Improvement in swallowing safety after injection laryngoplasty in patients with unilateral vocal paralysis complicated with aspiration.

BACKGROUND: The benefit of injection laryngoplasty (IL) on voice for unilateral vocal fold paralysis (UVFP) is supported increasingly in literatures, yet less is known for swallowing. Also, prevalence of patient-reported dysphagia is substantially higher than instrumental studies. This prospective study focused on swallowing outcomes, with predetermined flexible endoscopic evaluation of swallowing (FEES) protocol that simulates daily life situation. METHODS: Adult patients with UVFP and aspiration receiving IL were recruited. Voice outcome measurements, as well as swallowing outcomes including Eating Assessment Tool (EAT-10) and FEES, which challenged patients with different fluid volumes: 10 mL, 20 mL, and 90 mL cup sipping were evaluated. RESULTS: Significant improvements were demonstrated in all voice outcomes. Significant changes were also presented inEAT-10 (P < 0.01). Pre-operatively, penetration-aspiration scale (PAS) was 1.5 ± 1.3, 1.9 ± 1.7 and 2.3 ± 1.8 for 10 mL, 20 mL and 90 mL serial sipping, and improved to 1.1 ± 0.3, 1.1 ± 0.4 and 1.4 ± 0.7 post-operatively (P < 0.01). Safe swallowing (PAS ≤ 2) was achieved in all, except for one patient, who presented with a post-injection PAS of 4 (material enters the airway, contacts the vocal folds, and is ejected from the airway) on 90 mL cup sipping, whose pre-injection PAS was 7 (residue in trachea). CONCLUSION: Maintaining swallowing function suitable for social environment is important. Our results demonstrated the feasibility of the predetermined FEES protocol, and positive effects of IL on both voice and swallowing outcomes.

Proactive Swallowing Rehabilitation in Patients with Recurrent Oral Cancer Receiving Salvage Treatment: Long-Term Swallowing-Related Outcomes.

The present study aimed to evaluate the impact of proactive swallowing rehabilitation on swallowing function and quality of life in patients with recurrent oral cancer in the first 2 years after salvage treatment. Consecutive adult patients with recurrent oral cancer who received salvage surgery and free flap reconstruction were recruited prospectively, to whom proactive swallowing rehabilitation was provided. Body weight (BW); fiberoptic endoscopic evaluation of swallowing (FEES), functional oral intake scale (FOIS), and diet level; 10-item eating assessment tool (EAT-10), and MD Anderson Dysphagia Inventory (MDADI); and adherence at baseline, 1, 3, 6, 12, 18 and 24 months were evaluated. A total of 50 patients were included during May 2018 to July 2020. Compared to the baseline, significant deterioration in BW, FOIS, and MDADI was noted at one month. However, a trend of recovery was observed in BW and FOIS from one month, and in MDADI from three months. All patients were free of tube feeding at 18-24 months and tolerated diet with special preparations or compensation. Safe swallowing could be achieved in approximately 80% participants after 12 months of diet modification or compensatory maneuvers. Proactive swallowing therapy was feasible in patients with recurrent oral cancer receiving salvage treatment. Although this patient population might have pre-existing dysphagia from previous treatments, rehabilitation could facilitate safe per oral intake and maintain adequate nutrition with adaptive maneuvers or compensatory strategies. Patients who underwent proactive swallowing rehabilitation had better recovery in the functional oral intake level.

Histology-based and cytology-based needle sampling for targeted next-generation sequencing in the indeterminate thyroid tumors.

PURPOSE: To establish the optimal and minimally invasive diagnostic approach for targeted next-generation sequencing (NGS) in the indeterminate thyroid tumors. METHODS: The patients with indeterminate thyroid tumors were prospectively recruited and analyzed in a single tertiary medical center. We performed FNA and core needle biopsy (CNB) at the surgical specimens to confirm the quality of each sampling procedure. Cytological diagnosis by FNA, histological diagnosis by CNB and confirmed diagnosis by final surgery were compared to demonstrate the agreement among these approaches for the indeterminate thyroid tumors. The quality of the samples from FNA and CNB was evaluated, respectively to determine the optimal approach for targeted NGS. Finally, we performed ultrasound-guided CNB and FNA (US-CNB and US-FNA) on one case to confirm the clinical feasibility of being a pre-operative minimally invasive diagnostic approach. RESULTS: A total of 6 female patients (average age: 50.83 ± 15.18 years) with indeterminate thyroid tumors (average size: 1.79 ± 0.91 cm) were recruited for further analyses. The pathological diagnoses could be obtained by CNB in the first five cases, and the sample quality of CNB for targeted NGS was better than that of FNA, even after 10X dilution. The gene mutations associated with thyroid malignancy could be detected by NGS. In the case treated with US-CNB, the pathological and targeted NGS results were successfully obtained, which suggested the possibility of thyroid malignancy to facilitate immediate decision of subsequent treatment. CONCLUSION: CNB could serve as a minimally invasive diagnostic approach in the indeterminate thyroid tumors by providing pathological diagnoses and qualified samples for detection of mutated genes, which facilitates appropriate and immediate management.

Incorporation of ultrasound-guided core biopsy with flow cytometry to assist the diagnosis of cervical lymphoma.

PURPOSE: The main purpose of surgery for cervical lymphoma is only for tissue sampling. To establish a patient-friendly diagnostic approach, we investigated the feasibility of ultrasound-guided core biopsy with flow cytometry in the patients with suspected cervical lymphoma. METHODS: We prospectively recruited patients with suspected cervical lymphoma from Nov 2017 till Jan 2021 in a referral medical center and performed retrospective interpretation of the prospectively acquired data. Ultrasound-guided core biopsy as the tissue sampling approach for the targeted lesions was performed in all patients. The ultrasound-guided core biopsy samples were analyzed by immunohistochemical stains and flow cytometry. The sample quality and the rate of definite and decisive diagnosis obtained by ultrasound-guided core biopsy alone and ultrasound-guided core biopsy with flow cytometry were evaluated. RESULTS: Total 81 consecutive patients were recruited for analysis. All ultrasound-guided core biopsy samples were qualified for analysis of pathology and flow cytometry. Pathologically, the diagnoses were definite and compatible with their flow cytometry results in 70 patients (86.42%). Either newly-diagnosed or recurrent cervical lymphoma/lymphoproliferative disorders with histologic transformation could be diagnosed by ultrasound-guided core biopsy with flow cytometry. Nine of the 11 patients with pathologically indefinite diagnosis became clinically decisive when flow cytometry was incorporated into the process, which improved the rate of decisive diagnosis to 98.77% (Odds ratio [95% CI]: 6.21 [1.28, 58.96]). CONCLUSION: Ultrasound-guided core biopsy combined with flow cytometry is suggested to serve as the first-line and patient-friendly diagnostic approach for the patients with suspected cervical lymphoma.

Effects of surgery on the relationship between subglottic pressure and fundamental frequency in vocal fold dynamics in patients with benign laryngeal diseases.

PURPOSE: Subglottic pressure (Ps) and fundamental frequency (F0) play important roles in governing vocal fold (VF) dynamics. Theoretical description, model simulation, excised larynx and animal models have been used in previous studies, yet clinically applicable measurements are still lacking. This study aimed to evaluate the effects of surgery for benign laryngeal lesions by investigating the relationship between F0 and Ps. METHODS: Patients with benign laryngeal lesions who underwent phonosurgery were prospectively recruited. Participants were instructed to sustain voicing the vowel /o/ at three incremental frequencies four semitones apart in the modal register (F01, F02, F03). F0 was estimated by VF vibration on the accelerometer. Ps change was achieved and measured using the airflow interruption method. RESULTS: Thirteen patients with a mean age (SD) of 43.5 (12.4) years were included. The change in F0 per unit change of Ps, which is the slope (Hz/kPa) of the regression line of the frequency-pressure data pairs, decreased as the tension of the VF increased. The slopes significantly increased after the operation for F01 and F02 (36.43 ± 14.68 preoperatively, 53.91 ± 30.71 postoperatively, p = 0.011 and 26.02 ± 10.71; 34.85 ± 17.92, p = 0.046, respectively). In addition, there was a significant decrease in phonation threshold pressure and improvements in the grade, roughness, breathiness, asthenia, strain scale, and the voice handicap inventory-10. CONCLUSIONS: The relationship between F0 and Ps may serve as an objective assessment of the outcomes in the treatment of benign laryngeal diseases with clinical relevance.

Application of ultrasound in distinguishing the incipient microtumor from inherent lymph nodes of the parotid glands.

BACKGROUND: Parotid microtumors (size ≤ 1 cm) pose a significant clinical challenge due to their malignant potential and risks associated with surgery. It is imperative to explore the diagnostic workflow that incorporates ultrasound (US) in order to make appropriate clinical decisions with minimal invasiveness. METHODS: The patients receiving both US and ultrasound-guided fine needle aspiration (USFNA) for the parotid microtumors in a medical center were retrospectively recruited. The ultrasonic features, cytology of USFNA, and final surgical pathology were analyzed to differentiate the tumor origins and their malignant potential. RESULTS: From August 2009 to March 2016, a total of 92 patients were enrolled in the study. The short axis, long-to-short axis ratio, and presence of an echogenic hilum were found to be significantly useful in distinguishing lymphoid tissue origin from salivary gland origin, which was confirmed by USFNA. An irregular border was predictive for malignant parotid microtumors from both origins. Intra-tumoral heterogeneity was also identified as a significant feature associated with malignant lymph nodes. USFNA was able to confirm all malignant lymph nodes, but it had a false negative rate of 8.5% in parotid microtumors of salivary gland origin. Based on the analysis of US and USFNA results, a diagnostic workflow for parotid microtumors was proposed. CONCLUSION: US and USFNA can be helpful in classifying the origins of parotid microtumors. US-FNA carries the risk of producing false negative results specifically for microtumors originating from salivary glands, but not lymphoid tissue. The diagnostic workflow, which incorporates both US and USFNA, assists in determining the clinical decision for diagnosing and managing parotid microtumors.

The efficacy of incorporating ultrasound-guided core biopsy into the clinical workflow of indeterminate thyroid tumors.

BACKGROUND: Ultrasound-guided core biopsy (USCB) is a minimally invasive sampling procedure which may help to confirm the diagnoses of the thyroid tumors with indeterminate results of ultrasound-guided fine-needle aspiration (USFNA). Although with potential advantages, the working protocol of introducing USCB in the routine practice has not been established yet. This study aims to evaluate the efficacy of USCB when it is included in the clinical workflow of assessing the thyroid tumors with indeterminate USFNA results after a long-term follow up. METHODS: Between 2009 and 2016, consecutive patients receiving thyroid USFNA were reviewed retrospectively in the tertiary referral hospital. The patients, who finally received USCB for their thyroid tumors after repeated indeterminate USFNA results, were recruited. The important sonographic features in facilitating specific diagnoses by USCB, differentiating malignancy from benignity, and confirming origins of thyroid tumors were analyzed and the role of USCB was investigated. RESULTS: Thirty-nine patients met the inclusion criteria were analyzed. The specific diagnoses were confirmed in 23 patients (59%) by USCB. Taller than wide, ill-defined margin and hypoechogenicity helped in differentiating malignant tumors and the latter two features were pertinent to the success of applying USCB for specific diagnosis. No sonographic features were able to differentiate the thyroid malignancy from extra-thyroid origins exclusively. Thyroid USCB facilitated clinical decision making in 37 of the 39 patients (94.9%) with indeterminate USFNA results. CONCLUSION: The USCB is a cost-effective sampling procedure for confirming the diagnosis of indeterminate thyroid tumors and their clinical management, especially for those malignancies from extra-thyroid origins.

An alternative surgical technique for advanced tongue/tongue base cancer without free flap reconstruction.

BACKGROUND/PURPOSE: Locally advanced tongue or tongue base cancer is recommended to be treated by radical resection that is usually detrimental to physiological functions. This study reports the efficacy and treatment outcome of the patients who had received total glossectomy and laryngeal suspension without lip-split mandibulotomy and free flap reconstruction to preserve laryngopharyngeal function. METHODS: From 2010 to 2018, 37 consecutive patients who had received the surgery were retrospectively recruited. RESULTS: The overall five-year survival is 72%. The postoperative dependent rate of feeding tube and tracheostomy largely decreases within 1-year follow-up. Treated by this surgical method, these patients are free from facial disfiguration, donor site morbidity, and destructive mastication and occlusion. It is also feasible to perform this surgical technique in the recurrent cases previously treated by chemoradiation. CONCLUSION: Total glossectomy with laryngeal suspension can be successfully applied to locally advanced tongue or tongue base cancer, and benefits the patients with improved survival and preserved physiological function. Especially surgeons for free flap reconstruction are understaffed at some regional or district hospitals.

Distinguishing lupus lymphadenitis from Kikuchi disease based on clinicopathological features and C4d immunohistochemistry.

OBJECTIVES: Distinguishing Kikuchi disease (KD) from lupus lymphadenitis (LL) histologically is nearly impossible. We applied C4d immunohistochemical (IHC) stain to develop diagnostic tools. METHODS: We retrospectively investigated clinicopathological features and C4d IHC staining in an LL-enriched development cohort (19 LL and 81 KD specimens), proposed risk stratification criteria and trained machine learning models, and validated them in an external cohort (2 LL and 55 KD specimens). RESULTS: Clinically, we observed that LL was associated with an older average age (33 vs 25 years; P=0.005), higher proportion of biopsy sites other than the neck [4/19 (21%) vs 1/81 (1%); P=0.004], and higher proportion of generalized lymphadenopathy compared with KD [9/16 (56%) vs 7/31 (23%); P=0.028]. Histologically, LL involved a larger tissue area than KD did (P=0.006). LL specimens exhibited more frequent interfollicular pattern [5/19 (26%) vs 3/81 (4%); P=0.001] and plasma cell infiltrates (P=0.002), and less frequent histiocytic infiltrates in the necrotic area (P=0.030). Xanthomatous infiltrates were noted in 6/19 (32%) LL specimens. Immunohistochemically, C4d endothelial staining in the necrotic area [11/17 (65%) vs 2/62 (3%); P<10-7], and capillaries/venules [5/19 (26%) vs 7/81 (9%); P=0.048] and trabecular/hilar vessels [11/18 (61%) vs 8/81 (10%); P<10-4] in the viable area was more common in LL. During validation, both the risk stratification criteria and machine learning models were superior to conventional histological criteria. CONCLUSIONS: Integrating clinicopathological and C4d findings could distinguish LL from KD.

Observation of antiferromagnetic correlations in the Hubbard model with ultracold atoms.

Ultracold atoms in optical lattices have great potential to contribute to a better understanding of some of the most important issues in many-body physics, such as high-temperature superconductivity. The Hubbard model--a simplified representation of fermions moving on a periodic lattice--is thought to describe the essential details of copper oxide superconductivity. This model describes many of the features shared by the copper oxides, including an interaction-driven Mott insulating state and an antiferromagnetic (AFM) state. Optical lattices filled with a two-spin-component Fermi gas of ultracold atoms can faithfully realize the Hubbard model with readily tunable parameters, and thus provide a platform for the systematic exploration of its phase diagram. Realization of strongly correlated phases, however, has been hindered by the need to cool the atoms to temperatures as low as the magnetic exchange energy, and also by the lack of reliable thermometry. Here we demonstrate spin-sensitive Bragg scattering of light to measure AFM spin correlations in a realization of the three-dimensional Hubbard model at temperatures down to 1.4 times that of the AFM phase transition. This temperature regime is beyond the range of validity of a simple high-temperature series expansion, which brings our experiment close to the limit of the capabilities of current numerical techniques, particularly at metallic densities. We reach these low temperatures using a compensated optical lattice technique, in which the confinement of each lattice beam is compensated by a blue-detuned laser beam. The temperature of the atoms in the lattice is deduced by comparing the light scattering to determinant quantum Monte Carlo simulations and numerical linked-cluster expansion calculations. Further refinement of the compensated lattice may produce even lower temperatures which, along with light scattering thermometry, would open avenues for producing and characterizing other novel quantum states of matter, such as the pseudogap regime and correlated metallic states of the two-dimensional Hubbard model.

Point-of-care ultrasound in otolaryngology and head and neck surgery: A prospective survey study.

PURPOSE: The ultrasound applications, examination facilities and methods used by otolaryngology and head and neck surgeons may vary and be different. This study was conducted to assess the methods used for head-and-neck point-of-care ultrasound (POCUS). METHODS: This prospective survey study was conducted from 1 July 2018 to 31 December 2019. The surgeons of otolaryngology and head neck surgery who used POCUS in their daily practice were recruited for analyses. RESULTS: In total, 30 male and 14 female surgeons who used neck POCUS were recruited. Thirty-nine (89%) surgeons placed patients in a supine position with the head toward the operator. Forty (91%) surgeons performed US-guided fine needle aspiration (FNA), and 35 (80%) surgeons did not use local anesthesia during US-FNA. Thirty-nine (88%) surgeons used the long-axis method to harvest the specimen, and forty-one (93%) used a free-hand method. Most surgeons (25, 57%) used 22G needles for US-FNA, and 29 (66%) used 18G for US-guided core-needle biopsy (CNB). For the cost analysis, reimbursements for US-related procedures were relatively cheaper than those for computer tomography (CT) and magnetic resonance imaging (MRI). CONCLUSION: POCUS can be performed by otolaryngology and head and neck specialists with a wide scope of applications and in a cost-effective manner.

Objective evaluation of biomaterial effects after injection laryngoplasty - Introduction of artificial intelligence-based ultrasonic image analysis.

OBJECTIVE: Hyaluronic acid (HA) can be degraded over time. However, persistence of the effects after injection laryngoplasty (IL) for unilateral vocal fold paralysis (UVFP), longer than expected from HA longevity, has been observed. The purpose of the study was to develop a methodology with clinical utility for objective evaluation of the temporal change in HA volume after IL using artificial intelligence (AI)-based ultrasonic assessment. DESIGN, SETTING AND PARTICIPANTS: Imaging phantoms simulating injected HA were built in different volumes for designing the algorithm for machine learning. Subsequently, five adult patients who had undergone IL with HA for UVFP were recruited for clinical evaluation. MAIN OUTCOME MEASURES: Estimated volumes were evaluated for injected HA by the automatic algorithm as well as voice outcomes at 2 weeks, and 2 and 6 months after IL. RESULTS: On imaging phantoms, contours on each frame were described well by the algorithm and the volume could be estimated accordingly. The error rates were 0%-9.2%. Moreover, the resultant contours of the HA area were captured in detail for all participants. The estimated volume decreased to an average of 65.76% remaining at 2 months and to a minimal amount at 6 months while glottal closure remained improved. CONCLUSION: The volume change of the injected HA over time for an individual was estimated non-invasively by AI-based ultrasonic image analysis. The prolonged effect after treatment, longer than HA longevity, was demonstrated objectively for the first time. The information is beneficial to achieve optimal cost-effectiveness of IL and improve the life quality of the patients.

P53 ICE CRIM mouse: a tool to generate mutant allelic series in somatic cells and germ lines for cancer studies.

The clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology facilitates somatic genome editing to reveal cooperative genetic interactions at the cellular level without extensive breeding between different mutant animals. Here we propose a transgenic inducible Cas9 effector-CRISPR mutagen ( ICE CRIM) mouse model in which CRISPR/Cas9-mediated somatic mutagenesis events can occur in response to Cre expression. The well-known tumor suppressor gene, Trp53, and 2 important DNA mismatch repair genes, Mlh1 and Msh2, were selected to be our somatic mutagenesis targets. Amplicon-based sequencing was performed to validate the editing efficiency and to identify the mutant allelic series. Crossed with various Cre lines, the Trp53 ICE CRIM alleles were activated to generate targeted cancer gene somatic or germ line mutant variants. We provide experimental evidence to show that an activated ICE CRIM can mutate both targeted alleles within a cell. Simultaneous disruption of multiple genes was also achieved when there were multiple single-guide RNA expression cassettes embedded within an activated ICE CRIM. Our mouse model can be used to generate mutant pools in vivo, which enables a functional screen to be performed in situ. Our results also provide evidence to support a monoclonal origin of hematopoietic neoplasms and to indicate that DNA mismatch repair deficiency accelerates tumorigenesis in Trp53 mutant genetic background.-Fan, H.-H., Yu, I.-S., Lin, Y.-H., Wang, S.-Y., Liaw, Y.-H., Chen, P.-L., Yang, T.-L., Lin, S.-W., Chen, Y.-T. P53 ICE CRIM mouse: a tool to generate mutant allelic series in somatic cells and germ lines for cancer studies.

Platelet-Rich Fibrin Facilitates One-Stage Cartilage Repair by Promoting Chondrocytes Viability, Migration, and Matrix Synthesis.

The main aim of this study is to develop a one-stage method to combine platelet-rich fibrin (PRF) and autologous cartilage autografts for porcine articular cartilage repair. The porcine chondrocytes were treated with different concentrations of PRF-conditioned media and were evaluated for their cell viability and extracellular glycosaminoglycan (GAG) synthesis during six day cultivation. The chemotactic effects of PRF on chondrocytes on undigested cartilage autografts were revealed in explant cultures. For the in vivo part, porcine chondral defects were created at the medial femoral condyles of which were (1) left untreated, (2) implanted with PRF combined with hand-diced cartilage grafts, or (3) implanted with PRF combined with device-diced cartilage grafts. After six months, gross grades, histological, and immunohistochemical analyses were compared. The results showed that PRF promotes the viability and GAG expression of the cultured chondrocytes. Additionally, the PRF-conditioned media induce significant cellular migration and outgrowth of chondrocytes from undigested cartilage grafts. In the in vivo study, gross grading and histological scores showed significantly better outcomes in the treatment groups as compared with controls. Moreover, both treatment groups showed significantly more type II collagen staining and minimal type I collagen staining as compared with controls, indicating more hyaline-like cartilage and less fibrous tissue. In conclusion, PRF enhances the viability, differentiation, and migration of chondrocytes, thus, showing an appealing capacity for cartilage repair. The data altogether provide evidences to confirm the feasibility of a one-stage, culture-free method of combining PRF and cartilage autografts for repairing articular cartilage defects. From translational standpoints, these advantages benefit clinical applications by simplifying and potentiating the efficacy of cartilage autograft transplants.

Estimating vocal fold stiffness: Using the relationship between subglottic pressure and fundamental frequency of phonation as an analog.

OBJECTIVE: The stiffness of the vocal folds is an important factor in voice production, yet clinically applicable measurements are still lacking. It has been demonstrated in an in vivo canine model that fundamental frequency (F0 ) increased linearly as subglottic pressure (Ps ) increased, but with a lesser slope for higher levels of vocal fold tension. In this study, the relationship between F0 and Ps was investigated using the airflow interruption method in awake patients non-invasively. DESIGN: Healthy volunteers enrolled for evaluation. SETTING: Single-centre. PARTICIPANTS: Thirty-three healthy volunteers aged 20 and older were recruited, with one excluded for a recent asthma attack. MAIN OUTCOME MEASURES: The relationships between F0 and Ps , described as the slope (Hz/kPa), were investigated when the participants sustained voicing the vowel/o/at 3 incremental frequencies 4 semitones apart in the modal register (F1, F2 and F3). RESULTS: Thirty-two healthy volunteers (20 females, 12 males) aged 20-47 years were enrolled for final analyses. There was a statistically significant difference in the slopes of the linear regression lines of F0 -Ps , depending on the frequency with which the vowel/o/ was produced (P < .001). The slope differed significantly between F2 and F1 (P < .001; P = .015), F3 and F1 (P < .001; P = .002) and F3 and F2 (P < .001; P = .005) for both women and men, respectively. CONCLUSIONS: It was demonstrated that the higher the vocal fold tension, the smaller the slope between F0 and Ps . Using the relationship between F0 and Ps as an analog of vocal fold stiffness is potentially practical for clinical application.

Intravital multiphoton microscopic imaging platform for ocular surface imaging.

The purpose of this study is to provide an intravital noninvasive multiphoton microscopic platform for long-term ocular imaging in transgenic fluorescent mice with subcellular resolution. A multiphoton microscopic system with tunable laser output was employed. We designed a mouse holder incorporated with stereotaxic motorized stage for in vivo three-dimensional imaging of ocular surface in 3 transgenic mouse line with fluorescent protein (FP) expression to visualize distinct structures. With our imaging platform and the expression of FPs, we obtained the three-dimensional images across the whole cornea from epithelium to endothelium and in conjunctiva with subcellular resolution in vivo. Specified EGFP expression in corneal epithelium of K5-H2B-EGFP mice helped to identify both corneal and limbal epithelial cells while ubiquitous nuclear FP expression in R26R-GR mice allowed us to visualized nuclei of all cell types. Universal membrane-localized FP in mT/mG mice outlined all cell boundaries, nerve fibers, and capillaries. The simultaneously collected second harmonic generation signals from collagenous stroma provided architectural contrast. Time-lapsed recording enabled monitoring the mitotic activity of corneal epithelial cells and limbal epithelial cells. We developed an intravital multiphoton microscopic stereotaxic imaging platform and showed that, by incorporating FP-expressing transgenic mice, this platform enables in vivo 4-dimensional ophthalmic study at subcellular resolution.

The Pretreatment Neutrophil-to-Lymphocyte Ratio is a Prognostic Determinant of T3-4 Hypopharyngeal Squamous Cell Carcinoma.

OBJECTIVE: This study aimed to investigate the clinicopathological factors that influence recurrence and survival in patients who undergo operations for T3-4 hypopharyngeal squamous cell carcinomas (SCCs). MATERIALS AND METHODS: One hundred and five patients who underwent surgery between 2001 and 2008 for advanced hypopharyngeal SCCs were consecutively enrolled and reviewed. RESULTS: The pretreatment neutrophil-to-lymphocyte ratio (NLR; median 3.22, range 0.62-46.50) was associated with disease recurrence and patient survival. A difference in the 5-year cumulative disease recurrence rate between patients with high (≥3.22) and low (<3.22) NLRs was significant (60.4 and 36.5%, respectively; p = 0.004). A multivariate analysis confirmed that an NLR ≥3.22 was an independent indicator of a poor prognosis for advanced hypopharyngeal SCC, as per the following parameters: overall survival (hazard ratio [HR] 2.53, 95% confidence interval [CI] 1.48-4.30, p = 0.001), disease-specific survival (HR 2.45, 95% CI 1.38-4.34, p = 0.002), and disease-free survival (HR 2.18, 95% CI 1.24-3.83, p = 0.007). Additional prognostic factors per the survival analyses included lymph node density, surgical margin, lymphovascular invasion, and perineural invasion. CONCLUSIONS: An NLR ≥3.22 is associated with a higher risk of disease recurrence and poor survival in patients with T3-4 hypopharyngeal SCCs. We propose the use of the NLR to broaden the current TNM staging system; the development of a more effective treatment protocol for patients with high NLRs will be essential.

Lymph Node Ratio Predicts Recurrence and Survival for Patients with Resectable Stage 4 Hypopharyngeal Cancer.

BACKGROUND: This study aimed to investigate the clinicopathologic prognostic predictors of stage 4 hypopharyngeal cancer and to extend the traditional tumor-node-metastasis classification system to advance its predictive ability. METHODS: The study enrolled 120 patients with pathologically stage 4 hypopharyngeal cancer treated with pharyngolaryngectomy and neck dissection between 2001 and 2007. RESULTS: The study showed a 5-year overall survival (OS) of 44.6%, a disease-specific survival (DSS) of 51.6%, and a disease-free survival (DFS) of 48% for all the patients. In the multivariate analysis, a lymph node (LN) ratio of 0.113 or higher was a significant poor prognostic factor for OS (hazard ratio [HR] 1.89; 95% confidence interval [CI] 1.17-3.05; p = 0.009), DSS (HR 2.17; 95% CI 1.29-3.64; p = 0.003), and DFS (HR, 2.24; 95% CI 1.12-4.52; p = 0.024) in stage 4 hypopharyngeal cancer. In addition, pretreatment neutrophil-lymphocyte ratio, lymphovascular invasion, and margin status also were predictors of survival outcomes. Furthermore, the study found that disease recurrence differed significantly between the patients with a LN ratio of 0.113 or higher (68.2%) and those with a LN ratio lower than 0.113 (39.5%) (p = 0.002). CONCLUSIONS: A LN ratio of 0.113 or higher is a strong predictor of disease recurrence and survival for patients with stage 4 hypopharyngeal cancer.

Age-related hearing loss and dementia: a 10-year national population-based study.

Age-related hearing loss (ARHL) is postulated to affect dementia. Our study aims to investigate the relationship between ARHL and the prevalence, and 10-year incidence of dementia in the Taiwan National Health Insurance Research Database (NHIRD). We selected patients diagnosed with ARHL from the NHIRD. A comparison cohort comprising of patients without ARHL was frequency-matched by age, sex, and co-morbidities, and the occurrence of dementia was evaluated in both cohorts. The ARHL cohort consisted of 4108 patients with ARHL and the control cohort consisted of 4013 frequency-matched patients without ARHL. The incidence of dementia [hazard ratio (HR), 1.30; 95% confidence interval (CI 1.14-1.49); P = 0.002] was higher among ARHL patients. Cox models showed that being female (HR, 1.34; 95% CI 1.07-1.68), as well as having co-morbidities, including chronic liver disease and cirrhosis, rheumatoid arthritis, hypertension, diabetes mellitus, stroke, head injury, chronic kidney disease, coronary artery disease, alcohol abuse/dependence, and tobacco abuse/dependence (HR, 1.27; 95% CI 1.11-1.45), were independent risk factors for dementia in ARHL patients. We found ARHL may be one of the early characteristics of dementia, and patients with hearing loss were at a higher risk of subsequent dementia. Clinicians should be more sensitive to dementia symptoms within the first 2 years following ARHL diagnosis. Further clinical studies of the relationship between dementia and ARHL may be necessary.