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.

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.

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.

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.

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.

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.

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.

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.

Expression of hypoxia-inducible factor-1α (HIF-1α) in infiltrating inflammatory cells is associated with chronic allograft dysfunction and predicts long-term graft survival.

BACKGROUND: In chronic kidney failure, a hypoxic state, infiltrating inflammatory cells play a crucial role in the progression to end-stage renal disease. No studies have evaluated the influence of hypoxia and infiltrating inflammatory cells on chronic allograft dysfunction. METHODS: Renal transplant recipients who underwent renal allograft biopsy with interstitial fibrosis/tubular atrophy (IF/TA) were enrolled and renal allograft tissue sections were processed for immunohistochemical staining including hypoxia-inducible factor-1α (HIF-1α), nitrotyrosine, α-smooth muscle actin and e-cadherin. Patients with total renal tissue HIF score ≥1 were defined as positive for HIF-1α. To assess the phenotype of the infiltrating cells, dual staining of HIF-1α with CD45, CD68 and CD3 was performed. The correlation between HIF-1α score and Banff's score was analysed. Clinical parameters including renal survival among patients with or without an expression of HIF-1α were compared. RESULTS: Out of 55 patients enrolled, 23 patients (41.8%) had an HIF-1α score ≥1 (Group B). Compared with Group A (total renal HIF score <1), Group B had a significantly higher Banff score of interstitial infiltrates (i) (P = 0.029), vascular fibrous intimal thickening (cv) (P = 0.007) and arteriolar hyaline thickening (ah) (P = 0.026). Clinically, patients with an HIF-1α score were associated with a poor graft survival. Significantly inferior allograft survival was noted in Group B. HIF scores had an adjusted hazard ratio of 3.25 (95% confidence inteval: 1.71-6.16, P = 0.0003) in allograft failure. CONCLUSIONS: We first demonstrated the expression of HIF-1α protein among infiltrating inflammatory cells in areas with IF/TA in patients with chronic allograft dysfunction.

Effect of different hemodialyzers on serum levels of interleukin-6, interleukin-10 and interleukin-18.

BACKGROUND: The blood and membrane contact during dialysis may elicit an immune reaction. The current study looked at the impact of different dialyzers on blood levels of cytokines. METHODS: During the first month, randomly selected patients were treated with one dialyzer (PF-170H) and then crossed over to another dialyzer (FLX-18GW) during the next month. Pre- and postdialysis blood samples were assayed for interleukin (IL)-6, IL-10 and IL-18. RESULTS: A significant drop of postdialysis systolic blood pressure (pre vs. post 156.4 ± 31.8 vs. 143.1 ± 24.8 mm Hg, p = 0.014) and diastolic pressure (80.7 ± 12.7 vs. 73.4 ± 10.9 mm Hg, p = 0.002) were found when patients were dialyzed with PF-170H. A significant increase of postdialysis IL-18 levels was found in both groups (pre vs. post 605.5 ± 278.6 vs. 690.6 ± 315.3 pg/ml, p = 0.016, for PF-170H and 556.4 ± 231.0 vs. 647.3 ± 282.6 pg/ml, p = 0.067, for FLX-18GW). There was a positive correlation between IL-6 and IL-10 levels (p < 0.0001). CONCLUSION: We demonstrated a significant increase of postdialysis serum IL-18 level when either dialyzer was used. There is a strong correlation between serum levels of IL-6 and IL-10.

Clinical outcome of elderly peritoneal dialysis patients with assisted care in a single medical centre: a 25 year experience.

AIM: Peritoneal dialysis (PD) is an alternative treatment for elderly patients with end-stage renal disease (ESRD). In Taiwan, non-professional personnel are employed to provide assisted care for elderly patients. Whether assisted care is appropriate for elderly patients is unknown. The aim of this paper is to evaluate the outcomes of assisted care in a single centre. METHODS: This is a retrospective cohort study in a single medical centre. The outcomes were derived from the assessment of patient survival, technique survival and peritonitis incidence between self-care patients and assisted-care patients. RESULTS: From 1984 to 2010, there were 138 elderly PD patients at Taichung Veterans General Hospital, of which 70% were assisted-care patients and 30% self-care patients. The mean duration of PD survival was 49.2 months in self-care patients, which was significantly longer than the 17.0 months of assisted-care patients (P < 0.05). Using the multivariate Cox proportion regression model to adjust for risk factors, it was found that self-care patients had a lower risk in both patient survival (Hazard Ratio 0.15; 95% confidence interval (CI) 0.2-0.94, P < 0.05) and technique survival (Hazard ratio; 0.11, 95% CI 0.1-0.9, P < 0.05). Fluid overloading was the major cause of technique failure in assisted-care patients. Type of assistance was not a risk factor for PD-related peritonitis. CONCLUSION: Our elderly assisted care had patients had a poorer survival and technique survival rates than those of the self-care patients. We argue that this is because early recognition of medical deterioration and early medical intervention are necessary for a better outcome for elderly PD patients.

In-hospital mortality risk estimation in patients with acute nonvariceal upper gastrointestinal bleeding undergoing hemodialysis: a retrospective cohort study.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a major cause of clinical bleeding among patients with end-stage renal disease (ESRD). This study aimed to investigate the association between mortality and UGIB in patients with uremia. METHODS: From 2004 to 2010, a tertiary hospital-based retrospective cohort comprising 322 patients undergoing hemodialysis was investigated. All the patients were diagnosed with UGIB according to the International Classification of Diseases, 9th Revision (ICD-9) that included peptic ulcer bleeding, duodenal ulcer bleeding, and other symptoms. UGIB was required to be one of the first three discharge diagnoses. Rehospitalization within 3 days after discharge was regarded as the same course. Exclusion criteria were age <20 years, previous gastric resection or vagotomy, esophageal and gastric variceal bleeding, or gastric cancer within the first 2 years of the index hospitalization. RESULTS: The all-cause in-hospital mortality rate of patients with UGIB undergoing hemodialysis was high, with the first-month mortality rate of 13.7%, sixth-month mortality rate of 26.7%, and first-year mortality rate of 27.0%. Using Cox regression models, we found that the high mortality rate of the UGIB group was significantly correlated with older age [adjusted hazard ratio (HR) = 1.02, 95% confidence interval (CI) = 1.01-1.04], female sex (adjusted HR = 1.62, 95% CI = 1.05-2.51), infection during hospitalization (adjusted HR = 1.85, 95% CI = 1.13-3.03), single episodic UGIB (adjusted HR = 2.00, 95% CI = 1.08-3.70), abnormal white blood cell (WBC) count (adjusted HR = 1.59, 95% CI = 1.03-2.45), and albumin level ≤3 g/dL (adjusted HR = 2.67, 95% CI = 1.51-4.72). CONCLUSION: In conclusion, patients with ESRD who are admitted with primary UGIB have a profoundly increased risk of all-cause in-hospital mortality during the follow-up period.

The effectiveness of a specially designed shoulder chair for closed reduction of acute shoulder dislocation in the emergency department: a randomised control trial.

STUDY OBJECTIVE: The objective of this study was to demonstrate the effectiveness of a specially designed chair for closed reduction of acute shoulder dislocations. METHOD: This was a prospective, non-blinded randomised controlled trial conducted in a university affiliated emergency department (ED). The inclusion criteria were (1) age ≥18 years; (2) anterior or posterior shoulder dislocation without fracture of the surgical neck of the humerus; (3) patient who is able to communicate and cooperate. Participants were randomly assigned using a computer generated random number sequence into one of two groups--either the traditional practice group or Oxford chair group. Administration of intravenous sedation was only permitted in the traditional practice group due to the concerns of sedation use in the sitting position while unsupported on the chair. The primary outcome measure was length of ED stay. The secondary outcome measures were length of time for the procedure, successful reduction rate, levels of pain experienced by patients in different time periods before and after the reduction. RESULT: Sixty eligible patients were recruited, 30 in each group. The median lengths of stay in the ED in Oxford chair group (n=30) and traditional method group (n=30) were 152 min and 173 min respectively (p=0.183). The median procedure time was 3 min for the Oxford chair group compared to 5 min in the traditional method group (p=0.179). The success rate for the Oxford chair method was 77% (23/30). There were no statistically or clinically significant differences of pain score at any point. CONCLUSIONS: The chair method had a 77% success rate in reducing acute shoulder dislocations without sedation. There was no difference in pain level experienced by patients between the chair method and the traditional method. Patient factors, including patients who have had previous shoulder surgery and patients who have fracture dislocations, contribute to the reduced efficacy of the chair method. It remains possible that the chair method may reduce patient length of stay in the ED in uncomplicated patients.

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.

Cyclosporine-induced tubular vacuolization: the role of Bip/Grp78.

Cyclosporine (CsA) nephrotoxicity shows characteristic tubular vacuolization (TV) which is endoplasmic reticulum (ER) in origin. However, the cellular events of CsA-induced TV and CsA-induced ER remained unclear. The aim of the present study was to study the nature of TV and the correlation to ER stress. Using proximal tubule NRK-52E cells in vitro and an in vivo model of acute CsA nephrotoxicity, we confirmed that CsA-induced TV was ER in origin and potentially reversible. Our results showed that CsA-induced ER stress and involved ER integrated stress response-related proteins (Bip/Grp78, ATF6, IRE1 and CHOP) but not cytoplasmic ER stress-related chaperones (HSP70, HSP40, HSP27, HSP90 and HSP60). Importantly, Bip/Grp78 was overexpressed on the membrane of TV and suppression of Bip/Grp78 blocked TV formation. In addition, suppression of Bip/Grp78-enhanced CsA-induced cell death and CsA-induced TV formation and Bip/Grp78 overexpression had a characteristic striped pattern in the tubulointerstitium. In summary, we demonstrate that CsA-induced TV was a potentially reversible process in which Bip/Grp78 overexpression is essential for TV formation. It is possible that Bip/Grp78 expression and TV formation may be involved in cellular defense mechanism against CsA nephrotoxicity.

Impact of posttransplantation glomerulonephritis on long-term outcome of kidney transplants: single-center 20-year experience.

BACKGROUND: Successful renal transplantation has been performed in patients with end-stage renal disease and has been routine in patients with end-stage renal failure for more than two decades. Despite advances in the use of immunosuppressants, there has been only modest improvement in long-term allograft survival. Accumulating data have demonstrated that chronic rejection and recurrent glomerulonephritis are major causes of long-term allograft loss. However, data regarding the long-term impact of posttransplantation glomerulonephritis (PTGN) on ethnic Chinese populations are still unavailable. METHODS: From 1984 to 2010, a total of 268 patients who underwent renal allograft biopsies were reviewed retrospectively. Renal outcomes were compared by Kaplan-Meier analysis, and risk factors for renal survival and all-cause mortality were analyzed using the Cox proportional hazards model. RESULTS: In all, 85 patients (31.7%) had PTGN, and the mean time of disease onset was 5.32±5.18 years after transplantation. Among the 85 PTGN cases, 33 (39%) were immunoglobulin A (IgA) nephropathy, 24 (28%) were focal segmental glomerulosclerosis, and 8 (9.4%) were membranous GN. Significant risk was associated with posttransplant IgA GN in hepatitis B virus carriers (odds ratio 5.371, 95% confidence interval 1.68, 17.19; p=0.0064). A total of 45 PTGN patients had allograft loss, of whom 49% had IgA nephropathy. Patients with PTGN had inferior allograft survival rates compared to those with other pathologic findings (p<0.0003). CONCLUSIONS: Taken together, our results indicate that PTGN had a strong negative impact on long-term kidney graft survival. Posttransplant IgA nephropathy is a leading cause of allograft loss in Chinese kidney transplant patients with PTGN.

Higher serum levels of soluble intracellular cell adhesion molecule-1 and soluble vascular cell adhesion molecule predict peripheral artery disease in haemodialysis patients.

AIM: Serum levels of soluble intracellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM) and monocyte chemotactic protein 1 (MCP-1), are elevated in patients with peripheral artery disease (PAD). However, the levels of these cell adhesion molecules in patients undergoing haemodialysis (HD) are unclear. METHOD: A total of 112 HD patients were included and PAD was diagnosed using the ankle-brachial index and Doppler ultrasound. Serum levels of sICAM-1, sVCAM-1 and MCP-1 were assayed using enzyme linked immunosorbent assay. RESULTS: Out of 106 HD patients, 31 (27.7%) were diagnosed with PAD. After adjusting for risk factors, higher serum levels of sVCAM-1 and sICAM-1 were associated with PAD in HD patients, with an odds ratio of 5.3 (95% CI 3.3-65.5) and 2.7 (95% CI 1.2-21.8) respectively. Using sVCAM-1 and sICAM-1 for diagnosis of PAD in HD patients, sVCAM-1 had a sensitivity of 72.4% and specificity of 62.3% for sVCAM-1 and sICAM-1 had a sensitivity of 89.3% and a specificity of 40%. MCP-1 was not associated with PAD in HD patients. In addition, the fistula of HD patients with PAD had a lower A-V access flow. CONCLUSION: sVCAM-1 and sICAM-1 was associated with higher risk of PAD in HD patients. Moreover, HD patients with PAD had a lower blood flow and lower A-V access flow. Our results showed that sVCAM-1 and sICAM-1 may be used as screening markers for PAD in HD patients.

Interleukin-2 receptor antagonist does not decrease biopsy-proven acute rejection among adult Chinese kidney transplant recipients.

Induction therapy with interleukin-2 receptor antagonist (IL2RA) is widely used for renal transplant recipients and this study aimed to examine the impact of IL2RA among Chinese renal transplant recipients. Two hundred and thirty-eight Chinese renal transplant recipients aged 18-65 years at the Taichung Veterans General Hospital from January 2004 to July 2009 were retrospectively studied to assess the influence of IL2RA on biopsy-proven acute rejection (BPAR) within 1 year. Secondary outcomes included acute rejection rate in the first 3 months, delayed graft function, post-transplant diabetes mellitus, and malignancy. Cox proportional hazard analysis was used for multivariate analysis. Of all the patients, 116 received IL2RA (basiliximab, n = 44; daclizumab, n = 72) and 122 had no induction therapy. The mean follow-up duration was 43.3 months (range, 1-79 months). Overall, 227 (95.4%) patients completed the 12-month follow-up period with a functioning graft. No difference of BPAR was observed between the two groups and the secondary outcomes were also similar. After adjusting potential covariates with Cox regression, IL2RA use still provided no benefit on BPAR. In conclusion, there is no benefit of IL2RA in decreasing BPAR was observed in our study. Routine use of IL2RA for adult Chinese kidney transplant recipients may not be as effective as we thought before. More research is still needed to elucidate the effect of IL2RA among Chinese kidney transplant recipients.

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.