Comparison of royal college of pathologists and college of american pathologists definition for positive margins in oral cavity squamous cell carcinoma.

BACKGROUND: Pathological margin assessment is an essential component of surgical management of oral cavity squamous cell carcinoma (OCSCC), however, in many studies, variable definitions of involved margins have been used. The purpose of the present study was to compare the prognostic ability of involved margins according to Royal College of Pathologists (RCPath) and College of American Pathologists (CAP) guidance. METHODS: Retrospective study of 300 patients with previously untreated OCSCC undergoing definitive surgical management. Main specimen margin status was defined according to RCPath guidance and CAP guidance. "Final margin status", incorporated the results of frozen sections and extra tumour bed resections. The prognostic impact of each margin definition was studied using univariate analysis, and in multivariate models including T-stage (AJCC 8th edition), nodal status (pN+), extranodal extension (ENE), and use of adjuvant radiotherapy. RESULTS: Both RCPath and CAP positive margins were associated with local recurrence (LR), disease-specific survival (DSS), and overall survival (OS) on univariate analysis, while final margin status was associated with LR and DSS, but not OS. On multivariate analysis, only CAP positive main specimen margin status was independently associated with LR (odds ratio 2.44, 95% CI 1.37, 4.34), DSS (odds ratio 2.28, 95% CI 1.31, 3.82), and OS (odds ratio 1.59, 95% CI 1.04, 2.42). CONCLUSIONS: Involved main specimen margin as defined by CAP guidance has the advantage of being an independent prognosticator of LR and survival in our cohort.

Pre-operative testing for SARS-CoV-2 and outcomes in otolaryngology surgery during the pandemic: A multi-center experience.

INTRODUCTION: Preoperative testing for COVID-19 has become widely established to avoid inadvertent surgery on patients with COVID-19 and prevent hospital outbreaks. METHODS: A prospective cross sectional study was carried out in two university hospitals examining the pre-operative protocols for patients undergoing otolaryngology surgery and the incidence of COVID-19 within 30 days of surgery in patients and the otolaryngologists performing surgery. RESULTS: One hundred and seventy-three patients were recruited. One hundred and twenty-three (71%) patients "cocooned" for 14 days prior to surgery. All completed a questionnaire prior to admission. One hundred and fifty-six patients (90%) had reverse transcriptase-polymerase chain reaction (RT-PCR) nasopharyngeal swabs, 14 patients (8%) had CT thorax. No cases of COVID-19 were detected among patients followed up at 30 days. Two surgeons developed COVID-19 early during the study period. CONCLUSION: Current pre-operative testing protocols consisting primarily of questionnaires and RT-PCR resulted in zero cases of COVID in this cohort. It is possible that COVID-19 restrictions and high proportion of patients cocooning preoperatively were factors in ensuring a low rate of COVID-19 post-operatively.

An interesting case report of delayed presentation of visual loss from an Ethmoid Mucocoele. Should we offer emergency decompression?

Paranasal sinus mucocoeles commonly involve the frontoethmoidal sinuses and can rarely present with vision changes due to expansion and invasion through the orbit. A 50-year-old female presented out of hours with an acute, 16-h history of complete left sided visual loss, on a background of 3 days of visual changes. A left ethmoid mucocoele extending into the left orbital apex causing compression of the optic nerve was diagnosed on imaging. Emergency endoscopic sinus surgery with decompression and marsupialization of the ethmoid mucocoele was performed, which resulted in improvement of vision. This case is unusual due to improvement in vision despite the length of visual loss prior to surgical intervention. This case demonstrates the importance of considering rhinological causes for vision loss, and how critical early identification and surgical intervention can be to prevent serious complications such as permanent vision loss.

Customized hydrogel substrates for serum-free expansion of functional hMSCs.

We describe a screening approach to identify customized substrates for serum-free human mesenchymal stromal cell (hMSC) culture. In particular, we combine a biomaterials screening approach with design of experiments (DOE) and multivariate analysis (MVA) to understand the effects of substrate stiffness, substrate adhesivity, and media composition on hMSC behavior in vitro. This approach enabled identification of poly(ethylene glycol)-based and integrin binding hydrogel substrate compositions that supported functional hMSC expansion in multiple serum-containing and serum-free media, as well as the expansion of MSCs from multiple, distinct sources. The identified substrates were compatible with standard thaw, seed, and harvest protocols. Finally, we used MVA on the screening data to reveal the importance of serum and substrate stiffness on hMSC expansion, highlighting the need for customized cell culture substrates in optimal hMSC biomanufacturing processes.

Synthetic, Chemically Defined Polymer-Coated Microcarriers for the Expansion of Human Mesenchymal Stem Cells.

Mesenchymal stem cells (MSC), also called marrow stromal cells, are adult cells that have attracted interest for their potential uses in therapeutic applications. There is a pressing need for scalable culture systems due to the large number of cells needed for clinical treatments. Here, a tailorable thin polymer coating-poly(poly(ethylene glycol) methyl ether methacrylate-ran-vinyl dimethyl azlactone-ran-glycidyl methacrylate) [P(PEGMEMA-r-VDM-r-GMA); PVG]-to the surface of commercially available polystyrene and glass microcarriers to create chemically defined surfaces for large-scale cell expansion is applied. These chemically defined microcarriers create a reproducible surface that does not rely on the adsorption of xenogenic serum proteins to mediate cell adhesion. Specifically, this coating method anchors PVG copolymer through ring opening nucleophilic attack by amine residues on poly-l-lysine that is pre-adsorbed to the surface of microcarriers. Importantly, this anchoring reaction preserves the monomer VDM reactivity for subsequent functionalization with an integrin-specific Arg-Gly-Asp peptide to enable cell adhesion and expansion via a one-step reaction in aqueous media. MSCs cultured on PVG-coated microcarriers achieve sixfold expansion-similar to the expansion achieved on PS microcarriers-and retain their ability to differentiate after harvesting.

Microcarriers with Synthetic Hydrogel Surfaces for Stem Cell Expansion.

Microcarriers are scalable support surfaces for cell growth that enable high levels of expansion, and are particularly relevant for expansion of human mesenchymal stem cells (hMSCs). The goal of this study is to develop a poly(ethylene glycol) (PEG)-based microcarrier coating for hMSC expansion. Commercially available microcarriers do not offer customizability of microcarrier surface properties, including elastic modulus and surface cell adhesion ligands. The lab has previously demonstrated that tuning these material properties on PEG-based hydrogels can modulate important cellular growth characteristics, such as cell attachment and expansion, which are important in microcarrier-based culture. Eosin-Y is adsorbed to polystyrene microcarriers and used as a photoinitiator for thiol-ene polymerization under visible light. Resultant PEG coatings are over 100 µm thick and localized to microcarrier surfaces. This thickness is relevant for cells to react to mechanical properties of the hydrogel coating, and coated microcarriers support hMSC attachment and expansion. hMSC expansion is highly favorable on coated microcarriers in serum-free media, with doubling times under 25 h in the growth phase, and retained osteogenic and adipogenic differentiation capacity after culture on microcarriers. These microcarriers with defined, synthetic coatings enable tailorable surfaces for cell expansion that may be suitable for a variety of biomanufacturing applications.

Stem cell bioprinting for applications in regenerative medicine.

Many regenerative medicine applications seek to harness the biologic power of stem cells in architecturally complex scaffolds or microenvironments. Traditional tissue engineering methods cannot create such intricate structures, nor can they precisely control cellular position or spatial distribution. These limitations have spurred advances in the field of bioprinting, aimed to satisfy these structural and compositional demands. Bioprinting can be defined as the programmed deposition of cells or other biologics, often with accompanying biomaterials. In this concise review, we focus on recent advances in stem cell bioprinting, including performance, utility, and applications in regenerative medicine. More specifically, this review explores the capability of bioprinting to direct stem cell fate, engineer tissue(s), and create functional vascular networks. Furthermore, the unique challenges and concerns related to bioprinting living stem cells, such as viability and maintaining multi- or pluripotency, are discussed. The regenerative capacity of stem cells, when combined with the structural/compositional control afforded by bioprinting, provides a unique and powerful tool to address the complex demands of tissue engineering and regenerative medicine applications.

Microcapsules and 3D customizable shelled microenvironments from laser direct-written microbeads.

Microcapsules are shelled 3D microenvironments, with a liquid core. These core-shelled structures enable cell-cell contact, cellular proliferation and aggregation within the capsule, and can be utilized for controlled release of encapsulated contents. Traditional microcapsule fabrication methods provide limited control of capsule size, and are unable to control capsule placement. To overcome these limitations, we demonstrate size and spatial control of poly-l-lysine and chitosan microcapsules, using laser direct-write (LDW) printing, and subsequent processing, of alginate microbeads. Additionally, microbeads were used as volume pixels (voxels) to form continuous 3D hydrogel structures, which were processed like capsules, to form custom shelled aqueous-core 3D structures of prescribed geometry; such as strands, rings, and bifurcations. Heterogeneous structures were also created with controlled initial locations of different cell types, to demonstrate the ability to prescribe cell signaling (heterotypic and homotypic) in co-culture conditions. Herein, we demonstrate LDW's ability to fabricate intricate 3D structures, essentially with "printed macroporosity," and to precisely control structural composition by bottom-up fabrication in a bead-by-bead manner. The structural and compositional control afforded by this process enables the creation of a wide range of new constructs, with many potential applications in tissue engineering and regenerative medicine. Biotechnol. Bioeng. 2016;113: 2264-2274. © 2016 Wiley Periodicals, Inc.

Pluripotency markers are differentially induced by MEK inhibition in thyroid and melanoma BRAFV600E cell lines.

Oncogenic mutations in BRAF are common in melanoma and thyroid carcinoma and drive constitutive activation of the MAPK pathway. Molecularly targeted therapies of this pathway improves survival compared to chemotherapy; however, responses tend to be short-lived as resistance invariably occursCell line models of melanoma and thyroid carcinoma, +/- BRAF(V600E) activating mutation, were treated with the MEK inhibitor PD0325901. Treated and naive samples were assayed for expression of key members of the MAPK pathway. Global microRNA expression profiling of naive and resistant cells was performed via next generation sequencingand indicated pluripotency pathways in resistance. Parental cell lines were progressed to holoclones to confirm the miRNA stemness profileMembers of the MIR302/373/374/520 family of embryonic stem cell specific cell cycle regulating (ESCC) microRNAs were identified as differentially expressed between resistant BRAF(V600E) melanoma and thyroid cell lines. Upregulated expression of gene and protein stemness markers, upregulated expression of MAPK pathway genes and downregulation of the ESCC MIR302 cluster in BRAF(V600E) melanoma indicated an increased stem-like phenotype in resistant BRAF(V600E) melanoma. Conversely, downregulated expression of gene and protein stemness markers, downregulated expression of MAPK pathway genes, upregulation of the ESCC MIR520 cluster, reeexpression of cell surface receptors, and induced differentiation-associated morphology in resistant BRAF(V600E) indicate a differentiated phenotype associated with MEK inhibitor resistance in BRAF(V600E) thyroid cellsThe differential patterns of resistance observed between BRAF(V600E) melanoma and thyroid cell lines may reflect tissue type or de novo differentiation, but could have significant impact on the response of primary and metastatic cells to MEK inhibitor treatment. This study provides a basis for the investigation of the cellular differentiation/self-renewal access and its role in resistance to MEK inhibition.

A congenital foregut malformation with a laryngeal bronchus.

We present the case of a 2-month-old boy who required intubation at birth for stridor, at which point a supraglottic cyst was noted. With recurrence of the cyst, a subsequent computed tomographic scan and magnetic resonance imaging demonstrated a mass encroaching on the larynx, descending into the mediastinum, and encasing the major vessels. A median sternotomy and transcervical incision enabled excision of a well-defined mass with a laryngeal attachment. This attachment was consistent with a bronchus on histopathologic investigation. To our knowledge, this is the first reported case of ectopic lung tissue arising from the larynx and descending into the mediastinum.

Recent advances in bioprinting and applications for biosensing.

Future biosensing applications will require high performance, including real-time monitoring of physiological events, incorporation of biosensors into feedback-based devices, detection of toxins, and advanced diagnostics. Such functionality will necessitate biosensors with increased sensitivity, specificity, and throughput, as well as the ability to simultaneously detect multiple analytes. While these demands have yet to be fully realized, recent advances in biofabrication may allow sensors to achieve the high spatial sensitivity required, and bring us closer to achieving devices with these capabilities. To this end, we review recent advances in biofabrication techniques that may enable cutting-edge biosensors. In particular, we focus on bioprinting techniques (e.g., microcontact printing, inkjet printing, and laser direct-write) that may prove pivotal to biosensor fabrication and scaling. Recent biosensors have employed these fabrication techniques with success, and further development may enable higher performance, including multiplexing multiple analytes or cell types within a single biosensor. We also review recent advances in 3D bioprinting, and explore their potential to create biosensors with live cells encapsulated in 3D microenvironments. Such advances in biofabrication will expand biosensor utility and availability, with impact realized in many interdisciplinary fields, as well as in the clinic.

'Case reporting of rare adverse events in otolaryngology': can we defend the case report?

The study of errors in medicine has proliferated since the publication of The Institute of Medicine Report 'TO ERR IS HUMAN' in 2000. Case nuances and process of care issues are valuable areas to explore if the goal is to provide the health care worker with the knowledge to avoid future errors. Meta-analysis and randomized controlled trials provide a large data base of evidence towards improvement and opportunities, but it is suggested that case reports can still provide valuable clinical information. The aim is to use the published literature to produce a series of rare harm case reports in E.N.T. The methods include systematic literature review. Journals searched in PUBMED were 60. Rare harm case obtained from the search were 5,322. Rare harm case reports not reported in any other form of evidence-based medicine were 40. Yes, the case report can be defended as it is an important pillar of evidence-based medicine.

Effect of burn-out temperature on magnetic keepers in cast noble metal alloy posts.

STATEMENT OF PROBLEM: Early loss of magnetic keepers in cast gold posts is seen in clinical practice. PURPOSE: The purpose of this vitro study was to investigate the effect of burn-out temperature on the retention of magnetic keepers in cast gold alloy and on the thickness of the oxide layer at the keeper-alloy interface. MATERIAL AND METHODS: One hundred and five keepers (Magfit EX) were cast with gold alloy (Protor 3) at 3 different burn-out temperatures: 500 degrees C, 600 degrees C, or 700 degrees C (n=35). To test for retention of keepers, 60 specimens (n=20) were tested to failure in tension mode in a universal testing machine (UTM); 45 specimens (n=15) were sectioned, and the interface was evaluated under a scanning electron microscope (SEM). Tensile force data were analyzed with 1-way ANOVA, and SEM data were analyzed with 1-way repeated measures ANOVA. Bonferroni multiple comparisons were performed for post hoc analysis (alpha=.05). RESULTS: Retention of the keepers was significantly higher at lower burn-out temperatures (P<.001). The retention of the keepers became unpredictable and immediate failures were observed at a burn-out temperature of 700 degrees C. Oxide formation at the keeper-alloy interface was significantly less at lower burn-out temperatures (P<.001). CONCLUSIONS: A burn-out temperature of 500 degrees C for casting the Magfit EX keeper with type IV high-strength gold alloy is recommended.

A quality assessment of the casting process on magnetic keepers.

PURPOSE: The objective of this study was to qualitatively investigate the effect of the burn-out (mold) temperature, investment material, and casting alloy on the surface integrity of the Magfit EX keeper. MATERIALS AND METHODS: Forty-two Magfit EX keepers were waxed-up, invested in five investment materials (Beauty-Cast, Cristobalite, CM-10, Cera-Fina, Castorit-super), and subjected to burn-out temperatures ranging from 450 to 700 degrees C at intervals of 50 degrees C. The keeper samples were then cast into copings with three alloys (Castwell, Protor 3, Optimum) under standard conditions. The keeper surfaces were then examined under a microscope, and the compositions were assessed by an X-ray micro-analyzer in a scanning electron microscope (SEM). A new keeper served as control. RESULTS: At a burn-out temperature of 550 degrees C, the keeper surface started to disintegrate. X-ray micro-analysis showed an increase in oxygen content with increasing temperature. At 700 degrees C, the keeper surface disintegrated, and the composition differed markedly from that of the new keeper. The keeper surfaces were intact with all investments except those with Beauty-Cast. The keeper surfaces were found to be damaged when the casting alloy was Optimum. CONCLUSIONS: Beauty-Cast investment with a burn-out temperature of 700 degrees C is unsuitable for casting the Magfit EX keeper-coping unit. Also, high fusing alloys are not recommended for casting Magfit EX keepers.