen X, with prevention of calcification. This study compares biochemical properties of human cartilage to TE cartilage from umbilical cord mesenchymal stem cells (UCMSCs). Our goal is to establish a baseline for clinically useful TE cartilage. METHODS: Discarded cartilage from conchal bowl, microtic ears, preauricular tags, rib, and TE cartilage were evaluated for collagen I, II, X, calcium, glycosaminoglycans, elastin, and fibrillin I and III. Human UCMSCs were chondroinduced on 2D surfaces and 3D D,L-lactide-co-glycolic acid (PLGA) fibers. RESULTS: Cartilage samples demonstrated similar staining for collagens I, II, and X, elastin, and fibrillin I and III, but differed from rib. TE pellets and PLGA-supported cartilage were similar to auricular samples in elastin and fibrillin I staining. TE samples were exclusively stained for fibrillin III. Only microtic samples demonstrated calcium staining. CONCLUSIONS: TE cartilage expressed similar levels of elastin, fibrillin I, and collagens I and X when compared to native cartilage. Microtic cartilage demonstrated elevated calcium, suggesting this abnormal tissue may not be a viable cell source for TE cartilage. TE cartilage appears to recapitulate the embryonic development of fibrillin III, which is not expressed in adult tissue, possibly providing a strategy to control TE elastic cartilage phenotype.

Effects of connective tissue growth factor on the regulation of elastogenesis in human umbilical cord-derived mesenchymal stem cells.

BACKGROUND: A key to clinical microtia reconstruction is construct flexibility. The most significant current limitation to engineered elastic cartilage is maintaining an elastic phenotype, which is principally dependent on elastin production (although other parameters, including maintenance of a ratio above 1 for collagens II to I, minimizing collagen X content, and presence of adequate matrix fibrillin for elastin binding, all play supporting roles). Connective tissue growth factor (CTGF), a compound secreted by chondrocytes, has been shown to promote an elastic phenotype in mature rabbit chondrocytes; however, CTGF effect on undifferentiated mesenchymal stem cells (MSCs) has not been characterized. The principal aim of this study is to analyze CTGF effect on elastin production in umbilical cord (UC)-derived MSCs and to determine optimal timing of treatment to maximize elastin production. METHODS: Human UCMSCs (hUCMSCs) were isolated from Wharton jelly using an explant technique, grown to passage 3, seeded onto nanofiber scaffolds, and chondroinduced for 21 days. Nanofiber scaffolds were electrospun using solubilized poly L-lactide/D-lactide/glycolide (PLGA). Chondrogenic media was supplemented with 25 µg/mL CTGF starting at day 0 or 7. Messenger RNA (mRNA) for Collagen I, II, X, fibrillin, and elastin was quantified by RT-PCR; glycosaminoglycan (GAG) matrix deposition was assessed and normalized by cellular DNA content. Elastin protein was assessed by Western blot analysis. All experiments were performed in triplicate with MSCs from 4 distinct cords. Multiway analysis of variance with Newman-Keuls post test was used to determine statistical significance. RESULTS: Connective tissue growth factor treatment results in increased GAG/DNA ratio; the differentiation index was maintained above 1 in all conditions, with increased collage II noted at days 7 and 14 in CTGF conditions; no difference in collagen X or fibrillin mRNA was noted. Increased elastin mRNA and protein were noted at day 14 in conditions treated with CTGF at day 7 after differentiation. CONCLUSIONS: Connective tissue growth factor leads to maximal elastin increase in UCMSCs after 7 days of chondroinduction and not in undifferentiated MSCs. With appropriately timed treatment, CTGF may be a useful adjunct in maintaining an elastic cartilage phenotype in engineered cartilage from human UCMSCs.

Analysis of human auricular cartilage to guide tissue-engineered nanofiber-based chondrogenesis: implications for microtia reconstruction.

OBJECTIVE: Nanofiber-supported, in vitro-generated cartilage may represent an optimal starting material for the development of a cartilage implant for use in microtia reconstruction. To do so, the authors aim to first characterize the molecular composition of endogenous auricular cartilage and determine if human umbilical cord mesenchymal stem cells (hUCMSCs) can be differentiated into cartilage in vitro. STUDY DESIGN: Prospective, controlled. SETTING: Academic research laboratory. SUBJECTS AND METHODS: Human ear cartilage from normal adults, pediatric patients with microtia, and pediatric patients with preauricular appendages (n = 2) was analyzed for collagens I, II, and X and elastin expression. In parallel, hUCMSCs were cultured on either polycaprolactone (PCL) or D, L-lactide-co-glycolic acid (PLGA) nanofiber scaffolds for 21 days under chondrogenic conditions. Cells were harvested for histologic, biochemical, and quantitative polymerase chain reaction analysis. Control cells were grown under both chondrogenic and nonchondrogenic conditions in the absence of nanofiber scaffolds. RESULTS: Histological analysis of human ear cartilage revealed similar levels and distribution of collagens I and X and elastin. Collagen II was not highly expressed in the microtia samples. hUCMSC cultures stained positively for glycosaminosglycans (GAG) and sulfated proteoglycans. Compared to control cells, hUCMSCs grown on PLGA nanofiber scaffolds had a higher differentiation index (P ≤ .012) and higher levels of collagen X mRNA expression (P ≤ .006). CONCLUSION: These data provide information regarding the composition of endogenous ear cartilage and suggest that hUCMSCs grown on PLGA nanofiber scaffolds may represent an optimal starting material for the development of a cartilage implant for use in microtia reconstruction.