Ming-Shao Tsai

Sleep apnea and risk of vertigo: A nationwide population-based cohort study: Sleep Apnea and Risk of Vertigo

To investigate the risk of vertigo in patients with sleep apnea.

Chang Gung Research Database: A multi-institutional database consisting of original medical records

Background The Chang Gung Research Database (CGRD) is a de-identified database derived from original medical records of Chang Gung Memorial Hospital (CGMH), which comprises seven medical institutes located from the northeast to southern regions of Taiwan. The volume of medical services performed in CGMH is large, and clinical and scientific studies based on the CGRD are reported to be of high quality. However, the CGRD as a useful database for research has not been analyzed before. The objective of the study was to analyze the CGRD with regard to its characteristics and coverage of Taiwans population. Methods We performed a nationwide cohort study using population-based data from the Taiwan National Health Insurance Research Database (NHIRD). All patients who had any medical record of outpatient visits or admission between January 1, 1997, and December 31, 2010, were included, and the sex ratio, age distribution, socioeconomic status, urbanicity, severity of illness, prevalence of specific disease, and coverage of the CGRD were analyzed. Results The sex ratio, age distribution, socioeconomic status, and urbanicity of the population of the CGRD are different from those of Taiwan NHIRD and medical centers in Taiwan (all the pairwise p < 0.05). The severity of comorbidities, and prevalence of specific diseases of the population of the CGRD are significantly higher than those of Taiwan NHIRD and medical centers in Taiwan for both outpatient and inpatient samples (all the pairwise p < 0.05). The overall coverage of the CGRD was 21.2% for outpatients and 12.4% for inpatients. The disease-specific coverage of the CGRD was 27–34% for outpatients and 14–21% for inpatients. Conclusions The CGRD is a multi-institutional, original medical record-based research database with high overall and disease-specific coverage of Taiwan. The population of the CGRD has significantly higher severity of comorbidities, and prevalence of specific diseases than those of Taiwan NHIRD and medical centers in Taiwan.

Risk of acute epiglottitis in patients with preexisting diabetes mellitus: A population-based case–control study

Objective Studies have revealed that 3.5%–26.6% of patients with epiglottitis have comorbid diabetes mellitus (DM). However, whether preexisting DM is a risk factor for acute epiglottitis remains unclear. In this study, our aim was to explore the relationship between preexisting DM and acute epiglottitis in different age and sex groups by using population-based data in Taiwan. Methods We analyzed data between January 2000 and December 2013 obtained from the Taiwan National Health Insurance Research Database. The case group consisted of 2,393 patients with acute epiglottitis. The control group comprised 9,572 individuals without epiglottitis, frequency matched by sex, age, urbanization level, and income. Underlying DM was retrospectively assessed in the cases and controls. Univariate and multivariate logistic regression analyses were used to investigate the associations between underlying DM and acute epiglottitis. Results Of the 2,393 patients, 180 (7.5%) had preexisting DM, whereas only 530 (5.5%) of the 9,572 controls had preexisting DM. Multivariate logistic regression analyses indicated that preexisting DM was significantly associated with acute epiglottitis (adjusted odds ratio [aOR] = 1.42, 95% confidence interval [CI] = 1.15–1.75, P = 0.004). Subgroup analysis showed that the association between DM and epiglottitis remained significant for men (aOR = 1.57, 95% CI: 1.19–2.08, p = 0.002) but not for women. Age-stratified analysis revealed a significant association between DM and acute epiglottitis in patients aged 35–64 years. Use of anti-diabetic agents was not significantly associated with the development of acute epiglottitis among diabetic patients, including oral hypoglycemic agents (OHA) alone (aOR = 0.88, 95% CI = 0.53–1.46, p = 0.616), and OHA combined with insulin/ insulin alone (aOR = 1.30, 95% CI = 0.76–2.22, p = 0.339). The association between presence of diabetes complications and the occurrence of acute epiglottitis was also not significant among diabetic patients in this study setting (aOR = 0.86, 95% CI = 0.59–1.26, p = 0.439). Conclusions The results of our large-scale population-based case–control study indicate that preexisting DM is one of the possible factors associated with the development of acute epiglottitis. Physicians should pay attention to the symptoms and signs of acute epiglottitis in DM patients, particularly in men aged 35–64 years.

Epigenetic therapy regulates the expression of ALDH1 and immunologic response: Relevance to the prognosis of oral cancer

OBJECTIVES Aldehyde dehydrogenase 1 (ALDH1) is associated with tumorigenesis, and shown to identify cancer stem cells (CSC)-like cells. We aimed to investigate the significance of ALDH1 in oral squamous cell carcinoma (OSCC) and its correlation with DNMT3b and immune evasion in the present study. METHODS We retrospectively analyzed the clinical outcomes of OSCC patients and examined its correlation with the levels of ALDH1 in tumors and circulating myeloid-derived suppressor cells (MDSCs) in the peripheral blood. Furthermore, the relationships between the DNMT3b, ALDH1 expression, and immune response were examined via clinical specimens and cellular and animal experiments. We also investigated the therapeutic potential of DNA hypomethylating agents in OSCC. RESULTS Our data revealed that the levels of ALDH1 expression were linked to treatment resistance, CSC-like properties, higher circulating MDSC and poor prognosis for OSCC. The radiation resistance noted in ALDH1-positive tumors was associated with augmented radiation-induced increases in the expression of programmed death ligand (PD-L1) and the activation of MDSCs. Furthermore, there was a positive link between ALDH1 and DNMT3b expression shown by clinical specimens and cellular experiments. DNA hypomethylating agents attenuated the radioresistance of ALDH1-positive cancer cells associated with the decreased ALDH1 and the increased DNA damages. In addition, the activation of MDSCs and the expression of PD-L1 were significantly attenuated by epigenetic therapy. CONCLUSIONS Our findings suggested that ALDH1 played an important role in treatment response and the tumor-promoting microenvironment in OSCC. Moreover, epigenetic therapy could be a promising strategy for the treatment of OSCC.

Mortality in tongue cancer patients treated by curative surgery: a retrospective cohort study from CGRD

Background Our study aimed to compare the outcomes of surgical treatment of tongue cancer patients in three different age groups. Methods From 2004 to 2013, we retrospectively analyzed the clinical data of 1,712 patients who were treated in the four institutions constituting the Chang Gung Memorial Hospitals (CGMH). We divided and studied the patients in three age groups: Group 1, younger (<65 years); Group 2, young old (65 to <75); and Group 3, older old patients (≥75 years). Results Multivariate analyses determined the unfavorable, independent prognostic factors of overall survival to be male sex, older age, advanced stage, advanced T, N classifications, and surgery plus chemotherapy. No significant differences were found in adjusted hazard ratios (HR) of death in early-stage disease (stage I–II) among Group 1 (HR 1.0), Group 2 (HR 1.43, 95% confidence interval (CI) [0.87–2.34], p = 0.158), and Group 3 (HR 1.22, 95% CI [0.49–3.03], p = 0.664) patients. However, amongst advanced-stage patients (stage (III–IV)), Group 3 (HR 2.53, 95% CI [1.46–4.38], p = 0.001) showed significantly worse survival than the other two groups after other variables were adjusted for. Fourteen out of 21 older old, advanced-staged patients finally died, and most of the mortalities were non-cancerogenic (9/14, 64.3%), and mostly occurred within one year (12/14, 85%) after cancer diagnosis. These non-cancer cause of death included underlying diseases in combination with infection, pneumonia, poor nutrition status, and trauma. Conclusions Our study showed that advanced T classification (T3–4), positive nodal metastasis (N1–3) and poorly differentiated tumor predicted poor survival for all patients. Outcome of early-stage patients (stage I–II) among three age groups were not significantly different. However, for advanced-stage patients (stage III–IV), the older old patients (≥75) had significantly worse survival than the other two patient groups. Therefore, for early-stage patients, age should not deny them to receive optimal treatments. However, older old patients (≥75) with advanced cancer should be comprehensively assessed by geriatric tools before surgical treatment and combined with intensive postoperative care to improve outcome, especially the unfavorable non-cancerogenic mortalities within one year after cancer diagnosis.

Acute human immunodeficiency virus infection presenting as mononucleosis-like illness, acute hepatitis, and aseptic meningoencephalitis.

Common clinical presentations of acute human immunodeficiencyvirus (HIV) infection includepharyngitis, fever, fatigue, rash, and headache [1]. Mononucleosis-like illness (MLI), aseptic meningitis, hepatitis, pneumonitis, acute myocarditis, and pneumocystic pneumonia are rare manifestations, and have not been reported with concomitant occurrence [1,2]. We report herein a case of acute HIV infection with complicated presentations, including MLI, acute hepatitis, splenomegaly, and aseptic meningoencephalitis. A previously healthy 27-year-old man, denying unprotected sexual exposure or intravenous drug use, presented with sore throat and a fever of up to 39.1 C and lasting for 2 weeks. A physical examination revealed bilateral exudative tonsillitis with generalized maculopapular skin rash. Laboratory tests found a normal white blood cell count with a predominance of lymphocytes (Table 1). Serum biochemistry revealed elevated AST, ALT, r-GT, LDH, and CRP. Infection of hepatitis virus was excluded according to the serologic tests. Abdominal ultrasound showed parenchymal liver disease and splenomegaly. The skin rash biopsy appeared as lymphocytic vasculitis with a negative lupus band test. The patient complained of headache and conscious disturbance with several episodes of involuntary four-limb twitching lasting for 1e2 minutes, with spontaneous recovery. Computed tomography of the brain revealed no intracranial lesions. An electroencephalogram (EEG) showed diffuse cortical dysfunction. Venous ammonia level was within a normal range. The cytology of cerebral-spinal fluid showed predominant lymphocytes (75%) without bacteria. Aseptic meningoencephalitis was suspected. Acute HIV infection ranked high in the

Unilateral Vocal Fold Paralysis and Risk of Pneumonia: A Nationwide Population-Based Cohort Study:

Objective To investigate pneumonia risk among patients with unilateral vocal fold paralysis (UVFP). Study Design Retrospective population-based cohort study. Setting This study used data from the National Health Insurance Research Database of Taiwan, a nationwide population-based database. Subjects and Methods A total of 419 patients newly diagnosed with UVFP between January 1, 1997, and December 31, 2013, were identified from the Longitudinal Health Insurance Database 2000, a nationally representative database of 1 million randomly selected patients. Moreover, 1676 patients without UVFP were matched to patients with UVFP at a 1:4 ratio based on age, sex, socioeconomic status, urbanization level, and site-specific cancers. Patients were followed up until death or the end of the study period (December 31, 2013). The primary outcome was the occurrence of pneumonia. Results The cumulative incidence of pneumonia was significantly higher for patients with UVFP than those without UFVP (P < .001). The adjusted Cox proportional hazard model showed that UVFP was significantly associated with a higher incidence of pneumonia (hazard ratio, 1.97; 95% CI, 1.35-2.86; P < .001). Subgroup analyses demonstrated that UVFP was an independent risk factor of pneumonia for 4 subgroups: young (18-50 years), older (≥51 years), male, and cancer. Conclusion This is the first nationwide population-based cohort study to investigate the association between UVFP and pneumonia. The findings indicate that UVFP is an independent risk factor of pneumonia. Given the study results, physicians should be aware of the potential for pneumonia occurrence following UVFP.

NVP-BEZ235, a dual PI3K-mTOR inhibitor, suppresses the growth of FaDu hypopharyngeal squamous cell carcinoma and has a synergistic effect with Cisplatin

NVP-BEZ235 is a dual phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) inhibitor. A dual approach targeting more than one downstream effector is a promising strategy for treating cancers. The aim of this study was to evaluate the effect of NVP-BEZ235 in treating FaDu hypopharyngeal squamous cell carcinoma (HSCC), either alone or in combination with cisplatin. We found mTOR expression was higher in patients with HSCC. In the in vitro study, treatment with NVP-BEZ235 alone attenuated cell proliferation and suppressed p-p70S6K and p-4E-BP1 expression in FaDu cells. When NVP-BEZ235 was combined with Cisplatin, apoptosis was induced more effectively than with either drug alone. In mice with a FaDu xenograft, cotreatment with NVP-BEZ235 and Cisplatin engendered synergistic effects and produced a greater antitumor response than did treatment with either drug alone. Resected tumor samples also showed decreased p-p70S6K expression. Collectively, these data demonstrate that NVP-BEZ235 inhibits HSCC growth through phospho-p70S6K suppression and has a synergistic effect with Cisplatin in treating HSCC. The data also provide a strategy for more effective HSCC treatment.

Autologous thyroid cartilage graft implantation in medialization laryngoplasty: a modified approach for treating unilateral vocal fold paralysis

Medialization laryngoplasty is the standard surgical treatment for unilateral vocal fold paralysis. This study presents a modified approach in which a thyroid cartilage graft is implanted in medialization laryngoplasty. 22 patients who underwent this approach were included in the study. The results revealed that glottal incompetence and vocal performance were markedly improved following surgery, and the follow-up period ranged from 6 to 74 months (mean, 21.4 months). Acoustic analysis revealed significant improvements in the maximum phonation time (from 3.51 to 7.89 seconds, p < 0.001), F0 (from 221.7 to 171.0 Hertz, p = 0.025), and jitter (from 7.68 to 3.19, p < 0.001). Perceptual assessment revealed a significant decrease in voice grading (from 2.59 to 1.41, p < 0.001), roughness (from 1.82 to 1.23, p = 0.004), and voice breathiness (from 2.55 to 1.23, p < 0.001). None of the patients exhibited severe wound infection, tissue rejection, or other complications attributed to the surgical procedure. In conclusion, autologous thyroid cartilage implantation in medialization laryngoplasty medializes the vocal cord, minimizes the glottal gap, and improves the voice of patients with vocal fold paralysis. This procedure is characterized by simplicity, safety, and acceptable results.

Predictive Value of the Pretreatment Neutrophil-to-Lymphocyte Ratio in Head and Neck Squamous Cell Carcinoma

This study assessed the significance of the neutrophil-to-lymphocyte ratio (NLR) in head and neck squamous cell carcinoma (HNSCC), and the relationships of the NLR with the aldehyde dehydrogenase 1 (ALDH1) level in tumors and the proportion of myeloid-derived suppressor cells (MDSCs) in the peripheral circulation. In total, 227 HNSCC patients who had received curative treatment at our hospital were enrolled into the present study. The NLR of each HNSCC patient before treatment was calculated. The associations of NLR with various clinicopathological parameters and prognoses were then examined. In addition, correlations between the proportion of MDSCs and level of ALDH1 with the NLR were assessed. Our data revealed that an elevated NLR was significantly correlated with the risk of developing locoregional recurrence and with a reduced overall survival in HNSCC patients. Multivariate analyses revealed that the NLR pretreatment and surgical resection were significantly correlated with the rate of treatment failure and the overall survival rate in HNSCC patients. Furthermore, the levels of ALDH1 in tumors and MDSCs in the peripheral circulation were significantly correlated with the prognosis of HNSCC, and the NLR was positively correlated with MDSC levels in the circulation and ALDH1 staining intensity in tumor specimens. In conclusion, the NLR has power in predicting the expression of ALDH1 in tumors, the circulating level of MDSCs, and the prognosis in HNSCC. We suggest that the NLR is an important biomarker that can assist the clinician and patient in making informed decisions regarding treatment options for HNSCC patients.