3D Printing for the Development of Palatal Defect Prosthetics.

Background: Three-dimensional (3D) printing has emerged as a promising new technology for the development of surgical prosthetics. Research in orthopedic surgery has demonstrated that using 3D printed customized prosthetics results in more precise implant placements and better patient outcomes. However, there has been little research on implementing customized 3D printed prosthetics in otolaryngology. The program sought to determine whether computed tomography (CT) serves as feasible templates to construct 3D printed palatal obturator prosthetics for defects in patients who have been treated for head and neck cancers. Observations: A retrospective review of patients with palatal defects was conducted and identified 1 patient with high quality CTs compatible with 3D modeling. CTs of the patient's craniofacial anatomy were used to develop a 3D model and a Formlabs 3B+ printer printed the palatal prosthetic. We successfully developed and produced an individualized prosthetic using CTs from a veteran with head and neck deformities caused by cancer treatment who was previously treated at the Veterans Affairs Palo Alto Health Care System. This project was successful in printing patient-specific implants using CT reproductions of the patient's craniofacial anatomy, particularly of the palate. The program was a proof of concept and the implant we created was not used on the patient. Conclusions: Customized 3D printed implants may allow otolaryngologists to enhance the performance and efficiency of surgeries and better rehabilitate and reconstruct craniofacial deformities to restore appearance and function to patients. Additional research will strive to enhance the therapeutic potential of these prosthetics to serve as low-cost, patient-specific implants.

Mood Disorders and Aggressive Traits Mediate Effects of Reported Childhood Adversity on Suicide Attempt Risk.

BACKGROUND: Childhood adversity (CA) is linked to suicidal behavior as well as to mood disorders and aggressive traits. This raises the possibility that depression and aggressive traits mediate the relationship of childhood adversity to suicide risk. Moreover, it is not known if they operate independently or interactively. AIMS: To determine whether, and how, mood disorders and aggressive traits mediate the effects of reported physical and sexual abuse on future suicidal behavior. METHODS: Five hundred and forty-eight subjects, offspring of parents with mood disorders, were interviewed at baseline and at yearly follow-ups with questionnaires assessing aggression, mood disorders, and suicidal behavior. The mediation analysis involved a three-step process, testing the relationships between (1) CA and attempt; (2) CA and putative mediators; and (3) putative mediators and suicide attempt, adjusting for CA. RESULTS: Aggressive trait severity and mood disorder onset each mediated the relationship between CA and future suicide attempts. Greater aggression severity also raised the hazard of the development of a mood disorder. If aggressive trait severity was clearly elevated, then onset of mood disorder did not increase further the hazard of the suicide attempt. Including family as a random effect had a much bigger effect on attempt outcome for physical abuse compared with sexual abuse. CONCLUSIONS: Amelioration of aggressive traits and treatment of mood disorders in CA-exposed offspring of a parent with a mood disorder may prevent future suicide attempts and may reduce the risk of mood disorder. Familial factors influence the impact of childhood physical abuse but not sexual abuse. HIGHLIGHTSChildhood Adversity (CA) predicted future mood disorder and aggression severity.Depression and aggression mediate the relationship between CA and suicide attempts.When one mediator is present, the presence of the other does not increase the hazard.Between family variation contributed much more to suicidal behavior outcomes relative to the effect of physical abuse, but sexual abuse contributed to suicidal outcomes more than family variation.

Enhanced recovery after cleft palate repair: A quality improvement project.

BACKGROUND: Children undergoing cleft palate repair present challenges to postoperative management due to several factors that can complicate recovery. Utilization of multimodal analgesic protocols can improve outcomes in this population. We report experience designing and implementing an enhanced recovery after surgery (ERAS) pathway for cleft palate repair to optimize postoperative recovery. AIMS: The primary aim was to implement an ERAS pathway with >70% bundle adherence to achieve a 30% reduction in postoperative opioid consumption within 12 months. Our secondary aims assessed intraoperative opioid consumption, length of stay, timeliness of oral intake, and respiratory recovery. METHODS: A multidisciplinary team of perioperative providers developed an ERAS pathway for cleft palate patients. Key drivers included patient and provider education, formal pathway creation and implementation, multimodal pain therapy, and target-based care. Interventions included maxillary nerve blockade and enhanced intra- and postoperative medication regimens. Outcomes were displayed as statistical process control charts. RESULTS: Pathway compliance was 77.0%. Patients during the intervention period (n = 39) experienced a 49% reduction in postoperative opioid consumption (p < .0001) relative to our historical cohort (n = 63), with a mean difference of -0.33 ± 0.11 mg/kg (95% CI -0.55 to -0.12 mg/kg). Intraoperative opioid consumption was reduced by 36% (p = .002), with a mean difference of -0.27 ± 0.09 mg/kg (95% CI -0.45 to -0.09 mg/kg). Additionally, patients in the intervention group had a 45% reduction in time to first oral intake (p = .02) relative to our historical cohort, with a mean difference of -3.81 ± 1.56 h (95% CI -6.9 to -0.70). There was no difference in PACU or hospital length of stay, but there was a significant reduction in variance of all secondary outcomes. CONCLUSION: Opioid reduction and improved timeliness of oral intake is possible with an ERAS protocol for cleft palate repair, but our protocol did not alter PACU or hospital length of stay.

Utility of videolaryngoscopy for diagnostic and therapeutic interventions in head and neck surgery.

BACKGROUND: Videolaryngoscopy is commonly used by anesthesiologists to manage difficult airways. Recently otolaryngologists have reported use in select procedures; to date there is limited evaluation in head and neck surgery. MATERIALS AND METHODS: Patients who underwent direct laryngoscopy (DL) with use of GlideScope videolaryngoscopy (GVL) were retrospectively identified from a tertiary care Veterans Affairs hospital. GVL was used to assist or replace traditional laryngoscopes for diagnostic and therapeutic procedures. RESULTS: Nineteen patients (48-83 years old) underwent 21 procedures. Difficult endotracheal intubation was reported in 53% of patients. GVL replaced traditional DL in 76% of cases, assisted evaluation prior to traditional DL in 10%, and rescued failed traditional DL in 14%. No complications occurred. Three indications for GVL were identified. DISCUSSION: GVL was safe in our experience and provides unique benefits in selected scenarios in head and neck surgery. Otolaryngologists can consider videolaryngoscopy as a complement to traditional DL.

Where Dysphagia Begins: Polypharmacy and Xerostomia.

BACKGROUND: Xerostomia, the subjective sensation of dry mouth, contributes to dysarthria, dysphagia, and diminished quality of life. Polypharmacy is a known and modifiable risk factor for xerostomia. The objective of this study was to evaluate the prevalence of dry mouth, the relationship between dry mouth and other oral conditions, and the impact of polypharmacy on dry mouth. METHODS: This study was a retrospective cross-sectional study of all patients seen in fiscal year (FY) 2015 (October 1, 2014 to September 30, 2015) at the VA Palo Alto Health Care System (VAPAHCS), a tertiary care US Department of Veterans Affairs (VA) hospital. Patients diagnosed with xerostomia were identified using ICD-9 codes (527.7, 527.8, R68.2) and Systemized Nomenclature of Medicine Clinical Terms (SNOMED CT) codes (87715008, 78948009). RESULTS: Of all the patients seen at VAPAHCS during FY 2015, 138 had a diagnostic code for xerostomia; of those patients, 84 had at least 1 documented speech, dentition, or swallowing (SDS) problem, and 55 (39.9%) were taking ≥ 12 medications, more than twice as many patients as in any one of the other groups studied (0-2, 3-5, 6-8, and 9-11 medications taken). Although 4,971 total patients seen at VAPAHCS had documented SDS problems during FY 2015, of those patients only 77 (1.5%) had an additional recorded diagnosis of xerostomia. CONCLUSIONS: Heightened physician awareness regarding the signs and symptoms of and risk factors for xerostomia is needed to improve health care providers' ability to diagnose dry mouth. Polypharmacy also must be considered when developing new strategies for preventing and treating xerostomia.

Hydroxyapatite mineral enhances malignant potential in a tissue-engineered model of ductal carcinoma in situ (DCIS).

While ductal carcinoma in situ (DCIS) is known as a precursor lesion to most invasive breast carcinomas, the mechanisms underlying this transition remain enigmatic. DCIS is typically diagnosed by the mammographic detection of microcalcifications (MC). MCs consisting of non-stoichiometric hydroxyapatite (HA) mineral are frequently associated with malignant disease, yet it is unclear whether HA can actively promote malignancy. To investigate this outstanding question, we compared phenotypic outcomes of breast cancer cells cultured in control or HA-containing poly(lactide-co-glycolide) (PLG) scaffolds. Exposure to HA mineral in scaffolds increased the expression of pro-tumorigenic interleukin-8 (IL-8) among transformed but not benign cells. Notably, MCF10DCIS.com cells cultured in HA scaffolds adopted morphological changes associated with increased invasiveness and exhibited increased motility that were dependent on IL-8 signaling. Moreover, MCF10DCIS.com xenografts in HA scaffolds displayed evidence of enhanced malignant progression relative to xenografts in control scaffolds. These experimental findings were supported by a pathological analysis of clinical DCIS specimens, which correlated the presence of MCs with increased IL-8 staining and ductal proliferation. Collectively, our work suggests that HA mineral may stimulate malignancy in preinvasive DCIS cells and validate PLG scaffolds as useful tools to study cell-mineral interactions.

Temporal Bone CT Scan for Malleal Ligaments Assessment.

OBJECTIVE: To determine the feasibility of using temporal bone computed tomography (CT) scans to identify malleal ligaments and the prevalence of calcification in malleal ligaments. STUDY DESIGN: Retrospective case review. CT scans were blindly and retrospectively reviewed by two physicians (a radiologist and a nonradiologist). Scans differed by slice thickness, and included both conventional CT and cone beam CT (CBCT). SETTING: Ambulatory tertiary referral center. PATIENTS: One hundred fifty-one temporal bone CT scans, obtained between the years 2014 and 2017, were initially screened, which included 302 ears. Patients with previous tympanomastoid surgery or middle ear opacification were excluded, leaving 187 ears in the study. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURE: Percentage of visible normal and calcified malleal ligaments. RESULTS: Scans with submillimeter slice thickness were more likely to demonstrate all three malleal ligaments than those with 1 ml and larger slices (83.7% versus 50.0% for nonradiologist, p < 0.0001; 59.6 versus 34.8% for radiologist, p < 0.0001). Calcification was seen in 11.8% of ears reviewed. The ability to detect malleal ligaments with cone beam CT was 86.2%, while the rate with conventional CT was 71.1%, a difference that persisted when controlling for slice thickness. Interobserver agreement for the detection of malleal ligaments was 65% with a Cohen's kappa coefficient of κ = 0.27. CONCLUSION: Visualization of the malleal ligaments using CT scans is feasible in a majority of aerated ears. Detection of malleal ligaments improves with thinner slice thickness and cone-beam technique. Low interobserver agreement suggests the importance of experience and a need for standardized review.

Temporal Changes in Esophageal Cancer Mortality by Geographic Region: A Population-based Analysis.

Purpose To analyze differences in esophageal cancer survival by geographic region of the U.S. from the 1970s to the 2000s, and attribute the causes of these discrepancies. Methods Raw data were obtained from the Surveillance Epidemiology and End Results (SEER) program of the National Cancer Institute. Patients were stratified by decade of diagnosis and by geographic region (East, Hawaii/Alaska, Midwest, Southwest, and West), containing SEER registries. The Kaplan-Meier method with the log-rank test was used to compare the overall survival (OS) among these geographic groups. A multivariate Cox Proportional Hazard analysis was conducted to evaluate the impact of the following factors on differences in survival: patient age, gender, race, tumor stage, site, histology, treatment method, and metropolitan size. Results A total of 87,834 patients were identified. OS has increased significantly since 1973, with five-year OS improving from 4.9% (the 1970s) to 15.3% (2000s) (P<0.001). Residence in the East was prognostic for higher OS compared to all the other regions, with a median OS of six months in the 1970s and 12 months in the 2000s (P<0.001). The multivariate analysis revealed increased age, African American race, distant disease, non-distal tumor location, squamous cell histology, and no radiation therapy were associated with worse OS. The West and East had the highest amount of cancer centers (12 and seven, respectively). And the East had the highest number of cancer centers per person (5.7E-07) while the South had the lowest (1.6E-07). Conclusions There are disparities in esophageal cancer survival and quality of care through different geographic regions of the U.S., which may be attributed to a combination of the unbalanced distribution of medical resources, the regional differences in cancer biology, and other lifestyle and socioeconomic factors. More research should be conducted to further characterize regional differences and guide the implementation of improvements in survival.

Three-Dimensional Mechanical Loading Modulates the Osteogenic Response of Mesenchymal Stem Cells to Tumor-Derived Soluble Signals.

Dynamic mechanical loading is a strong anabolic signal in the skeleton, increasing osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) and increasing the bone-forming activity of osteoblasts, but its role in bone metastatic cancer is relatively unknown. In this study, we integrated a hydroxyapatite-containing three-dimensional (3D) scaffold platform with controlled mechanical stimulation to investigate the effects of cyclic compression on the interplay between breast cancer cells and BM-MSCs as it pertains to bone metastasis. BM-MSCs cultured within mineral-containing 3D poly(lactide-co-glycolide) (PLG) scaffolds differentiated into mature osteoblasts, and exposure to tumor-derived soluble factors promoted this process. When BM-MSCs undergoing osteogenic differentiation were exposed to conditioned media collected from mechanically loaded breast cancer cells, their gene expression of osteopontin was increased. This was further enhanced when mechanical compression was simultaneously applied to BM-MSCs, leading to more uniformly deposited osteopontin within scaffold pores. These results suggest that mechanical loading of 3D scaffold-based culture models may be utilized to evaluate the role of physiologically relevant physical cues on bone metastatic breast cancer. Furthermore, our data imply that cyclic mechanical stimuli within the bone microenvironment modulate interactions between tumor cells and BM-MSCs that are relevant to bone metastasis.