The Efficacy and Safety of an Indocyanine Green-Macroaggregated Albumin-Hyaluronic Acid Mixture (LuminoMark™) for Surgical Localization of Recurrent Thyroid Cancer.

BACKGROUND: The recurrence of thyroid cancer poses challenges compounded by postoperative fibrosis and anatomic changes. By overcoming the limitations of current localizing dye techniques, indocyanine green-macroaggregated albumin-hyaluronic acid (ICG-MAA-HA) mixture dye promises improved localization. This study aimed to evaluate the efficacy and safety of the dye for recurrent thyroid cancer. METHODS: The nine patients in this study underwent surgery and postoperative ultrasonography. The dye was injected into recurrent lesions in all the patients preoperatively. During surgery, the lesions were confirmed with an imaging system before and after excision. If the lesion was unidentifiable with the naked eye, surgical excision was performed under the corresponding fluorescent guide. Side effects related to the dye injection and completeness of the surgery were evaluated. RESULTS: No side effects such as bleeding, skin tattooing, or pain during or after the dye injection were reported, and no discoloration occurred that interfered with the surgical field of view during surgery. In three cases (33.3 %), because it was difficult to localize metastatic lesions with the naked eye, the operation was successfully completed using an imaging system. The completeness of the surgical resection was confirmed by ultrasonography after an average of 5 months postoperatively. CONCLUSION: The study found that ICG-MAA-HA dye effectively located metastatic and recurrent thyroid cancer and had favorable results in terms of minimal procedural side effects and potential for assisting the surgeon. A large-scale multi-institutional study is necessary to prove the clinical significance regarding patient survival and disease control.

Clinical outcomes of bulky parotid gland cancers: need for self-examination and screening program for early diagnosis of parotid tumors.

BACKGROUND: Early detection and diagnosis of parotid gland cancer (PGC) are essential to improve clinical outcomes, because Tumor-Node-Metastasis stage at diagnosis is a very strong indicator of prognosis in PGC. Nevertheless, some patients still present with large parotid mass, maybe due to the unawareness or ignorance of their disease. In this study, we aimed to present the clinical outcomes of bulky PGC (defined by a 4 cm cutoff point for T3-4 versus T1-2 tumors), to emphasize the necessity of a self-examination tool for parotid gland tumor. METHODS: We retrospectively reviewed 60 consecutive cases with bulky (equal to and greater than 4 cm in the longest diameter, determined radiologically) malignant tumors arising from the parotid gland from 1995 to 2016. The clinical and pathological factors were analyzed to identify risk factors for poor outcomes using Cox proportional hazard models. In addition, we designed a self-examination tool for parotid gland tumors, similar to breast self-examination for breast cancer detection. RESULTS: Patients with bulky parotid cancer showed 48.9% 5-year and 24.5% 10-year overall survival rates and a 47.9% risk of high-grade malignancy. The common pathological diagnoses were carcinoma ex pleomorphic adenoma (18.3%), adenocarcinoma (16.7%), mucoepidermoid carcinoma (16.7%), salivary duct carcinoma (16.7%), and adenoid cystic carcinoma (11.7%). Survival analyses revealed that tumor size (hazard ratio, HR = 1.262 upon increase of 1 cm, 95% confidence interval, 95%CI 1.059-1.502), lymph node metastasis (HR = 2.999, 95%CI 1.048-8.583), and high tumor grade (HR = 4.148, 95%CI 1.215-14.154) were independent prognostic factors in multivariable analysis. Functional preservation of the facial nerve was possible only in less than half of patients. CONCLUSION: In bulky PGC, lymph node metastasis at diagnosis and high tumor grade indicated poor survival outcomes, and functional outcomes of the facial nerve were suboptimal. Thus, a public effort seems to be necessary to decrease these patients with bulky PGC, and to increase patients' self-awareness of their disease. As a way of early detection, we proposed a parotid self-examination tool to detect parotid gland tumors at an early stage, which is similar to breast self-examination.

Tumor dimension-dependent microscopic extensions of hypopharyngeal cancer: Therapeutic implications for larynx-preserving hypopharyngectomy.

INTRODUCTION: Hypopharyngeal cancer (HPC) is well characterized by the early submucosal spread of cancer cells into adjacent subsites of the hypopharynx and deep tissues, advocating a wide extent of treatment. However, the microscopic extensions (ME) from gross tumors, according to the primary tumor dimensions, has not been reported in detail. METHODS: We included patients who underwent upfront curative surgery, and retrospectively reviewed pathology specimens from 45 HPC cases. The distance of the MEs, defined as tumor infiltration beyond the gross tumor border on the submucosal and deep sides, was measured. We analyzed potential correlations between MEs and various physical tumor factors. RESULTS: A rough linear correlation between the submucosal ME and the maximal diameter of tumors was found (p < .001, r2 = 0.225). Deep MEs did not correlate with tumor physical factors. However, the MEs differed significantly by the T status (p = .033 and .015 in submucosal and deep sides). In T1-2 tumors, the submucosal MEs were less than 0.5 cm, whereas those of T3-4 tumors were 1.5-2.0 cm. CONCLUSION: In HPC, local MEs beyond the gross tumor border correlated with primary tumor T status. Our findings support that the surgical safety margin for HPC can be adjusted according to tumor dimension.

Lessons learned from reviewing a hospital's disaster response to the hydrofluoric acid leak in Gumi city in 2012.

BACKGROUND: This study analyzed the characteristics of hydrogen fluoride-exposed patients (HFEPs) treated in the emergency department (ED) of a local university hospital, and reviewed the hospital's disaster response according to space, staff, supplies, and systems (4Ss). METHODS: This retrospective observational chart review and descriptive study included 199 HFEPs among 2588 total ED patients who visited a local university emergency medical center for treatment between September 27, 2012 and October 20, 2012, following a hydrofluoric acid leak at the Hube Globe factory in Gumi City, Republic of Korea. Descriptive results concerning the 4Ss were obtained by interviewing ED specialist staff physicians on duty during the study period. In accordance with American Burn Association criteria, patients requiring burn center referral were assigned to the major burn group (MBG) as severe condition. RESULTS: During the acute phase (within 8 h after leak initiation), there were 43 patients in the ED, which was staffed with 3 doctors and 3 nurses, without 4S resources. Of these 43 patients, there were 8 HFEPs (100%) in the MBG and 0 in the non-MBG (NMBG). During the subacute phase (24 h after the acute phase), there were 262 patients in the ED including 167 HFEPs, of whom 45 (26.95%) were in the MBG and 122 (73.05%) were in the NMBG. The ED was then staffed with 6 doctors (3 on day shift and 3 on night shift) and 10 nurses (3 on day shift, 4 on evening shift, and 3 on night shift), and no 4S resources were available. Throughout the study period, no 4Ss were available. First, there was no expansion of ED space or secured disaster reserve beds. Second, there was no increase in manpower with duty time adjustments or duty relocation for ED working personnel. Third, there was no logistics reinforcement (e.g., antidote or personal protective equipment). Fourth, there were no disaster-related measures for the administration department, decontamination zone setup, safety diagnostic testing, or designated disaster triage implementation. CONCLUSIONS: The hospital's disaster response was insufficient for all aspects of the 4Ss. Detailed guidance concerning a hospital disaster management plan is required.

Effect of eosinophils activated with Alternaria on the production of extracellular matrix from nasal fibroblasts.

BACKGROUND: Eosinophils and fibroblasts are known to play major roles in the pathogenesis of nasal polyps. Fungi are commonly found in nasal secretion and are associated with airway inflammation. OBJECTIVE: To investigate whether activated eosinophils by airborne fungi can influence the production of extracellular matrix (ECM) from nasal fibroblasts. METHODS: Inferior turbinate and nasal polyp fibroblasts were stimulated with Alternaria or Aspergillus, respectively, for 24 hours and ECM messenger RNA (mRNA) and protein expressions were measured. Eosinophils isolated from healthy volunteers were stimulated with Alternaria or Aspergillus for 4 hours then superoxide, eosinophil peroxidase, and transforming growth factor ß1 were measured. Then activated eosinophils were cocultured with nasal fibroblasts for 24 hours, and ECM mRNA expressions were measured. RESULTS: Alternaria strongly enhanced ECM mRNA expression and protein production from nasal fibroblasts. Alternaria also induced the production of superoxide, eosinophil peroxidase, and transforming growth factor ß1 from eosinophils, and activated eosinophils enhanced ECM mRNA expression when they were cocultured without the Transwell insert system. CONCLUSION: Eosinophils activated with Alternaria enhanced ECM mRNA expression from nasal polyp fibroblasts. Alternaria plays an important role in tissue fibrosis in the pathogenesis of nasal polyps by directly or indirectly influencing the production of ECM from nasal fibroblasts.

Mediating effects of nocturnal blood pressure and morning surge on the contributions of arterial stiffness and sodium intake to morning blood pressure: A path analysis.

BACKGROUND: The aim of this study was to evaluate the mediating effects of nocturnal blood pressure (BP) and morning surge on the contribution of arterial stiffness and sodium intake to morning BP in a middle-aged general population. METHODS: The study included 124 subjects aged 30-59 years, from rural Yeoju County, Gyeonggi Province, South Korea. Ambulatory BP monitoring, 24 h urinary sodium excretion (24 h UNa) and brachial-ankle pulse wave velocity (baPWV) measurements were performed in all subjects. RESULTS: The mean ± SD age was 48.1 ± 8.2 years and the proportion of male subjects was 41.1%. After adjusting for covariates, morning systolic blood pressure (SBP) was significantly correlated with morning surge [coefficient = 0.761, 95% confidence interval (CI) 0.651-0.872, p < 0.001], nocturnal SBP (coefficient = 0.576, 95% CI 0.454-0.698, p < 0.001) and baPWV (coefficient = 3.550, 95% CI 1.447-5.653, p = 0.001). Path analysis modeling revealed that baPWV had significant direct (0.035, p = 0.013) and indirect effects (0.042, p = 0.012) on morning SBP. The indirect effect mediated by nocturnal SBP was statistically significant (0.054, p = 0.005), but the indirect effect mediated by the morning surge was not significant. The 24 h UNa had no significant direct or indirect effects on morning SBP. CONCLUSION: baPWV had significant direct and indirect effects on morning SBP. The indirect effect was mediated by nocturnal SBP, but not by morning surge. The 24 h UNa had neither significant direct nor indirect effects on morning SBP.

The effects of cervical traction, cranial rhythmic impulse, and Mckenzie exercise on headache and cervical muscle stiffness in episodic tension-type headache patients.

[Purpose] The purpose of this study was to examine the effects of cervical traction treatment, cranial rhythmic impulse treatment, a manual therapy, and McKenzie exercise, a dynamic strengthening exercise, on patients who have the neck muscle stiffness of the infrequent episodic tension-type (IETTH) headache and frequent episodic tension-type headache(FETTH), as well as to provide the basic materials for clinical interventions. [Subjects] Twenty-seven subjects (males: 15, females: 12) who were diagnosed with IETTH and FETTH after treatment by a neurologist were divided into three groups: (a cervical traction group (CTG, n=9), a cranial rhythmic contractiongroup (CRIG, n=9), and a McKenzie exercise group (MEG, n=9). An intervention was conducted for each group and the differences in their degrees of neck pain and changes in muscle tone were observed. [Results] In the within-group comparison of each group, headache significantly decreased in CTG. According to the results of the analysis of the muscle tone of the upper trapezius, there was a statistically significant difference in MEG on the right side and in CRIG on the left side. According to the results of the analysis of the muscle tone of the sternocleidomastoid muscle, there was a statistically significant difference in MEG on the right side and in CRIG on the left side. [Conclusion] In the comparison of the splenius capitis muscle between the groups, there was a statistically significant difference on the right side. Hence, compared to the other methods, cervical traction is concluded to be more effective at reducing headaches in IETTH and FETTH patients.

Extent of local invasion and safe resection in cT1-2 tonsil cancer.

BACKGROUND: Although intraoral resection of small-sized tonsil cancer achieves excellent tumor control, the extent of local invasion and adequate safety margin in resection have not been studied. Thus, we aim to determine the extent of local invasion in terms of mucosal spread and deep infiltration in stage T1-2 tonsil cancer. METHODS: We re-analyzed the surgical specimens from 49 cT1-2 tonsil cancers. Microscopic tumor cell extension from the tumor gross boundary of specimens was assessed in representative sections of each tumor. We also tested whether local extension correlates with human papilloma virus (HPV) status of tumors. RESULTS: The extent of microscopic deep invasion from the gross tumor border was 0.52 ± 0.41 mm, which was significantly less than that of mucosal spread (0.83 ± 0.61 mm, P = 0.01) in cT1-2 tonsil cancer. The microscopic deep invasion correlated with tumor size (rho = 0.703, P < 0.001). We found tumor invasion into superior constrictor muscles in 58.1%, no cases of tumor invasion into the deep fascia. In terms of HPV status (genotyping plus p16 staining), there were no differences in microscopic tumor extension. CONCLUSION: Our detailed pathologic analyses confirm that an oropharyngectomy including the superior constrictor muscle is an oncologically safe procedure for stage T1-2 tonsil cancer.

Clonal evolution of long-term expanding head and neck cancer organoid: Impact on treatment response for personalized therapeutic screening.

OBJECTIVES: In biobanking based on patient-derived organoids (PDO), the genetic stability of organoid lines is critical for the clinical relevance of PDO with parental tumors. However, data on mutational heterogeneity and clonal evolution of PDO and their effects on treatment response are insufficient. METHODS: To investigate whether head and neck cancer organoids (HNCOs) could maintain the genetic characteristics of their original tumors and elucidate the clonal evolution process during a long-term passage, we performed targeted sequencing, covering 377 cancer-related genes and adopted a sub-clonal fraction model. To explore therapeutic response variability between an early and late passage (>passage 6), we generated dose-response curves for drugs and radiation using two HNCO lines. RESULTS: Using 3D ex vivo organoid culture protocol, we successfully established 27 HNCOs from 39 patients with an overall success rate of 70% (27/39). Their mutational profiles were highly concordant, with three of the HNCOs analyzed showing greater than 70% concordance. Only one HNCO displayed less than 50% concordance. However, many of these organoid lines displayed clonal evolution during serial passaging, although major cancer driver genes and VAF distributions were shared between early and later passages. We also found that all late passages of HNCOs tended to be more sensitive to radiation than early passages, similar to drug response results. CONCLUSIONS: We report the establishment of HNCO lines derived from 27 patients and demonstrate their genetic concordance with corresponding parental tumors. Furthermore, we show serial changes in mutational profiles of HNCO along with long passage culture and the impact of these clonal evolutions on response to radiotherapy.

Comparative Longitudinal Analysis of Malignant Transformation in Pleomorphic Adenoma and Recurrent Pleomorphic Adenoma.

Background: Recurrence in pleomorphic adenoma (PA) has been debated as a risk factor for malignant transformation (MT). In this study, we investigated whether recurrence is a risk factor for MT, by longitudinally analyzing cases with recurrent PA (RPA), and carcinomas from PA (CXPA) or RPA (CXRPA). Methods: The study population included 24 CXPA, 24 RPA, 6 CXRPA, and 386 PA cases (study period 2010−2018). Time and event data were collected from the medical documents to identify the time−event sequences. Results: The time interval to MT in CXRPA was significant longer than that of benign recurrence (median 342.0 vs. 109.5 months). In CXRPA, the recurrence intervals were not shorter than those in RPA according to recurrence frequency. Crudely, the MT rate was 5.9% among primary cases and 20.0% among recurrent cases. However, the time-adjusted MT rates increased up to 11.4% (incubation time > 60 months) and 20.0% (>120 months) in primary cases, which were not different from recurrent cases. Conclusion: In these longitudinal analyses, we did not find any clinical evidence that recurrence facilitates MT in the background of PA. Instead, a long incubation time seems to be a key factor for MT of underlying RPA.

Comparative Analysis of Hydrogen Fluoride-Exposed Patients Based on Major Burn Criteria After the 2012 Gumi City Chemical Leak Disaster.

This study conducted to analyze and compare the epidemiological and clinical characteristics of hydrogen fluoride-exposed patients based on major burn criteria for the appropriate emergency department (ED) response to a mass casualty chemical spill. This retrospective cross-sectional study included the records of patients (n = 199) who visited the ED of Gumi City University Hospital from September 27, 2012, to October 20, 2012. Subjects were included in the major burn group (MBG) if they presented with wounds that required referral to a burn center according to the American Burn Association guidelines or in the nonmajor burn group (NMBG) if not. Males were predominant in both the MBG (n = 55, 48 males) and NMBG (n = 144, 84 males; P < .05). The most prevalent timeline for visiting the ED was the phase which included 9-32 hours post-leak of hydrogen fluoride, including 45 patients (81.8%) in the MBG and 122 patients (84.7%) in the NMBG (P < .001). The respiratory tract was the site of greatest damage in patients in both the MBG and NMBG (n = 47, 85.5% vs n = 142, 98.6%, P < .001). Regarding dispositions, all patients in the NMBG were discharged (n = 144, 100%); however, eight patients (14.5%) in the MBG underwent other dispositions (discharge against medical advice, five patients; admission, one patient; death, two patients, P < .05). Patient outcomes after major chemical contamination events should be characterized in future studies to maximize the quality of patient care.

Association between Sleep Duration and Symptoms of Depression Aged between 18 and 49: The Korea National Health and Nutrition Examination Survey (KNHANES â ¦) from 2016 to 2018.

This study aimed to determine the association between symptoms of depression and sleep duration in a representative sample of the Korean population. Using national cross-sectional data from the seventh Korea National Health and Nutrition Examination Surveys (KNHANES-VII), 5461 adults aged 18−49 years were analyzed using logistic regression models. The proportions of participants with total daily sleep durations (24 h) of <6 h, 6−8 h, and ≥9 h were 26.2%, 60.6%, and 13.3%, respectively. The proportions of individuals with symptoms of depression in the <6 h, 6−8 h, and ≥9 h sleep duration groups were 37.4%, 46.3%, and 16.3%, respectively. The odds ratios (ORs) were significantly higher in the <6 h and ≥9 h sleep groups than in the 6−8 h sleep group. There was a significant association between short (<6 h/day) and long (≥9 h/day) sleep duration and symptoms of depression among the general Korean population. In particular, our findings suggest that short sleep (<6 h/day) is more associated with symptoms of depression than long sleep (≥9 h/day).

A novel 3D pillar/well array platform using patient-derived head and neck tumor to predict the individual radioresponse.

Predicting individual radiotherapy (RT) response is valuable in managing head and neck squamous cell carcinoma (HNSCC). We assessed the feasibility of our novel 3D culture platform to measure radioresponse using patient-derived cells (PDCs) from HNSCC patients. Cells from the FaDu line and tumor samples from 39 HNSCC patients were cultivated serially in MatrigelTM on a 3D pillar/well array culture system. The 3D tumor models were exposed to 0 to 8 Gy of radiation dose, and the radioresponse index (RTauc, area under the dose-response curve) was measured quantitatively with Calcein AM staining of live tumor cells. Calcein AM fluorescence showed reduced density and the number of FaDu colonies as radiation increased, implying a dose-dependent effect on cell viability in the 3D pillar/well culture system. 3D tumor models using PDCs were established successfully from 39 HNSCC patient tumor samples, maintaining original genomic and pathological characteristics. These 3D tumor models were exposed to ionizing radiation on a 3D pillar/well array, with a mean period of 12 days from tumor harvest to the measurement of RTauc. The RTauc of all PDCs varied from 3.5 to 9.4, and the lower 40th percentile (Z-score = -0.26) was considered a good radioresponse group with a threshold RTauc of 4.6. The good radioresponse group showed fewer adverse features than others. As of the last follow-up, recurrence-free survival was better in the good radioresponse group (p = 0.037). 3D pillar/well array platforms using PDC could rapidly quantify radioresponse index in patients with HNSCC, showing potential as a novel prognosticator.

Utilization of Traditional Korean Medicine Services by the Older Population: A Cross-Sectional Study.

Korean healthcare service is divided into conventional medicine and traditional Korean medicine (TKM). This cross-sectional study compared the older population (65 years and older) with two groups of the general population (19-50 years and 51-64 years) to understand the current patterns in the use of TKM services by the older population. Using data from the 2017 National Survey of TKM Usage, we analyzed the main purpose and diseases or symptoms for TKM use, the reason for choosing TKM over other types of medicine, and the treatments provided. Both age groups sought TKM services to "[treat] a disease". The top five diseases and symptoms in the older adult (65 and older) group were musculoskeletal and are as follows: arthritis and joint diseases (37.8%, n = 166), disc-related diseases (25.5%, n = 112), back pain (8.4%, n = 37), frozen shoulder and shoulder pain (7.7%, n = 34), and sprain (5.9%, n = 26). The most frequently used treatments for these diseases were acupuncture, moxibustion, cupping, and physiotherapy. The present study suggests that older adults primarily used TKM clinics for the treatment of musculoskeletal diseases. Further studies are necessary to assess the clinical effectiveness of conventional medicine versus TKM versus a combination of both in treating musculoskeletal disorders.

Nasal ciliated cells are primary targets for SARS-CoV-2 replication in the early stage of COVID-19.

The upper respiratory tract is compromised in the early period of COVID-19, but SARS-CoV-2 tropism at the cellular level is not fully defined. Unlike recent single-cell RNA-Seq analyses indicating uniformly low mRNA expression of SARS-CoV-2 entry-related host molecules in all nasal epithelial cells, we show that the protein levels are relatively high and that their localizations are restricted to the apical side of multiciliated epithelial cells. In addition, we provide evidence in patients with COVID-19 that SARS-CoV-2 is massively detected and replicated within the multiciliated cells. We observed these findings during the early stage of COVID-19, when infected ciliated cells were rapidly replaced by differentiating precursor cells. Moreover, our analyses revealed that SARS-CoV-2 cellular tropism was restricted to the nasal ciliated versus oral squamous epithelium. These results imply that targeting ciliated cells of the nasal epithelium during the early stage of COVID-19 could be an ideal strategy to prevent SARS-CoV-2 propagation.

Development and immunopathological characteristics of an Alternaria-induced chronic rhinosinusitis mouse model.

Airborne fungi are associated with upper and lower airway inflammatory diseases. Alternaria is commonly found in nasal secretions and induces the production of chemical mediators from sinonasal mucosa. This study aimed to establish an Alternaria-induced chronic rhinosinusitis (CRS) mouse model and determine the influence of host allergic background on the immunopathological characteristics of CRS. BALB/c mice were used for establishing the CRS model. Alternaria was intranasally instilled for 8 or 16 weeks with or without ovalbumin (OVA) presensitization. Total serum IgE and Alternaria-specific IgE levels were measured by enzyme-linked immunosorbent assay (ELISA). Interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels in nasal lavage fluid (NLF) and splenocytes were measured by ELISA and their mRNAs and levels of associated transcription factors in sinonasal mucosa were determined with quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). Hematoxylin-eosin staining and periodic acid-Schiff staining were performed to evaluate histological changes. Total serum IgE was increased in both allergic and non-allergic CRS. IL-4 was strongly expressed in NLF in both allergic and non-allergic CRS at 16 weeks and not only eosinophils but also neutrophils were increased in NLF of non-allergic CRS mice. The levels of Th1, Th2, and Treg cytokines and transcription factor mRNAs were significantly increased in sinonasal mucosa of non-allergic CRS mice. Both inflammatory cell infiltration and goblet cell hyperplasia were increased in CRS mice. Repeated intranasal instillation of Alternaria results in sinonasal inflammation with inflammatory cell infiltration. The sinonasal mucosal immune responses against Alternaria were shown to differ depending on the host allergic background.

A rapid quantification of invasive phenotype in head and neck squamous cell carcinoma: A novel 3D pillar array system.

BACKGROUND: The widely used in vitro invasion assays for head and neck squamous cell carcinoma (HNSCC) are wound healing, transwell, and organotypic assays. However, these are still lab-intensive and time-consuming tasks. For the rapid detection and high throughput screening of invasiveness in 3D condition, we propose a novel spheroid invasion assay using commercially available pillar platform system. MATERIALS AND METHODS: Using the pillar-based spheroid invasion assay, migration and invasion was evaluated in three patient-derived cells (PDCs) of HNSCC. Immunofluorescence of live cells was used for the quantitative measurement of migratory and invaded cells attached to the pillar. Expression of epithelial-mesenchymal transition (EMT)-related gene (snai1/2) was measured by qRT-PCR. We also tested the impact of drug treatments (cisplatin, docetaxel) on the changes in the invasive phenotype. RESULTS: All PDCs successfully formed spheroid at 4 days and can be measured invasiveness within 7 days. Intriguingly, one PDC (#1) obtained from the advanced stage showed robust migration, invasion and higher transcription of snai1/2, compared with the other two PDCs. Furthermore, the invasion ratio of the control spheroids was about 70% while the invasion ratios of drug-treated spheroids were lower than 50%, and the difference showed statistical significance (p < 0.01). CONCLUSION: The presented spheroid invasion assay using pillar array could be useful for the evaluation of cancer cell behavior and physiology in response to diverse therapeutic drugs.

Safe surgical tracheostomy during the COVID-19 pandemic: A protocol based on experiences with Middle East Respiratory Syndrome and COVID-19 outbreaks in South Korea.

BACKGROUND: A subset of patients with COVID-19 require intensive respiratory care and tracheostomy. Several guidelines on tracheostomy procedures and care of tracheostomized patients have been introduced. In addition to these guidelines, further details of the procedure and perioperative care would be helpful. The purpose of this study is to describe our experience and tracheostomy protocol for patients with MERS or COVID-19. MATERIALS AND METHODS: Thirteen patients with MERS were admitted to the ICU, 9 (69.2%) of whom underwent surgical tracheostomy. During the COVID-19 outbreak, surgical tracheostomy was performed in one of seven patients with COVID-19. We reviewed related documents and collected information through interviews with healthcare workers who had participated in designing a tracheostomy protocol. RESULTS: Compared with previous guidelines, our protocol consisted of enhanced PPE, simplified procedures (no limitation in the use of electrocautery and wound suction, no stay suture, and delayed cannula change) and a validated screening strategy for healthcare workers. Our protocol allowed for all associated healthcare workers to continue their routine clinical work and daily life. It guaranteed safe return to general patient care without any related complications or nosocomial transmission during the MERS and COVID-19 outbreaks. CONCLUSION: Our protocol and experience with tracheostomies for MERS and COVID-19 may be helpful to other healthcare workers in building an institutional protocol optimized for their own COVID-19 situation.

YAP/TAZ direct commitment and maturation of lymph node fibroblastic reticular cells.

Fibroblastic reticular cells (FRCs) are immunologically specialized myofibroblasts of lymphoid organ, and FRC maturation is essential for structural and functional properties of lymph nodes (LNs). Here we show that YAP and TAZ (YAP/TAZ), the final effectors of Hippo signaling, regulate FRC commitment and maturation. Selective depletion of YAP/TAZ in FRCs impairs FRC growth and differentiation and compromises the structural organization of LNs, whereas hyperactivation of YAP/TAZ enhances myofibroblastic characteristics of FRCs and aggravates LN fibrosis. Mechanistically, the interaction between YAP/TAZ and p52 promotes chemokine expression that is required for commitment of FRC lineage prior to lymphotoxin-ß receptor (LTßR) engagement, whereas LTßR activation suppresses YAP/TAZ activity for FRC maturation. Our findings thus present YAP/TAZ as critical regulators of commitment and maturation of FRCs, and hold promise for better understanding of FRC-mediated pathophysiologic processes.