Publications by authors named "Huihua Li"

165 Publications

Outcomes of arteriovenous fistula in elderly patients on maintenance haemodialysis.

Int Urol Nephrol 2021 Mar 6. Epub 2021 Mar 6.

Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore.

Background: The optimal vascular access strategy in elderly patients receiving haemodialysis (HD) remains controversial. We aim to report the outcomes of arteriovenous fistula (AVF) in elderly patients initiated on maintenance HD in our centre.

Methods: Medical records of 688 incident patients initiated on HD from 2010 to 2012 in a tertiary centre were retrospectively reviewed. Patients' characteristics and AVF outcomes were compared among those < 65 years (non-elderly), ≥ 65-75 years (early elderly) and ≥ 75 years (late elderly).

Results: There were 418 non-elderly, 184 early elderly and 86 late elderly patients. There is a higher proportion of brachiocephalic and brachiobasilic fistula created in the late elderly (24.9% vs. 37.0% vs. 41.8%, p = 0.001). The outcomes of accesses created were comparable in the 3 age groups with similar proportions of functional AVFs (80.4% vs. 79.3% vs. 75.6%, p = 0.832) and comparable 1-, 3- and 5-year primary and secondary patency rates (p = 0.351 and 0.282, respectively). However, a longer maturation time (2.78 vs. 2.86 vs. 3.72 months, p = 0.010) and a higher mean number of interventions to assist maturation of the first AVF were required in late elderly patients (0.19 vs. 0.22 vs. 0.35, p = 0.014). Following AVF creation, median patient survival in the non-elderly, early and late elderly was 65.2 vs. 55.1 vs. 49.8 months respectively.

Conclusion: AVFs created in elderly patients have comparable outcomes compared to non-elderly patients although more interventions are required to assist maturation with a longer maturation time necessitating early access creation to allow for time needed due to maturation delay.
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http://dx.doi.org/10.1007/s11255-021-02822-wDOI Listing
March 2021

High-intensity focused ultrasound in the management of adenomyosis: long-term results from a single center.

Int J Hyperthermia 2021 ;38(1):241-247

Department of Gynaecology, Third Xiangya Hospital, Central South University, Changsha, China.

Objective: To investigate the long-term clinical outcomes of patients with adenomyosis treated by high-intensity focused ultrasound (HIFU).

Materials And Methods: From June 2012 to January 2020, 2311 patients with adenomyosis were treated with HIFU at our center, 1982 patients who have complete clinical data were retrospectively reviewed. Among the patients who completed the follow-up, 485 were treated with HIFU alone, 289 were treated with HIFU followed by GnRH-a, 255 were treated with HIFU combined with Mirena and 594 were treated with HIFU combined with GnRH-a and Mirena. The dysmenorrhea severity pain score and average menorrhagia severity score before and at 3 months, 6 months, 1 year, 2 years, 3 years and 5 years after HIFU were compared. The adverse effects were recorded. In addition, the efficacy between patients treated with GnRH-a and/or Mirena were compared.

Results: After HIFU ablation, the dysmenorrhea severity pain score and the menorrhagia severity score were significantly decreased at each follow-up time point. However, it was observed that as the follow-up time increased, the effective rate of HIFU treatment in improving dysmenorrhea and menorrhagia decreased. The 6 months and 3 years follow-up results showed that the efficacy of HIFU combined with Mirena and HIFU combined with GnRH-a and Mirena were significantly higher than HIFU alone and HIFU combined with GnRH-a ( < 0.05). The major complications were rare.

Conclusion: HIFU is a safe and effective treatment for patients with adenomyosis. HIFU combined with Mirena or HIFU combined with GnRH-a and Mirena can significantly enhance the long-term treatment results.
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http://dx.doi.org/10.1080/02656736.2021.1886347DOI Listing
January 2021

Callosal angle in idiopathic normal pressure hydrocephalus: small angular mal-rotations of the coronal plane affect measurement reliability.

Neuroradiology 2021 Feb 5. Epub 2021 Feb 5.

Department of Diagnostic Radiology, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore.

Purpose: The callosal angle (CA) is a useful biomarker in the diagnosis and management of idiopathic normal pressure hydrocephalus (NPH). Used incorrectly, CA measurements are variable, affecting its reliability as a clinical tool. Our objectives are to evaluate (i) reproducibility of established CA measurements between trained raters and (ii) impact of minor angular mal-rotations of the true coronal plane on CA measurements.

Methods: CAs were measured by two independent raters on three-dimensional isovolumetric T1-weighted brain MRI of NPH patients and healthy controls using the established true coronal plane reformatted orthogonal to the plane containing the anterior-posterior commissural (AC-PC) line at the level of the posterior commissure. CA changes were subsequently evaluated when the coronal plane was mal-rotated by ± 5° and ± 10° in anterior-posterior and clockwise-anticlockwise directions. Inter-rater reliability of CA measurements was assessed using the intraclass correlation coefficient (ICC).

Results: On the true coronal plane, inter-rater ICC was excellent (0.973) for NPH patients and good (0.875) for controls. On mal-rotated coronal plane setups, ICC for CA was worse in controls (0.484-0.886) than NPH (0.879-0.981) groups and in clockwise-anticlockwise (0.484-0.956) than anterior-posterior (0.503-0.981) mal-rotations. CA changes secondary to mal-rotations from the true coronal plane were significant in NPH patients (P < 0.0001 to 0.0378) but not in controls (P > 0.1).

Conclusion: This is the first demonstration of how small angular mal-rotations of the coronal plane used for CA measurement affect its value and inter-rater reliability, highlighting the importance of a standardized protocol when measuring the CA in NPH workup.
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http://dx.doi.org/10.1007/s00234-021-02658-2DOI Listing
February 2021

Anti-cyclic citrullinated peptide but not rheumatoid factor is associated with ultrasound-detected bone erosion among rheumatoid arthritis patients with at least moderate disease activity.

Int J Rheum Dis 2020 Oct 17;23(10):1337-1343. Epub 2020 Aug 17.

Department of Rheumatology and Immunology, Singapore General Hospital, Singapore.

Aim: To investigate anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) in relation to ultrasound-detected joint inflammation and bone erosion in patients with rheumatoid arthritis (RA) as previous studies have mainly utilized radiographic damage as imaging outcomes.

Method: In this cross-sectional study, patients were grouped based on their Disease Activity Score at 28 joints (DAS28 < 3.2, DAS28 ≥ 3.2). Ultrasound variables (power Doppler and gray scale joint inflammation graded 0-3 semi-quantitatively; bone erosion graded Yes = 1/No = 0 dichotomously) were correlated with antibodies levels using Pearson correlation. Simple linear regression was used to characterize relationships between variables. Receiver operating characteristic (ROC) analysis was performed to determine statistically optimal cut-off values for identifying patient subgroups with ultrasound erosion scores >25th, >50th and >75th percentiles.

Results: One thousand and eighty joints and 1800 joint recesses from 36 peripheral joint sites were scanned in 30 adult RA patients (mean disease duration, 70.3 months; 93.3% female; 93.3% anti-CCP positive; 93.3% RF positive). In the DAS28 < 3.2 group, no significant correlations were found between antibody levels and ultrasound variables. In the DAS28 ≥ 3.2 group, anti-CCP levels correlated significantly (r = 0.46, P = .048) and were predictive (P = .048) of ultrasound erosion scores. Area under the ROC curve based on cut-off anti-CCP level of ≥95.2 to identify patients with ultrasound erosion scores >7 (75th percentile) was 0.72 (sensitivity = 83.3%, specificity = 53.8%).

Conclusion: The association of anti-CCP and RF with joint damage appears to differ in RA. Among patients with at least moderate disease activity (DAS28 ≥ 3.2), anti-CCP-but not RF-is associated with joint damage, being moderately correlated with ultrasound-detected bone erosion.
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http://dx.doi.org/10.1111/1756-185X.13933DOI Listing
October 2020

Validation of the kidney failure risk equation in predicting the risk of progression to kidney failure in a multi-ethnic Singapore chronic kidney disease cohort.

Singapore Med J 2020 Dec 2. Epub 2020 Dec 2.

Department of Renal Medicine, Singapore General Hospital, Singapore.

Introduction: The Kidney Failure Risk Equation (KFRE) was developed to predict the risk of progression to end-stage kidney disease (ESKD). Although the KFRE has been validated in multinational cohorts, the Southeast Asian population was under-represented. This study aimed to validate the KFRE in a multi-ethnic Singapore chronic kidney disease (CKD) cohort.

Methods: Stage 3-5 CKD patients referred to the renal medicine department at Singapore General Hospital in 2009 were included. The primary outcome (time to ESKD) was traced until 30 June 2017. The eight- and four-variable KFRE (non-North America) models using age, gender, estimated glomerular filtration rate, urine albumin-creatinine ratio, serum albumin, phosphate, bicarbonate and calcium were validated in our cohort. Cox regression, likelihood ratio (χ2), adequacy index, Harrell's C-index and calibration curves were calculated to assess the predictive performance, discrimination and calibration of these models on the cohort.

Results: A total of 1,128 patients were included. During the study period, 252 (22.3%) patients reached ESKD at a median time to ESKD of 84.8 (range 0.1-104.7) months. Both the eight- and four-variable KFRE models showed excellent predictive performance and discrimination (eight-variable: C-index 0.872, 95% confidence interval [CI] 0.850-0.894, adequacy index 97.3%; four-variable: C-index 0.874, 95% CI 0.852-0.896, adequacy index 97.9%). There was no incremental improvement in the prediction ability of the eight-variable model over the four-variable model in this cohort.

Conclusion: The KFRE was validated in a multi-ethnic Singapore CKD cohort. This risk score may help to identify patients requiring early renal care.
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http://dx.doi.org/10.11622/smedj.2020170DOI Listing
December 2020

A novel use of combined thermal and ultrasound imaging in detecting joint inflammation in rheumatoid arthritis.

Eur J Radiol 2021 Jan 20;134:109421. Epub 2020 Nov 20.

Department of Rheumatology and Immunology, Singapore General Hospital, Singapore; Duke-NUS Medical School, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Health Services Research Unit, Singapore General Hospital, Singapore.

Purpose: To evaluate the use of combined thermal and ultrasound imaging to assess joint inflammation in rheumatoid arthritis (RA).

Method: 22-joint (bilateral hands) thermography and ultrasonography were performed. For each patient, the MAX, MIN and AVG represent the sum of the temperature differences with a control temperature, for the respective maximum (Tmax), minimum (Tmin) and average (Tavg) temperatures at the joints. MAX (PD), MIN (PD) and AVG (PD) represent the results of combined thermal imaging with a patient's total ultrasound power Doppler (PD) joint inflammation score (Total PD) (when Total PD > median score, MAX, MIN and AVG was multiplied by a factor of 2, otherwise MAX (PD), MIN (PD) and AVG (PD) remained the same as the MAX, MIN and AVG). Pearson correlation and linear regression were used to assess correlation and characterize relationships of imaging parameters with the 28-joint disease activity score (DAS28).

Results: In this cross-sectional study, 814 joints were examined in 37 adult RA patients (75.7 % female, 75.7 % Chinese; mean DAS28, 4.43). Among the imaging parameters, only MAX (PD) and AVG (PD) correlated significantly with DAS28 (correlation coefficient (95 % CI): MAX (PD), 0.393 (0.079, 0.636), P = 0.016; AVG (PD): 0.376 (0.060, 0.624), P = 0.022). Similarly, only MAX (PD) and AVG (PD) demonstrated a statistically significant relationship with DAS28 (regression coefficient (95 % CI): MAX (PD), 0.009 (0.002, 0.015), P = 0.016; AVG (PD), 0.011 (0.002, 0.020), P = 0.022).

Conclusions: Novel use of combined thermal and ultrasound imaging in RA shows superiority to either imaging alone in terms of correlation with DAS28.
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http://dx.doi.org/10.1016/j.ejrad.2020.109421DOI Listing
January 2021

Joint damage in rheumatoid arthritis: Lessons learned from an extended 36-joint ultrasonography and 28-joint Disease Activity Score assessments.

Int J Rheum Dis 2021 Jan 7;24(1):106-111. Epub 2020 Nov 7.

Department of Rheumatology and Immunology, Singapore General Hospital, Singapore.

Aim: To study joint damage severity in rheumatoid arthritis (RA) patients classified using ultrasound power Doppler (PD) and gray-scale (GS) joint inflammation outcomes and the 28-joint Disease Activity Score (DAS28).

Method: Ultrasound erosion scores were compared between (a) patients in group 1 (PD positive and GS ≥ median score), group 2 (PD negative and GS ≥ median score) and group 3 (PD positive and GS < median score) vs group 4 (PD negative and GS < median score) and (b) patients with high, moderate and low DAS28 scores vs those in DAS28 remission. Comparative analyses were performed using the 2-sample Student's t test.

Results: There were 1080 joints and 1800 joint recesses from 36 joints scanned in 30 RA adult patients (mean DAS28, 3.58; mean disease duration, 70.3 months) in this cross-sectional study. The mean and 95% CI ultrasound erosion scores were significantly higher (P = .026) for groups 1 (9.75, 6.69-12.81) vs 4 (3.4, 1.11-5.69) with a difference (95% CI) of 6.35 (0.78-11.83), but not significantly different (P values all > .05) for (a) groups 2 and 3 vs 4 and (b) patients with high, moderate and low DAS28 scores vs those in DAS28 remission.

Conclusion: Severity of ultrasound-detected bone erosions was significantly greater when both positive PD and a greater degree of GS joint inflammation were present in RA. This association was not observed when either component was absent. Single time point ultrasound joint inflammation assessment - and not DAS28 - is reflective of joint damage severity in RA patients.
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http://dx.doi.org/10.1111/1756-185X.14013DOI Listing
January 2021

Immunohistochemical scoring of CD38 in the tumor microenvironment predicts responsiveness to anti-PD-1/PD-L1 immunotherapy in hepatocellular carcinoma.

J Immunother Cancer 2020 08;8(2)

Division of Pathology, Singapore General Hospital, Singapore

Introduction: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated mortality globally. Immune-checkpoint blockade (ICB) is one of the systemic therapy options for HCC. However, response rates remain low, necessitating robust predictive biomarkers. In the present study, we examined the expression of CD38, a molecule involved in the immunosuppressive adenosinergic pathway, on immune cells present in the tumor microenvironment. We then investigated the association between CD38 and ICB treatment outcomes in advanced HCC.

Methods: Clinically annotated samples from 49 patients with advanced HCC treated with ICB were analyzed for CD38 expression using immunohistochemistry (IHC), multiplex immunohistochemistry/immunofluorescence (mIHC/IF) and multiplex cytokine analysis.

Results: IHC and mIHC/IF analyses revealed that higher intratumoral CD38 cell proportion was strongly associated with improved response to ICB. The overall response rates to ICB was significantly higher among patients with high proportion of total CD38cells compared with patients with low proportion (43.5% vs 3.9%, p=0.019). Higher responses seen among patients with a high intratumoral CD38cell proportion translated to a longer median progression-free survival (mPFS, 8.21 months vs 1.64 months, p=0.0065) and median overall survival (mOS, 19.06 months vs 9.59 months, p=0.0295). Patients with high CD38CD68macrophage density had a better mOS of 34.43 months compared with 9.66 months in patients with low CD38CD68 macrophage density. CD38 macrophages produce more interferon γ (IFN-γ) and related cytokines, which may explain its predictive value when treated with ICB.

Conclusions: A high proportion of CD38 cells, determined by IHC, predicts response to ICB and is associated with superior mPFS and OS in advanced HCC.
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http://dx.doi.org/10.1136/jitc-2020-000987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451957PMC
August 2020

Risk stratification of patients with atrial fibrillation in the emergency department.

Am J Emerg Med 2020 09 11;38(9):1807-1815. Epub 2020 Jun 11.

Department of Emergency Medicine, Singapore General Hospital, Singapore, 1 Hospital Crescent, Outram Rd, 169608, Singapore; Health Services & Systems Research, Duke-NUS Medical School, Singapore, 8 College Rd, Singapore 169857, Singapore. Electronic address:

Introduction And Methods: Early and accurate risk stratification of patients with atrial fibrillation (AF) in the emergency department (ED) could aid the physician in determining a timely treatment strategy appropriate to the severity of disease. We conducted a retrospective review of 243 adult patients who presented to a tertiary ED with AF in 2017. Primary outcome studied was 30-day adverse event (a composite outcome of repeat visit to the ED, cardiovascular complications, and all-cause mortality). Secondary outcome studied was 90-day all-cause mortality. We compared the performance of the RED-AF, AFTER and CHA2DS2-VASc score by plotting receiver operating characteristic (ROC) curves and estimating the areas under curves (AUC), and assessed the potential to further improve the tools with their incorporation of new variables.

Results: Existing scoring tools had poor predictive value for 30-day adverse events, with the RED-AF score performing comparatively better, followed by the AFTER and CHA2DS2-VASc score. All scores performed collectively better to predict 90-day mortality, with the AFTER score performing the best, followed by the RED-AF and CHA2DS2-VASc score. By incorporating heart rate at initial presentation to the ED as a variable into the AFTER Score, we generated a Modified AFTER Score with superior predictive performance above existing scores for 90-day mortality.

Conclusion: Existing scores collectively performed poorly to predict 30-day adverse outcomes, but the AFTER and Modified AFTER score showed good predictive value for 90-day mortality. Further studies should be done to validate their use in guiding clinician's disposition of patients with AF in the ED.
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http://dx.doi.org/10.1016/j.ajem.2020.06.018DOI Listing
September 2020

Circular RNA Circ_0000064 promotes the proliferation and fibrosis of mesangial cells via miR-143 in diabetic nephropathy.

Gene 2020 Oct 16;758:144952. Epub 2020 Jul 16.

Department of Endocrinology Tongren Hospital Affiliated to Jiaotong University, Shanghai, China. Electronic address:

Diabetic nephropathy (DN) as one of the most frequent microvascular complications of diabetic patients causes chronic renal failure and end-stage renal disease. Noncoding RNAs including circular RNAs (circRNAs) and micro RNAs (miRNAs) were widely reported to play a critical role in numerous human diseases including DN. This research was designed to investigate the role of circ_0000064 in diabetic nephropathy progression. The results showed that circ_0000064 significantly promoted mesangial cells proliferation and aggravated fibrosis in DN. In the subsequent mechanism investigation, we found that circ_0000064 was involved in this process by targeting micro RNA miR-143. The inhibition of miR-143 significantly reverses the effect of circ_0000064 silencing on DN. In conclusion, we demonstrated the regulatory role of circ_0000064 in DN and clarified that circ_0000064 play a role in DN via targeting miR-143. Circ_0000064 and miR-143 also showed the potential as a biomarker for DN.
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http://dx.doi.org/10.1016/j.gene.2020.144952DOI Listing
October 2020

Anoectochilus roxburghii polysaccharide prevents carbon tetrachloride-induced liver injury in mice by metabolomic analysis.

J Chromatogr B Analyt Technol Biomed Life Sci 2020 Sep 2;1152:122202. Epub 2020 Jun 2.

Fujian Key Laboratory of Physiology and Biochemistry for Subtropical Plant, Fujian Institute of Subtropical Botany, 361006 Xiamen, China.

Anoectochilus roxburghii (Wall.) Lindl, a traditional Chinese medicine, is used for the effective treatment of liver disease in China. Anoectochilus roxburghii polysaccharide (ARPT) is an important constituent of Anoectochilus roxburghii. ARPT exerts a hepatoprotective effect and contributes directly to the therapeutic benefit of Anoectochilus roxburghii. However, the hepatoprotective mechanism of ARPT requires further elucidation. The present study was designed to assess the effects and underlying mechanism of ARPT when used to pretreat carbon tetrachloride (CCl)-induced liver injury in mice. Mice were randomly divided into three groups: control group (no ARPT treatment or liver injury), model group (liver injury induced with CCl), and the ARPT group (ARPT pretreatment followed by liver injury). A metabolomic method, based on liquid chromatography combined with mass spectrometry (LC-MS) and pattern recognition analysis, was applied. The data were analyzed with principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), to determine differentiating metabolites in the serum and liver tissue between the experimental groups. The PCA and OPLS-DA scores plots of the serum and liver tissue samples based on the LC-MS data showed a clear separation between the control and liver injury model group, while the ARPT-treated group showed a trend of close with the control. There were eleven metabolites [PS(O-18:0/0:0), phosphocholine, phenylalanine, hippuric acid, α-ketoisovaleric acid, metyrosine, leucinic acid, ketoleucine, Cer(d18:1/19:0), α-kamlolenic acid, and 4-formyl indole] were identified as candidate biomarkers in the serum samples, eight such metabolites (valine, phosphohydroxypyruvic acid, phosphocholine, ornithine, indole, xanthine, uridine, and glucose 6-phosphate) were found in the liver tissue samples, and one metabolite (phosphocholine) was observed in both the serum and liver tissue samples. These endogenous metabolites are considered to be in response to the hepatoprotective effects of ARPT and are involved in amino acid metabolism, lipid metabolism, gut bacteria metabolism, energy metabolism, and the methylation pathway. These findings suggest that ARPT mitigates the metabolic effect of CCl-induced hepatotoxicity in mice by affecting at least five different pathways. LC-MS-based metabolomics provides a powerful approach for identifying potential biomarkers and for elucidating the protective mechanisms of traditional Chinese medicines against disease.
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http://dx.doi.org/10.1016/j.jchromb.2020.122202DOI Listing
September 2020

Presence of Hepatic Steatosis Does Not Increase the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Over Long Follow-Up.

Microbiol Insights 2020 13;13:1178636120918878. Epub 2020 May 13.

Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore.

Background: Chronic hepatitis B (CHB) infection and nonalcoholic fatty liver disease (NAFLD) are liver diseases which may lead to hepatocellular carcinoma (HCC) formation. Both disease entities have been attributed independently to increase risk of HCC development. While concomitant hepatic steatosis in patients with CHB are becoming more frequent in view of increasing NAFLD prevalence, there is no conclusive evidence linking presence of hepatic steatosis and increased HCC risk in patients with CHB infection. This study explores the association of hepatic steatosis among CHB-infected individuals in HCC development.

Methods: This is a retrospective study on a cohort of patients with CHB who underwent liver biopsy between January 2000 and December 2014. They were stratified according to presence and severity of histologically proven hepatic steatosis and subsequently followed up to evaluate the association between hepatic steatosis and HCC development.

Results: Among 289 patients with a median follow-up of 111.1 months, hepatic steatosis was present in 185 patients (64.0%). In all, 27 patients developed HCC on follow-up and 21 of them had hepatic steatosis. Univariate Cox analysis showed that age (hazard ratio [HR] = 1.08, 95% CI = 1.042-1.12), type 2 diabetes mellitus (T2DM) (HR = 4.00, 95% CI = 1.622-9.863), and Ishak score (HR = 1.221, 95% CI = 1.014-1.472) were associated with HCC development, whereas multivariate Cox analysis demonstrated that age and T2DM (HR = 2.69, 95% CI = 1.072-6.759) were significant risk factors for development of HCC.

Conclusions: Concurrent hepatic steatosis in patients with CHB infection is not a risk factor for hepatocellular carcinoma formation.
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http://dx.doi.org/10.1177/1178636120918878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223198PMC
May 2020

Increased Alternative Complement Pathway Function and Improved Survival during Critical Illness.

Am J Respir Crit Care Med 2020 07;202(2):230-240

Acute Lung Injury Center of Excellence, Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine.

Complement is crucial for host defense but may also drive dysregulated inflammation. There is limited understanding of alternative complement function, which can amplify all complement activity, during critical illness. We examined the function and key components of the alternative complement pathway in a series of critically ill patients and in a mouse pneumonia model. Total classical (CH50) and alternative complement (AH50) function were quantified in serum from 321 prospectively enrolled critically ill patients and compared with clinical outcomes. Alternative pathway (AP) regulatory factors were quantified by ELISA ( = 181) and examined via transcriptomics data from external cohorts. Wild-type, , and mice were infected intratracheally with (KP) and assessed for extrapulmonary dissemination. AH50 greater than or equal to median, but not CH50 greater than or equal to median, was associated with decreased 30-day mortality (adjusted odds ratio [OR], 0.53 [95% confidence interval (CI), 0.31-0.91]), independent of chronic liver disease. One-year survival was improved in patients with AH50 greater than or equal to median (adjusted hazard ratio = 0.59 [95% CI, 0.41-0.87]). Patients with elevated AH50 had increased levels of AP factors B, H, and properdin, and fewer showed a "hyperinflammatory" subphenotype (OR, 0.30 [95% CI, 0.18-0.49]). Increased expression of proximal AP genes was associated with improved survival in two external cohorts. AH50 greater than or equal to median was associated with fewer bloodstream infections (OR, 0.67 [95% CI, 0.45-0.98). Conversely, depletion of AP factors, or AH50 less than median, impaired serum control of KP that was restored by adding healthy serum. mice demonstrated increased extrapulmonary dissemination and serum inflammatory markers after intratracheal KP infection compared with wild type. Elevated AP function is associated with improved survival during critical illness, possibly because of enhanced immune capacity.
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http://dx.doi.org/10.1164/rccm.201910-2083OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365364PMC
July 2020

Challenges and Strategies for High-Energy Aqueous Electrolyte Rechargeable Batteries.

Angew Chem Int Ed Engl 2021 Jan 16;60(2):598-616. Epub 2020 Jul 16.

Helmholtz Institute Ulm (HIU), Helmholtzstrasse 11, 89081, Ulm, Germany.

Aqueous rechargeable batteries are becoming increasingly important to the development of renewable energy sources, because they promise to meet cost-efficiency, energy and power demands for stationary applications. Over the past decade, efforts have been devoted to the improvement of electrode materials and their use in combination with highly concentrated aqueous electrolytes. Here the latest ground-breaking advances in using such electrolytes to construct aqueous battery systems efficiently storing electrical energy, i.e., offering improved energy density, cyclability and safety, are highlighted. This Review aims to timely provide a summary of the strategies proposed so far to overcome the still existing hurdles limiting the present aqueous batteries technologies employing concentrated electrolytes. Emphasis is placed on aqueous batteries for lithium and post-lithium chemistries, with potentially improved energy density, resulting from the unique advantages of concentrated electrolytes.
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http://dx.doi.org/10.1002/anie.202004433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818224PMC
January 2021

Mortality and Neurological Outcomes in Out-of-Hospital Cardiac Arrest Patients With and Without Targeted Temperature Management in a Multiethnic Asian Population.

Ann Acad Med Singap 2020 Mar;49(3):127-136

Department of Emergency Medicine, Singapore General Hospital, Singapore.

Introduction: The use of targeted temperature management (TTM) is increasing although adoption is still variable. We describe our 6-year experience and compare the mortality and neurological outcomes of out-of-hospital cardiac arrest (OHCA) patients with and without the use of TTM in a multiethnic Asian population.

Materials And Methods: We performed a retrospective observational study at a tertiary academic medical centre. OHCA survivors admitted to our hospital between April 2010‒December 2016 were included. Outcomes of interest were 30-day mortality postresuscitation, Cerebral Performance Category (CPC) and Overall Performance Category (OPC) scores.

Results: A total of 121 of 261 patients (46.3%) underwent TTM. TTM patients were younger (TTM 60.0 years old vs no TTM 63.7 years old, = 0.047). There was no difference in the initial arrest rhythm of shockable origin between the 2 groups ( = 0.289). There was suggestion of lower 30-day mortality (TTM 24.3% vs no TTM 31.4%, = 0.214), higher and good CPC/OPC scores (TTM 19.0% vs no TTM 15.7%, = 0.514) with TTM although this did not reach statistical significance. On multivariable logistic regression analysis, TTM was not associated with 30-day mortality ( = 0.07). However, older age, initial non-shockable rhythm and increased duration from arrest to return of spontaneous circulation were associated with increased mortality. Malay ethnicity was associated with a poorer CPC/ OPC score.

Conclusion: Adoption and outcomes of TTM postresuscitation is variable and there is still a need to optimise management of the identified predictors of survival and good neurological outcomes while TTM is being used.
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March 2020

Adverse Events and Discontinuation Rates Associated with Sirolimus Treatment in Adult Renal Transplant Patients in Latin America vs Non-Latin American Countries.

Transplant Proc 2020 Apr 17;52(3):767-774. Epub 2020 Mar 17.

Pfizer Inc, Collegeville, PA.

Background: Sirolimus is approved for prophylaxis of organ rejection following renal transplantation. Rates of treatment-emergent adverse events (TEAEs) leading to sirolimus discontinuation differ geographically.

Methods: Rates of TEAEs, serious AEs (SAEs), and discontinuations were evaluated in 3 clinical trials of conversion from calcineurin inhibitors to sirolimus. Posttransplantation, patients were treated over 4 years (study 1), over 1 year (study 2), and over 2 years (study 3). TEAEs, SAEs, and discontinuation rates were compared between Latin America (LATAM) vs North America (NA) and Europe/rest of world (EU/ROW). Data from studies 2 and 3, with similar times to conversion, were pooled.

Results: Study 1 comprised 551 patients (LATAM, n=189); studies 2/3 comprised 395 (LATAM, n=111). LATAM patients were significantly younger than NA or EU/ROW patients in study 1 and studies 2/3 (P < .0001), with a lower proportion of white patients and higher proportion of patients of other races in LATAM vs NA (P < .0001) and EU/ROW (P = .02) groups. Almost all patients reported TEAEs. Discontinuation because of medical events was significantly lower (P < .05) in LATAM vs NA or EU/ROW. Hypercholesterolemia and hypertriglyceridemia were more common, and anemia and peripheral edema less common in LATAM; diarrhea and proteinuria did not differ by region. Types of AEs leading to discontinuation did not differ by region.

Conclusion: LATAM renal transplant recipients converted to sirolimus were more likely to remain on therapy than patients in other regions.
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http://dx.doi.org/10.1016/j.transproceed.2020.01.040DOI Listing
April 2020

Link Between Elevated Long-Term Resting Heart Rate Variability and Pulse Pressure Variability for All-Cause Mortality.

J Am Heart Assoc 2020 03 16;9(6):e014122. Epub 2020 Mar 16.

Department of Cardiology Institute of Cardiovascular Diseases First Affiliated Hospital of Dalian Medical University Dalian Liaoning China.

Background Elevated long-term systolic blood pressure and resting heart rate (RHR) variability are suggested to amplify the risk of all-cause mortality (ACM). However, the link between increased RHR and pulse pressure for ACM remained unclear. Methods and Results This study analyzed 46 751 individuals from Kailuan Cohort Study for the end outcome of ACM. A Cox regression model was used to estimate hazard ratios for death events. Kaplan-Meier analysis was performed to study the differences in survival as stratified by the SD, coefficient of variation, and average real variability of RHR and pulse pressure quartiles. A total of 1667 deaths (<65 years of age=866/40351, ≥65 years of age=801/6400) were recorded over 4.97±0.69 years follow-up. Participants under the age of 65 years in the third and fourth quartiles of pulse pressure SD had an independent increase in risk for ACM (hazard ratio [95% CI], 1.16 [1.06-1.28]; and 1.19 [1.05-1.35], respectively). Additionally, participants >65 years of age had a higher risk for ACM across quartiles of RHR-SD. The hazard ratio (95% CI) for the subjects in quartiles 2, 3, and 4 were 1.81 (1.10-2.97), 2.31 (1.37-1.3.90), and 2.64 (1.63-4.29), respectively. Conclusions An elevated long-term RHR variability combined with an increased pulse pressure variability or vice versa amplifies the risk of ACM.
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http://dx.doi.org/10.1161/JAHA.119.014122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335531PMC
March 2020

High-Voltage Operation of a VO Cathode in a Concentrated Gel Polymer Electrolyte for High-Energy Aqueous Zinc Batteries.

ACS Appl Mater Interfaces 2020 Apr 19;12(13):15305-15312. Epub 2020 Mar 19.

Helmholtz Institute Ulm (HIU), Helmholtzstrasse 11, 89081 Ulm, Germany.

Gel-type polymer electrolytes are very promising to replace liquid electrolytes, addressing the leakage concerns in batteries. In this work, we report a concentrated gel polymer electrolyte for aqueous zinc-metal batteries, which manifests superior Zn stripping/plating reversibility and electrolyte stability, combined with a promising electrochemical stability window and robust water-retention ability. Quasi-solid-state Zn/VO batteries employing such an electrolyte reach a specific energy of 326 W h kg at 20 mA g based on the cathode mass and a capacity retention of 93% over 600 cycles at 500 mA g. Moreover, the cell performs well in the 0-40 °C temperature range without significant capacity loss. These results represent important steps toward the development of high-energy aqueous zinc batteries.
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http://dx.doi.org/10.1021/acsami.0c02102DOI Listing
April 2020

Evaluation of Mortality During Long-Term Treatment with Tafamidis for Transthyretin Amyloidosis with Polyneuropathy: Clinical Trial Results up to 8.5 Years.

Neurol Ther 2020 Jun 27;9(1):105-115. Epub 2020 Feb 27.

Pfizer Inc, New York, NY, USA.

Introduction: The effects of tafamidis on mortality in Val30Met and non-Val30Met patients with transthyretin amyloidosis with polyneuropathy (ATTR-PN) were evaluated.

Methods: The analyses were based on cumulative data from the Val30Met patients in the 18-month double-blind registration study and its 12-month open-label extension study, the non-Val30Met patients of the 12-month open-label study, and both patient groups in the ongoing 10-year extension study. Kaplan-Meier analyses of time to death from first treatment dose were performed. For the Val30Met group, two treatment groups were analyzed: those who received tafamidis in both the parent and extension studies (T-T) and those who received placebo in the parent study and switched to tafamidis in the extension studies (P-T).

Results: Kaplan-Meier estimates (95% confidence interval [CI]) were available up to 9 years for the Val30Met group, at which time 85.9% (53.1-96.4) and 91.1% (77.9-96.6) of the patients in the T-T and P-T groups, respectively, were alive. For the non-Val30Met group, estimates were available up to 8 years from the first dose, and the percentage of patients alive was 75.9% (47.7-90.2).

Conclusion: Long-term tafamidis treatment may confer survival benefit in patients with ATTR-PN.

Trial Registration: ClinicalTrials.gov identifier: NCT00409175, NCT00791492, NCT00630864, and NCT00925002.
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http://dx.doi.org/10.1007/s40120-020-00180-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229124PMC
June 2020

SRSF1 mediates cytokine-induced impaired imatinib sensitivity in chronic myeloid leukemia.

Leukemia 2020 07 12;34(7):1787-1798. Epub 2020 Feb 12.

Cancer and Stem Cell Biology Programme, Duke-NUS Medical School, Singapore, Singapore.

Patients with chronic myeloid leukemia (CML) who are treated with tyrosine kinase inhibitors (TKIs) experience significant heterogeneity regarding depth and speed of responses. Factors intrinsic and extrinsic to CML cells contribute to response heterogeneity and TKI resistance. Among extrinsic factors, cytokine-mediated TKI resistance has been demonstrated in CML progenitors, but the underlying mechanisms remain obscure. Using RNA-sequencing, we identified differentially expressed splicing factors in primary CD34 chronic phase (CP) CML progenitors and controls. We found SRSF1 expression to be increased as a result of both BCR-ABL1- and cytokine-mediated signaling. SRSF1 overexpression conferred cytokine independence to untransformed hematopoietic cells and impaired imatinib sensitivity in CML cells, while SRSF1 depletion in CD34 CP CML cells prevented the ability of extrinsic cytokines to decrease imatinib sensitivity. Mechanistically, PRKCH and PLCH1 were upregulated by elevated SRSF1 levels, and contributed to impaired imatinib sensitivity. Importantly, very high SRSF1 levels in the bone marrow of CML patients at presentation correlated with poorer clinical TKI responses. In summary, we find SRSF1 levels to be maintained in CD34 CP CML progenitors by cytokines despite effective BCR-ABL1 inhibition, and that elevated levels promote impaired imatinib responses. Together, our data support an SRSF1/PRKCH/PLCH1 axis in contributing to cytokine-induced impaired imatinib sensitivity in CML.
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http://dx.doi.org/10.1038/s41375-020-0732-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682023PMC
July 2020

PD-L1 expression is an unfavourable prognostic indicator in Asian renal cell carcinomas.

J Clin Pathol 2020 Aug 24;73(8):463-469. Epub 2020 Jan 24.

Anatomical Pathology, Singapore General Hospital, Singapore

Background/aims: The programmed cell death receptor 1 (PD-1) checkpoint inhibitor, nivolumab, has been approved for the treatment of metastatic renal cell carcinoma (RCC). However, the understanding of the expression and distribution of PD ligand 1 (PD-L1) in the tumour immune microenvironment and its prognostic role in an Asian cohort is limited. Our group investigated PD-L1 protein expression in a cohort of Asian patients with RCC of mixed ethnicity, using two commercially available antibody clones.

Methods: E1L3N and SP263 anti-PD-L1 clones were used to categorise RCCs of various histological subtypes, diagnosed at our institution between 1995 and 2008, into PD-L1-positive or PD-L1-negative groups, based on a 1% Tumour Proportion Score (TPS) cut-off.

Results: In total, 267 (83%) clear cell (cc)RCC and 55 (17%) non-ccRCC cases were studied. Overall PD-L1 protein expression rates for the entire cohort were 13% and 8% for the E1L3N and SP263 clones, respectively. Patients bearing PD-L1-positive tumours experienced significantly decreased disease-free survival (DFS; E1L3N: p=0.01; SP263: p=0.03) but not overall survival, compared with those with PD-L1-negative tumours. Multivariate survival analysis further confirmed the results of the E1L3N clone (HR 1.85, 95% CI 1.10 to 3.13, p=0.02), but not SP263, after adjusting for pathological stage, histological subtype and grade. The addition of PD-L1 (E1L3N) TPS to clinicopathological features significantly increased the prognostic value for DFS (∆LRχ=5.25; p=0.022), compared with clinicopathological features alone.

Conclusions: PD-L1 protein expression was associated with an unfavourable prognosis in our study cohort. PD-L1 (E1L3N) expression was an independent prognostic indicator of clinical outcome in all RCCs when using a 1% cut-off.
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http://dx.doi.org/10.1136/jclinpath-2019-206092DOI Listing
August 2020

Mobile technology: Usage and perspective of patients and caregivers presenting to a tertiary care emergency department.

World J Emerg Med 2020 ;11(1):5-11

Department of Emergency Medicine, Singapore General Hospital, Singapore.

Background: Developments in information technology (IT) have driven a push in healthcare innovation in the emergency department (ED). Many of these applications rely on mobile technology (MT) such as smartphones but not everyone is comfortable with MT usage. Our study aims to characterize the technology usage behavior of users in the ED so as to guide the implementation of IT interventions in the ED.

Methods: A cross-sectional survey was conducted in the emergency department of a tertiary hospital. Patients and their caregivers aged 21 and above were recruited. The survey collected demographic information, technology usage patterns, and participant reported comfort level in the usage of MT. We performed descriptive statistics and multivariate logistic regression to identify factors differentially associated with comfort in usage of MT.

Results: A total of 498 participants were recruited, and 299 (60%) were patients. English was the most commonly written and read language (66.9%) and 64.2% reported a comfort level of 3/5 or more in using MT. Factors that were associated with being comfortable in using MT include having a tertiary education, being able to read and write English, as well as being a frequent user of IT. Caregivers were more likely to display these characteristics.

Conclusion: A large proportion of ED patients are not comfortable in the usage of MT. Factors that predicted comfort level in the usage of MT were common amongst caregivers. Future interventions should take this into consideration in the design of MT interventions.
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http://dx.doi.org/10.5847/wjem.j.1920-8642.2020.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885587PMC
January 2020

Extended 36-joint sonographic examination: What it reveals about bone erosions in patients with rheumatoid arthritis.

J Clin Ultrasound 2020 Jan 25;48(1):14-18. Epub 2019 Oct 25.

Department of Rheumatology and Immunology, Singapore General Hospital, Singapore, Singapore.

Purpose: To identify joints commonly exhibiting bone erosions using an extended 36-joint sonographic (US) examination in patients with rheumatoid arthritis (RA) and to study bone erosion in relation to US-detected joint inflammation.

Methods: In this cross-sectional study, power Doppler (PD) and gray-scale (GS) joint inflammation scores (semi-quantitative [0-3] grading) at each joint recess were summed to obtain a combined US score (CUS). Bone erosion was scored as present/absent. Generalized Estimating Equations were used to compare mean US scores between joint recesses with and without bone erosion.

Results: Bone erosion was found in 144/1080 (13.3%) joints and 189/1800 (10.5%) joint recesses in 30 RA patients. The five joints most frequently associated with bone erosion were: wrist, n = 49/144 (34.0%); first MTPJ, n = 19/144 (13.2%); thumb IPJ, n = 13/144 (9.0%); second MCPJ, n = 11/144 (7.6%); and third MCPJ, n = 11/144 (7.6%). Mean (95% CI) US scores for joint recesses with and without bone erosion were PD: 0.36 (0.21, 0.50) vs 0.01 (0.00, 0.02); GS: 1.77 (1.54, 2.00) vs 0.47 (0.40, 0.55); and CUS: 2.13 (1.78, 2.47) vs 0.49 (0.41, 0.57) (all differences significant at P < .001).

Conclusion: The five joints most frequently showing bone erosion were identified. Joint recesses with bone erosion are more likely to exhibit greater PD and GS joint inflammation severity.
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http://dx.doi.org/10.1002/jcu.22785DOI Listing
January 2020

Cancer patients with potential eligibility for vascular endothelial growth factor antagonists use have an increased risk for cardiovascular diseases comorbidities.

J Hypertens 2020 03;38(3):426-433

Department of Cardiology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China.

Background: Recent studies have reported the prevalence of cardiovascular diseases (CVDs) among cancer patients following the use of the vascular endothelial growth factor (VEGF) signaling inhibitors. However, data for patients with a history of cancer before active cancer treatment are lacking. This study aims to investigate the distribution of CVD-related comorbidities before cancer treatment in potential VEGF antagonists candidates.

Methods: A total of 22 500 newly diagnosed cancer patients registered from 1 January 2011 to 31 December 2017 were included. Cancer patients with colorectal cancer (CRC), renal cell carcinoma (RCC), thyroid cancer, hepatocellular carcinoma (HCC), and lung cancer were selected.

Results: Hypertension (HTN), coronary heart diseases, atrial fibrillation, and heart failure were top CVD comorbidities among studied cancers. HTN was the most prevalent CVD (26.0%). The prevalence of HTN in RCC, CRC (33.5 and 29.4% respectively) was significantly higher than that in HCC, lung cancer, and thyroid cancer patients (25.1, 24.5, and 23.1%, respectively). Among cancer patients with HTN, the majority of cancer patients fall in grade III (75.7%) and very high cardiovascular risk level (85.4%). Out of the 5847 HTN patients, 26% were not in antihypertensive use, and 34.2% failed to achieve the target blood pressure.

Conclusion: Cancer patients carry a high burden of CVD-related comorbidities before the application of VEGF antagonists. HTN is the most prevalent comorbid condition, and cancer patients with HTN constitute substantial cardiovascular risks and a higher co-prevalence of other CVDs.
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http://dx.doi.org/10.1097/HJH.0000000000002277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012358PMC
March 2020

Characteristics, behaviour and role of biomarkers in metastatic triple-negative breast cancer.

J Clin Pathol 2020 Mar 28;73(3):147-153. Epub 2019 Sep 28.

Duke-NUS Medical School, Singapore, Singapore

Aims: Characterising the factors responsible for metastatic triple-negative breast cancer (TNBC) is of significant importance, considering its high mortality rate and scant data. In this study, we evaluated the characteristics, clinical behaviour and role of biomarkers (androgen receptor (AR), oestrogen receptor beta (ERβ) and p53) in metastatic TNBC.

Methods: Immunohistochemistry was performed for AR, ERβ and p53 on 125 primary TNBCs with known metastasis and correlated with clinicopathological parameters and outcome. and mRNA profiling was also carried out on 34 tumours from the same series and correlated with outcomes.

Results: In this cohort, grade 3 and pT2 tumours predominated. The most common site for metastasis was the lung and pleura (41, 32.8%), and 15 (12.0%) cases demonstrated metastasis in multiple sites. Among these, 92% of tumours metastasised without preceding local recurrences. Five- and ten-year overall survival (OS) rates were 27% and 7.2%, while 5- and 10- year survival rates after metastasis were 9.6% and 3.2% respectively. AR, ERβ and p53 protein expressions were observed in 16%, 96.8% and 58.1% of tumours, respectively. A combinational phenotype of AR-ERβ+p53+ tumours was associated with poorer OS (HR 1.543, 95%CI 1.030 to 2.310, p=0.035). Higher mRNA levels were significantly associated with favourable OS (p=0.015) and survival after metastasis (p=0.027).

Conclusions: Metastatic TNBC harboured aggressive behaviour and displayed predominantly visceral metastasis with most metastatic events occurring without intervening local recurrences. A combinational phenotype of AR-ERβ+p53+ was significantly associated with poorer OS.
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http://dx.doi.org/10.1136/jclinpath-2019-206078DOI Listing
March 2020

Expression of CD38 on Macrophages Predicts Improved Prognosis in Hepatocellular Carcinoma.

Front Immunol 2019 4;10:2093. Epub 2019 Sep 4.

Division of Pathology, Singapore General Hospital, Singapore, Singapore.

CD38 is involved in the adenosine pathway, which represents one of the immunosuppressive mechanisms in cancer. CD38 is broadly expressed across immune cell subsets, including human macrophages differentiated from monocytes, but expression by tissue-resident macrophages remains to be demonstrated. Tissue samples were obtained from 66 patients with hepatocellular carcinoma (HCC) from Singapore and analyzed using immunohistochemistry. Tumor-infiltrating leukocytes (TILs) were further examined using DEPArray™, and the phenotype of freshly isolated TILs was determined using flow cytometry. CD38 was frequently co-expressed with the macrophage-specific marker CD68. CD38CD68 macrophage density was associated with improved prognosis after surgery, while total CD68 macrophage density was associated with poor prognosis. DEPArray™ analysis revealed the presence of large (>10 μm), irregularly shaped CD45CD14 cells that resembled macrophages, with concurrent CD38 expression. Flow cytometry also revealed that majority of CD14HLA-DR cells expressed CD38. CD38 expression was clearly demonstrated on human macrophages in an setting. The positive association identified between CD38 macrophage density and prognosis may have implications for routine diagnostic work.
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http://dx.doi.org/10.3389/fimmu.2019.02093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738266PMC
November 2020

Detecting joints with erosion(s) in rheumatoid arthritis: a novel individualized-ultrasound method performs better than existing methods.

Jpn J Radiol 2019 Nov 14;37(11):793-797. Epub 2019 Sep 14.

Department of Rheumatology and Immunology, Singapore General Hospital, Outram Road, Singapore, Singapore.

Purpose: To determine if a novel individualized-ultrasound (IUS) method can detect more joints with erosion(s) in rheumatoid arthritis (RA) patients versus existing methods.

Materials And Methods: The IUS method selects up to 7 or 14 ultrasonographically most inflamed joints whereas existing methods pre-fix 7 or 14 joints for ultrasonography. Using ultrasonography, the mean total inflammatory score (TIS), mean number of affected joints and mean number of joints with erosion(s) were compared between novel and existing methods among 30 RA patients using the paired Student t test.

Results: Using 7-joint approach, comparing IUS versus existing methods, the mean (95% CI) for TIS, number of affected joints, and number of joints with erosion(s) were: 2.18 (1.88, 2.48) versus 0.95 (0.78, 1.11); 7 (7, 7) versus 4.43 (3.93, 4.94); 3.20 (2.44, 3.96) versus 1.33 (0.94, 1.72), respectively. Using 14-joint approach, comparing IUS versus existing methods, the mean (95% CI) for TIS, number of affected joints, and number of joints with erosion(s) were: 3.17 (2.75, 3.6) versus 1.71 (1.38, 2.04); 13.5 (13.05, 13.95) versus 8.13 (7.24, 9.02); 4.23 (3.13, 5.34) versus 2.77 (2.03, 3.50), respectively. p values all < 0.0001.

Conclusions: A novel IUS method detects substantially more joints with erosion(s) in RA patients versus existing methods.
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http://dx.doi.org/10.1007/s11604-019-00870-yDOI Listing
November 2019

Differentiating Parkinson's disease motor subtypes using automated volume-based morphometry incorporating white matter and deep gray nuclear lesion load.

J Magn Reson Imaging 2020 03 31;51(3):748-756. Epub 2019 Jul 31.

Singapore General Hospital, Singapore.

Background: Periventricular leukoaraiosis may be an important pathological change in postural instability gait disorder (PIGD), a motor subtype of Parkinson's disease (PD). Clinical diagnosis of PIGD may be challenging for the general neurologist.

Purpose: To evaluate 1) the utility of a fully automated volume-based morphometry (Vol-BM) in characterizing imaging diagnostic markers in PD and PIGD, including, 2) novel deep gray nuclear lesion load (GMab), and 3) discriminatory performance of a Vol-BM model construct in classifying the PIGD subtype.

Study Type: Prospective.

Subjects: In all, 23 PIGD, 21 PD, and 20 age-matched healthy controls (HC) underwent MRI brain scans and clinical assessments.

Field Strength/sequence: 3.0T, sagittal 3D-magnetization-prepared rapid gradient echo (MPRAGE), and fluid-attenuated inversion recovery imaging (FLAIR) sequences.

Assessment: Clinical assessment was conducted by a movement disorder neurologist. The MR brain images were then segmented using an automated multimodal Vol-BM algorithm (MorphoBox) and reviewed by two authors independently.

Statistical Testing: Brain segmentation and clinical parameter differences and dependence were assessed using analysis of variance (ANOVA) and regression analysis, respectively. Logistic regression was performed to differentiate PIGD from PD, and discriminative reliability was evaluated using receiver operating characteristic (ROC) analysis.

Results: Significantly higher white matter lesion load (WMab) (P < 0.01), caudate GMab (P < 0.05), and lateral and third ventricular (P < 0.05) volumetry were found in PIGD, compared with PD and HC. WMab, caudate and putamen GMab, and caudate, lateral, and third ventricular volumetry showed significant coefficients (P < 0.005) in linear regressions with balance and gait assessments in both patient groups. A model incorporating WMab, caudate GMab, and caudate GM discriminated PIGD from PD and HC with a sensitivity = 0.83 and specificity = 0.76 (AUC = 0.84).

Data Conclusion: Fast, unbiased quantification of microstructural brain changes in PD and PIGD is feasible using automated Vol-BM. Composite lesion load in the white matter and caudate, and caudate volumetry discriminated PIGD from PD and HC, and showed potential in classification of these disorders using supervised machine learning.

Level Of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:748-756.
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http://dx.doi.org/10.1002/jmri.26887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027785PMC
March 2020

A comprehensive safety profile of tafamidis in patients with transthyretin amyloid polyneuropathy.

Amyloid 2019 Dec 27;26(4):203-209. Epub 2019 Jul 27.

Pfizer Inc. , New York , NY , USA.

Tafamidis is approved in over 40 countries to delay neurologic progression in patients with transthyretin amyloid polyneuropathy (ATTR-PN). A comprehensive, integrated analysis of safety data from interventional, observational and surveillance studies of tafamidis in ATTR-PN patients was conducted. Safety data from all sponsored, completed, or ongoing, Phase 2/3 studies of tafamidis in ATTR-PN patients as of 3 January 2017 were pooled. Also assessed were safety data from the ongoing Transthyretin Amyloidosis Outcomes Survey (THAOS) as of 3 January 2017 and post-marketing surveillance reports as of 31 March 2017. There were 137 patients in Phase 2/3 studies (mean duration of tafamidis exposure, 44.2 months), with 134 (97.8%) experiencing ≥1 treatment-emergent adverse event (TEAE) and 46 (33.6%) ≥1 treatment-emergent serious adverse event (TESAE). The most common TEAEs were diarrhoea (26.3%), urinary tract infection (UTI; 25.5%) and influenza (21.2%). In THAOS, 661 subjects had tafamidis exposure (mean duration, 27.6 months), with 250 (37.8%) experiencing ≥1 TEAE and 96 (14.5%) ≥1 TESAE. The most common TEAE was UTI (6.1%). Post-marketing surveillance reports generally reflected the known safety profile of tafamidis. This analysis did not reveal any significant new safety findings; tafamidis was generally safe and well tolerated in ATTR-PN patients. NCT00409175, NCT00791492, NCT00630864, NCT01435655, NCT00925002, and NCT00628745.
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http://dx.doi.org/10.1080/13506129.2019.1643714DOI Listing
December 2019

A prospective study of clinical characteristics and outcomes of acute kidney injury in a tertiary care Centre.

BMC Nephrol 2019 07 26;20(1):282. Epub 2019 Jul 26.

Department of Renal Medicine, Academia, Singapore General Hospital, 20 College Road, Singapore, 169856, Singapore.

Background: Acute kidney injury (AKI) is a major global health problem. We aim to evaluate the epidemiology, risk factors and outcomes of AKI episodes in our single centre.

Methodology: We prospectively identified 422 AKI and acute on chronic kidney disease episodes in 404 patients meeting KDIGO definitions using electronic medical records and clinical data from 15th July to 22nd October 2016, excluding patients with baseline estimated GFR (eGFR) of < 15 mL/min. Patients were followed up till 6 months after AKI diagnosis.

Results: The mean age was 65.8 ± 14.1. Majority of patients were male (58.2%) of Chinese ethnicity (68.8%). One hundred and thirty-two patients (32.6%) were diagnosed in acute care units. Seventy-five percent of patients developed AKI during admission in a non-Renal specialty. Mean baseline eGFR was 50.2 ± 27.7 mL/min. Mean creatinine at AKI diagnosis was 297 ± 161 μmol/L. Renal consultations were initiated at KDIGO Stages 1, 2 and 3 in 58.9, 24.5 and 16.6% of patients, respectively. Three hundred and ten (76.7%) patients had a single etiology of AKI with the 3 most common etiologies of AKI being pre-renal (27.7%), sepsis-associated (25.5%) and ischemic acute tubular necrosis (15.3%). One hundred and nine (27%) patients received acute renal replacement therapy. In-hospital mortality was 20.3%. Six-month mortality post-AKI event was 9.4%. On survival analysis, patients with KDIGO Stage 3 AKI had significantly shorter survival than other stages.

Conclusion: AKI is associated with significant in-hospital to 6-month mortality. This signifies the pressing need for AKI prevention, early detection and intervention in mitigating reversible risk factors in order to optimize clinical outcomes.
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http://dx.doi.org/10.1186/s12882-019-1466-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660929PMC
July 2019