Comparison of diclofenac with tramadol, tizanidine or placebo in the treatment of acute low back pain and sciatica: multi-center randomized controlled trial.

BACKGROUND: Low back pain (LBP) is a leading cause of disability worldwide and has posed numerous health and socioeconomic challenges. This study compared whether nonsteroidal anti-inflammatory drugs (NSAIDs) in combination with tramadol, tizanidine or placebo would be the best treatment regime to improve the Roland Morris Disability Questionnaire (RMDQ) scores at 1 week. METHODS: This was a multi-center, double-blind, randomized, and placebo-controlled trial including adult patients with acute LBP and sciatica in three emergency departments in Hong Kong. Patients were randomized to the receive tramadol 50 mg, tizanidine 2 mg, or placebo every 6 hours for 2 weeks in a 1:1:1 ratio. The RMDQ and other secondary outcomes were measured at baseline, Day 2, 7, 14, 21, and 28. Data were analyzed on an intention to treat basis. Crude and adjusted mean differences in the changes of RMDQ and NRS scores from baseline to Day 7 between tizanidine/tramadol and placebo were determined with 95% confidence intervals. RESULTS: Two hundred and ninety-one patients were analyzed with the mean age of 47.4 years and 57.7% were male. The primary outcome of mean difference in RMDQs on Day 7 (compared with baseline) was non-significant for tizanidine compared with placebo (adjusted mean difference - 0.56, 95% CI -2.48 to 1.37) and tramadol compared with placebo (adjusted mean difference - 0.85, 95% CI -2.80 to 1.10). Only 23.7% were fully compliant to the treatment allocated. Complier Average Causal Effect analysis also showed no difference in the primary outcome for the tizanidine and tramadol versus placebo. CONCLUSION: Among patients with acute LBP and sciatica presenting to the ED, adding tramadol or tizanidine to diclofenac did not improve functional recovery.

Incidence and Predictors of Acute Coronary Syndrome in Patients on Maintenance Hemodialysis: A Prospective Cohort Study.

Background: Cardiovascular diseases are the leading cause of death among patients on hemodialysis, with approximately 40% of the cardiovascular deaths linked to acute coronary syndrome. We aimed to investigate the incidence and risk factors of acute coronary syndrome in patients undergoing hemodialysis. Methods: Patients undergoing hemodialysis were prospectively enrolled from January 2018. Data regarding hospitalization due to acute coronary syndrome were collected at 3-month intervals through December 31, 2021. Cox regression model was used to estimate the association between baseline factors and incident acute coronary syndrome during follow-up. Results: Patients' mean age was 66 years, 48% were men, and 16% had a history of coronary artery disease at enrolment. Over a median follow-up of 1,187 days, 85 patients were hospitalized due to acute coronary syndrome. Left main or triple vessel disease was identified in 67 patients. Risk factors associated with incident acute coronary syndrome included aging, male sex, smoking, low diastolic blood pressure, and baseline comorbidities, in addition to dialysis factors including low urea clearance, central venous catheter use, and history of dialysis access dysfunction. After multivariate analysis, age, diabetes, hyperlipidemia, smoking, and frequent interventions for vascular access remained significant risk factors. Conclusions: A high acute coronary syndrome incidence was observed in our cohort, with traditional risk factors playing a consistent role with that in the general population. A history of frequent dialysis access dysfunction was also associated with incident acute coronary syndrome.

Early sepsis care with the National Early Warning Score 2-guided Sepsis Hour-1 Bundle in the emergency department: hybrid type 1 effectiveness-implementation pilot stepped wedge randomised controlled trial (NEWS-1 TRIPS) protocol.

INTRODUCTION: Early sepsis treatment in the emergency department (ED) is crucial to improve patient survival. Despite international promulgation, the uptake of the Surviving Sepsis Campaign (SSC) Hour-1 Bundle (lactate measurement, blood culture, broad-spectrum antibiotics, 30 mL/kg crystalloid for hypotension/lactate ≥4 mmol/L and vasopressors for hypotension during/after fluid resuscitation within 1 hour of sepsis recognition) is low across healthcare settings. Delays in sepsis recognition and a lack of high-quality evidence hinder its implementation. We propose a novel sepsis care model (National Early Warning Score, NEWS-1 care), in which the SSC Hour-1 Bundle is triggered objectively by a high NEWS-2 (≥5). This study aims to determine the feasibility of a full-scale type 1 hybrid effectiveness-implementation trial on the NEWS-1 care in multiple EDs. METHODS AND ANALYSIS: We will conduct a pilot type 1 hybrid trial and prospectively recruit 200 patients from 4 public EDs in Hong Kong cluster randomised in a stepped wedge design over 10 months. All study sites will start with an initial period of standard care and switch in random order at 2-month intervals to the NEWS-1 care unidirectionally. The implementation evaluation will employ mixed methods guided by the Reach, Effectiveness, Adoption, Implementation and Maintenance framework, which includes qualitative and quantitative data from focus group interviews, staff survey and clinical record reviews. We will analyse the 14 feasibility outcomes as progression criteria to a full-scale trial, including trial acceptability to patients and staff, patient and staff recruitment rates, accuracy of sepsis screening, protocol adherence, accessibility to follow-up data, safety and preliminary clinical impacts of the NEWS1 care, using descriptive statistics. ETHICS AND DISSEMINATION: The institutional review boards of all study sites approved this study. This study will establish the feasibility of a full-scale hybrid trial. We will disseminate the findings through peer-reviewed publications, conference presentations and educational activities. TRIAL REGISTRATION NUMBER: NCT05731349.

The TriAGe + score for vertigo or dizziness: A validation study in a university hospital emergency department in Hong Kong.

OBJECTIVE: Patients with dizziness commonly present to Emergency Departments (ED) and 6% of these patients will be diagnosed with acute stroke. The TriAGe+ score comprises of eight clinical parameters and stratifies patients into four risk groups. The Japanese authors reported that the tool performed well, so our aim was to validate this diagnostic tool in our ED in Hong Kong. MATERIALS AND METHODS: A single-center retrospective observational study was conducted in the ED of our university hospital in Hong Kong. The primary outcome was the diagnosis of an acute cerebrovascular event. Receiver operator characteristic (ROC) analysis was performed to determine the best cut-off score. Secondary outcomes included univariable and multivariable analyses of stroke predictors. RESULTS: 455 patients aged 18 years or above with dizziness or vertigo at ED triage were recruited between 19 July and 30 September 2021. The overall prevalence of stroke was 11.9%. The median TriAGe+ score was 7 (IQR = 4-9). The AUC was 0.9. At a cut-off >5, sensitivity was 96.4% (95%CI: 87.3-99.5) and the negative likelihood ratio was 0.09 (95%CI: 0.02-0.3). At a cut-off >10, specificity was 99.8% (95%CI: 98.6-100.0), and the positive likelihood ratio was 237.6 (95%CI: 33.1-1704). On multivariable analyses, atrial fibrillation, blood pressure, gender, dizziness (not vertigo) and no history of dizziness, vertigo or labyrinth/vestibular disease were found to be positively associated with stroke outcomes significantly. CONCLUSION: The TriAGe+ score is an efficient stroke prediction score for patients presenting to the ED with dizziness.

Risks and outcomes of critical limb ischemia in hemodialysis patients: a prospective cohort study.

Background: Peripheral arterial disease (PAD) is more common in patients receiving maintenance hemodialysis than in the general population. Critical limb ischemia (CLI), the most severe form of PAD, is associated with high amputation and mortality risk. However, few prospective studies are available evaluating this disease's presentation, risk factors and outcomes for patients receiving hemodialysis. Methods: The Hsinchu VA study, a prospective multicentre study, investigated the impact of clinical factors on cardiovascular outcomes of patients receiving maintenance hemodialysis from January 2008 until December 2021. We evaluated the presentations and outcomes of patients with newly diagnosed PAD and the correlations of clinical variables with newly diagnosed CLI. Results: Of 1136 study participants, 1038 had no PAD on enrolment. After a median follow-up period of 3.3 years, 128 had newly diagnosed PAD. Of these, 65 presented with CLI, and 25 underwent amputation or died from PAD. Patients presenting with CLI had more below-the-knee (52%) and multi-level (41%) disease, and completely occluded segments (41%), and higher risk for amputation or PAD-related death compared with patients without CLI (27.7% vs 9.5%, P = .01). After multivariate adjustment, disability, diabetes mellitus, current smoking and atrial fibrillation were significantly associated with newly diagnosed CLI. Conclusions: Patients undergoing hemodialysis had higher rates of newly diagnosed CLI than the general population. Those with disabilities, diabetes mellitus, smoking and atrial fibrillation may require careful examination for PAD. Trial registration: Hsinchu VA study, ClinicalTrials.gov identifier: NCT04692636.

Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by Cordyceps cicadae Mycelia via Mg+2 Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro.

Fruiting bodies of Cordyceps cicadae (CC) have been reported to have a therapeutic effect in chronic kidney disease. Due to the rare and expensive resources from natural habitats, artificially cultivated mycelia using submerged liquid cultivation of CC (CCM) have been recently developed as an alternative to scarce sources of CC. However, little is known regarding potential protective effects of CCM against cyclosporine A (CsA)-induced acute nephrotoxicity in vivo and in vitro. In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). At the end of the study on day 8, all rats were sacrificed, and the blood and kidneys retrieved. CsA-induced acute nephrotoxicity was evident by increased levels of blood urea nitrogen (BUN). Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. Examination of hematoxylin and eosin stained kidney tissues revealed that the combined treatment of CCM slightly improved vacuolization in renal tubules upon CsA-induced damage. CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity.

The association of long-term blood pressure variability with hemodialysis access thrombosis.

Background: Blood pressure variability (BPV) is an important risk factor for cardiovascular events in hemodialysis patients. We sought to determine the impact of BPV on hemodialysis access thrombosis. Methods: We enrolled 1,011 prevalent hemodialysis patients from 12 hemodialysis centers since January 2018 and followed them until December 2020. Predialysis blood pressure (BP) was assessed at 12-week intervals. The coefficient of variation derived from 36 consecutive BP measurements was used as the metric for variability. The primary outcome was incident hemodialysis access thrombosis. Linear regression models were used to assess factors associated with BPV at baseline. Kaplan-Meier curves of the time until vascular access events were drawn and log-rank tests were calculated. Cox proportional hazards models were performed to assess the association of BPV with incident vascular access events. Results: The average coefficient of variance for systolic BPV was 10.9%. BPV was associated with age, body mass index, mean BP, diabetes, coronary and peripheral artery disease, history of access dysfunction, graft access, intradialytic hypotension, and use of antihypertensive medications. There were 194 access thrombosis events and 451 access stenosis events during a median follow-up period of 30 months. After adjustment of potential confounding factors, BPV was associated with increased risk of access thrombosis [hazard ratio = 1.27, 95% confidence interval (CI), 1.18-1.44, per 1 standard deviation increase in BPV]. The patients in the highest BPV quartile had 2.45 times the risk of thrombosis (CI, 1.62-3.70). The association was independent of average BP, intradialytic hypotension, and comorbidities. Similar trends of association were found in the subgroups analyzed. Comparative analysis using a time-varying variable model and different metrics of BPV showed consistent results. Conclusion: Our findings underscored the impact of BP fluctuation on vascular access thrombosis.

Impact of AIS 2015 versus 1998 on injury severity scoring and mortality prediction - single centre retrospective comparison study.

BACKGROUND: A key component of trauma system evaluation is the Injury Severity Score (ISS). The ISS is dependent on the AIS, and as AIS versions are updated this effects the number of patients within a health system which are considered severely injured (ISS >15). This study aims to analyse the changes comparing AIS1998 and AIS2015, and its impact on injury severity scoring and survival prediction model in a major trauma centre. METHODS: This retrospective study reviewed all blunt trauma admissions from 1 January 2020 to 31 December 2020 from the trauma registry of Prince of Wales Hospital, Hong Kong. Patients were manually double coded with AIS1998 and AIS2015 by the same experienced trauma nurse who have completed both AIS 1998 and AIS 2015 Courses. AIS patterns and Injury Severity Scores (ISS) derived from AIS 1998 and 2015 were compared using the Wilcoxon Signed Rank Test. The area under the receiving operator curve (AUROC) was compared based on the Trauma and Injury Severity Score (TRISS) model using AIS 1998 and AIS 2015. RESULTS: 739 patients were included. There were 34 deaths within 30 days (30-day mortality rate 4.6%). Patients coded with AIS2015 compared with AIS1998 had significant reductions in the classification of serious, severe and critical categories of AIS, with a substantial increase in the mild and moderate categories. The largest reduction was observed in the head and neck region (Z = -11.018, p < 0.001), followed by the chest (Z = -6.110, p < 0.001), abdomen (Z = -4.221, p < 0.001) and extremity regions (Z = -4.252, p < 0.001). There was a 27% reduction in number of cases with ISS >15 in AIS2015 compared with AIS1998. Rates of 30-day mortality, ICU admission, emergency operation and trauma team activation of ISS > 15 using AIS 1998 were similar to the cut off for New Injury Severity Score (NISS) >12 using AIS 2015. The AUROC from the TRISS (AIS2015) was 0.942, and not different from the AUROC for TRISS (AIS1998) of 0.936. The sensitivity and specificity were 93.9% and 82.1% for TRISS (AIS2015), and 93.9% and 76.0% for TRISS (AIS1998). CONCLUSION: Trauma centres should be aware of the impact of the AIS2015 update on the benchmarking of trauma care, and consider the need for updating the ISS cut off for major trauma definitions.

Association of Frailty With Thrombosis of Hemodialysis Vascular Access: A Prospective Taiwanese Cohort Study.

RATIONALE & OBJECTIVE: Frailty, a multidimensional construct, has been associated with poor outcomes in patients receiving maintenance dialysis. This study assessed the association of frailty with dialysis vascular access patency. STUDY DESIGN: Multicenter prospective cohort study. SETTING & PARTICIPANTS: 761 prevalent patients receiving hemodialysis at 9 centers in Taiwan as of January 2018. EXPOSURE: Performance-based frailty was defined as 3 of the following: unintentional weight loss, weakness, exhaustion, low physical activity, and slow gait speed. Patients were categorized as prefrail if they had 1 or 2 of these characteristics. OUTCOME: Rate of and time to dialysis access thrombosis. Data regarding vascular access events were collected for 30 months after enrollment through December 31, 2020. ANALYTICAL APPROACH: Logistic regression analysis was used to estimate the association of clinical characteristics with frailty. Cox proportional hazards regression analysis was used to estimate the association of frailty with vascular access thrombosis adjusted for known clinical risk factors. RESULTS: The patients' mean age was 66 years, 46% were female, 18% had synthetic graft accesses, and 82% arteriovenous fistulas. Overall, 31% were frail, 35% were prefrail, and 34% were not frail. The frailty phenotype was associated with age, female sex, low body mass index, diabetes mellitus, and prior stroke. During a median follow-up of 731 days, 161 patients (21%) had access thrombosis events (not frail, 14%; prefrail, 20%; frail, 30%; P < 0.001). Frail patients had a higher risk of vascular access thrombosis than nonfrail patients (HR, 2.31 [95% CI, 1.55-3.39], P < 0.001). After multivariable adjustment for age and comorbidities, frailty remained significantly associated with access thrombosis for both fistulas and grafts. LIMITATIONS: Limited generalizability and potential residual confounding. CONCLUSIONS: Frailty is associated with an increased risk of vascular access thrombosis. These findings highlight the risks of access failure experienced by frail patients receiving hemodialysis.

Return to work after injury in Hong Kong: prospective multi-center cohort study.

PURPOSE: Trauma remains a major cause of morbidity and disability worldwide; however, reliable data on the health status of an urban Asian population after injury are scarce. The aim was to evaluate 1-year post-trauma return to work (RTW) status in Hong Kong. METHODS: This was a prospective, multi-center cohort study involving four regional trauma centers from 2017 to 2019 in Hong Kong. Participants included adult patients entered into the trauma registry who were working or seeking employment at the time of injury. The primary outcome was the RTW status up to 1 year. The Extended Glasgow Outcome Scale, 12-item Short Form (SF-12) survey and EQ5D were also obtained during 1-, 3-, 6-, 9-, and 12-month follow-ups. Multivariable Cox proportional hazards regression analysis was used for analysis. RESULTS: Six hundred and seven of the 1115 (54%) recruited patients had RTW during the first year after injury. Lower physical requirements (p = 0.003, HR 1.51) in pre-injury job nature, higher educational levels (p < 0.001, HR 1.95), non-work-related injuries (p < 0.001, HR 1.85), shorter hospital length of stay (p = 0.007, HR 0.98), no requirement for surgery (p = 0.006, HR 1.34), and patients who could be discharged home (p = 0.006, HR 1.43) were associated with RTW within 12 months post-injury. In addition, 1-month outcomes including extended Glasgow Outcome Scale ≥ 6 (p = 0.001, HR 7.34), higher mean SF-12 physical component summary (p = 0.002, HR 1.02) and mental component summary (p < 0.001, HR 1.03), and higher EQ5D health index (p = 0.018, HR 2.14) were strongly associated with RTW. CONCLUSIONS: We have identified factors associated with failure to RTW during the first year following in Hong Kong including socioeconomic factors, injury factors and treatment-related factors and 1-month outcomes. Future studies should focus on the interventions that can impact on RTW outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03219424.

RISC II is superior to TRISS in predicting 30-day mortality in blunt major trauma patients in Hong Kong.

PURPOSE: Hong Kong (HK) trauma registries have been using the Trauma and Injury Severity Score (TRISS) for audit and benchmarking since their introduction in 2000. We compare the mortality prediction model using TRISS and Revised Injury Severity Classification, version II (RISC II) for trauma centre patients in HK. METHODS: This was a retrospective cohort study with all five trauma centres in HK. Adult trauma patients with Injury Severity Score (ISS) > 15 suffering from blunt injuries from January 2013 to December 2015 were included. TRISS models using the US and local coefficients were compared with the RISC II model. The primary outcome was 30-day mortality and the area under the receiver operating characteristic curve (AUC) for tested models. RESULTS: 1840 patients were included, of whom 1236/1840 (67%) were male. Median age was 59 years and median ISS was 25. Low falls were the most common mechanism of injury. The 30-day mortality was 23%. RISC II yielded a superior AUC of 0.896, compared with the TRISS models (MTOS: 0.848; PATOS: 0.839; HK: 0.858). Prespecified subgroup analyses showed that all the models performed worse for age ≥ 70, ASA ≥ III, and low falls. RISC II had a higher AUC compared with the TRISS models in all subgroups, although not statistically significant. CONCLUSION: RISC II was superior to TRISS in predicting the 30-day mortality for Hong Kong adult blunt major trauma patients. RISC II may be useful when performing future audit or benchmarking exercises for trauma in Hong Kong.

Intramuscular midazolam, olanzapine, or haloperidol for the management of acute agitation: A multi-centre, double-blind, randomised clinical trial.

BACKGROUND: The safety and effectiveness of intramuscular olanzapine or haloperidol compared to midazolam as the initial pharmacological treatment for acute agitation in emergency departments (EDs) has not been evaluated. METHODS: A pragmatic, randomised, double-blind, active-controlled trial was conducted from December 2014 to September 2019, in six Hong Kong EDs. Patients (aged 18-75 years) with undifferentiated acute agitation requiring parenteral sedation were randomised to 5 mg intramuscular midazolam (n = 56), olanzapine (n = 54), or haloperidol (n = 57). Primary outcomes were time to adequate sedation and proportion of patients who achieved adequate sedation at each follow-up interval. Sedation levels were measured on a 6-level validated scale (ClinicalTrials.gov Identifier: NCT02380118). FINDINGS: Of 206 patients randomised, 167 (mean age, 42 years; 98 [58·7%] male) were analysed. Median time to sedation for IM midazolam, olanzapine, and haloperidol was 8·5 (IQR 8·0), 11·5 (IQR 30·0), and 23·0 (IQR 21·0) min, respectively. At 60 min, similar proportions of patients were adequately sedated (98%, 87%, and 97%). There were statistically significant differences for time to sedation with midazolam compared to olanzapine (p = 0·03) and haloperidol (p = 0·002). Adverse event rates were similar across the three arms. Dystonia (n = 1) and cardiac arrest (n = 1) were reported in the haloperidol group. INTERPRETATION: Midazolam resulted in faster sedation in patients with undifferentiated agitation in the emergency setting compared to olanzapine and haloperidol. Midazolam and olanzapine are preferred over haloperidol's slower time to sedation and potential for cardiovascular and extrapyramidal side effects. FUNDING: Research Grants Council, Hong Kong.

Major trauma care in Hong Kong and Germany: a trauma registry data benchmark study.

BACKGROUND: Trauma remains a leading cause of death and effective trauma management within a well-developed trauma system has been shown to reduce morbidity and mortality. A trauma registry, as an integral part of a mature trauma system, can be used to monitor the quality of trauma care and to provide a means to compare local versus international standards. Hong Kong and Germany both have highly developed health care services. We compared the performance of trauma systems including outcomes among major trauma victims (ISS > 15) over a 3-year period (2013-2015) in both settings using trauma registry data. METHODS: This study was a retrospective analysis of prospectively collected data from trauma registries in Hong Kong and Germany. Data from 01/2013 to 12/2015 were extracted from the trauma registries of the five trauma centers in Hong Kong and the TraumaRegister DGU® (TR-DGU). The study cohort included adults (≥ 18 years) with major trauma (ISS > 15). Data related to patient characteristics, nature of the injury, prognostic parameters to calculate the RISC II score, outcomes and clinical management were collected and compared. RESULTS: Datasets from 1,864 Hong Kong and 10,952 German trauma victims were retrieved from respective trauma registries. The unadjusted mortality in Hong Kong (22.4%) was higher compared to Germany (19.2%); the difference between observed and expected mortality was higher in Hong Kong (+ 2.7%) than in Germany (- 0.5%). The standardized mortality ratio (SMR) in Hong Kong and Germany were 1.138 (95% CI 1.033-1.252) and 0.974 (95% CI 0.933-1.016), respectively, and the adjusted death rate in Hong Kong was significantly higher compared to the calculated RISC II data. However, patients in Hong Kong were significantly older, had more pre-trauma co-morbidities, more head injuries, shorter hospital and ICU stays and lower ICU admission rates. CONCLUSION: Hong Kong had a higher mortality rate and a statistically significantly higher standardized mortality ratio (SMR) after RISC II adjustment. However, multiple differences existed between trauma systems and patient characteristics.

Oral Prednisolone in the Treatment of Acute Gout: A Pragmatic, Multicenter, Double-Blind, Randomized Trial.

BACKGROUND: Two recent double-blind, randomized, controlled trials (RCTs) showed that oral steroids and nonsteroidal anti-inflammatory drugs have similar analgesic effectiveness for management of gout, but the trials had small sample sizes and other methodological limitations. OBJECTIVE: To compare the effectiveness and safety of oral prednisolone versus oral indomethacin in patients presenting to emergency departments (EDs) with acute gout. DESIGN: Multicenter, double-blind, randomized equivalence trial. Patients were randomly assigned (1:1 ratio) to receive either indomethacin or prednisolone. (ISRCTN registry number: ISRCTN45724113). SETTING: Four EDs in Hong Kong. PARTICIPANTS: 416 patients aged 18 years or older. MEASUREMENTS: Analgesic effectiveness was defined as changes in pain (at rest or with activity) greater than 13 mm on a 100-mm visual analogue scale. Outcomes were measured during the first 2 hours in the ED and from days 1 to 14. RESULTS: 376 patients completed the study. Equivalent and clinically significant within-group reductions in mean pain score were observed with indomethacin and prednisolone in the ED (approximately 10 mm [rest] and 20 mm [activity]) and from days 1 to 14 (approximately 25 mm [rest] and 45 mm [activity]). No major adverse events occurred during the study. During the ED phase, patients in the indomethacin group had more minor adverse events than those in the prednisolone group (19% vs. 6%; P < 0.001). During days 1 to 14, 37% of patients in each group had minor adverse events. LIMITATION: Diagnosis of gout was usually based on clinical criteria rather than examination of joint fluid. CONCLUSION: Oral prednisolone and indomethacin had similar analgesic effectiveness among patients with acute gout. Prednisolone is a safe, effective first-line option for treatment of acute gout. PRIMARY FUNDING SOURCE: Health and Health Services Research Grant Committee of the Hong Kong Government.

Current Safety of Renal Allograft Biopsy With Indication in Adult Recipients: An Observational Study.

Renal biopsy remains the golden standard diagnosis of renal function deterioration. The safety in native kidney biopsy is well defined. However, it is a different story in allograft kidney biopsy. We conduct this retrospective study to clarify the safety of allograft kidney biopsy with indication.All variables were grouped by the year of biopsy and they were compared by Mann-Whitney U test (for continuous variables) or Chi-square test (for categorical variables). We collected possible factors associated with complications, including age, gender, body weight, renal function, cause of uremia, status of coagulation, hepatitis, size of needle, and immunosuppressants.We recruited all renal transplant recipients undergoing allograft biopsy between January of 2009 and December of 2014. This is the largest database for allograft kidney biopsy with indication. Of all the 269 biopsies, there was no difference in occurrence among the total 14 complications (5.2%) over these 6 years. There were only 3 cases of hematomas (1.11%), 6 gross hematuria (2.23%), 1 hydronephrosis (0.37%), and 2 hemoglobin decline (0.74%). The outcome of this cohort is the best compared to all other studies, and it is even better than the allograft protocol kidney biopsy. Among all possible factors, patients with pathological report containing "medullary tissue only" were susceptible to complications (P < 0.001, 1.8 of relative risk).In modern era, this study demonstrates the safety of allograft kidney biopsy with indication. Identifying the renal capsule before biopsy to avoid puncture into medulla is the most important element to prevent complications.

Age-related immune clearance of hepatitis B virus infection requires the establishment of gut microbiota.

A unique feature of hepatitis B virus (HBV) infection in humans is that viral clearance heavily depends on the age of exposure. However, the reason for this remains unclear. Here we show that gut microbiota contribute to the age dependence of HBV immunity in a hydrodynamic transfection mouse model. Although adult (12-wk-old) C3H/HeN mice cleared HBV within 6 wk postinjection (wpi), their young (6-wk-old) counterparts remained HBV-positive at 26 wpi. Sterilization of gut microbiota from 6 to 12 wk of age using antibiotics prevented adult mice from rapidly clearing HBV. Young mice with the Toll-like-receptor (TLR) 4 mutation (C3H/HeJ) exhibited rapid HBV clearance. The results suggest that an immuno-tolerating pathway to HBV prevailed in young mice, before the establishment of gut bacteria, through a TLR4-dependent pathway and that the maturation of gut microbiota in adult mice stimulated liver immunity, resulting in rapid HBV clearance.

Urokinase gene 3'-UTR T/C polymorphism is associated with malignancy and ESRD in idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults, and 25% of MN patients proceed to ESRD. Urokinase plasminogen activator (uPA) may play an important role in reducing renal fibrosis. This study was conducted to clarify the relationship between uPA gene polymorphisms and clinical manifestations of MN. We recruited 91 biopsy-diagnosed MN patients and 105 healthy subjects. Genotyping of uPA gene 3'-UTR T/C polymorphism was performed by polymerase chain reaction methods. The genotype distribution had no effect on the development of MN. Thirteen patients (15.9%; P = 0.008) acquired malignancies and seventeen (20.7%; P = 0.006) patients progressed to ESRD with the C/C genotype, but no patients with the T/C genotype did. In conclusion, we demonstrated that the presence of the uPA gene 3'-UTR C/C genotype was associated with ESRD as well as acquired malignancies in MN patients. These findings should prompt specific considerations for the treatment of MN patients to maintain a balance between treating disease entities and protecting the immune system from cancers.

Estimated glomerular filtration rate decline is a better risk factor for outcomes of systemic disease-related nephropathy than for outcomes of primary renal diseases.

BACKGROUND: Currently, the contribution of kidney function decline in renal and patient outcomes is unclear. There are few data on the associations of different etiologies of estimated glomerular filtration rate (eGFR) decline with outcomes in multidisciplinary care. The purpose of this investigation was to establish whether eGFR decline in patients with disease is an important risk factor for developing end-stage renal disease (ESRD) and death. METHODS: From December 1, 2001 to December 31, 2011, 5097 adults with chronic kidney disease (CKD) received biochemical tests, physical examinations, a pathological examination, and a comprehensive questionnaire. We used linear regression models and multivariate Cox proportional hazards model to examine the outcome of eGFR decline in renal diseases with different etiologies. RESULTS: Mean age was 68.1±16.1 (standard deviation, SD) years, and 63.3% patients were male. In the studied cohort, 58.2% of the patients had systemic disease-related nephropathy (SDRN), 29.4% had primary renal diseases (PRDs), and 12.4% had other etiologies. The eGFR decline in SDRN had a significant association with dialysis in the Cox proportional hazards model [crude hazard ratio (HR) = 1.07, 95% confidence interval (CI), 1.04 to 1.10; adjusted HR 1.05, 95% CI, 1.02 to 1.08]. Diabetic nephropathy (DN) had the most severe eGFR decline in CKD stages 3, 4, and 5, and all contributed to the initiation of dialysis and death regardless of whether DN with or without eGFR decline was considered to be the cause. Although hypertensive nephropathy (HN) was related to significant acceleration of eGFR decline, it did not lead to poor outcome. There were still discrepancies between eGFR decline and outcomes in PRDs, hypertensive nephropathy, and lupus nephritis. CONCLUSIONS: eGFR decline and CKD staging provide an informative guide for physicians to make proper clinical judgments in the treatment of CKD, especially SDRN. Poor control of the underlying systemic disease will thus lead to more rapid progression of SDRN.

Polysaccharide extract of Cordyceps sobolifera attenuates renal injury in endotoxemic rats.

Extracts derived from Cordyceps have been demonstrated to possess various pharmacological effects, including immunomodulatory, antitumor, hypoglycemic, and antioxidant activities. This study was aimed to clarify the role of CS-P, a polysaccharide fraction isolated from Cordyceps sobolifera, in modulating nephrofunctional damage in a rat model of endotoxemia. CS-P (500 mg/kg body weight) was orally administered to rats for 4 weeks before the peritoneal injection of lipopolysaccharide (LPS, 10 mg/kg body weight). Pre-treatment with CS-P significantly attenuated the deleterious renal functions caused by LPS, i.e., elevated blood urea nitrogen and creatinine as well as urine protein. Histopathological examination of kidney tissues also demonstrated that CS-P improved LPS-induced pathological abnormalities. The induction of inducible nitric oxide synthase and the overproduction of nitric acid by LPS were also significantly reduced by CS-P via inhibiting nuclear factor-κB activation. In addition, CS-P pre-treatment suppressed the plasma levels of tumor necrosis factor-alpha and interleukin-6. Concurrently, CS-P supplementation potently suppressed the LPS-induced rise of lipid peroxidation and markedly enhanced the antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney. The present results suggested that CS-P pre-treatment could protect against LPS-triggered inflammatory responses and renal injury in rats.