Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

Background/Aims: Diagnosis of isolated laryngopharyngeal reflux symptoms (ILPRS), ie, without concomitant typical reflux symptoms (CTRS), remains difficult. Mean nocturnal baseline impedance (MNBI) reflects impaired mucosal integrity. We determined whether esophageal MNBI could predict pathological esophagopharyngeal reflux (pH+) in patients with ILPRS. Methods: In this cross-sectional study conducted in Taiwan, non-erosive or low-grade esophagitis patients with predominant laryngopharyngeal reflux symptoms underwent combined hypopharyngeal multichannel intraluminal impedance-pH monitoring when off acid suppressants. Participants were divided into the ILPRS (n = 94) and CTRS (n = 63) groups. Asymptomatic subjects without esophagitis (n = 25) served as healthy controls. The MNBI values at 3 cm and 5 cm above the lower esophageal sphincter (LES) and the proximal esophagus were measured. Results: Distal but not proximal esophageal median MNBI values were significantly lower in patients with pH+ than in those with pH– (ILPRS in pH+ vs pH–: 1607 Ω vs 2709 Ω and 1885 Ω vs 2563 Ω at 3 cm and 5 cm above LES, respectively; CTRS in pH+ vs pH–: 1476 vs 2307 Ω and 1500 vs 2301 Ω at 3 cm and 5 cm above LES, respectively, P < 0.05 for all). No significant differences of any MNBI exist between any pH– subgroups and healthy controls. The areas under the receiver operating characteristic curve in the ILPRS group were 0.75 and 0.80, compared to the pH– subgroup and healthy controls (P < 0.001 for both), respectively. Interobserver reproducibility was good (Spearman correlation 0.93, P < 0.0001). Conclusion Distal esophageal MNBI predicts pathological reflux in patients with ILPRS.

Background/Aims: Hypopharyngeal multichannel intraluminal impedance-pH (HMII-pH) technology incorporating 2 trans-upper esophageal sphincter impedance channels has been developed to detect pharyngeal reflux. We used the HMII-pH technique to validate the candidate pharyngeal acid reflux (PAR) episodes based on the dual-pH tracings and determined the interobserver reproducibility. Methods: We conducted a cross-sectional study in tertiary centers in Taiwan. Ninety patients with suspected laryngopharyngeal reflux and 28 healthy volunteers underwent HMII-pH test when off acid suppressants. Candidate PAR episodes were characterized by pharyngeal pH drops of at least 2 units and reaching a nadir pH of 5 within 30 seconds during esophageal acidification. Two experts manually independently identified candidate PAR episodes based on the dual-pH tracings. By reviewing the HMII-pH tracings, HMII-pH-proven PAR episodes were subsequently confirmed. The consensus reviews of HMII-pH-proven PAR episodes were considered to be the reference standard diagnosis. The interobserver reproducibility was assessed. Results: A total of 105 candidate PAR episodes were identified. Among them 84 (80.0%; 95% CI, 71.0-87.0%) were HMII-pH-proven PAR episodes (82 in 16 patients and 2 in 1 healthy subject). Patients tended to have more HMII-pH-proven PAR episodes than healthy controls (median and percentile values [25th, 75th, and 95th percentiles]: 0 [0, 0, 3] vs 0 [0, 0, 0], P = 0.067). The concordance rate in diagnosing HMII-pH-proven PAR episodes between 2 independent observers was 92.2%. Conclusion Our preliminary data showed that 80.0% (71.0-87.0%) of the proposed candidate PAR episodes were HMII-pH-proven PAR episodes, among which the interobserver reproducibility was good.

Background: Ultrasound-guided minimally invasive procedures are widely used to treat thyroid diseases. The objective of this study was to assess the efficacy and safety of ethanol ablation (EA) in comparison with other non-surgical options in the treatment of benign thyroid cystic nodules. Methods: We conducted a systematic search of studies on EA for thyroid cystic nodules, mainly in the Ovid-MEDLINE and Embase, Web of Science, and Cochrane databases. The standardized mean difference (SMD) of the volume reduction ratio (VRR) after EA versus other non-surgical treatments comprised the primary outcome, whereas the odds ratio (OR) of therapeutic success rates between the two groups comprised the secondary outcome. Results: The meta-analysis included 19 studies (four randomized controlled trials and 15 non-randomized studies) with 1,514 participants. The cumulative VRR of EA was 83.908% (95% confidence interval [CI], 79.358% to 88.457%). EA had a significantly higher pooled VRR (SMD, 0.381; 95% CI, 0.028 to 0.734; P=0.030), but not a significantly higher pooled therapeutic success rate (OR, 0.867; 95% CI, 0.132 to 5.689; P=0.880), than other forms of non-surgical management including radiofrequency ablation (RFA), polidocanol sclerotherapy, and simple aspiration with or without saline flush. However, the VRR and therapeutic success rate were not significantly different between EA and RFA. Major complications were recorded only in six patients (0.53%) with self-limiting dysphonia. Conclusion The role of EA as the first-line treatment for benign thyroid cysts and predominantly cystic nodules is supported by its high effectiveness and good safety profile compared to other currently available non-surgical options.

COVID-19/drug therapy* ; Humans ; Integrative Medicine ; Pandemics

The decreased efficacy and severe side effects of antibiotics, as well the increase of multidrug resistant pathogens are seriously threatening human health. It has become an urgent task for the whole world to actively respond to threats and establish effective prevention and control plans. Traditional Chinese medicine (TCM) has a long history with exact curative effect in the treatment of infectious diseases. It not only inhibits pathogens and eliminates endotoxin, but also has therapeutic effect on inflammation, immune abnormality and overall disorder caused by infection. Antibiotics mainly inhibit the pathogen itself, while the combination of TCM and antibiotics is complementary with each other and is considered as a feasible solution to the challenges. Some clinical observations have shown that TCM has potentiality of enhancing antibiotics efficiency and reducing toxicity. Exploring its mechanism is the necessary measure to optimize and popularize treatment regimen. Firstly, multi-level and multi-dimensional systematic pharmacology network analysis methods are used to predict the mechanism of TCM combined with antibiotics in the treatment of infectious diseases, so as to provide the evidence for further empirical research and selection of test indicators. Then by following the principle of corresponding drug use in specific TCM syndromes, the antibiotics and TCM are individually and jointly applied to treat patients with specific syndrome conditions of infectious diseases. Besides routine and comprehensive evaluation of synergistic and attenuated effect of the combined drug use, multi-omics technique is also used to find the subtle effects of these two drugs at a molecular level. The sensitive and stable clinical biomarkers of synergism and attenuation of combined drug use are determined by using biomolecular network analysis technology. Finally, taking these biomarkers as clues, the biotransformation process and regulation mechanism of the biomarkers are traced back in animal models of infectious diseases and cell level, and all of these are clinically verified. As a result, the mechanism of efficacy enhancing and toxicity reducing of combined drug use can be revealed, providing basis for the promotion and application of such combined drug use.

Leptin is a peptide hormone, which has a central role in the regulation of body weight; it also exerts many potentially atherogenic effects. Ferulic acid ethyl ester (FAEE) has been approved for antioxidant properties. The aim of this study was to investigate whether FAEE can inhibit the atherogenic effects of leptin and the possible molecular mechanism of its action. Both of cell proliferation and migration were measured when the aortic smooth muscle cell (A10 cell) treated with leptin and/or FAEE. Phosphorylated p44/42MAPK, cell cycle-regulatory protein (for example, cyclin D1, p21, p27), beta-catenin and matrix metalloproteinase-9 (MMP-9) proteins levels were also measured. Results demonstrated that leptin (10, 100 ng ml-1) significantly increased the proliferation of cells and the phosphorylation of p44/42MAPK in A10 cells. The proliferative effect of leptin was significantly reduced by the pretreatment of U0126 (0.5 muM), a MEK inhibitor, in A10 cells. Meanwhile, leptin significantly increased the protein expression of cyclin D1, p21, beta-catenin and decreased the expression of p27 in A10 cells. In addition, leptin (10 ng ml-1) significantly increased the migration of A10 cells and the expression of MMP-9 protein. Above effects of leptin were significantly reduced by the pretreatment of FAEE (1 and 10 muM) in A10 cells. In conclusion, FAEE exerts multiple effects on leptin-induced cell proliferation and migration, including the inhibition of p44/42MAPK phosphorylation, cell cycle-regulatory proteins and MMP-9, thereby suggesting that FAEE may be a possible therapeutic approach to the inhibition of obese vascular disease.
Animals ; Antioxidants/*pharmacology ; Aorta/cytology/*drug effects ; Caffeic Acids/*pharmacology ; Cell Line ; Cell Movement/*drug effects ; Cell Proliferation/*drug effects ; Leptin/*metabolism ; Matrix Metalloproteinase 9/metabolism ; Muscle, Smooth, Vascular/cytology/drug effects ; Myocytes, Smooth Muscle/cytology/*drug effects ; Rats ; beta Catenin/metabolism

Adult ; Autoantibodies ; immunology ; Common Variable Immunodeficiency ; diagnosis ; etiology ; Female ; Humans ; Interferon-gamma ; immunology ; Penicillium ; pathogenicity

BACKGROUNDIdentification of hospitalized carbapenem-resistant Enterobacteriaceae (CRE)-positive patient is important in preventing nosocomial transmission. The objective of this study was to illustrate the implementation of proactive infection control measures in preventing nosocomial transmission of CRE in a healthcare region of over 3200 beds in Hong Kong between October 1, 2010 and December 31, 2011.

METHODSThe program included active surveillance culture in patients with history of medical tourism with hospitalization and surgical operation outside Hong Kong within 12 months before admission, and "added test" as an opportunistic CRE screening in all fecal specimens submitted to the laboratory. Outbreak investigation and contact tracing were conducted for CRE-positive patients. Serial quantitative culture was performed on CRE-positive patients and the duration of fecal carriage of CRE was analyzed.

RESULTSDuring the study period, a total of 6533 patients were screened for CRE, of which 76 patients were positive (10 from active surveillance culture, 65 from "added test", and 1 secondary case from contact tracing of 223 patients with no nosocomial outbreak), resulting in an overall rate of CRE fecal carriage of 1.2%. The median time of fecal carriage of CRE was 43 days (range, 13-119 days). Beta-lactam-beta-lactamase-inhibitors, cephalosporins, and fluoroquinolones were associated significantly with high fecal bacterial load when used 90 days before CRE detection, while use of cephalosporins, carbapenems, and fluoroquinolones after CRE detection are significantly associated with longer duration of carriage. The duration of fecal carriage of CRE also correlates significantly with the initial fecal bacterial load (Pearson correlation: 0.53; P = 0.02).

CONCLUSIONProactive infection control measures by enhanced surveillance program identify CRE-positive patients and data obtained are useful for the planning of and resource allocation for CRE control.

Anti-Bacterial Agents ; therapeutic use ; Carbapenems ; therapeutic use ; Cephalosporins ; therapeutic use ; Drug Resistance, Bacterial ; Enterobacteriaceae ; drug effects ; Enterobacteriaceae Infections ; prevention & control ; transmission ; Fluoroquinolones ; therapeutic use ; Humans ; Infection Control ; methods

BACKGROUNDProactive infection control management is crucial in preventing the introduction of multiple drug resistant organisms in the healthcare setting. In Hong Kong, where vancomycin-resistant enterococci (VRE) endemicity is not yet established, contact tracing and screening, together with other infection control measures are essential in limiting intra- and inter-hospital transmission. The objective of this study was to illustrate the control measures used to eradicate a VRE outbreak in a hospital network in Hong Kong.

METHODSWe described an outbreak of VRE in a healthcare region in Hong Kong, involving a University affiliated hospital and a convalescent hospital of 1600 and 550 beds respectively. Computer-assisted analysis was utilized to facilitate contact tracing, followed by VRE screening using chromogenic agar. Multi-locus sequence typing (MLST) was performed to assess the clonality of the VRE strains isolated. A case-control study was conducted to identify the risk factors for nosocomial acquisition of VRE.

RESULTSBetween November 26 and December 17, 2011, 11 patients (1 exogenous case and 10 secondary cases) in two hospitals with VRE colonization were detected during our outbreak investigation and screening for 361 contact patients, resulting in a clinical attack rate of 2.8% (10/361). There were 8 males and 3 females with a median age of 78 years (range, 40 - 87 years). MLST confirmed sequence type ST414 in all isolates. Case-control analysis demonstrated that VRE positive cases had a significantly longer cumulative length of stay (P < 0.001), a higher proportion with chronic cerebral and cardiopulmonary conditions (P = 0.001), underlying malignancies (P < 0.001), and presence of urinary catheter (P < 0.001), wound or ulcer (P < 0.001), and a greater proportion of these patients were receiving β-lactam/β-lactamase inhibitors (P = 0.009), carbapenem group (P < 0.001), fluoroquinolones (P = 0.003), or vancomycin (P = 0.001) when compared with the controls.

CONCLUSIONExtensive contact tracing and screening with a "search-and-confine" strategy was a successful tool for outbreak control in our healthcare region.

Aged ; Aged, 80 and over ; Enterococcus faecium ; growth & development ; pathogenicity ; Female ; Gram-Positive Bacterial Infections ; epidemiology ; prevention & control ; Hong Kong ; epidemiology ; Humans ; Male ; Middle Aged ; Vancomycin Resistance