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BACKGROUND: Traditional Chinese medicine (TCM) plays an important role in the primary care system in many places, but research evidence on its effectiveness is largely lacking. The aim of the present study was to compare the effectiveness between TCM and Western medicine (WM) consultations in primary care. OBJECTIVES: To evaluate whether medical consultations could improve the quality of life and health condition of patients in primary care and to find out whether there was any difference in the effectiveness bewteen TCM and WM. DESIGN, SETTING AND SUBJECTS: This was a prospective, longitudinal study on 290 patients of one TCM public and 841 patients of two WM general outpatient clinics (GOPC) in Hong Kong when they consulted for an episodic illness. METHODS: All patients attending a TCM GOPC in TWH, and the two WM GOPC (TWH and ALC), who fullfilled the inclusion criteria were invited to participate. Each patient answered a structured questionnaire on the presenting complaint, socio-demography, chronic morbidity and service utilization, the Chinese Quality of Life instrument (ChQOL) and the SF-36V2 Health Survey immediately before and two weeks after the doctor consultation. The Global Rating on change Scale (GRS) was also administered in the week 2 assessment. OUTCOME MEASURES: The primary outcomes were changes in the ChQOL and SF-36V2 HRQOL scores. Secondary outcomes included the GRS score. The significance of the change within individual were tested by paired t-tests. The differences in change in scores between WM and TCM were tested by independent sample-t-tests or chi-square, as appropriate. Multivariate regresions were used to determine the independent effect of type of medicine on the change in HRQOL scores. RESULTS: Mean ChQOL and SF-36V2 scores of subjects improved significantly two weeks after TCM or WM consultations in all domains except for the Physical form domain of ChQOL. The greatest improvements were found in the SF-36V2 physical-health related domains. 78% TCM clinics and 71% of subjects WM clinics reported an improvement in GRS. The proportion of subjects who had improvement in HRQOL scores were lower among subjects consulting the WM clinic (72.3%) than those consulting TCM clinics (100%) but the difference was not significant after correction for baseline scores. CONCLUSIONS: Both TCM and WM consultations were associated with significant improvement in HRQOL in over 90% of patients. There was no singificant difference between the effectiveness of TCM and WM consultations. The results support the role of TCM as an alternative primary care service in Hong Kong. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Severe acute respiratory syndrome (SARS) caused by coronavirus has become an epidemic affecting many regions worldwide. Fourteen percent to 20% of patients require endotracheal intubation and ventilator support. Some of these patients may require tracheostomy subsequently. This procedure, when performed without protection, may lead to infection of the medical and nursing staff taking care of the patient.Study Design: Based on clinical information of three patients.Methods: The authors carried out an emergency tracheostomy and changed the tracheostomy tube for one patient and performed elective tracheostomy in another two patients.Results: No medical or nursing staff member was infected after carrying out the procedure while taking all the precautions and wearing the appropriate protective apparel.Conclusion: The authors have prepared guidelines for performing a safe tracheostomy under both elective and emergency conditions. Surgeons who might be involved in performing the tracheostomy should become familiar with these guidelines and the appropriate protective apparel. [ABSTRACT FROM AUTHOR]

Background and Aims: HCC recurrence frequently occurs after curative surgery. Histological microvascular invasion (MVI) predicts recurrence but cannot provide preoperative prognostication, whereas clinical prediction scores have variable performances., Approach and Results: Recurr-NET, a multimodal multiphasic residual-network random survival forest deep-learning model incorporating preoperative CT and clinical parameters, was developed to predict HCC recurrence. Preoperative triphasic CT scans were retrieved from patients with resected histology-confirmed HCC from 4 centers in Hong Kong (internal cohort). The internal cohort was randomly divided in an 8:2 ratio into training and internal validation. External testing was performed in an independent cohort from Taiwan.Among 1231 patients (age 62.4y, 83.1% male, 86.8% viral hepatitis, and median follow-up 65.1mo), cumulative HCC recurrence rates at years 2 and 5 were 41.8% and 56.4%, respectively. Recurr-NET achieved excellent accuracy in predicting recurrence from years 1 to 5 (internal cohort AUROC 0.770-0.857; external AUROC 0.758-0.798), significantly outperforming MVI (internal AUROC 0.518-0.590; external AUROC 0.557-0.615) and multiple clinical risk scores (ERASL-PRE, ERASL-POST, DFT, and Shim scores) (internal AUROC 0.523-0.587, external AUROC: 0.524-0.620), respectively (all p < 0.001). Recurr-NET was superior to MVI in stratifying recurrence risks at year 2 (internal: 72.5% vs. 50.0% in MVI; external: 65.3% vs. 46.6% in MVI) and year 5 (internal: 86.4% vs. 62.5% in MVI; external: 81.4% vs. 63.8% in MVI) (all p < 0.001). Recurr-NET was also superior to MVI in stratifying liver-related and all-cause mortality (all p < 0.001). The performance of Recurr-NET remained robust in subgroup analyses., Conclusions: Recurr-NET accurately predicted HCC recurrence, outperforming MVI and clinical prediction scores, highlighting its potential in preoperative prognostication., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background and Aim: We aimed to investigate the effect of metabolic dysfunction-associated steatotic liver disease (MASLD) on three-dose BNT162b2 immunogenicity to the omicron variant., Methods: Adult recipients of three doses of BNT162b2 were prospectively recruited between May and December 2021. The serology of the neutralizing antibody by live virus microneutralization (vMN) to the omicron variant was measured at baseline, day 180, and day 360 after the first dose. The primary outcome was seroconversion (vMN titer ≥ 10) at day 360. Exposure of interest was MASLD, defined as hepatic steatosis (controlled attenuation parameter ≥ 248 dB/m on transient elastography) plus at least one of five cardiometabolic risk factors. Subjects with prior COVID-19 were excluded. A multivariable logistic regression model was used to derive the adjusted odds ratio of seroconversion with MASLD by adjusting for age, sex, antibiotic use, and proton pump inhibitor use., Results: One hundred forty-eight BNT162b2 recipients (male: 48 [32.4%]; median age: 51.0 years [interquartile range, IQR: 44.5-57.3]) were recruited. The median time from the first dose to the third dose was 8.5 months (IQR: 7.9-8.9). MASLD subjects had a lower seroconversion rate than non-MASLD ones (89.6% vs 99.0%; P = 0.007). MASLD was the only independent risk factor for seroconversion (adjusted odds ratio: 0.051, 95% confidence interval: 0.002-0.440). Subgroup analysis of immunogenicity at 4 months after the third dose shows significantly lower vMN titer (13.06 [IQR: 7.69-22.20] vs 33.49 [IQR: 24.05-46.53]; P = 0.004) and seroconversion rate (76.9% vs 97.4%; P = 0.016) in MASLD than non-MASLD subjects, but not within 4 months from the third dose (vMN titer: 46.87 [IQR: 33.12-66.02] vs 41.86 [IQR: 34.47-50.91], P = 0.240; seroconversion rate: 94.3% vs 100%, P = 0.131)., Conclusion: Metabolic dysfunction-associated steatotic liver disease was a risk factor for poorer immunogenicity to the omicron variant, with a more pronounced waning effect compared among three-dose BNT162b2 recipients., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aims: We investigated whether empagliflozin reduces hepatic steatosis in patients with metabolic dysfunction-associated steatotic liver disease without diabetes mellitus., Approach and Results: This was an investigator-initiated, double-blind, randomized, placebo-controlled trial recruiting adult subjects from the community. Eligible subjects without diabetes mellitus (fasting plasma glucose < 7 mmol/L and HbA1c < 6.5%) who had magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥ 5% were randomly allocated to receive empagliflozin 10 mg daily or placebo (1:1 ratio) for 52 weeks (end of treatment, EOT). MRI-PDFF was conducted at baseline and EOT. The primary outcome was the difference in change of MRI-PDFF between the 2 groups at EOT. Secondary outcomes were hepatic steatosis resolution (MRI-PDFF < 5%), alanine aminotransferase drop ≥ 17 U/L, MRI-PDFF decline ≥ 30%, a combination of both, and changes of anthropometric and laboratory parameters at EOT. All outcomes were based on intention-to-treat analysis. Of 98 recruited subjects (median age: 55.7 y [IQR:49.5-63.4]; male:54 [55.1%]), 97 (empagliflozin:49, placebo:48; median MRI-PDFF:9.7% vs 9.0%) had MRI-PDFF repeated at EOT. The Empagliflozin group had a greater reduction in median MRI-PDFF compared to the placebo group (-2.49% vs. -1.43%; p = 0.025), with a nonsignificant trend of resolution of hepatic steatosis (44.9% vs. 28.6%; p = 0.094). There was no significant difference in alanine aminotransferase drop ≥ 17 U/L (16.3% vs. 12.2%; p = 0.564), MRI-PDFF drop ≥ 30% (49.0% vs. 40.8%; p = 0.417), and composite outcome (8.2% vs. 8.2%; p = 1.000). Empagliflozin group had a greater drop in body weight (-2.7 vs. -0.2 kg), waist circumference (-2.0 vs. 0 cm), fasting glucose (-0.3 vs. 0 mmol/L), and ferritin (-126 vs. -22 pmol/L) (all p < 0.05)., Conclusions: Empagliflozin for 52 weeks reduces hepatic fat content in subjects with nondiabetic metabolic dysfunction-associated steatotic liver disease. (ClinicalTrials.gov Identifier: NCT04642261)., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background: In patients with schizophrenia, Diankuang Mengxing Decoction with antipsychotics is one of the treatments for it. However, little information is available regarding the difference between the therapeutic effect of Diankuang Mengxing Decoction with antipsychotics and other treatments. Systematic evaluation is conducted to assess the efficacy and safety of Diankuang Mengxing Decoction and other antipsychotics, which are used to treat schizophrenia., Methods: We performed a systematic review (PROSPERO ID: CRD42023414603). This entailed a computerized search of several research databases from their respective dates of establishment until April 11, 2023, which collected clinical randomized controlled trials of Diankuang Mengxing Decoction combined with antipsychotics. The databases that contributed to this study were PubMed, Web of Science, Embase, EBSCOhost, Cochrane, Scopus, and Google Scholar. Each publication was screened according to defined inclusion and exclusion criteria, and appropriate literature was extracted and evaluated for quality, for which meta-analysis was performed using RevMan 5.4., Results: A literature review of 456 publications resulted in the inclusion of 18 randomized controlled trials with data collected from a total of 1636 patients. Meta-analytical results showed combination with risperidone, olanzapine, chlorpromazine, clozapine, ziprasidone, or aripiprazole increased the overall effectiveness of Diankuang Mengxing Decoction when treating schizophrenia (P < . 00001), among whom olanzapine demonstrated the greatest enhancement (Z = 3.65, odds ratio = 4.26, 95% CI: 1.96-9.28, P = .0003). The 4-week/30-day treatment (P = .0003) and a dosage of 400 mL/d of Diankuang Mengxing Decoction (P = .0004) were more effective. Also, there were widespread reductions to the Positive And Negative Syndrome Scale (PANSS) total scores, PANSS-positive symptom scores, PANSS-negative symptom scores, general psychopathology scores (P < .05 for all), as well as the incidence of adverse effects (Z = 2.79, odds ratio = 0.34, 95% CI: 0.16-0.73, P = .005) in patients with schizophrenia., Conclusion: The combination of Diankuang Mengxing Decoction with different antipsychotics can improve the overall prognosis of patients with schizophrenia; Diankuang Mengxing Decoction combined olanzapine, a dosage of 400 mL/d and a duration of 4 weeks/30 days being the best in this regard, by alleviating the symptoms and diminishing the disorder's adverse effects. To build on this work, more large-sample, multi-center, and high-quality clinical studies in the future would help to further validate our findings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Red blood cells (RBCs) express the nucleic acid-binding toll-like receptor 9 (TLR9) and bind CpG-containing DNA. However, whether human RBCs express other nucleic acid-binding TLRs is unknown. Here we show that human RBCs express the RNA sensor TLR7. TLR7 is present on the red cell membrane and is associated with the RBC membrane protein Band 3. In patients with SARS-CoV2-associated sepsis, TLR7-Band 3 interactions in the RBC membrane are increased when compared with healthy controls. In vitro, RBCs bind synthetic ssRNA and RNA from ssRNA viruses. Thus, RBCs may serve as a previously unrecognized sink for exogenous RNA, expanding the repertoire of non-gas exchanging functions performed by RBCs., (© 2024. The Author(s).)

Background: The spillover impact from disrupted healthcare services for non-COVID-infected diabetes mellitus (DM) patients caused by the reshuffling of the manpower during the pandemic remains understudied, especially in Hong Kong where healthcare resources were already strained before the pandemic., Aim: To evaluate the spill-over effect of the Pandemic on Hong Kong diabetes patients, we examined the change in all-cause mortality and the incidence of cardiovascular disease (CVD) from 2012 to 2021., Method: This retrospective cohort study analyzed data from Hong Kong Hospital Authority healthcare records covering all publicly provided care. Adults diagnosed with DM on/before December 31, 2010, without CVD before January 2012 were included. The 2016-2019 average all-cause mortality and the incidence of CVD after age-standardization represented the pre-pandemic levels. Subjects would leave the cohort after being infected with COVID-19., Results: A cohort of 159,693 patients with diabetes was identified and followed up for 10 years from January 2012 to December 2021. Compared to the pre-pandemic levels, 2020 saw a 12% increase in age-standardized mortality per 10,000 diabetic patients (incidence rate ratio [95% CI]: 1.12 [1.10 - 1.14]), but no significant change in age-standardized CVD incidence. However, in 2021, there were 11% (1.11[1.10 - 1.13]) and 13% (1.13 [1.11 - 1.15]) more new CVD cases and deaths, respectively, versus the pre-pandemic period., Conclusion: The COVID-19 outbreak in 2020 had negative spillover impacts on DM patients without COVID-19 in Hong Kong, with a higher mortality in 2020 and 2021 compared with the pre-pandemic level., (© British Journal of General Practice 2024.)

Red blood cells (RBCs), traditionally recognized for their role in transporting oxygen, play a pivotal role in the body's immune response by expressing TLR9 and scavenging excess host cell-free DNA. DNA capture by RBCs leads to accelerated RBC clearance and triggers inflammation. Whether RBCs can also acquire microbial DNA during infections is unknown. Murine RBCs acquire microbial DNA in vitro and bacterial-DNA-induced macrophage activation was augmented by WT but not TLR9-deleted RBCs. In a mouse model of polymicrobial sepsis, RBC-bound bacterial DNA was elevated in WT but not in erythroid TLR9-deleted mice. Plasma cytokine analysis revealed distinct sepsis endotypes, characterized by persistent hypothermia and hyperinflammation in the most severely affected subjects. RBC-TLR9 deletion attenuated plasma and tissue IL-6 production in the most severe endotype. Parallel findings in human subjects confirmed that RBCs from septic patients harbored more bacterial DNA compared to healthy individuals. Further analysis through 16S sequencing of RBC-bound DNA illustrated distinct microbial communities, with RBC-bound DNA composition correlating with plasma IL-6 in patients with sepsis. Collectively, these findings unveil RBCs as overlooked reservoirs and couriers of microbial DNA, capable of influencing host inflammatory responses in sepsis.

Background and Aims: We aimed to perform a network meta-analysis (NWM) to examine comparative effectiveness of non-selective beta blockers (NSBBs) on prophylaxis of gastroesophageal variceal bleeding (GVB) and mortality benefit., Methods: MEDLINE (OVID) and EMBASE databases were searched for eligible randomized clinical trials (RCTs) from inception to July 3, 2021. Outcomes of interest included primary/secondary prophylaxis of GVB, failure to achieve hepatic venous pressure gradient (HVPG) decremental response, liver-related and all-cause mortality. A Bayesian NWM was performed to derive relative risk (RR) with 95% credible intervals (CrIs). The ranking probability of each NSBB was assessed by surface under cumulative ranking curve (SUCRA)., Results: Thirty-three RCTs including 3,188 cirrhosis patients with gastroesophageal varices were included. Compared with placebo, nadolol ranked first for reducing variceal bleeding [RR:0.25, (95% CrI:0.11-0.51); SUCRA:0.898], followed by carvedilol [RR:0.33, (95% CrI: 0.11-0.88); SUCRA:0.692] and propranolol [RR:0.52, (95% CrI:0.37-0.75); SUCRA:0.405]. Carvedilol was more effective than propranolol in achieving HVPG decremental response [RR:0.43, (95% CrI: 0.26-0.69)]. Carvedilol ranked first for reducing all-cause mortality [RR: 0.32, (95% CrI:0.17-0.57); SUCRA:0.963), followed by nadolol [RR:0.48, (95% CI:0.29-0.77); SUCRA:0.688], and propranolol [RR:0.77, (95% CI:0.58-1.02); SUCRA: 0.337]. Similar findings were observed for liver-related mortality. Carvedilol ranked the safest. The RR of adverse events was 4.38, (95% CrI:0.33-161.4); SUCRA:0.530, followed by propranolol [RR: 7.54, (95% CrI:1.90-47.89); SUCRA:0.360], and nadolol [RR: 18.24, (95% CrI:91.51-390.90); SUCRA:0.158]., Conclusions: Carvedilol is the preferred NSBB with better survival benefit and lower occurrence of adverse events among patients with gastroesophageal varices., Competing Interests: MFY has been an editorial board member of Journal of Clinical and Translational Hepatology since 2022. The other authors have no conflict of interests related to this publication., (© 2023 Authors.)

Ethnopharmacological Relevance: Hypertensive nephropathy (HN) is a complication of hypertension. Taohongsiwu decoction (THSWD) is used clinically but its application in the prevention and treatment of HN remains unelucidated., Aim of Study: This study aims to explore the potential targets and molecular mechanisms of THSWD in the treatment of HN., Materials and Methods: A network pharmacology approach was used to predict the components and targets of THSWD for treating HN. Animal experiments were performed to verify the network pharmacology findings., Results: 205 targets were identified and regarded as potential targets of THSWD in HN treatment. Subsequently, we screened 17 hub genes and identified TP53 as the most critical one. KEGG enrichment analysis showed that p53 signaling pathway might play a significant role. In vivo experiments indicated that high-salt diets can lead to high blood pressure, kidney injury, inflammation, and fibrosis. Furthermore, the altered levels of biomarkers (Iron, malondialdehyde, catalase, ferritin, transferrin, Superoxide dismutase and Glutathione Peroxidase 4) provided evidence of ferroptosis. We found that the ferroptosis inhibitor ferrostatin-1 (Fer-1) and THSWD could significantly alleviate HN by suppressing ferroptosis. THSWD and Fer-1 treatment downregulated the protein and mRNA expression of p53, p21, RB, and CTNNB1, which were upregulated by high salt. Meanwhile, THSWD and Fer-1 reversed the downregulation of Nrf2 caused by high-salt diet., Conclusions: Our results suggested that THSWD attenuate HN induced by a high-salt diet through inhibiting ferroptosis via the p53/Nrf2/p21 pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Antibiotics may increase the risk of COVID-19 among non-vaccinated subjects via probable gut dysbiosis. We aimed to investigate whether antibiotics also affect the clinical outcomes of COVID-19 vaccine recipients. Methods: This was a territory-wide cohort study of 3,821,302 COVID-19 vaccine recipients (aged ≥ 18 years) with ≥2 doses of either BNT162b2 or CoronaVac. Exclusion criteria included prior COVID-19, prior gastrointestinal surgery, and immunocompromised status. The primary outcome was COVID-19 infection and secondary outcomes included COVID-19-related hospitalization and severe infection (composite of intensive care unit admission, ventilatory support, and/or death). Exposure was pre-vaccination antibiotic use (within 180 days of first vaccine dose). Covariates included age, sex, Charlson Comorbidity Index, and concomitant medication use. Subjects were followed from the index date (first dose vaccination) until outcome occurrence, death, an additional dose of vaccination, or 15 November 2022. Propensity score (PS) matching and a Poisson regression model were used to estimate the adjusted incidence rate ratio (aIRR) of outcomes with antibiotic use. Results : Among 342,338 PS matched three-dose vaccine recipients (mean age: 57.4 years; male: 45.1%) with a median follow-up of 13.6 months (IQR: 9.2-16.3), antibiotics were associated with a higher risk of COVID-19 infection (aIRR: 1.16;95% CI: 1.14-1.19), hospitalization (aIRR: 1.75;95% CI: 1.65-1.86), and severe infection (aIRR: 1.60; 95% CI: 1.21-2.11). Notably, antibiotic use was associated with a higher risk of severe infection and death among CoronaVac recipients (aIRR: 1.62 95% CI: 1.18-2.22 and aIRR: 2.70, 95% CI: 1.54-4.73 for the two secondary outcomes, respectively), but not BNT162b2 recipients. Conclusions: Pre-vaccination use of antibiotics was associated with a higher risk of COVID-19 infection, hospitalization, and severe disease outcomes.

Background: Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor approved for the treatment for several mature B-cell malignancies. Reactivation of hepatitis B virus (HBV) is a well-described complication in patients with chronic HBV infection or prior HBV exposure undergoing cytotoxic or immunosuppressive chemotherapy for hematologic malignancies. This phenomenon has been frequently reported with rituximab. However, published data on the risk of HBV reactivation induced by ibrutinib are scarce. Cases of HBV reactivation in hematologic patients receiving ibrutinib therapy have recently been described, but limited only to overt hepatitis B patients or seropositive occult hepatitis B patients., Case Presentation: We report the first case of HBV reactivation during ibrutinib treatment in an asymptomatic 82-year-old woman with seronegative occult hepatitis B patient (i.e., negative for HBsAg, anti-HBc and anti-HBs). Four months after ibrutinib treatment, her liver function test (LFT) was deranged, with seroconversion to HBsAg positivity. Serum hepatitis B virus DNA was quantified to be 1.92 × 10 8 IU/ml. Antiviral treatment was initiated, and viral load was gradually suppressed with improvement in LFT., Conclusions: Our case illustrated that in populations with a high incidence of HBV exposure, systematic screening for HBV exposure is essential prior to ibrutinib treatment, followed by serial monitoring of serologic and molecular markers of hepatitis B. There is a need for an international consensus to support the recommendation of antiviral prophylaxis against HBV reactivation in patients using ibrutinib., (© 2023. The Author(s).)

Background: We aimed to investigate the effect of non-alcoholic fatty liver disease (NAFLD) on BNT162b2 immunogenicity against wild-type SARS-CoV-2 and variants and infection outcome, as data are lacking., Methods: Recipients of two doses of BNT162b2 were prospectively recruited. Outcomes of interest were seroconversion of neutralizing antibody by live virus microneutralization (vMN) to SARS-CoV-2 strains (wild-type, delta and omicron variants) at day 21, 56 and 180 after first dose. Exposure of interest was moderate-to-severe NAFLD (controlled attenuation parameter ≥ 268 dB/M on transient elastography). We calculated adjusted odds ratio (aOR) of infection with NAFLD by adjusting for age, sex, overweight/obesity, diabetes and antibiotic use., Results: Of 259 BNT162b2 recipients (90 (34.7%) male; median age: 50.8 years (IQR: 43.6-57.8)), 68 (26.3%) had NAFLD. For wild type, there was no difference in seroconversion rate between NAFLD and control groups at day 21 (72.1% vs. 77.0%; p = 0.42), day 56 (100% vs. 100%) and day 180 (100% and 97.2%; p = 0.22), respectively. For the delta variant, there was no difference also at day 21 (25.0% vs. 29.5%; p = 0.70), day 56 (100% vs. 98.4%; p = 0.57) and day 180 (89.5% vs. 93.3%; p = 0.58), respectively. For the omicron variant, none achieved seroconversion at day 21 and 180. At day 56, there was no difference in seroconversion rate (15.0% vs. 18.0%; p = 0.76). NAFLD was not an independent risk factor of infection (aOR: 1.50; 95% CI: 0.68-3.24)., Conclusions: NAFLD patients receiving two doses of BNT162b2 had good immunogenicity to wild-type SARS-CoV-2 and the delta variant but not the omicron variant, and they were not at higher risk of infection compared with controls.

Background: Taohong Siwu Decoction (THSWD) is a classic prescription of traditional Chinese medicine. Recent research has shown that the practical components of THSWD have specific curative effects on various cardiovascular diseases, including hypertension, suggesting THSWD could effectively lower blood pressure (BP) with fewer side effects. However, little information is available regarding the effectiveness of THSWD combined with antihypertensive medicine on hypertension., Objective: This meta-analysis aimed to study the efficacy and safety of THSWD in treating hypertension., Methods: According to the search strategy, 8 databases were searched, including China Knowledge Network (CNKI), Wanfang Database, VIP Database, Pubmed, China Biomedical Literature Database (CBM), web of science, EMBASE and Cochrane Library, for the randomized controlled trial of THSWD on hypertension. 9 RCTs were included and 827 patients were involved. This meta-analysis used RevMan 5.4 to evaluate the articles., Results: This review included 9 RCTs. All studies were THSWD with the antihypertensive drug compared with single antihypertensive western medicine. The total effective rate of THSWD combined with corresponding western medicine was significantly improved (Relative risk = 1.26; 95% CI: 1.16-1.37, P < .00001), which could effectively reduce the systolic BP (MD = -15.28 mm Hg; 95% CI: -20.17 to -10.40, P < .00001=, diastolic BP (MD = -9.70 mm Hg; 95% CI: -12.66 to -6.73, P < .00001), Triglycerides (MD = -1.48, 95%CI: -2.09 to -0.87, P < .00001), total cholesterol (MD = -1.43, 95% CI: -1.63 to -1.24, P < .00001) and low density lipoprotein cholesterol (MD = -0.93, 95% CI: -1.07 to -0.80, P < .00001). Compared with the single routine western medicine group, THSWD combined with the corresponding western medicine increased serum high-density lipoprotein (MD = 0.41, 95% CI: 0.35 to 0.46, P < .00001)., Conclusion: THSWD combined with antihypertensive drugs in treating hypertension was curative in lowering BP, improving blood lipid levels and reducing the incidence of adverse reactions compared to antihypertensive medications treatment. However, more high-quality studies are needed due to the biased results and the small number of studies for further verification of the effectiveness of THSWD, and providing a new treatment for clinical reference., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Gut microbiota can be associated with COVID-19 vaccine immunogenicity. We investigated whether recent antibiotic use influences BNT162b2 vaccine immunogenicity. Methods: BNT162b2 recipients from three centers were prospectively recruited. Outcomes of interest were seroconversion of neutralising antibody (NAb) at day 21, 56 and 180 after first dose. We calculated the adjusted odds ratio (aOR) of seroconversion with antibiotic usage (defined as ever use of any antibiotics within six months before first dose of vaccine) by adjusting for covariates including age, sex, smoking, alcohol, and comorbidities. Results: Of 316 BNT162b2 recipients (100 [31.6%] male; median age: 50.1 [IQR: 40.0-57.0] years) recruited, 29 (9.2%) were antibiotic users. There was a trend of lower seroconversion rates in antibiotic users than non-users at day 21 (82.8% vs. 91.3%; p = 0.14) and day 56 (96.6% vs. 99.3%; p = 0.15), but not at day 180 (93.3% vs. 94.1%). A multivariate analysis showed that recent antibiotic usage was associated with a lower seroconversion rate at day 21 (aOR 0.26;95% CI: 0.08-0.96). Other factors associated with a lower seroconversion rate after first dose of the BNT162b2 vaccine included age ≥ 60 years (aOR: 0.34;95% CI: 0.13-0.95) and male sex (aOR: 0.14, 95% CI: 0.05-0.34). There were no significant factors associated with seroconversion after two doses of BNT16b2, including antibiotic use (aOR: 0.03;95% CI: 0.001-1.15). Conclusions: Recent antibiotic use may be associated with a lower seroconversion rate at day 21 (but not day 56 or 180) among BNT162b2 recipients. Further long-term follow-up data with a larger sample size is needed to reach a definite conclusion on how antibiotics influence immunogenicity and the durability of the vaccine response.

Background/aims: Studies of hepatic steatosis (HS) effect on COVID-19 vaccine immunogenicity are lacking. We aimed to compare immunogenicity of BNT162b2 and CoronaVac among moderate/severe HS and control subjects., Methods: Two hundred ninety-five subjects who received BNT162b2 or CoronaVac vaccines from five vaccination centers were categorized into moderate/severe HS (controlled attenuation parameter ≥268 dB/m on transient elastography) (n=74) or control (n=221) groups. Primary outcomes were seroconversion rates of neutralising antibody by live virus Microneutralization (vMN) assay (titer ≥10) at day21 (BNT162b2) or day28 (CoronaVac) and day56 (both). Secondary outcome was highest-tier titer response (top 25% of vMN titer; cutoff: 160 [BNT162b2] and 20 [CoronaVac]) at day 56., Results: For BNT162b2 (n=228, 77.3%), there was no statistical differences in seroconversion rates (day21: 71.7% vs. 76.6%; day56: 100% vs. 100%) or vMN geometric mean titer (GMT) (day21: 13.2 vs. 13.3; day56: 91.9 vs. 101.4) among moderate/severe HS and control groups respectively. However, lower proportion of moderate/severe HS patients had highest-tier response (day56: 5.0% vs. 15.5%; P=0.037). For CoronaVac (n=67, 22.7%), there was no statistical differences in seroconversion rates (day21: 7.1% vs. 15.1%; day56: 64.3% vs. 83.0%) or vMN GMT (5.3 vs. 5.8,) at day28. However, moderate/severe HS patients had lower vMN GMT (9.1 vs. 14.8, P=0.021) at day 56 with lower proportion having highest-tier response (21.4% vs. 52.8%, P=0.036)., Conclusion: While there was no difference in seroconversion rate between moderate/severe HS and control groups after two doses of vaccine, a lower proportion of moderate/severe HS patients achieved highest-tier response for either BNT162b2 or CoronaVac.

Background: Recent studies suggested that use of antibiotics may interfere with treatment responses to immune checkpoint inhibitors (ICIs). We determined whether concurrent use of antibiotics during ICI therapy was associated with adverse outcomes in patients with advanced hepatocellular carcinoma (HCC)., Methods: This is a territory-wide retrospective cohort study including all advanced HCC patients who received ICIs (nivolumab, pembrolizumab, or ipilimumab) between January 2014 and December 2019. Exclusion criteria included prior liver transplantation and use of cabozantinib, regorafenib, or ramucirumab. The exposure of interest was concurrent antibiotic use within 30 days before or after the commencement of ICI. The adjusted hazard ratio (aHR) of cancer-related mortality and all-cause mortality with antibiotic use was derived by propensity score (PS) matching in 1:2 ratio of covariates including baseline characteristics, causes of cirrhosis, Child-Pugh status, prior HCC treatment, comorbidities, concurrent medications, and laboratory results including alpha fetoprotein., Results: A total of 395 HCC patients who had received ICIs were included. During a median follow-up of 16.5 months (interquartile range [IQR]: 5.6-44.3), there were 286 (72.4%) deaths including 231 cancer-related deaths. The median time from the first ICI to event was 7.7 months (IQR: 4.0-16.8). PS matching of 56 antibiotic users with 99 nonusers showed that concurrent antibiotic use with ICI was associated with higher cancer-related (aHR: 1.66; 95% CI: 1.08-2.54) and all-cause mortality (aHR: 1.63; 95% CI: 1.17-2.28)., Conclusions: Concurrent antibiotic use during immunotherapy was associated with higher mortality in patients with advanced HCC. Further studies should examine the role of gut dysbiosis on responses to ICI., Competing Interests: K.S.C. has received speaker fee from AstraZeneca. W.K.L. has received speaker fee from Eisai, Ipsen and honorarium for attending advisory board for Janssen and Pfizer., (Copyright © 2021 by S. Karger AG, Basel.)

Introduction: We aimed to describe long-term clinical outcomes in chronic hepatitis B (CHB) patients after HBsAg seroclearance, and identify factors that modify disease outcomes., Methods: CHB patients with HBsAg seroclearance occurring between 1986 and 2017 were recruited. Primary outcome was cirrhosis/hepatocellular carcinoma (HCC), and secondary outcomes were hepatic decompensation, liver-related death/transplantation, and all-cause mortality. Multivariable Cox model included demographics, prior antivirals, comorbidities, drugs (statins, metformin, proton-pump inhibitors, non-selective beta-blockers), and laboratory parameters (platelet, liver function test, prothrombin time, alpha-fetoprotein [AFP], anti-HBs). Statin users were propensity score matched (PSM) with non-users (1:2 ratio) for survival analysis of all outcomes., Results: Of 913 patients with HBsAg seroclearance (male: 613 [67.1%]; median age: 53.4 years [18.5-87.0]), 129 (14.1%) were statin users. During median follow-up of 7.7 years (up to 29.1 years), 64/833 (7.7%) developed cirrhosis, 25/905 (2.8%) developed HCC, 3/913 (0.3%) underwent transplantation, and 76/913 (8.3%) died. Statins were associated with lower cirrhosis/HCC risk (adjusted hazard ratio [aHR]: 0.44; 95% CI 0.20-0.96; aHR for every 1-year increase in use: 0.85; 95% CI 0.75-0.97). Statin users had no hepatic decompensation or liver-related death/transplantation (vs 18/778 [2.3%] and 18/784 [2.3%] cases in statin non-users, respectively). Statins were also associated with lower all-cause mortality risk (aHR: 0.21; 95% CI 0.08-0.53). PSM yields consistent results for beneficial effects of statins (log-rank p < 0.05 for all outcomes). Other factors for cirrhosis/HCC included increasing age (aHR: 1.06), diabetes (aHR: 2.03), higher creatinine (aHR: 1.008), GGT > 50U/L (aHR: 3.25), and AFP > 9 ng/mL (aHR: 10.14)., Conclusion: Patients with HBsAg seroclearance have favorable long-term survival. However, liver-related adverse outcomes still develop, necessitating further investigations on beneficial effects of statins., (© 2021. Asian Pacific Association for the Study of the Liver.)

Aim: To investigate the role of the gut microbiome in regulating key insulin homeostasis traits (insulin sensitivity, insulin secretion and insulin clearance) whose dysfunction leads to type 2 diabetes (T2D)., Materials and Methods: The Microbiome and Insulin Longitudinal Evaluation Study (MILES) focuses on African American and non-Hispanic white participants aged 40-80 years without diabetes. Three study visits are planned (at baseline, 15 and 30 months). Baseline measurements include assessment of the stool microbiome and administration of an oral glucose tolerance test, which will yield indexes of insulin sensitivity, insulin secretion and insulin clearance. The gut microbiome profile (composition and function) will be determined using whole metagenome shotgun sequencing along with analyses of plasma short chain fatty acids. Additional data collected include dietary history, sociodemographic factors, health habits, anthropometry, medical history, medications and family history. Most assessments are repeated 15 and 30 months following baseline., Results: After screening 875 individuals, 129 African American and 224 non-Hispanic white participants were enrolled. At baseline, African American participants have higher blood pressure, weight, body mass index, waist and hip circumferences but similar waist-hip ratio compared with the non-Hispanic white participants. On average, African American participants are less insulin-sensitive and have higher acute insulin secretion and lower insulin clearance., Conclusions: The longitudinal design and robust characterization of potential mediators will allow for the assessment of glucose and insulin homeostasis and gut microbiota as they change over time, improving our ability to discern causal relationships between the microbiome and the insulin homeostasis traits whose deterioration determines T2D, setting the stage for future microbiome-directed therapies to prevent and treat T2D., (© 2020 John Wiley & Sons Ltd.)

COVID-19, the disease caused by the SARS-CoV-2 virus, can progress to multi-organ failure characterized by respiratory insufficiency, arrhythmias, thromboembolic complications and shock. The mortality of patients hospitalized with COVID-19 is unacceptably high and new strategies are urgently needed to rapidly identify and treat patients at risk for organ failure. Clinical epidemiologic studies demonstrate that vulnerability to organ failure is greatest after viral clearance from the upper airway, which suggests that dysregulation of the host immune response is a critical mediator of clinical deterioration and death. Autopsy and pre-clinical evidence implicate aberrant complement activation in endothelial injury and organ failure. A potential therapeutic strategy warranting investigation is to inhibit complement, with case reports of successful treatment of COVID-19 with inhibitors of complement. However, this approach requires careful balance between the host protective and potential injurious effects of complement activation, and biomarkers to identify the optimal timing and candidates for therapy are lacking. Here we report the presence of complement activation products on circulating erythrocytes from hospitalized COVID-19 patients using flow cytometry. These findings suggest that novel erythrocyte-based diagnostics provide a method to identify patients with dysregulated complement activation.

Introduction: Studies have found that increased mobile phone use (MPU) is associated with multiple health issues such as depression, disordered sleep and pain. However, the current situation and interrelationships of these problems remain unexplored in the Hong Kong population., Objectives: This study aimed to understand the situation and problematic use of mobile phones by Hong Kong secondary school students and to investigate depressive symptoms, bodily pain and daytime sleepiness and the associations of these factors with MPU in Hong Kong secondary school students., Methods: This quantitative cross-sectional design study was based on self-administered questionnaires completed at five secondary schools. The questionnaire comprised five sections: MPU as measured by the Chinese version of the 10-Item Mobile Phone Problem Use Scale (CMPPUS-10); depressive symptoms according to the Depression Anxiety Stress Scale-21 Chinese Version (DASS-21); bodily pain according to the Brief Pain Inventory Short Form Chinese (BPISF-C); daytime sleepiness as measured using the Chinese version of the Epworth Sleepiness Scale (CESS) and socio-demographic questions., Results: A total of 686 students were recruited. The CMPPUS-10 score correlated positively with the average daily duration of MPU and the presence of depression, daytime sleepiness and bodily pain. Problematic mobile phone users received significantly higher scores for depression severity, bodily pain and daytime sleepiness. Health problems were significantly more severe in female than in male students. Bodily pain and daytime sleepiness mediated the relationship of MPU with depression., Conclusions: Problematic MPU was associated with depression, bodily pain and daytime sleepiness. These findings will inform further studies of MPU-related health problems., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Most previous studies of interferon-alpha/beta (IFN-α/β) response antagonism by alphaviruses have focused upon interruption of IFN-α/β induction and/or receptor signaling cascades. Infection of mice with Venezuelan equine encephalitis alphavirus (VEEV) or Sindbis virus (SINV) induces serum IFN-α/β, that elicits a systemic antiviral state in uninfected cells successfully controlling SINV but not VEEV replication. Furthermore, VEEV replication is more resistant than that of SINV to a pre-existing antiviral state in vitro. While host macromolecular shutoff is proposed as a major antagonist of IFN-α/β induction, the underlying mechanisms of alphavirus resistance to a pre-existing antiviral state are not fully defined, nor is the mechanism for the greater resistance of VEEV. Here, we have separated viral transcription and translation shutoff with multiple alphaviruses, identified the viral proteins that induce each activity, and demonstrated that VEEV nonstructural protein 2-induced translation shutoff is likely a critical factor in enhanced antiviral state resistance of this alphavirus., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A gold standard of antiviral vaccination has been the safe and effective live-attenuated 17D-based yellow fever virus (YFV) vaccines. Among more than 500 million vaccinees, only a handful of cases have been reported in which vaccinees developed a virulent wild type YFV infection. This efficacy is presumed to be the result of both neutralizing antibodies and a robust T cell response. However, the particular immune components required for protection against YFV have never been evaluated. An understanding of the immune mechanisms that underlie 17D-based vaccine efficacy is critical to the development of next-generation vaccines against flaviviruses and other pathogens. Here we have addressed this question for the first time using a murine model of disease. Similar to humans, vaccination elicited long-term protection against challenge, characterized by high neutralizing antibody titers and a robust T cell response that formed long-lived memory. Both CD4+ and CD8+ T cells were polyfunctional and cytolytic. Adoptive transfer of immune sera or CD4+ T cells provided partial protection against YFV, but complete protection was achieved by transfer of both immune sera and CD4+ T cells. Thus, robust CD4+ T cell activity may be a critical contributor to protective immunity elicited by highly effective live attenuated vaccines.

S-Glutathionyl-hydroquinone reductases (GS-HQRs) are a new class of glutathione transferases, widely present in bacteria, halobacteria, fungi, and plants. They catalyze glutathione (GSH)-dependent reduction of GS-trichloro-p-hydroquinone to trichloro-p-hydroquinone. Since GS-trichloro-p-hydroquinone is uncommon in nature, the extensive presence of GS-HQRs suggests they use common GS-hydroquinones. Here we demonstrate that several benzoquinones spontaneously reacted with GSH to form GS-hydroquinones via Michael addition, and four GS-HQRs from yeast and bacteria reduced the GS-hydroquinones to the corresponding hydroquinones. The spontaneous and enzymatic reactions led to the reduction of benzoquinones to hydroquinones with the concomitant oxidation of GSH to oxidized glutathione (GS-SG). The enzymes did not use GS-benzoquinones or other thiol-hydroquinones, for example, S-cysteinyl-hydroquinone, as substrates. Apparent kinetic parameters showed the enzymes preferred hydrophobic, bulky substrates, such as GS-menadiol. The broad substrate range and their wide distribution suggest two potential physiological roles: channeling GS-hydroquinones back to hydroquinones and reducing benzoquinones via spontaneous formation of GS-hydroquinones and then enzymatic reduction to hydroquinones. The functions are likely important in metabolic pathways with quinone intermediates.

Lignocellulosic biomass is usually converted to hydrolysates, which consist of sugars and sugar derivatives, such as furfural. Before yeast ferments sugars to ethanol, it reduces toxic furfural to non-inhibitory furfuryl alcohol in a prolonged lag phase. Bioreduction of furfural may shorten the lag phase. Cupriavidus necator JMP134 rapidly reduces furfural with a Zn-dependent alcohol dehydrogenase (FurX) at the expense of ethanol (Li et al. 2011). The mechanism of the ethanol-dependent reduction of furfural by FurX and three homologous alcohol dehydrogenases was investigated. The reduction consisted of two individual reactions: ethanol-dependent reduction of NAD(+) to NADH and then NADH-dependent reduction of furfural to furfuryl alcohol. The kinetic parameters of the coupled reaction and the individual reactions were determined for the four enzymes. The data indicated that limited NADH was released in the coupled reaction. The enzymes had high affinities for NADH (e.g., K ( d ) of 0.043 μM for the FurX-NADH complex) and relatively low affinities for NAD(+) (e.g., K ( d ) of 87 μM for FurX-NAD(+)). The kinetic data suggest that the four enzymes are efficient "furfural reductases" with either ethanol or NADH as the reducing power. The standard free energy change (ΔG°') for ethanol-dependent reduction of furfural was determined to be -1.1 kJ mol(-1). The physiological benefit for ethanol-dependent reduction of furfural is likely to replace toxic and recalcitrant furfural with less toxic and more biodegradable acetaldehyde.

Ethanol is a renewable biofuel, and it can be produced from lignocellulosic biomass. The biomass is usually converted to hydrolysates that consist of sugar and sugar derivatives, such as furfural. Yeast ferments sugar to ethanol, but furfural higher than 3 mM is inhibitory. It can take several days for yeast cells to reduce furfural to non-inhibitory furfuryl alcohol before producing ethanol. Bioreduction of furfural to furfuryl alcohol before fermentation may relieve yeast from furfural toxicity. We observed that Cupriavidus necator JMP134, a strict aerobe, rapidly reduced 17 mM furfural to less than 3 mM within 14 min with cell turbidity of 1.0 at 600 nm at 50°C. The rapid reduction consumed ethanol. The "furfural reductase" (FurX) was purified, and it oxidized ethanol to acetaldehyde and reduced furfural to furfuryl alcohol with NAD(+) as the cofactor. The protein was identified with mass spectrometry fingerprinting to be a hypothetical protein belonging to Zn-dependent alcohol dehydrogenase family. The furX-inactivation mutant of C. necator JMP134 lost the ability to rapidly reduce furfural, and Escherichia coli producing recombinant FurX gained the ability. Thus, an alcohol dehydrogenase enabled bacteria to rapidly reduce furfural with ethanol as the reducing power.

IgG4-related sclerosing disease is a recently recognized syndrome characterized by mass-forming lesions in exocrine glands or extranodal tissues due to lymphoplasmacytic infiltrates and sclerosis, a raised serum IgG4 level and increased IgG4+ plasma cells in the involved tissues. We report the morphologic features of the enlarged regional (n=3) and nonregional lymph nodes (n=3) in patients with this syndrome. The patients presented with autoimmune pancreatitis, lymphoplasmacytic sclerosing cholangitis, chronic sclerosing dacryoadenitis, or chronic sclerosing sialadenitis. The histologic features of the lymph nodes could be categorized into 3 patterns: Castleman diseaselike, follicular hyperplasia, and interfollicular expansion by immunoblasts and plasma cells. The percentage of IgG4+/IgG+ plasma cells was markedly elevated (mean 62% vs. 9.9% in 54 control lymph nodes comprising a wide variety of reactive conditions). We also report 6 cases of primary lymphadenopathy characterized by increased IgG4+/IgG+plasma cells (mean 58%). These cases share many clinical and pathologic similarities with IgG4-related sclerosing disease. In fact, 2 of these patients developed lymphoplasmacytic sclerosing cholangitis or lacrimal and submandibular gland involvement during the clinical course. These cases therefore probably represent primary lymph node manifestation of the disease. The importance of recognition of the lymphadenopathic form of IgG4-related sclerosing disease lies in the remarkable response to steroid therapy, and the potential of mistaking the disease for lymphoma either clinically or histologically.

Background: Thoracoscopic mobilization of the esophagus for pharyngolaryngoesophagectomy allows dissection under direct vision, and therefore it potentially results in fewer complications than conventional transhiatal mobilization. In this article we report our experience with this approach. It was also hypothesized that a learning curve existed and that results have improved over time., Patients and Methods: From July 1994 until January 2004, 57 patients underwent pharyngolaryngoesophagectomy in our institution. Intraoperative events and postoperative outcome were prospectively documented, and long-term follow-up data were also studied. Results were compared between the first 30 patients and the last 27 patients., Results: There were no significant differences between the two groups with respect to the various clinicopathological characteristics. There was no difference in the median thoracoscopic time between the first 30 and last 27 patients at 90 and 75 min, respectively, p = 0.18. For the complete procedure there was significantly less blood loss in the later group; median (range) blood loss 700 (164-3000) ml versus 400 (100-1200) ml, p = 0.002. Overall pulmonary complications occurred in 12 patients (40%) in the first group versus 13 (48%) in the second group, p = 0.6. The incidence of atrial arrhythmia was also similar, affecting 6 (20%) patients and 3 (11%), respectively, p = 0.47. Hospital mortality rates were 13.3% and 7.4%, p = 0.67. Two-year survival rates were no different (46% versus 45% p = 0.85)., Conclusions: Although, subjectively, operating skills have improved over time, better results in the second half of this series could not be demonstrated clearly, likely because the operating surgeons had prior extensive experience in esophageal and thoracoscopic procedures.

Objective: The aim of this study was to evaluate the effectiveness of 904-nm low-level laser therapy (LLLT) in the management of lateral epicondylitis., Background Data: Lateral epicondylitis is characterized by pain and tenderness over the lateral elbow, which may also result in reduction in grip strength and impairment in physical function. LLLT has been shown effective in its therapeutic effects in tissue healing and pain control., Methods: Thirty-nine patients with lateral epicondylitis were randomly assigned to receive either active laser with an energy dose of 0.275 J per tender point (laser group) or sham irradiation (placebo group) for a total of nine sessions. The outcome measures were mechanical pain threshold, maximum grip strength, level of pain at maximum grip strength as measured by the Visual Analogue Scale (VAS) and the subjective rating of physical function with Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire., Results: Significantly greater improvements were shown in all outcome measures with the laser group than with the placebo group (p < 0.0125), except in the two subsections of DASH., Conclusion: This study revealed that LLLT in addition to exercise is effective in relieving pain, and in improving the grip strength and subjective rating of physical function of patients with lateral epicondylitis.

Background: The aim of this study was to evaluate the clinical outcome of patients who underwent craniofacial resection for tumour in the anterior skull base at the University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong between January 1993 and June 2003., Methods: A retrospective review was conducted. The duration of follow up ranged from 1.7 to 119 months (median, 41.8 months). The setting was a tertiary referral centre. Thirty-nine patients, 23 males and 16 females, aged 8-79 years were included. Thirty-four patients had malignant tumour and five patients had benign pathology. The tumour pathology was diversified. Nineteen patients had no treatment before the surgery, and the remaining 20 patients had received surgery, radiotherapy or combined treatment before resection. Patients were given postoperative irradiation and/or chemotherapy depending on the pathology of the tumour and the extent of the disease and clearance at the time of surgery., Results: There was no operative mortality. Complications occurred in 10 patients and among them, three required reoperation. The other complications were managed successfully with conservative measures. The 5-year actuarial disease-free survival for patients with benign and malignant pathology was 100 and 77.6%, respectively. For patients with malignant pathology, 5-year actuarial disease-free survival was 90% when the resection margin was negative at surgery. However, the survival dropped to 53.6% when the resection margin was involved macroscopically., Conclusion: Craniofacial resection was an appropriate surgical approach with acceptable morbidity in selected patients with tumour located at the anterior skull base. Complete excision of malignant tumour could achieve 90% 5-year disease-free actuarial survival.

Objective: To investigate whether the mechanism of a combined surfactant and inhaled nitric oxide (iNO) in improvement of oxygenation and mitigation of lung injury is associated with suppression of nuclear transcription factor kappa B (NF-kappaB) in the lung tissue of ventilated rabbits with meconium aspiration., Methods: Adult rabbits (weight 2.0-3.5 kg, n = 33) were anesthetized, intratracheally received human meconium, and were subjected to pressure support ventilation for 30-60 min to induce hypoxemic respiratory failure and lung injury. They were then treated for 6 h in groups: control animals; rabbits receiving iNO; animals receiving surfactant (100 mg/kg), and rabbits receiving both iNO and surfactant. iNO was delivered continuously by mass flow controller in sequence at 1, 10, 20, and 40 ppm each for 60 min at 30-min intervals., Results: Improvement in oxygenation and lung mechanics was found in the animals receiving both iNO and surfactant, associated with a marked response to iNO at 10 and 20 ppm (p < 0.05), a significantly higher ratio of disaturated phosphatidylcholine to total proteins, a lower surface tension of phospholipids from bronchoalveolar lavage fluid, a lower wet-to-dry lung weight ratio and lower lung injury scores, and better alveolar aeration. The iNO- and surfactant-treated groups had only transient or moderate-to-intermediate improvement in the associated parameters. The expression of NF-kappaB in lung tissue was enhanced in the control group, attenuated in the groups treated with either iNO or surfactant, and significantly suppressed in the group receiving both iNO and surfactant., Conclusion: Improvements of lung mechanics and gas exchange and mitigation of lung injury by the combined surfactant and iNO are related to suppression of NF-kappaB expression in lung tissue of ventilated rabbits with hypoxemic respiratory failure., (Copyright (c) 2005 S. Karger AG, Basel)

Background: Pulse dye laser has been used with variable degrees of success in the treatment of hypertrophic scars, and although earlier reports suggested a significant degree of improvement, more recent studies have raised concern about its effectiveness. Furthermore, most previous studies examined its use in patients with light skin types, and the use of pulse dye laser in dark-skinned patients for the treatment of hypertrophic scars is not well established., Objective: The objective was to assess the role of pulsed dye laser therapy in the treatment and prevention of hypertrophic scars in Chinese persons., Methods: Twenty-nine patients (35 scars) who had scars for less than 6 months were recruited into the prevention group, and 27 patients (36 scars) who had scars for more than 6 months were recruited into the treatment arm of the study. Each received pulse dye laser treatment (585 nm, 1.5-msec pulse duration, 5-mm spot size, 7-8 J/cm(2)) for three to six treatments at 8-week intervals. Half of the scar was treated with the laser and the other half was used as a control. All patients were assessed for subjective improvement with the use of a structured questionnaire and objectively with ultrasonography for thickness and a cutometer for viscoelasticity. Scars were marked on every patient and mapped with a translucent paper at the first appointment to ensure the consistency of location. At the end of the study, 15 patients from the prevention group (15 scars) and 23 patients from the treatment group (34 scars) agreed to return for spectrophotometer assessment., Results: Fifty-four percent of patients in the prevention group and 66% of patients in the treatment group considered their scars to be better or much better. For both groups of patients, there was significant improvement in term of pruritics after laser treatment. For objective assessment, although scar thickness reduced significantly compared to baseline in the treatment group, such change was not significant when changes in the control side were taken into consideration. There was insignificant change in viscoelasticity. Spectrophometer assessment indicated a significant degree of lightening in the treatment group., Conclusion: Our study indicated that although there was significant symptomatic improvement, there was an insignificant degree of objective improvement in terms of scar thickness and viscoelasticity in the prevention group compared to the control group. Our findings are in line with several previous controlled studies and contradict the results of several others. Such differences can be due to differences in assessment methodology, laser settings, skin type, and scar location. Suprapurpuric pulsed dye laser should not be considered as the standard of practice for the treatment and prevention of hypertrophic surgical scars especially in the chest in Asians patients.

Hypothesis: Hepatic arterial anastomosis by means of a microvascular technique can be performed with a high success rate in live donor liver transplantation in adult recipients., Design: Retrospective analysis of data collected prospectively., Setting: Tertiary referral center., Patients: From September 28, 1993, through December 23, 2002, 28 children received left lateral segment grafts (n = 23) or left lobe grafts (n = 5), and 124 adults received left lobe (n = 6) or right lobe (n = 118) grafts. Microvascular technique was used for hepatic arterial anastomosis. Attention was paid to exposure, orientation of the axis of arterial ends, and matching of size. Long microinstruments were used for arterial ends deeply located inside an adult's abdominal cavity. An average of 16 stitches was used for a vessel anastomosis 3 mm in diameter., Interventions: Intraoperative and postoperative Doppler ultrasonography were performed., Main Outcome Measures: Hepatic artery thrombosis rate., Results: All hepatic arterial anastomoses were patent after reconstruction. Complications occurred in 3 patients. They had hepatic arterial thrombosis at 19 days, 25 days, and 3 months after liver transplantation. The overall complication rate was 2%., Conclusion: With attention to exposure, appropriate instruments, and experience, a low complication rate of 2% can be achieved in hepatic arterial anastomosis by using a microvascular technique, even in adult patients with the liver graft situated deeply in the abdominal cavity.

Background and Objectives: The role of 1,320 Nd:YAG in non-ablative skin rejuvenation in Asians is has not been established. Furthermore, no study has investigated the effectiveness of 1,320 Nd:YAG laser in the treatment of atrophic scarring in Asians. The objective of our study was to investigate the effectiveness of 1,320 Nd:YAG laser in wrinkle reduction and the treatment of atrophic acne scarring in Asians., Study Design/materials and Methods: Twenty-seven female patients were included in the study: seven were treated for acne scarring and the others for wrinkle reduction. A 1,320 nm Nd:YAG laser (Cooltouch II, Roseville, CA) was used to treat both the cheeks and forehead for the patients with wrinkles, and both cheeks only for patients with atrophic acne scarring. All patients received treatment in the post-auricular areas. A spot size of 10 mm was used, and three passes were performed (two pre-cooling and one post-cooling). Patients were treated monthly for 6 months. All patients were subjectively assessed before and after their last treatment sessions using a structured questionnaire, and objectively assessed by the use of clinical photographs for by independent observers. A cutometer was used to assess viscoelasticity, and biopsies were taken at the post-auricular site for assessment by a pathologist., Results: The overall degree of patients' satisfaction was rated as 4.9 (range 0-9.8) for wrinkle reduction and 4 (range 0-10) for acne scarring. In terms of objective assessment by independent observers, the degree of improvement was considered to be mild or no change in most cases. The independent pathologist who assessed the degree of improvement in terms of increased collagen production detected no change in 8 patients, mild improvement in 9, and moderate improvement in 10. There was also improvement in term of epidermal thickness in 13 cases. Assessment by viscoelasticity indicated a significant degree of improvement in most parameters in both groups of patients. Blistering occurred in five cases, all in the central facial areas, and post-inflammatory hyperpigmentation occurred in three cases. All cases of PIH resolved after the use of 4% hydroquinoine. There was no scarring or hypopigmentation., Conclusions: The 1,320 nm Nd:YAG laser is effective for wrinkle reduction and atrophic acne scar improvement, but to further enhance the clinical outcome a combination approach with another device such as IPL and a surgical technique such as subcision is necessary., (Copyright 2004 Wiley-Liss, Inc.)

Purpose: The efficacy of salvage treatment of recurrent head and neck squamous cell carcinomas (HNSCC) after primary curative surgery was evaluated., Methods: The management outcome of 377 patients who had recurrent squamous cell carcinoma of oral cavity, oropharynx, hypopharynx, and larynx after primary curative surgery was reviewed., Results: The surgical salvage rates of recurrence were 29% local, 30% tracheostomal, 56% unilateral nodal recurrence of previously undissected neck, 32% of unilateral neck recurrence after prior neck dissection, and 11% lung metastasis. The 5-year tumor-free actuarial survival rates of those patients who received surgical salvage was 35% for local recurrence, 32% for unilateral nodal recurrence of the previously undissected neck, and 18% for nodal recurrence of the previously dissected neck. One patient of six with tracheostomal recurrence salvaged with surgery and one patient of six with lung metastasis salvaged with lobectomy survived without tumor at 5 years. There was no 5-year survivor of all patients salvaged with other nonsurgical methods. The mean survival of patients without surgical salvage was 6 months., Conclusions: There was a moderate chance of cure after surgical salvage of locoregional recurrent HNSCC. Surgical salvage was, however, only feasible for early recurrent tumor. Close follow-up surveillance of early recurrence is essential after primary treatment of patients., (Copyright 2003 Wiley Periodicals, Inc.)

Objective: To evaluate dose response of inhaled nitric oxide (iNO) for surfactant-treated rabbits with meconium aspiration-induced acute lung injury (ALI) and hypoxemic respiratory failure (HRF), and variation of measured iNO by continuous NO delivery in pressure support ventilation (PSV)., Methods: Adult rabbits (2.0 - 3.5 kg, n = 33) were randomized to receive intratracheal meconium instillation for 30 min and subjected to following treatment (n = 6 - 8). There were 4 groups: Control (C); NO, iNO at 1, 10, 20 and 40 x 10(-6) each for 60 min at 30 min interval of disconnection; Surf, intratracheal instillation of porcine lung surfactant phospholipids (100 mg/kg); SNO, both iNO and surfactant as in the NO and Surf groups; and a normal group (N), which did not undergo meconium aspiration but received sham deliveries of normal saline. All the animals were treated with PSV for 6 h. iNO levels at different input and sampling sites in the NO and SNO groups were detected by on-line chemiluminescent technique. The blood gas and lung mechanics were measured during the experiments every 2 h., Results: (1) Meconium aspiration induced ALI and severe HRF (PaO(2)/FiO(2) < 200 mmHg) and depressed dynamic compliance of respiratory system (Cdyn) and airway resistance (Raw). In both Surf and NO groups modestly improved oxygenation was observed. In the SNO, values for PaO(2)/FiO(2) were improved from (185 +/- 39) mmHg at baseline to (301 +/- 123) mmHg at 6 h, while moderate or transient improvement was observed in both Surf and NO groups. Cdyn and Raw were only improved for short time in the Surf, NO and SNO groups. iNO had a mild response at 1 x 10(-6) to good response at 10 and 20 x 10(-6), but no further improvement occurred at 40 x 10(-6). The response of iNO in NO group was relatively transient compared to the SNO group. (2) When iNO was connected to the ventilator circuit, the connected site should be placed before humidifier to minimize fluctuation of iNO concentration, and sampling site for iNO monitoring should be placed adequately to eliminate artifact., Conclusions: iNO synergistically improved surfactant effects on oxygenation and lung mechanics. Continuous supply of iNO with non-continuous flow ventilator provided stable NO within accepted target range with least variation.

The most common concern in patients with Madelung syndrome who are seeking cosmetic improvement is the deposition of fat in the cervicofacial region. Surgical experience in a series of 15 patients was summarised to provide guidelines for a rational approach to a better aesthetic outcome. The records and clinical photographs of these patients were reviewed. Outcome was assessed in terms of adequacy of debulking, final overall symmetry, smoothness of contour, prominence of scar, and necessity for multiple sessions. Open excision was the preferred primary treatment. A long mid-neck, transverse skin crease incision provided good exposure and was superior to multiple local incisions. Other surgical details worth noting include subplatysmal dissection, thick skin flaps, dissection around instead of into lipomas, appropriate removal of redundant skin, adequate reduction of tumour size instead of total excision, haemostasis, suction drainage, and layered skin closure. Liposuction was a useful adjunct for contouring the sides of the jaws in selected patients.