Enhancing regional control in p16-negative oropharyngeal cancer: A propensity score-matched analysis of upfront neck dissection and definitive chemoradiotherapy.

BACKGROUND: The presence of p16 and neck disease is important predictors of prognosis for oropharyngeal squamous cell carcinoma (OPSCC). Patients who are p16-negative and have clinically node-positive (cN+) disease generally have worse oncologic outcomes. This study aimed to investigate whether upfront neck dissection (UFND) could provide potential benefits for patients with cN+ p16-negative OPSCC. METHODS: Through this retrospective study, 76 patients with cN+ p16-negative OPSCC were analyzed, those who received either definite concurrent chemoradiotherapy (CCRT group) or UFND followed by chemoradiotherapy (UFND group). The primary endpoints were regional recurrence-free survival (RRFS), disease-specific survival (DSS), and overall survival (OS). Factors associated with survival were evaluated by univariate and multivariate analysis. Survival between the two groups was compared by propensity score-matched analysis. RESULTS: Matched 23 patients in each group through propensity analysis, the UFND group showed a significantly better 5-year RRFS (94.1% vs 61.0%, p = 0.011) compared to the CCRT group. Univariate analysis revealed that UFND was the sole factor associated with regional control (hazard ratio [HR] = 0.110; 95% CI, 0.014-0.879; p = 0.037). Furthermore, the study found that the CCRT group was associated with a higher dose of radiotherapy and exhibited a significantly higher risk of mortality due to pneumonia. CONCLUSION: The study indicated that UFND followed by CCRT may be a potential treatment option for patients with cN+ p16-negative OPSCC, as it can reduce the risk of regional recurrence. Additionally, the study highlights that definite CCRT is connected to a larger dose of radiotherapy and a higher risk of fatal pneumonia. These findings could be beneficial in informing clinical decision-making and improving treatment outcomes for patients with OPSCC.

Dilemmas and support strategies in dementia care: Experiences of case managers in Taiwan.

Objective: This study aimed to examine the dilemmas encountered and the countermeasures adopted by case managers, who care for individuals with dementia. The study also aimed to identify the types of support and assistance case managers require.Methods: In this qualitative study, the researchers conducted semi-structured interviews with 10 case managers, six from integrated dementia care centers and four from community-based dementia care centers in Taiwan.Results: The results are as follows: (1) Case managers providing services for individuals with dementia primarily encountered two major dilemmas, including cognitive differences (such as a lack of understanding of dementia, differences in ideas about dementia care, and distrust of the professionalism of case managers) with family members and their own insufficient professional capabilities, which made it difficult to reach a consensus on caregiving with family members and address the diverse conditions of individuals with dementia. (2) In response to these dilemmas, case managers adopted various approaches to enhance families' understanding of dementia and facilitate reaching a consensus on care. They also improved their professional capabilities through team discussions and resource networking. (3) The support and assistance required by case managers are continuous learning, the enhancement of their professional competencies, organizational support, and workload management.Conclusion: The findings of this study contribute to an understanding of the dilemmas faced by case managers in Taiwan's centers for integrated dementia care and community-based dementia care centers during policies implementation, as well as the strategies they adopted and the assistance they required. These results can also offer recommendations for policies, professional training, dementia services, and resources to reduce the disparity between policy and practice.

Differences in patient-physician communication between the emergency department and other departments in a hospital setting in Taiwan.

BACKGROUND: Communication fosters trust and understanding between patients and physicians, and specific communication steps help to build relationships. Communication in the emergency department may be different from that in other departments due to differences in medical purposes and treatments. However, the characteristics of communication in the clinical settings of various departments have not been explored nor compared. OBJECTIVES: This study aimed to construct the steps in patient-physician communication based on the Roter Communication Model and compare communication performance between the emergency department and three other clinical settings-internal medicine, surgery, and family medicine departments. METHODS: Both qualitative and quantitative approaches were adopted. First, in-depth interviews were used to analyze clinical communication steps and meanings. Then, a quantitative questionnaire was designed based on the interview results to investigate differences in communication between the emergency department and the other three departments. Qualitative and quantitative data were analyzed from 20 interviews and 98 valid questionnaires. RESULTS: Patient-physician communication consists of four steps and ten factors. The four steps-greeting and data gathering, patient education and counseling, facilitation and patient activation, and building a relationship-had significant progressive effects. Patient education and counseling had an additional significant effect on building a relationship. The emergency department performed less well in the facilitation and patient activation, building a relationship step and the evaluation method, enhancement method, and attitude factors than the other departments. CONCLUSIONS: To improve the quality of patient-physician communication in the emergency department, physicians should strengthen the steps of facilitation and patient activation to encourage patients' active engagement in their health care.

The Physician-Patient Communication Behaviors Among Medical Specialists in a Hospital Setting.

Effective physician-patient communication builds robust physician-patient relationships and reduces medical disputes. However, much is unknown about the differences that exist in the communication behaviors of physicians in different departments. Using a mixed-methods research approach, the researchers used Roter Interaction Analysis System to uncover the communication behaviors of internists, surgeons, family physicians, and emergency physicians at a regional hospital in Taiwan. Semi-structured interviews were conducted to collect the communication experiences of 20 physicians from the internal medicine, surgery, family medicine, and emergency departments. The characteristics were presented through descriptive statistics, bar charts, and dendrograms. Physician-patient communications consisted of four dimensions, 10 factors, and 31 behaviors. The characteristics are as follows: (1) Internists need to improve their overall performance in terms of physician-patient communication behaviors; (2) Surgeons performed well in building relationships through non-verbal methods; (3) Family physicians excelled in facilitation and patient activation. (4) Emergency physicians performed well in patient education and counseling. The characteristics of the aforementioned communication behaviors among internists, surgeons, family physicians, and emergency physicians can be used to construct indicators of physician-patient communication in each department and to develop patient-centered healthcare services in the future.

6'-O-Caffeoylarbutin from Que Zui tea ameliorates acetaminophen-induced liver injury via enhancing antioxidant ability and regulating the PI3K signaling pathway.

Que Zui tea (QT), a traditional herbal tea in China, has a significant hepatoprotective effect. 6'-O-Caffeoylarbutin (CA) is the most abundant chemical compound in the QT. However, the hepatoprotective effect of CA has not been investigated. This study is aimed to evaluate the protective effect of CA on acetaminophen (APAP) induced hepatotoxicity in vivo and in vitro and its possible underlying mechanism. In APAP-induced HepG-2 cells, CA inhibited intracellular ROS accumulation and cell apoptosis, and improved the expression of antioxidants including SOD, CAT and GSH. In APAP-administrated mice, CA pretreatment remarkably ameliorated the histopathological damage and inflammatory response, and antioxidant enzyme activity in the serum and liver tissues. Moreover, the immunohistochemistry and immunofluorescence assay results revealed that the CA markedly reduced ROS production and apoptosis, and activated antioxidant transcription factor Nrf2 in the liver. Meanwhile, molecular docking results showed that the strong binding force of CA and PI3K was due to the higher number of hydrogen- and π-bonds with active site residues. Notably, CA pretreatment significantly regulated the expression of PI3K, Akt, Nrf2, NQO1, HO-1, Bcl-2, Bax, caspase-3, and caspase-9 proteins in APAP-treated liver tissues. These data demonstrated that CA had a protective effect against APAP-induced hepatotoxicity via regulating the PI3K/Akt and Nrf2 signaling pathway.

Patient-physician communication in the emergency department in Taiwan: physicians' perspectives.

BACKGROUND: Effective patient-physician communication promotes trust and understanding between physicians and patients and reduces medical disputes. In this study, the Roter Interaction Analysis System was used to explore physician-patient communication behaviors in the emergency departments of Taiwanese hospitals. METHOD: Data was collected from the dialogues between 8 emergency physicians and 54 patients through nonparticipant observation, and 675 pieces of data were quantitatively and qualitatively analyzed. RESULTS: The results showed that: 1. Emergency physicians' communication behaviors are task-focused. They usually ask closed-ended questions to collect data to identify the symptoms quickly and provide medical treatment. 2. Socioemotion-oriented physician-patient communication behaviors are less common in the emergency department and only serve as an aid for health education and follow-up. Due to time constraints, it is difficult to establish relationships with patients and evoke their positivity. CONCLUSIONS: It is suggested that future education programs on physician-patient communication in the emergency department should focus on strengthening physicians' ability to communicate with patients in a more open way. They should adopt socioemotional-oriented communication skills, expressing respect and kindness, and allowing patients to briefly describe their symptoms and participate in the treatment process to achieve physician-patient consensus.

Clinical Approaches to Migrating Ingested Foreign Bodies in the Neck.

This report presents 2 unusual cases along with a review of the current literature. Further, it aims to propose an algorithm for the initial surgical management of migrating ingested foreign bodies, focusing on the use of fluoroscopy, rigid laryngopharyngoscopy, and an external surgical approach. A 42-year-old man presented with progressive odynophagia after swallowing a fish bone 20 days previously, and a 60-year-old woman presented with a painful enlarging mass over the left lower neck for 1 month. The first case involved a horizontally oriented pharyngeal fish bone with a portion in the neck, which was removed under fluoroscopic guidance and rigid laryngopharyngoscopy in succession. In the second case, there was an extraluminal fish bone that had migrated into the sternocleidomastoid muscle, which was retrieved through cervical incision. All foreign bodies were removed without complications. To the best of our knowledge, this is the second report of fluoroscopy-guided ingested foreign body retrieval and the first one with a proposed algorithm for the management of migrating ingested foreign body in the neck. The location and orientation of migrating ingested foreign bodies as well as their relation to structures in the neck are important factors in determining the surgical approach.

Intracerebral transplantation of autologous adipose-derived stem cells for chronic ischemic stroke: A phase I study.

Current therapy does not provide significant benefits for patients with chronic stroke. Pre-clinical studies suggested that autologous adipose-derived stem cells have benefits for the treatment of chronic stroke. This Phase I open-label study was conducted to demonstrate the safety and efficacy of autologous adipose-derived stem cells (GXNPC1) in chronic stroke. Three patients with chronic stroke were treated with stereotactic implantation of autologous adipose-derived stem cells (1 × 108 cells). The primary endpoints of safety evaluation included adverse events, over a 6 months post-implantation period. The secondary endpoints included improvements in neurological functions. Evolutional change of brain parenchyma was also followed with magnetic resonance imaging (MRI). All three participants improved significantly at 6 months follow-up. The extent of improvement from pre-treatment was: National Institutes of Health Stroke Scale improved 5-15 points, Barthel Index: 25-50 points, Berg balance scale 0-21 points and Fugl-Meyer modified sensation 3-28 points. All three patients had signal change along the implantation tract on MRI one month after surgery. There is no related safety issue through 6 months observation. Clinical measures of neurological symptoms of these patients with chronic stroke improved at 6 months without adverse effects after implantation of autologous adipose-derived stem cells (GXNPC1), which might be correlated with post-implantation changes on brain MRI. Clinical Trial Registration-URL: https://clinicaltrials.gov/ct2/show/NCT02813512?term=ADSC&cond=Stroke&cntry=TW&draw=2&rank=1 Unique identifier: NCT02813512.

The effect of ultra-high pretreatment on free, esterified and insoluble-bound phenolics from mango leaves and their antioxidant and cytoprotective activities.

Ultra-high pressure (UHP) is a novel non-thermal pretreatment method in food processing for improving the extraction yield of polyphenols and functional properties. The present work investigated the phenolic profiles, antioxidant activities, and cytoprotective effects of the free, esterified, and insoluble-bound phenolic fractions from mango leaves before and after ultra-high pressure (UHP) treatment. UHPLC-Q-Orbitrap-MS/MS analysis resulted in the identification of 42 phenolic compounds in the different phenolic forms. UHP pretreatment could significantly influence the contents of total phenols, total flavonoids and individual compounds in the different phenolic fractions (p < 0.05). After UHP pretreatment, these phenolic fractions exhibited greater antioxidant activity, and inhibited reactive oxygen species production and cell apoptosis (p < 0.05). Meanwhile, IBP were the most potential antioxidative and cytoprotective ingredients. Therefore, UHP pretreated mango leaves with enhanced bioactivity could be used as biological agents in the health food industry to improve its application and economic values.

Phenolic constituents, antioxidant activity and neuroprotective effects of ethanol extracts of fruits, leaves and flower buds from Vaccinium dunalianum Wight.

Vaccinium dunalianum Wight is an important healthy tea resource in China with health benefits. The chemical compositions and the possible bioactive substances in its fruits, leaves and flower buds extracts (FE, LE and FBE) were identified and characterized by UHPLC-HRMS/MS. Consequently, FE, LE and FBE were rich in phenolic and flavonoid compounds. Among them, 21 compounds were identified, and the main components were chlorogenic acid, quinic acid and 6'-O-caffeoylarbutin. Furthermore, their neuroprotection and mechanism on H2O2-induced neurotoxicity in PC12 cells were investigated. All the different concentrations of FE, LE and FBE were apparently inhibited the H2O2-induced ROS generation and apoptosis on PC12 cells. FBE showed stronger neuroprotective activity against H2O2-induced PC12 cell damage than those of FE and LE. The mechanism of neuroprotective effect might be related to the upregulation of endogenous antioxidant enzymes expressions and activation of the Nrf2/HO-1 signaling pathway.

Perineural invasion/lymphovascular invasion double positive predicts distant metastasis and poor survival in T3-4 oral squamous cell carcinoma.

Postoperative adjuvant therapy has been indicated by advanced T classification for T3-4 oral squamous cell carcinoma (OSCC) and the significance of perineural invasion (PNI) and lymphovascular invasion (LVI) in treatment for T3-4 OSCC remains unclear. Ninety-eight cumulative patients with T3-4 OSCC who underwent curative surgery between Jan 2002 and Dec 2010 were recruited and analyzed. Twenty-seven (27.6%) patients were PNI/LVI double positive. PNI/LVI double positive demonstrated independent predictive values for higher neck metastasis (LN+), higher distant metastasis (DM) and low 5-year disease-specific survival (DSS) rates (p < 0.001, p = 0.017, and p < 0.001, respectively) after controlling for other pathologic features of the primary tumors. A high DM rate of 33.3% was noted in PNI/LVI double-positive patients. Among the PNI/LVI double negative, single positive to double positive subgroups, increasing LN+, DM rates and decreasing DSS rate were observed. Among the 44 LN+ patients, PNI/LVI double positive remained associated with a markedly high DM rate of 42.9% and a poor 5-year DSS of 27.7%. PNI/LVI double positive plays important roles in prognostication and potential clinical application for T3-4 OSCC by independently predicting LN+, DM, and poor DSS, and can be used as a good marker to select DM high-risk patients for novel adjuvant therapy trials.

NM23-H1 Expression of Head and Neck Squamous Cell Carcinoma in Association With the Response to Irradiation.

A low NM23-H1 expression in head and neck squamous cell carcinoma (HNSCC) was found to be associated with poor clinical outcome. Therefore, we investigated the role of NM23-H1 in the susceptibility of HNSCC cells to irradiation and its clinical significance. An in vitro study was also conducted to validate the results. Furthermore, we used immunohistochemistry to analyze NM23-H1 expression found in specimens of 50 HNSCC patients with cervical metastases receiving postoperative radiotherapy. Low tumor NM23-H1 expression was associated with locoregional recurrence of HNSCC (p=0.040; Hazard ratio=5.62) and poor clinical outcome (p=0.001; Hazard ratio=4.90). To confirm the effect of NM23-H1 on radiation-induced cytotoxicity, we generated several stable clones derived from a human HNSCC cell line (SAS) using knockdown and overexpression of NM23-H1. Knockdown of NM23-H1 decreased the radio-sensitivity of SAS cells, possibly associated with a decrease in the radiation-induced G2/M-phase accumulation and upregulation of cyclin B1. On the contrary, overexpression of NM23-H1 can reverse the aforementioned adverse results. Consequently, we suggest that NM23-H1 expression may be considered as a potential therapeutic treatment option for HNSCC patients.

Comparative investigation of phytochemicals among ten citrus herbs by ultra high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry and evaluation of their antioxidant properties.

The citrus herbs have proved their important medicinal and nutritional values as medicine-food dual-purpose herbs, functional foods, or medical herbs in China. In this study, phytochemicals and antioxidant activity among ten typical citrus herbs (ethanol extracts) were investigated comprehensively. The major ingredients and their contents were analyzed by high-resolution mass spectrometry, and the differences of typical fragment ions between flavanone-7-O-rutinoside(s) and flavanone-7-O-neohesperidoside(s) were discriminated properly in negative electrospray ionization mode. Total polyphenols, total flavonoids, 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), and ferric reducing antioxidant power tests were performed, which indicated their beneficial values and antioxidant effects. The medicine-food dual-purpose herbs including Chenpi, Juluo, Daidaihua, Huajuhong, Xiangyuan, and Foshou exhibited antioxidant capacities significantly by decreasing intracellular reactive oxygen species intensity (P < 0.01), enhancing superoxide dismutase, catalase, and glutathione peroxidase activities (P < 0.01) in H2 O2 -induced RIN-m5F cells. Moreover, the functional foods Zhishi, Zhiqiao, and Qingpi showed moderate antioxidant bioactivity, while the medical herb Juhe showed weak antioxidant bioactivity, which were consistent with the multivariate analysis of their major flavonoids. The study provided a new sight for the chemical differentiation and practical application of citrus herbs as medicine-food dual-purpose herbs, functional foods, or medical herbs.

Phenolic Amides with Immunomodulatory Activity from the Nonpolysaccharide Fraction of Lycium barbarum Fruits.

The fruits of Lycium barbarum have a long history as an edible and medicinal food in Asian regions and have multiple consumption methods; the polysaccharides (LBPs) are commonly considered as their major immunological constituents. The current study revealed that the total phenolic amide moieties from L. barbarum fruits showed greater potential immunomodulatory activity in vivo than did LBPs. Through subsequent investigation on the immunological bioactive phenolic amides, three new phenolic amides, lyciumamides L-N (1-3), as well as 12 analogues, were obtained from the total phenolic amide fraction. Extensive spectroscopic methods were used to elucidate the new structures. Compounds 4-6 and 15 significantly promoted LPS-stimulated B splenocyte, while compounds 4-6 displayed accelerative effects on the proliferation of Con A-stimulated T lymphocytes at a concentration of 20.0 µg/mL. These data indicated that extracts from L. barbarum fruits enriched with phenolic amides could be developed as a nutritional dietary supplement for immunocompromised individuals.

Two new ent-atisane diterpenes from Sapium sebiferum.

Two new ent-atisane diterpenes, sebiferumnins K and L (1 and 2), were isolated from the branches of Sapium sebiferum, together with four known compounds, ent-3-oxoatis-16α, 17-acetonide (3), ent-l6α, 17-dihydroxyatisan-3-one (4), ent-atisane-3ß, 16α, 17-triol (5), ent-3α-hydroxyatis-16α,17-acetonide (6). The structures of these two ent-atisane diterpenes were elucidated by extensive analyses of the spectroscopic data. [Formula: see text].

Two new prenylated C6-C3 compounds from Illicium micranthum Dunn.

Phytochemical investigation of Illicium micranthum led to the isolation of two new prenylated C6-C3 compounds, 12-O-methyl-2,3-dehydroillifunone C (1) and illiciminone A (2), together with three known analogues (3-5) and one known sesquiterpene lactone (6). The structures were established by extensive spectroscopic characterization and the reported data. All the isolates were evaluated for their acetylcholinesterase (AChE) inhibition activity. Compound 5 showed weak inhibitory activity (46.0%) at 50 µM concentration.

Epigallocatechin-3-gallate downregulates PDHA1 interfering the metabolic pathways in human herpesvirus 8 harboring primary effusion lymphoma cells.

Primary effusion lymphoma (PEL) is an aggressive neoplasm correlated with human herpesvirus 8 (HHV8). Metabolic reprogramming is a hallmark of cancers. The alterations in cellular metabolism are important to the survival of HHV8 latently infected cells. Pyruvate dehydrogenase (PDH) controls the flux of metabolites between glycolysis and the tricarboxylic acid cycle (TCA cycle) and is a key enzyme in cancer metabolic reprogramming. Glutaminolysis is required for the survival of PEL cells. Glutamate dehydrogenase 1 (GDH1) converts glutamate into α-ketoglutarate supplying the TCA cycle with intermediates to support anaplerosis. Previously we have observed that epigallocatechin-3-gallate (EGCG) can induce PEL cell death and N-acetyl cysteine (NAC) attenuates EGCG induced PEL cell death. In this study, results showed that EGCG upregulated the expression of glucose transporter GLUT3, and reduced the expression of pyruvate dehydrogenase E1-alpha (PDHA1), the major regulator of PDH, and GDH1. NAC could partially reverse the effects of EGCG in PEL cells. Overexpression of PDHA1 in PEL cells or supplement of α-ketoglutarate attenuated EGCG induced cell death. EGCG also reduced the levels of oncometabolite D-2-hydroxyglutarate (D2HG). These results suggest that EGCG may modulate the metabolism of PEL cells leading to cell death.

Nerve-tumour interaction enhances the aggressiveness of oral squamous cell carcinoma.

OBJECTIVES: Perineural invasion (PNI) is a poor prognostic pathologic feature of oral squamous cell carcinoma (OSCC). The mechanisms of PNI remain poorly understood, and nerve-tumour interactions have been implicated for its pathogenesis. DESIGN AND SETTING: Systematic investigation of nerve-tumour interactions was performed using fresh human peripheral nerve. In vitro and in vivo models were used to determine the ability of human peripheral nerves to enhance OSCC migration/invasion. Retrospective cohort study was also carried out in one medical centre from 2001 to 2009. PARTICIPANTS: 314 T1-2 OSCC patients. MAIN OUTCOME MEASURES: In the transwell migration/invasion assay, the cells in five representative fields were counted. In the nerve implantation model, tumour size was estimated. PNI quantification by PNI focus number was carried out in the OSCC patients to correlate with cervical lymph node metastasis and oncologic outcomes. RESULTS: The transwell migration/invasion assay demonstrated that human peripheral nerves, compared with subcutaneous soft tissue, significantly enhanced the migration/invasion abilities of OSCC. Moreover, the enhanced migration was dose-dependent with increased length or number of peripheral nerve segments. The nerve implantation model showed that human peripheral nerve also enhanced OSCC growth in vivo. Finally, increased PNI focus number was found dose-dependently associated with increased cervical lymph node metastasis and decreased 5-year disease-specific survival rates. CONCLUSIONS: These results clearly indicated the presence of nerve-tumour interaction that involved paracrine influences leading to aggressiveness of OSCC. Further investigations are required to explore key cell types and molecules involved in nerve-tumour interactions for future therapeutic targeting of PNI in OSCC.

[Expression and clinical significance of runt-related transcription factor 3 in children with bronchiolitis].

OBJECTIVE: To study the mRNA level of runt-related transcription factor 3 (RUNX3) in children with bronchiolitis and its clinical significance in bronchiolitis. METHODS: A total of 54 young children with bronchiolitis were enrolled as the bronchiolitis group, among whom 28 with atopic constitution were enrolled in the atopic bronchiolitis group and 26 with non-atopic constitution were enrolled in the non-atopic bronchiolitis group. A total of 48 healthy young children were enrolled as the healthy control group, among whom 24 with atopic constitution were enrolled in the atopic healthy control group and 24 with non-atopic constitution were enrolled in the non-atopic healthy control group. Quantitative real-time PCR was used to measure the mRNA level of RUNX3 in peripheral blood mononuclear cells. ELISA was used to measure the serum levels of interleukin-4 (IL-4) and interferon gamma (IFN-γ). RESULTS: The bronchiolitis group had a significantly lower mRNA level of RUNX3 than the healthy control group, and the atopic bronchiolitis group had a significantly lower mRNA level of RUNX3 than the non-atopic bronchiolitis, atopic healthy control, and non-atopic healthy control groups (P<0.05). The bronchiolitis group had a significantly higher serum level of IL-4 than the healthy control group, and the atopic bronchiolitis group had a significantly higher serum level of IL-4 than the non-atopic healthy control group (P<0.05). The bronchiolitis group had a significantly lower serum level of IFN-γ than the healthy control group, and the atopic bronchiolitis group had a significantly lower serum level of IFN-γ than the non-atopic bronchiolitis, atopic healthy control, and non-atopic healthy control groups (P<0.05). The correlation analysis showed that the mRNA level of RUNX3 was negatively correlated with the serum level of IL-4 and was positively correlated with the serum level of IFN-γ (P<0.05). CONCLUSIONS: Measurement of RUNX3 gene expression in peripheral blood mononuclear cells has a certain value in identifying children with atopic constitution at high risk of asthma among children with bronchiolitis.