Trends in Swallowing Outcomes Following Deintensified Treatment in Selected p16+ Oropharyngeal Carcinoma.

Objective: Identify trends in swallowing outcomes in p16+ oropharyngeal squamous cell carcinoma following neoadjuvant chemotherapy+surgery (NAC+S) versus neoadjuvant chemotherapy+surgery+radiation (NAC+S+R). Study Design: Cohort study. Setting: Single academic institution. Methods: Swallowing outcome was measured using a validated questionnaire, MD Anderson Dysphagia Inventory (MDADI). MDADI scores were compared between NAC+S and NAC+S+R groups in short-term (<1 year), middle-term (1-3 years), and long-term (>3 years). Clinical factors associated with MDADI scores were explored using a linear mixed model. Statistical significance was established at p < .05. Results: Sixty-seven patients met the inclusion criteria and were divided into 2 groups: NAC+S (57 [85.1%]) and NAC+S+R (10 [14.9%]). All patients had improved MDADI scores in the middle-term compared to short-term (NAC+S: score increase = 3.43, p = .002; NAC+S+R: score increase = 11.18, p = .044), long-term compared to short-term (NAC+S: score increase = 6.97, p < .001; NAC+S+R: score increase = 20.35, p < .001), and long-term compared to middle-term (NAC+S: score increase = 3.54, p = .043; NAC+S+R: score increase = 9.18, p = .026). NAC+S patients had better MDADI scores than NAC+S+R patients at short-term (83.80 vs 71.26, p = .001). There was no significant difference in swallowing function in the middle-term or long-term. Conclusion: Regardless of treatment type, swallowing will likely be improved in the middle-term and long-term compared to the short-term. Patients treated with NAC+S+R will have worse short-term swallowing function. However, in the middle-term and long-term, there is no significant difference in swallowing function between patients treated with NAC+S and NAC+S+R.

Comparison of quality of life outcomes in a de-intensification treatment regimen for p16 + oropharyngeal cancer.

BACKGROUND: Platinum and taxane-based neoadjuvant chemotherapy with surgery (NAC + S) is a novel de-intensified treatment modality that is currently under investigation. METHODS: All patients treated for HPV positive OPSCC with NAC + S at a single institution between 2006 and 2020 were contacted to complete the University of Washington Quality of life questionnaire (UW-QOL) at least 2 years following the completion of treatment. RESULTS: The UW-QOL surveys were received from 25 of 48 eligible patients (52.1%). The mean follow-up time was 4.3 years (range 2.0-7.6 years). The overall mean score for the physical subscale was 92.4 (Standard deviation, SD = 10.9), and the social-emotional subscale was 91.1 (11.8). Compared to the normative cohort, the NAC + S cohort had a worse appearance (Mean scores Normative vs. NAC + S: 93 vs. 84.0, p = 0.009). CONCLUSION: NAC + S offers favorable long-term QOL, as evidenced by near-normal scores in most QOL domains.

Swallowing Function Following Neoadjuvant Chemotherapy and Transoral Robotic Surgery for Oropharyngeal Carcinoma: A 2-Year Follow-up.

OBJECTIVE: To evaluate 2-year follow-up swallowing function in patients with human papillomavirus-related oropharyngeal squamous cell carcinoma (HPV+ OPSCC) who completed neoadjuvant chemotherapy and transoral robotic surgery (NAC+S). STUDY DESIGN: Retrospective analysis of patients with OPSCC treated with NAC+S between 2010 and 2021. SETTING: A single academic institution. METHODS: This is a cross-sectional study of patient-reported swallowing function, assessed with the MD Anderson Dysphagia Inventory (MDADI) at least 2 years after completion of treatment. The inclusion criteria are patients with HPV+ OPSCC who underwent NAC+S at least 2 years ago. Those requiring adjuvant radiation or chemoradiation or experiencing relapse were excluded from the study. RESULTS: Completed MDADIs were received from 37 patients at a median 3.8 years posttreatment (interquartile range, 2.0-8.6 years). Of those, 94.6% (n = 35) were male and 81.1% (n = 30) were White. The median age at OPSCC diagnosis was 59.0 years (interquartile range, 41-80 years). The most frequent primary subsite of OPSCC was the base of the tongue (n = 20, 54.1%), followed by the tonsils (n = 16, 43.2%). In addition, 75.7% (n = 28) had stage IVa disease (TNM seventh edition), and 29 (78.4%) had scores ≥80, classified as optimal function. When compared with patients who received bilateral neck dissection, patients who received unilateral neck dissection were associated with an age <65 years old (P = .036) and lower clinical TNM stage (P = .04), as well as higher composite, emotional, functional, and physical MDADI scores (P = .017, .046, .013, and .05, respectively). CONCLUSION: Patients with OPSCC who were treated with NAC+S achieved satisfactory long-term swallowing outcomes. Unilateral neck dissection was significantly associated with higher MDADI scores in this patient cohort.

Patterning Neuroepithelial Cell Sheet via a Sustained Chemical Gradient Generated by Localized Passive Diffusion Devices.

Recent advances in human pluripotent stem cells (hPSCs)-derived in vitro models open a new avenue for studying early stage human development. While current approaches leverage the self-organizing capability of hPSCs, it remains unclear whether extrinsic morphogen gradients are sufficient to pattern neuroectoderm tissues in vitro. While microfluidics or hydrogel-based approaches to generate chemical gradients are well-established, these systems either require continuous pumping or encapsulating cells in gels, making it difficult for adaptation in standard biology laboratories and downstream analysis. In this work, we report a new device design that leverages localized passive diffusion, or LPaD for short, to generate a stable chemical gradient in an open environment. As LPaD is operated simply by media changing, common issues for microfluidic systems such as leakage, bubble formation, and contamination can be avoided. The device contains a slit carved in a film filled with solid gelatin and connected to a static aqueous morphogen reservoir. Concentration gradients generated by the device were visualized via DAPI fluorescent intensity and were found to be stable for up to 168 h. Using this device, we successfully induced cellular response of Madin-Darby canine kidney (MDCK) cells to the concentration gradient of a small-molecule drug, cytochalasin D. Furthermore, we efficiently patterned the dorsal-ventral axis of hPSC-derived forebrain neuroepithelial cells with the sonic hedgehog (Shh) signal gradient generated by the LPaD devices. Together, LPaD devices are powerful tools to control the local chemical microenvironment for engineering organotypic structures in vitro.

Outpatient Parotidectomy: A Retrospective Series.

OBJECTIVES: Recent literature suggests that outpatient head and neck surgery is safe and may decrease costs. This study assesses whether outpatient parotidectomy differs in complication type and rate from inpatient surgery. METHODS: Patients who underwent parotidectomy at our institution from 2011 to 2019 were retrospectively reviewed and divided by inpatient or outpatient status. Complications including infection, seroma, salivary fistula, hematoma, and flap necrosis, as well as readmission rates were tabulated. Drain placement, related to tumor size, was also analyzed using a receiver operating curve. RESULTS: 144 patients had available data for analysis. Nine of the 144 patients had complications. Seven of 98 outpatients and two of 46 inpatients had complications. There was no statistically significant difference in complication rate between the two groups (P = .518). Tumor size ≥4.62 cm3 was associated with drain placement (P = .044). CONCLUSION: Outpatient parotidectomy is a safe and viable alternative for carefully selected patients.

Endometrial cancer combined with polycystic ovary syndrome in 9 women under 40-years old: A case report.

The aim of the present study was to discuss the clinicopathological characteristics of endometrial carcinoma in young females with polycystic ovary syndrome (PCOS), and to review the current literature. A total of 9 patients with histopathologically confirmed endometrial cancer in young females with PCOS at the West China Second Hospital of Sichuan University between December 2007 and September 2013 were included. The clinicopathological characteristics of the patients were analyzed. The age range of the patients was 24-38 years (median age, 29), all of the cases had abnormal vaginal bleeding and endometrioid adenocarcinoma was the most common histopathological subtype observed (8 cases, 88.9%). Of the patients, 2 had well-differentiated cases and 7 patients had moderately differentiated cases. None of the patients received regular PCOS treatments and did not turn up for regular check-ups before they were diagnosed with endometrial carcinoma. Additionally, 7 patients received staging laparotomy with a total abdominal hysterectomy and bilateral salpingo-oophorectomy, 1 patient underwent an endometrial resection under hysteroscopy and the final patient received a high-dose of medroxyprogesterone treatment without surgery. In conclusion, doctors should take into consideration that young women with PCOS may also exhibit an endometrial carcinoma, and diagnosing and treating the endometrial carcinoma as early as possible in the young patients with PCOS is necessary.

Quantifying tensile forces at cell-cell junctions with a DNA-based fluorescent probe.

Cells are physically contacting with each other. Direct and precise quantification of forces at cell-cell junctions is still challenging. Herein, we have developed a DNA-based ratiometric fluorescent probe, termed DNAMeter, to quantify intercellular tensile forces. These lipid-modified DNAMeters can spontaneously anchor onto live cell membranes. The DNAMeter consists of two self-assembled DNA hairpins of different force tolerance. Once the intercellular tension exceeds the force tolerance to unfold a DNA hairpin, a specific fluorescence signal will be activated, which enables the real-time imaging and quantification of tensile forces. Using E-cadherin-modified DNAMeter as an example, we have demonstrated an approach to quantify, at the molecular level, the magnitude and distribution of E-cadherin tension among epithelial cells. Compatible with readily accessible fluorescence microscopes, these easy-to-use DNA tension probes can be broadly used to quantify mechanotransduction in collective cell behaviors.

Evaluating measurement accuracy and repeatability with a new device that records spatial knee movement.

PURPOSE: A novel portable system has been used to evaluate spatial knee movement, but its accuracy and repeatability is not known. The aim of this study was to investigate the accuracy and repeatability of the measurement. METHODS: Ten healthy participants were included, and the knee motion trajectory during walking were assessed. Six evaluations were conducted (three days by two raters) for each participant. The motion parameters at the key points and the range of motion were statistically analyzed. Intraclass correlation coefficients (ICC), standard error of the measurement (SEM), and the Bland-Altman method were used. RESULTS: For intra-rater repeatability, 1) the ICC values range from 0.75 to 0.9 for rotations; and 0.64 to 0.96 for translations. Among the ICC values, 100% of rotations and 90% of translations were not less than 0.70; 2) among the SEM values, 100% of rotations were not more than 5°, while 73.3% of translations were less than 3 mm. For inter-rater repeatability, 1) the ICC values range from 0.68 to 0.99 for rotations; and 0.57 to 0.93 for translations. Among the ICC values, 95.6% of rotations and 82.2% of translations were not less than 0.70; 2) among the SEM values, 100% of rotations were not more than 5°, and 48.9% of translations were less than 3 mm. The Bland-Altman plots showed good agreement for intra- and inter- repeatability. CONCLUSIONS: The results indicated that the accuracy and repeatability of the measurement were acceptable, except for the inter-rater repeatability for translation. This may help researchers and physicians better interpret the measurement data.

Heavy Metal Exposure Leads to Rapid Changes in Cellular Biophysical Properties.

Biophysical properties of cells, such as cell mechanics, cell shape, and cell migration, are emerging hallmarks for characterizing various cell functions. Conversely, disruptions to these biophysical properties may be used as reliable indicators of disruptions to cell homeostasis, such as in the case of chemical-induced toxicity. In this study, we demonstrate that treatment of lead(II) nitrate and cadmium nitrate leads to dosage-dependent changes in a collection of biophysical properties, including cellular traction forces, focal adhesions, mechanical stiffness, cell shape, migration speed, permeability, and wound-healing efficacy in mammalian cells. As those changes appear within a few hours after the treatment with a trace amount of lead/cadmium, our results highlight the promise of using biophysical properties to screen environmental chemicals to identify potential toxicants and establish dose response curves. Our systematic and quantitative characterization of the rapid changes in cytoskeletal structure and cell functions upon heavy metal treatment may inspire new research on the mechanisms of toxicity.

The effects of marathon running on three-dimensional knee kinematics during walking and running in recreational runners.

BACKGROUND: Running-related musculoskeletal injuries are common. Knee injuries are most frequent, and often occur during or shortly after marathons. RESEARCH QUESTION: The effects of a marathon on runners' knee kinematics remain unclear. No studies have shown comprehensive three-dimensional (3D) knee kinematic changes following a marathon. This study aimed to observe the effects of running a marathon on 3D knee kinematics and identify the phases of walking and running gait in which significant changes occur. METHODS: Based on an electronic survey, 10 healthy, recreational runners (20 knees) with similar running experience were included. Their 3D knee kinematics (during treadmill walking and running) were collected using a portable, optical motion capture system within 24 h before and within 6 h after running a marathon. RESULTS: All measurements after the marathon were compared with pre-marathon measurements. (1) For walking post-marathon: varus rotation increased by 1.8° [95% confidence interval (CI) 0.1-3.4, P = 0.036] at peak knee extension during stance; anterior translation increased by 2.2 mm (95% CI 0.3-4.1, P = 0.025) at initial contact; range of motion (ROM) in internal-external rotation increased less than 1°, P = 0.023; ROM in anteroposterior translation increased by 3.8 mm, P = 0.048. (2) For running post-marathon: flexion rotation increased by 1.6° (95% CI 0.2-2.9, P = 0.025) at initial contact; varus rotation increased by 2.0° (95% CI 0.2-3.8, P = 0.031) at peak knee extension during stance. SIGNIFICANCE: Significant differences in varus rotation and anterior translation were identified following a marathon, which could potentially contribute to injury. These results provide important information for runners and coaches about knee kinematic alterations following a marathon.

Single-Cell Optogenetic Control of Calcium Signaling with a High-Density Micro-LED Array.

Precise optogenetic control, ideally down to single cells in dense cell populations, is essential in understanding the heterogeneity of cell networks. Devices with such capability, if built in a chip scale, will advance optogenetic studies at cellular levels in a variety of experimental settings. Here we demonstrate optogenetic control of intracellular Ca2+ dynamics at the single cell level using a 16-µm pitched micro-light emitting diode (LED) array that features high brightness, small spot size, fast response, and low voltage operation. Individual LED pixels are able to reliably trigger intracellular Ca2+ transients, confirmed by fluorescence microscopy and control experiments and cross-checked by two genetically coded Ca2+ indicators. Importantly, our array can optogenetically address individual cells that are sub-10 µm apart in densely packed cell populations. These results suggest the possible use of the micro-LED array toward a lab-on-a-chip for single-cell optogenetics, which may allow for pharmaceutical screening and fundamental studies on a variety of cell networks.

Biomechanical Microenvironment Regulates Fusogenicity of Breast Cancer Cells.

Fusion of cancer cells is thought to contribute to tumor development and drug resistance. The low frequency of cell fusion events and the instability of fused cells have hindered our ability to understand the molecular mechanisms that govern cell fusion. We have demonstrated that several breast cancer cell lines can fuse into multinucleated giant cells in vitro, and the initiation and longevity of fused cells can be regulated solely by biophysical factors. Dynamically tuning the adhesive area of the patterned substrates, reducing cytoskeletal tensions pharmacologically, altering matrix stiffness, and modulating pattern curvature all supported the spontaneous fusion and stability of these multinucleated giant cells. These observations highlight that the biomechanical microenvironment of cancer cells, including the matrix rigidity and interfacial curvature, can directly modulate their fusogenicity, an unexplored mechanism through which biophysical cues regulate tumor progression.

Shaping nanoparticle fingerprints at the interface of cholesteric droplets.

The ordering of nanoparticles into predetermined configurations is of importance to the design of advanced technologies. Here, we balance the interfacial energy of nanoparticles against the elastic energy of cholesteric liquid crystals to dynamically shape nanoparticle assemblies at a fluid interface. By adjusting the concentration of surfactant that plays the dual role of tuning the degree of nanoparticle hydrophobicity and altering the molecular anchoring of liquid crystals, we pattern nanoparticles at the interface of cholesteric liquid crystal emulsions. In this system, interfacial assembly is tempered by elastic patterns that arise from the geometric frustration of confined cholesterics. Patterns are tunable by varying both surfactant and chiral dopant concentrations. Adjusting the particle hydrophobicity more finely by regulating the surfactant concentration and solution pH further modifies the rigidity of assemblies, giving rise to surprising assembly dynamics dictated by the underlying elasticity of the cholesteric. Because particle assembly occurs at the interface with the desired structures exposed to the surrounding water solution, we demonstrate that particles can be readily cross-linked and manipulated, forming structures that retain their shape under external perturbations. This study serves as a foundation for better understanding inter-nanoparticle interactions at interfaces by tempering their assembly with elasticity and for creating materials with chemical heterogeneity and linear, periodic structures, essential for optical and energy applications.

Towards organogenesis and morphogenesis in vitro: harnessing engineered microenvironment and autonomous behaviors of pluripotent stem cells.

Recently, researchers have been attempting to control pluripotent stem cell fate or generate self-organized tissues from stem cells. Advances in bioengineering enable generation of organotypic structures, which capture the cellular components, spatial cell organization and even some functions of tissues or organs in development. However, only a few engineering tools have been utilized to regulate the formation and organization of spatially complex tissues derived from stem cells. Here, we provide a review of recent progress in the culture of organotypic structures in vitro, focusing on how microengineering approaches including geometric confinement, extracellular matrix (ECM) property modulation, spatially controlled biochemical factors, and external forces, can be utilized to generate organotypic structures. Moreover, we will discuss potential technologies that can be applied to further control both soluble and insoluble factors spatiotemporally in vitro. In summary, advanced engineered approaches have a great promise in generating miniaturized tissues and organs in a reproducible fashion, facilitating the cellular and molecular understanding of embryogenesis and morphogenesis processes.

Minimally elevated preoperative parathyroid hormone level influences the management of primary hyperparathyroidism.

OBJECTIVES/HYPOTHESIS: To determine the effect of preoperative parathyroid hormone (PTH) level on the extent of surgery and the accuracy of parathyroid imaging in primary hyperparathyroidism. STUDY DESIGN: Retrospective cohort. METHODS: Final diagnosis of single-gland adenoma and its location versus multigland disease was established in this retrospective cohort study. Positive predictive value, negative predictive value, and accuracy of imaging were analyzed in relation to preoperative PTH levels. RESULTS: Eighty-seven percent of the 218 patients enrolled in the study underwent unilateral targeted operation and had a 97.9% (95% confidence interval: 95.8%-100%) success rate. However, in patients with PTH <65 pg/mL, 28.6% had bilateral exploration compared to 10.3% in those with PTH ≥65 pg/mL (P = .042). In patients with PTH <65 pg/mL, 7/21 (33.3%) had inaccurate sestamibi findings compared to 24/174 (13.8%) in patients with PTH ≥65 pg/mL (P = .047). CONCLUSIONS: Accuracy of sestamibi drops significantly, by threefold, in patients with mild primary hyperparathyroidism and PTH <65 pg/mL. Patients with PTH < 65 pg/mL have a 2.5-fold higher rate of bilateral operation to identify the hypersecreting gland(s) compared to patients with PTH ≥65 pg/mL. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1016-1021, 2018.

Visualizing Intercellular Tensile Forces by DNA-Based Membrane Molecular Probes.

Mechanical forces play critical roles in collective cell behaviors such as cell migration, proliferation, and differentiation. Extensive efforts have been made to measure forces between cells and extracellular matrices. However, force studies at cell-cell junctions remain a challenge. Herein, we reported a novel strategy to construct membrane DNA tension probes to visualize tensile forces at cell junctions. These lipid-modified probes can self-assemble onto cell membranes with high efficiency and stability. Upon experiencing tensile forces generated by neighboring cells, unfolding of the probes leads to a large increase in the fluorescence intensity. Compatible with readily accessible fluorescence microscopes, these easy-to-use membrane DNA tension probes can be broadly used to measure intercellular tensile forces.

Curvature-Driven Migration of Colloids on Tense Lipid Bilayers.

Inspired by proteins that generate membrane curvature, sense the underlying membrane geometry, and migrate driven by curvature gradients, we explore the question: Can colloids, adhered to lipid bilayers, also sense and respond to membrane geometry? We report the migration of Janus microparticles adhered to giant unilamellar vesicles elongated to present spatially varying curvatures. In our experiments, colloids migrate only when the membranes are tense, suggesting that they migrate to minimize membrane area. By determining the energy dissipated along a trajectory, the energy field is inferred to depend on the local deviatoric curvature, like curvature driven capillary migration on interfaces between immiscible fluids. In this latter system, energy gradients are larger, so colloids move deterministically, whereas the paths traced by colloids on vesicles have significant fluctuations. By addressing the role of Brownian motion, we show that the observed migration is analogous to curvature driven capillary migration, with membrane tension playing the role of interfacial tension. Since this motion is mediated by membrane shape, it can be turned on and off by dynamically deforming the vesicle. While particle-particle interactions on lipid membranes have been considered in many contributions, we report here an exciting and previously unexplored modality to actively direct the migration of colloids to desired locations on lipid bilayers.

Neoadjuvant chemotherapy and transoral surgery as a definitive treatment for oropharyngeal cancer: A feasible novel approach.

BACKGROUND: The purpose of this study was to present our evaluation of the outcome of oropharyngeal cancer managed with neoadjuvant chemotherapy and transoral surgery (TOS) with neck dissection as definitive treatment. METHODS: This is a case series of 17 patients with advanced oropharyngeal cancer who were treated with neoadjuvant chemotherapy followed by TOS. The treatment details and oncologic outcome are reported. The volumetric response of the tumor to neoadjuvant chemotherapy is evaluated and validated by histopathology. RESULTS: Seventeen patients with TNM stages III and IV oropharyngeal cancer constitute this series for survival analysis. On a median and mean follow-up of 31 and 40 months, respectively, 16 of the 17 patients were alive without recurrence. Disease-specific survival (DSS) and overall survival (OS) at 3 years were 94.1%. CONCLUSION: Adjuvant chemotherapy followed by TOS and neck dissection is a feasible and efficacious novel therapeutic approach for definitive management of moderately advanced oropharyngeal cancer, reserving radiotherapy (RT) for salvage or adverse features. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1837-1846, 2016.

Lassoing saddle splay and the geometrical control of topological defects.

Systems with holes, such as colloidal handlebodies and toroidal droplets, have been studied in the nematic liquid crystal (NLC) 4-cyano-4'-pentylbiphenyl (5CB): Both point and ring topological defects can occur within each hole and around the system while conserving the system's overall topological charge. However, what has not been fully appreciated is the ability to manipulate the hole geometry with homeotropic (perpendicular) anchoring conditions to induce complex, saddle-like deformations. We exploit this by creating an array of holes suspended in an NLC cell with oriented planar (parallel) anchoring at the cell boundaries. We study both 5CB and a binary mixture of bicyclohexane derivatives (CCN-47 and CCN-55). Through simulations and experiments, we study how the bulk saddle deformations of each hole interact to create defect structures, including an array of disclination lines, reminiscent of those found in liquid-crystal blue phases. The line locations are tunable via the NLC elastic constants, the cell geometry, and the size and spacing of holes in the array. This research lays the groundwork for the control of complex elastic deformations of varying length scales via geometrical cues in materials that are renowned in the display industry for their stability and easy manipulability.

Around the corner: Colloidal assembly and wiring in groovy nematic cells.

We study colloids suspended in nematic liquid crystal in grooves with homeotropic anchoring. We observe "eyelashes", topological dipole chains that follow the local, curved director field. These beget wires that connect the groove corners to topographical features on the cell lid to yield oriented, curvilinear colloidal wires spanning the cell, formed in a nonsingular director field. As the groove aspect ratio changes, we find different ground states and corroborate our observation with numerics. Our results rely upon on the scale of topographical features, the sharpness of edges, and the colloid-sourced distortions; all these elements can be exploited to guide the formation of reconfigurable structures in nematics.