A scalable, spin-free approach to generate enhanced induced pluripotent stem cell-derived natural killer cells for cancer immunotherapy.

Natural killer (NK) cells play a vital role in innate immunity and show great promise in cancer immunotherapy. Traditional sources of NK cells, such as the peripheral blood, are limited by availability and donor variability. In addition, in vitro expansion can lead to functional exhaustion and gene editing challenges. This study aimed to harness induced pluripotent stem cell (iPSC) technology to provide a consistent and scalable source of NK cells, overcoming the limitations of traditional sources and enhancing the potential for cancer immunotherapy applications. We developed human placental-derived iPSC lines using reprogramming techniques. Subsequently, an optimized two-step differentiation protocol was introduced to generate high-purity NK cells. Initially, iPSCs were differentiated into hematopoietic-like stem cells using spin-free embryoid bodies (EBs). Subsequently, the EBs were transferred to ultra-low attachment plates to induce NK cell differentiation. iPSC-derived NK (iNK) cells expressed common NK cell markers (NKp46, NKp30, NKp44, CD16 and eomesodermin) at both RNA and protein levels. iNK cells demonstrated significant resilience to cryopreservation and exhibited enhanced cytotoxicity. The incorporation of a chimeric antigen receptor (CAR) construct further augmented their cytotoxic potential. This study exemplifies the feasibility of generating iNK cells with high purity and enhanced functional capabilities, their improved resilience to cryopreservation and the potential to have augmented cytotoxicity through CAR expression. Our findings offer a promising pathway for the development of potential cellular immunotherapies, highlighting the critical role of iPSC technology in overcoming challenges associated with traditional NK cell sources.

Development of Physiologically Relevant Skin Organoids from Human Induced Pluripotent Stem Cells.

The development of skin organs for studying developmental pathways, modeling diseases, or regenerative medicine purposes is a major endeavor in the field. Human induced pluripotent stem cells (hiPSCs) are successfully used to derive skin cells, but the field is still far from meeting the goal of creating skin containing appendages, such as hair follicles and sweat glands. Here, the goal is to generate skin organoids (SKOs) from human skin fibroblast or placental CD34+ cell-derived hiPSCs. With all three hiPSC lines, complex SKOs with stratified skin layers and pigmented hair follicles are generated with different efficacies. In addition, the hiPSC-derived SKOs develop sebaceous glands, touch-receptive Merkel cells, and more importantly eccrine sweat glands. Together, physiologically relevant skin organoids are developed by direct induction of embryoid body formation, along with simultaneous inactivation of transforming growth factor beta signaling, activation of fibroblast growth factor signaling, and inhibition of bone morphogenetic protein signaling pathways. The skin organoids created in this study can be used as valuable platforms for further research into human skin development, disease modeling, or reconstructive surgeries.

Variations in the sleep-related breathing disorder index on polysomnography between men with HIV and controls: a matched case-control study.

BACKGROUND: Both sleep-related breathing disorders (SRBDs) and HIV infection can interfere with normal sleep architecture, and also cause physical and psychological distress. We aimed to understand the differences in the obstructive patterns, sleep architecture, physical and psychological distress when compared between people living with HIV (PLWH) and matched the severity of SRBDs controls. METHODS: A comparative study using matched case-control design was conducted. Men with HIV infection (case group) were enrolled from 2016 to 2019. A control group with HIV seronegative men were matched for SRBDs severity, and were selected from sleep medicine center database for comparison. RESULTS: The mean age of the 108 men (including 54 cases and 54 matched controls) was 33.75 years. Central-apnea index (CI) was higher in the case group rather than matched controls (mean CI, 0.34 vs. 0.17, p = 0.049). PLWH had a lower mean percentage of stage 3 sleep (10.26% vs. 13.94%, p = 0.034) and a higher percentage of rapid eye movement sleep (20.59% vs. 17.85%, p = 0.011) compared to matched controls. Nocturnal enuresis and sleepiness causing traffic accidents were more frequent complaint in PLWH compared to controls. CONCLUSIONS: Early detected SRBDs and subtypes in PLWH to begin treatment for the underlying cause could reduce the risk of sleepiness-related traffic accidents.

Two-stage deep-learning-based colonoscopy polyp detection incorporating fisheye and reflection correction.

BACKGROUND AND AIM: Colonoscopy is a useful method for the diagnosis and management of colorectal diseases. Many computer-aided systems have been developed to assist clinicians in detecting colorectal lesions by analyzing colonoscopy images. However, fisheye-lens distortion and light reflection in colonoscopy images can substantially affect the clarity of these images and their utility in detecting polyps. This study proposed a two-stage deep-learning model to correct distortion and reflections in colonoscopy images and thus facilitate polyp detection. METHODS: Images were collected from the PolypSet dataset, the Kvasir-SEG dataset, and one medical center's patient archiving and communication system. The training, validation, and testing datasets comprised 808, 202, and 1100 images, respectively. The first stage involved the correction of fisheye-related distortion in colonoscopy images and polyp detection, which was performed using a convolutional neural network. The second stage involved the use of generative and adversarial networks for correcting reflective colonoscopy images before the convolutional neural network was used for polyp detection. RESULTS: The model had higher accuracy when it was validated using corrected images than when it was validated using uncorrected images (96.8% vs 90.8%, P < 0.001). The model's accuracy in detecting polyps in the Kvasir-SEG dataset reached 96%, and the area under the receiver operating characteristic curve was 0.94. CONCLUSION: The proposed model can facilitate the clinical diagnosis of colorectal polyps and improve the quality of colonoscopy.

Distinct characteristics of various autoimmune liver diseases: A 22-year hospital-based study in Taiwan.

BACKGROUND AND AIM: The characteristics of autoimmune liver diseases (AILDs), including primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and PBC-AIH overlap syndrome (OS), have rarely been investigated and compared in Asia. METHODS: At the Taiwan tertiary referral center, 330 PBC patients (87% treated with ursodeoxycholic acid [UDCA]), 143 AIH patients (94.4% treated with immunosuppressive therapy [IST]) and 21 PBC-AIH OS patients (85.7% treated with UDCA and IST) were enrolled. RESULTS: Compared with AIH patients, PBC patients were older at baseline and had greater female-to-male sex ratios, alkaline phosphatase (ALP) and γ-glutamyl transferase (γ-GT) levels, and liver cirrhosis (LC), dyslipidemia, and hepatic and cardiometabolic complication rates. PBC patients had the lowest transaminase levels, whereas AIH patients had the highest transaminase levels. PBC patients had greater 22-year all-cause mortality and liver transplantation (ACMaLT) (43.5 vs 25.4%, P = 0.004), LC (75 vs 58.5%, P < 0.01), dyslipidemia (54.4 vs 45.9%, P = 0.001), and cerebrovascular accident (11.3 vs 0.8%, P = 0.019) cumulative incidences (CIs) than did AIH patients; PBC-AIH OS patients had greater systemic lupus erythematosus (28.9 vs 8.9%, P = 0.009) CI than did PBC patients. Baseline ALP (hazard ratio: 1.001), albumin (0.514), platelet count (0.997), and LC (3.438) were associated with ACMaLT; age (1.110), albumin (0.350), cirrhosis (46.219), and hepatitis C virus antibody positivity (5.068) were associated with hepatocellular carcinoma (HCC); and female sex (2.183) and body mass index (1.054) were associated with autoimmune diseases. CONCLUSIONS: Compared with AIH patients, PBC patients had greater cardiometabolic CI, and ACMaLT CI, which was associated with cholestasis, liver functional reserve and LC. Older AILD patients with LC and females with obesity demand special caution for the development of HCC and extrahepatic autoimmune diseases, respectively.

Temporal Trends of Inflammatory Bowel Diseases in Taiwan from 2016 to 2020: A Population-Based Study.

BACKGROUND: There are scanty population-based studies investigating the incidence and prevalence rates of inflammatory bowel disease (IBD) in Taiwan. AIMS: This study aimed to estimate the nationwide prevalence and incidence of IBD and identify its noticeable trends in Taiwan between 2016 and 2020. METHODS: A retrospective study by analyzing the data from the National Health Insurance Research Database of Taiwan. RESULTS: A total of 2595 patients with catastrophic IBD illness were registered from 2016 to 2020 in Taiwan (CD, 880; UC, 1715). The male-to-female ratio in the study sample was 1.83:1 for CD and 1.69:1 for UC. The median age of those registered with CD and UC was 37 and 47 years, respectively. The incidence rate of CD was 0.65 per 100,000 persons in 2016 and it was increased to 0.81 per 100,000 persons in 2020. The incidence rate of UC was 1.16 per 100,000 persons in 2016 and it was increased to 1.53 in 2020. Overall, the incidence of IBD was increase from 1.81 per 100,000 persons to 2.34 per 100,000 persons between 2016 and 2020. Overall, the prevalence rates of IBD was increase from 14.95 per 100,000 persons to 20.02 per 100,000 persons between 2016 and 2020. CONCLUSION: The epidemiological stages of IBD in Taiwan was considered in the acceleration in incidence stage, during which incidence rises and prevalence is relatively low. Understanding these geographical differences is important for the rising global burden of IBD.

Severity of tongue base collapse in various body positions in patients with obstructive sleep apnea: A trajectory analysis.

BACKGROUND: Drug-induced sleep endoscopy (DISE) is used for evaluating upper airway anatomy and determining airway obstruction patterns. It is typically performed with the patient in the supine position. Airway collapse severity is influenced by body position and level of consciousness; the resultant dynamic changes may vary across patients. In this study, we evaluated the severity of upper airway collapse through awake endoscopy and DISE and identified factors affecting the pattern of airway collapse severity. METHODS: This study included 66 patients with obstructive sleep apnea. The patients underwent type 1 polysomnography, tongue strength assessment, awake endoscopy in the sitting and supine positions, and DISE. Group-based trajectory modeling was performed to identify patients with different collapse severity patterns in different body positions and at different levels of consciousness. RESULTS: Patient with similar severity trajectory were assigned to the same group. Two different severity trajectories (group 1 and group 2) were identified at the tongue base level. Tongue depression strength varied significantly between groups 1 and 2 (47.00 vs. 35.00 kPa; P = .047). During awake endoscopy, collapse severity was significantly higher in group 2 than in group 1. Group 1 had lower rapid eye movement/nonrapid eye movement apnea-hypopnea index ratios and higher tongue depression strength than did group 2. CONCLUSION: In patients with obstructive sleep apnea, tongue strength may vary depending on body position. Our results should be interpreted with caution because of the limited sample size. Future studies should investigate the effect of oropharyngeal rehabilitation on tongue strength and collapse severity.

Virtual reality-based simulation learning on geriatric oral health care for nursing students: a pilot study.

BACKGROUND: There is a great need for training and education in the nursing curriculum to improve nurses' knowledge and skills to provide oral health care. METHODS: A pilot study was conducted to evaluate the use of a virtual reality (VR)-based Oral Health Care Learning System to train geriatric oral health care among nursing students. Fifty undergraduate nursing students were randomly assigned to experimental (n = 25) and control (n = 25) groups. The experimental group received the VR-based simulation training on geriatric oral health care and the training was implemented twice at two weeks apart from March to November 2021. The control group did not receive the training intervention. Knowledge, attitude, and self-efficacy of geriatric oral health care as well as the intention to assist oral health care for older adults were assessed at the beginning, second, and fourth weeks. Generalized estimating equations were used to analyze the effectiveness of the VR-based simulation training. RESULTS: After the first round of training, students in the experimental group had significantly greater improvements in knowledge and self-efficacy of geriatric oral health care than in the control group. After the second round of training, students in the experimental group had significantly greater improvements in knowledge, attitude, and self-efficacy of geriatric oral health care as well as the intention to assist oral health care for older adult than in the control group. CONCLUSIONS: The VR-based simulation training was effective to improve undergraduate nursing students' knowledge, attitudes and self-efficacy of geriatric oral health as well as the intention to assist oral health care for older adults. The VR-based simulation learning system is an effective tool to provide practice experiences to build confidence and skills and to bridge the gap of understudied geriatric oral health content in entry-level nursing curricula. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05248542; registration date 21/02/2022).

The effect of cumulative noise exposure on distortion product otoacoustic emissions.

OBJECTIVE: This study aimed to identify the characteristics of distortion product otoacoustic emissions (DPOAEs) that can be used to differentiate noise-induced hearing loss (NIHL) from age-related hearing loss. A potential index to detect NIHL was defined in terms of its susceptibility to cumulative noise exposure but not to age. DESIGN: In this cross-sectional cohort study, a job-exposure matrix was used to calculate the cumulative noise exposure. Multivariate linear regression models were used to examine how age and cumulative noise exposure associated with DPOAEs at individual frequencies after adjusting for hypertension, dyslipidaemia, tobacco use and alcohol consumption. STUDY SAMPLE: The pure-tone audiometry and DPOAEs data collected from 239 male workers in a steel factory. RESULTS: DPOAEs and DPOAE signal-to-noise ratios (SNRs) at all frequencies were found to be correlated with age, and those at 2, 3, 4 and 6 kHz were correlated with both age and noise exposure. The difference between DPOAE SNR at 1 and 3 kHz showed significant correlation with noise exposure but not with age. CONCLUSIONS: The results showed that this DPOAE index, the DPOAE SNR at 1 kHz minus the DPOAE SNR at 3 kHz, could add values to audiometric evaluation of NIHL.

Objective multidisciplinary measurements of sleep disturbance and autonomic dysfunction as risk factors for chronic subjective tinnitus.

PURPOSE: This observational study assessed sleep disturbance and autonomic dysfunction as risk factors for chronic subjective tinnitus through polysomnography (PSG) and autonomic function tests. METHODS: Adult patients with chronic subjective tinnitus who visited the department of otolaryngology in our hospitals (n = 40), along with controls without tinnitus (n = 80), were recruited. Individuals with an average hearing threshold level (HL) exceeding 25 dB HL and a known diagnosis of insomnia were excluded. Objective assessments comprised pure-tone audiometry, PSG, and autonomic function tests (e.g., the cold pressor test). RESULTS: Patients with prolonged sleep latency, lower sleep efficiency, and sympathetic hyperactivity had significantly higher risks of developing tinnitus. No interaction effect between poor sleep quality and sympathetic hyperactivity on tinnitus was detected. CONCLUSION: This is the first study to administer PSG and autonomic function tests to patients with chronic subjective tinnitus. Poor sleep quality and autonomic dysfunction were implicated as risk factors for tinnitus. PSG and the autonomic function tests helped identify tinnitus-related comorbidities and inform tinnitus treatment. Sleep disturbance and autonomic dysfunction did not exert an interaction effect on tinnitus. Further studies with a larger sample size and the inclusion of patients with more severe tinnitus are warranted.

Integrating domain knowledge with machine learning to detect obstructive sleep apnea: Snore as a significant bio-feature.

Our study's main purpose is to emphasise the significance of medical knowledge of pathophysiology before machine learning. We investigated whether combining domain knowledge with machine learning results might increase accuracy and minimise the number of bio-features used to detect obstructive sleep apnea (OSA). The present study analysed data on 36 self-reported symptoms and 24 clinical features obtained from 3,495 patients receiving polysomnography at a regional hospital and a medical centre. The area under the receiver operating characteristic (AUC) curve was used to evaluate patients with and without moderate or severe OSA using three prediction models on the basis of various estimation methods: the multiple logistic regression (MLR), support vector machine (SVM), and neural network (NN) methods. Odds ratios stratified by gender and age were also measured to account for clinicians' common sense. We discovered that adding the self-reported snoring item improved the AUC by 0.01-0.10 and helped us to rapidly achieve the optimum level. The performance of four items (gender, age, body mass index [BMI], and snoring) was comparable with that of adding two or more items (neck and waist circumference) for predicting moderate to severe OSA (Apnea-Hypopnea Index ≥15 events/hr) in all three prediction models, demonstrating the medical knowledge value of pathophysiology. The four-item test sample AUCs were 0.83, 0.84, and 0.83 for MLR, SVM, and NN, respectively. Participants with regular snoring and a BMI of ≥25 kg/m2 had a greater chance of moderate to severe OSA according to the stratified adjusted odds ratios. Combining domain knowledge into machine learning could increase efficiency and enable primary care physicians to refer for an OSA diagnosis earlier.

Sleep disturbance and psychological distress in adult patients with tinnitus.

BACKGROUND/PURPOSE: Sleep disturbance and psychological distress are among the most prevalent comorbidities of tinnitus. We aimed to clarify the dose-response effects of these phenomena with tinnitus severity. METHODS: This study enrolled adult patients with subjective tinnitus for more than 6 months was conducted from January 2017 to December 2018 in one tertiary medical center and one local hospital. Data collected included demographic data and questionnaires, namely Tinnitus Handicap Inventory (THI), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Hospital Anxiety and Depression Scale (HADS). RESULTS: In total, 1610 patients with tinnitus (1105 male, 68.6%) with mean age of 48.3 ± 14.3 years completed all questionnaires. The average THI score was 9.2 ± 19.4, and 82.4% of patients reported to have slight tinnitus (THI ranged 0-16). The mean PSQI score was 8.4 ± 4.3, and 70.8% of participants had sleep difficulty (PSQI > 5). Compared with patients with slight tinnitus, those with catastrophic tinnitus were mostly old women with lower body mass index, and had higher scores in ESS, PSQI, and HADS (all P < 0.05). In 1140 patients with sleep difficulty, independent factors influencing THI were age, ESS, and HADS, and positive correlations were observed between age-adjusted THI and ESS, HADS-A, and HADS-D (all P < 0.001). CONCLUSION: Old age, daytime sleepiness, and psychological distress are highly associated with tinnitus severity among patients with sleep difficulty. Management of sleep disturbance and psychological distress is necessary to control tinnitus.

[Cervical Primary Ewing's Sarcoma:Report of One Case].

Ewing's sarcoma in the cervix is characterized by extremely rare occurrence,high degree of malignancy,and rapid progression.The diagnosis of this disease is based on pathology and immunohistochemistry. The main image of the case reported in this paper showed the cervical cyst with solid mass,large volume,and uneven density and signal,and the solid part can be strengthened in enhanced scanning.Because of the rapid growth,the lesion is prone to liquefaction necrosis and bleeding.Since the metastasis occurs early,timely diagnosis is essential.

Integrating health literacy into a theory-based drug-use prevention program: a quasi-experimental study among junior high students in Taiwan.

BACKGROUND: In Taiwan, illegal drug use is a critical health problem during adolescence. Schools playa vital role in preventing students' illegal drug use. Accordingly, we developed and evaluated a school-based, drug-use prevention program integrating the theory of planned behavior (TPB) and health literacy for junior high school students. AIM: This study aimed to use a theory-based program to prevent students from illegal drug use in Taiwanese junior high school students. METHODS: We recruited 648 junior high school students aged around 13-14 years (grades 7 to 8 students) from 14 selected schools: N = 323 in the experimental group, N = 325 in the comparison group. The experimental group received 10 45-min sessions of a theory-based drug-use prevention program. The comparison group received traditional didactic teaching and drug refusal skill training. We used a generalized estimating equation (GEE) to analyze data. RESULTS: Results of paired t-tests indicated that drug-use health literacy and TPB-related variables improved in the experimental group. The GEE analyses indicated that participants in the experimental group also demonstrated significantly improved health literacy (p < 0.001) compared to the comparison group, especially for functional (p < 0.001) and critical health literacy (p = 0.017). The experimental group also showed significant post-intervention improvement in terms of subjective norm scores (p = 0.024). CONCLUSION: Study results demonstrated the effectiveness of a drug-use prevention program on health literacy and subjective norm through integrating the Theory of Planned Behavior and health literacy. The study supports that the future implementation of similar programs for junior high school students can integrate health literacy and subjective norms as two critical program components.

E-healthy diet literacy scale and its relationship with behaviors and health outcomes in Taiwan.

The study was to develop the e-healthy diet literacy (e-HDL) questionnaire based on the comprehensive health literacy (HL) conceptual framework, to examine the association among HL, e-HDL, health behaviors and outcomes. A nationwide study was conducted on 1342 adults aged 18 years and above, between April and September 2017. Multi-stage random sampling was used to recruit the participants from four regions and 19 cities and counties in Taiwan. HL and e-HDL were measured by HLS-SF12 and the e-healthy diet literacy questionnaire (e-HDLQ), respectively. Socio-demographics, behaviors (e.g. smoking, drinking and exercising) and health outcomes were also measured. Principal component analysis (PCA), linear regression models and logistic regression models were used. The mean age was 33.9 ± 11.4 years. The e-HDLQ was constructed with 11 items. A positive association between HL and e-HDL was found. In the multivariate analysis, HL and e-HDL were significantly lower in men and higher in those who used Facebook for searching information. HL was positively associated with the ability to pay for medication, and social status. The e-HDL was lower in older participants, and people who searched for healthy cooking, healthy food places or weight control, as compared with ones searched for nutritional therapies, while positively associated with education. Both HL and e-HDL were positively associated with health status and physical activities. In conclusion, the valid e-HDL survey tool was developed for general public use. The e-HDL strongly associated with HL, while both were determined by gender, online searching means and linked to health behaviors and outcomes.

Impact of mixed cryoglobulinemia on patients with spontaneous hepatitis C virus clearance: A 13-year prospective cohort study.

BACKGROUND: The prevalence and associations of mixed cryoglobulinemia (MC) in patients with spontaneous clearance of hepatitis C virus (HCV) remain elusive. MATERIALS AND METHODS: A 13-year prospective cohort study of patients with spontaneous HCV clearance was conducted in a tertiary care centre. Baseline characteristics, incident cardiovascular and neurologic events and cancers were analysed. RESULTS: Of 104 consecutive patients (mean age: 54.08 years old; females: 71 [68%]), 37 (34.6%) had MC and 6 (5.8%) had cirrhosis. MC (+) patients were more female (86% vs 58%, P = .002), had higher rate of cirrhosis (14% vs 1.5%, P = .012), higher levels of Immunoglobulin G (IgG; P = .001), IgM (P = .002) and fibrosis-4 (FIB-4) (P = .004), but lower levels of complement C4 (P = .034) than the MC (-) patients. Female gender (95% confidence interval [CI] of odds ratio: 1.402-26.715), levels of IgG (1.000-1.004), IgM (1.009-1.037) and FIB-4 (1.217-3.966) were independently associated with MC. Baseline rheumatoid factor (RF) levels were independently associated with incident cancer (95% CI hazard ratio [HR]: 1.001-1.030 [HR: 1.015], P = .039). With a cut-off value of 11.3 IU/mL, RF levels significantly predicted incident cancer (area under curve: 0.865, P = .002). No different cumulative incidences of cardiovascular and neurologic events, cancers or mortalities were identified between MC (+) and MC (-) patient. CONCLUSIONS: Approximately 1/3 of patients with spontaneous HCV clearance yielded MC, which harboured similar characteristics of MC in patients with chronic hepatitis C. Despite the negligible role of MC in the prognosis of patients with spontaneous HCV clearance, the connection between RF and incident cancer demands further investigation.

Prognostic and predictive factors for Taiwanese patients with advanced biliary tract cancer undergoing frontline chemotherapy with gemcitabine and cisplatin: a real-world experience.

BACKGROUND: Chemotherapy with gemcitabine and cisplatin has been the standard of care in first-line chemotherapy for advanced biliary tract cancer (BTC) since the trial ABC-02 was published in 2010. We aimed to investigate the prognostic and predictive factors of this regimen in a cohort of Taiwanese patients with advanced BTC. METHODS: A total of 118 patients with histologically confirmed BTC treated at Chang Gung Memorial Hospital at Linkou from 2012 to 2017 were retrospectively reviewed. RESULTS: The median progression-free survival (PFS) and overall survival (OS) were 3.6 months and 8.4 months, respectively. In the multivariate analysis, neutrophil to lymphocyte ratio (NLR) > 7.45, biliary drainage requiring both percutaneous transhepatic cholangiography drainage (PTCD) and internal stenting, and tumor responses with progressive diseases and not assessed were independent poor prognostic factors for PFS. Male sex, NLR > 7.45, alkaline phosphatase> 94 U/L, biliary drainage requiring both PTCD and internal stenting, and tumor responses with stable disease, progressive diseases and not assessed were independent poor prognostic factors for OS. Monocyte to lymphocyte ratio (MLR) ≤ 0.28 was the only significant predictive factor for the tumor response. Patients with complete response/partial response had significantly lower MLR than patients with other tumor responses. CONCLUSION: We identified three important prognostic factors, namely tumor response, NLR, and biliary drainage requiring both PTCD and internal stenting for both PFS and OS. MLR was the only significant predictive factor for the tumor response. These findings could provide physicians with more information to justify the clinical outcomes in patients with advanced BTC in real-world practice.

Non-alcoholic fatty liver disease among patients with sleep disorders: a Nationwide study of Taiwan.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. Studies have shown that sleep apnea is associated with NAFLD. However, studies on the association between sleep disorders in general and NAFLD are limited. We conducted a nationwide population-based longitudinal study to evaluate this potential association. METHODS: We identified patients diagnosed with sleep disorders in the years 2000 through 2005 in Taiwan using the National Health Insurance Research Database and selected an equal number of patients without sleep disorders from the same database as the comparison cohort. The patients were followed from the index date to the diagnosis of NAFLD or the end of 2013. We used Cox proportional hazards models to estimate the risk of NAFLD associated with sleep disorders. RESULTS: A total of 33,045 patients with sleep disorders were identified. The incidence of NAFLD was 14.0 per 10,000 person-year in patients with sleep disorders and 6.2 per 10,000 person-year in the comparison cohort. The adjusted hazard ratio (AHR) of NAFLD associated with sleep disorders was 1.78 (95% confidence interval [95%CI]: 1.46-2.16), and other independent risk factors included male sex (AHR = 1.31, 95%CI: 1.12-1.54), age 40-59 years (AHR = 1.49, 95%CI: 1.21-1.82), and dyslipidemia (AHR = 2.51, 95%CI: 2.08-3.04). In the subgroup analyses, both patients with (AHR = 2.24, 95%CI: 1.05-4.77) and without (AHR = 1.77, 95%CI: 1.46-2.15) sleep apnea had an increased risk of NAFLD. CONCLUSIONS: Sleep disorders are associated with NAFLD, even in patients without sleep apnea. Further studies are warranted to explore the mechanisms of the association.

Rescue therapy with rifabutin regimen for refractory Helicobacter pylori infection with dual drug-resistant strains.

BACKGROUND: There is no current standard rescue treatment for dual drug-resistant strains of Helicobacter pylori (H. pylori). This aim of this study was to investigate the efficacy of rifabutin-based triple therapy for patients infected with dual drug-resistant strains to clarithromycin and levofloxacin. METHODS: After 2 or 3 H. pylori treatment failures, patients underwent upper endoscopy with tissue biopsies. Phenotypic and genotypic resistances were determined using agar dilution test and polymerase chain reaction with direct sequencing, respectively. Patients infected with dual drug-resistant (clarithromycin and levofloxacin) strains and receiving rifabutin-based triple therapy (rifabutin 150 mg bid, amoxicillin 1 g bid and esomeprazole 40 mg bid for 10 days) were enrolled. Eradication status was determined by 13C-urea breath test 4 weeks after treatment completion. RESULTS: A total of 39 patients infected with dual drug-resistant strains were enrolled in this study, with a mean age of 55.9 years. The eradication rate was 79.5% (31/39) (95% confidence intervals: 54.96% ~ 111.40%). Adverse event was reported in 23.1% (9/39) of patients but they were mild and tolerable. In univariate analysis, no factor was identified as an independent predictor of eradication failure. CONCLUSIONS: Our current study demonstrated that rifabutin-based triple therapy was well tolerated and yielded an acceptable eradication rate for patients infected with dual drug-resistant strains of H. pylori.

Models of anatomically based oropharyngeal rehabilitation with a multilevel approach for patients with obstructive sleep apnea: a meta-synthesis and meta-analysis.

OBJECTIVES: Obstructive sleep apnea (OSA) is a sleep-related breathing disorder associated with dysfunction of oropharyngeal muscles to maintain upper airway patency during sleep. Oropharyngeal rehabilitation (OPR) was developed to restore, reconstruct, and reeducate oropharyngeal muscle function, but current protocols and effectiveness of OPR have been inconsistent. The purpose of this study was to review (1) indications of OPR, (2) protocols of OPR, and (3) effectiveness of OPR. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library and then conducted both meta-synthesis and meta-analysis according to the statement of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). RESULTS: A total of eight studies with 203 patients were included. By means of meta-synthesis, the patients with middle age, BMI < 40 kg/m2, mild-to-moderate OSA, and non-severe upper airway anatomical abnormality were found to benefit from OPR. The protocol of OPR was summarized to be an anatomically based, multilevel approach, including the retropalatal, retroglossal, hypopharyngeal, TMJ, and facial levels. By using meta-analysis, overall outcomes were presented as apnea hypopnea index (AHI) with significant improvement from 25.2 ± 7.8/h to 16.1 ± 6.6/h (mean difference [MD] - 9.8 [95% CI - 11.0 to - 8.6], p < 0.0001); the lowest oxygen saturation (LSAT) improved from 80.2 ± 4.7 to 83.8 ± 2.9% (MD 3.0% [95% CI 2.0 to 4.0], p < 0.0001); Epworth sleepiness scale (ESS) improved from 11.8 ± 1.9 to 6.3 ± 1.6 (MD - 5.9 [95% CI - 7.5 to - 4.2], p < 0.001), neck circumference (NC) from 35.2 ± 1.1 to 34.7 ± 0.9 cm (MD - 0.6 [95% CI - 0.9 to - 0.2], p = 0.002), BMI from 24.8 ± 3.7 to 24.8 ± 4.1 kg/m2 (MD - 0.0; 95% CI - 0.5 to 0.5, p = 0.95). All outcomes except BMI demonstrated significant improvement from OPR. CONCLUSIONS: Meta-analysis of previous OPR reports shows an improvement in AHI of 39%, compared with the usual surgical definition of success at 50%. Only mild and moderate cases of OSA were referred for OPR in the prior studies. In order to improve outcomes with OPR, a comprehensive approach to rehabilitation should be emphasized.