Large Cohort Of Chinese Patients Research Articles

The clinical features and outcomes of systemic AL amyloidosis: a cohort of 231 Chinese patients.

BackgroundFew data are available on the clinical features and outcomes of Chinese patients with systemic immunoglobulin light-chain (AL) amyloidosis. The aim of this study is to reveal the clinical picture and risk factors of disease progression in a large cohort of Chinese patients with AL amyloidosis.MethodsPatients in the Jinling Hospital amyloidosis registry from 2003 to 2011 were studied. The clinical and laboratory information were collected from first presentation to death or until the last available clinical follow-up. The patients' survival and renal outcomes were analyzed, and the relationships between the clinical parameters and survival were also assessed.ResultsA total of 231 patients were enrolled in this study, all the patients studied had renal involvement. One hundred and fifty-three (66.2%) were male, and the median age at diagnosis was 56 years. A total of 198 (85.7%) cases had light-chain λ-type. One hundred and forty-seven (63.6%) cases presented as nephrotic syndrome (NS), and 25% of patients had renal insufficiency at diagnosis. Liver involvement and NS appeared to be more common in patients of κ-type amyloidosis, and renal impairment is more severe in κ-type amyloidosis. The median survival time of all patients was 36.3 months, and the 1-, 2-, 3- and 5-year cumulative survival rates were 67, 53, 48 and 35%, respectively. Multivariate COX analysis showed that age, hepatic involvement and heart involvement can significantly influence survival in these patients. The median time that patients remained dialysis free was 50 months. The percentage of patients that remained dialysis free at 1, 2, 3 and 5 years were 78, 69, 62 and 37%, respectively. Multivariate COX analysis showed that serum creatinine and hypotension were the important risk factors of renal failure.Conclusionλ-Type is the most dominant type of AL amyloidosis in Chinese patients. The survival of patients with AL amyloidosis is poor. The risk factors included heart and hepatic involvement, hypotension and impairment of renal function. The high serum creatinine level and hypotension at diagnosis are associated with poor renal outcome.

Clinical characteristics and risk factors for major thrombosis in 604 Chinese patients with low-risk essential thrombocythemia

To analyze clinical and molecular characteristics of low-risk essential thrombocythemia (ET) in a large cohort of Chinese patients and to explore risk factors for major thrombosis and treatment strategies. Medical records of patients with an initial diagnosis of ET from March 1982 to May 2012 in our hospital were retrospectively analyzed. A total of 604 low-risk ET patients were enrolled with a median follow-up of 49 months (range:0-338). 43(7.1%) patients experienced major thrombotic events. Cox proportional hazards regression revealed JAK2 V617F mutation (HR=2.279; P=0.035) and cardiovascular risk factors (CVF) (HR=2.541; P=0.006) to be risk factors for total thrombotic events, while only CVF (HR=2.633; P=0.008) was risk factor for arterial thrombosis. None of the evaluated factors was related to venous thrombosis. Patients with both JAK2 V617F mutation and CVF had a worse thrombosis- free survival than those with only one risk factor (P<0.05). In patients with JAK2 V617F or CVF alone, antiplatelet treatment (P=0.016) significantly decreased the risk of thrombosis, while those with both JAK2 V617F and CVF could benefit from cytoreductive agents (P=0.018). Chinese low-risk ET patients have a lower risk of thrombosis than Caucasian low-risk ET patients. JAK2 V617F mutation and CVF are the most significant risk factors for thrombosis. Existence of both risk factors further increases the thrombotic risk. Treatment strategies on low-risk ET patients should be made based on presence or absence of risk factors.

Clinical Characteristics and Disease Predictors of a Large Chinese Cohort of Patients with Autosomal Dominant Polycystic Kidney Disease

ObjectiveAutosomal dominant polycystic kidney disease (ADPKD) is a relentlessly progressing form of chronic kidney disease for which there is no cure. The aim of this study was to characterize Chinese patients with ADPKD and to identify the factors which predict cyst growth and renal functional deterioration.MethodsTo analyze disease predicting factors we performed a prospective longitudinal observational study in a cohort of 541 Chinese patients with ADPKD and an eGFR ≥30 ml/min/1.73 m2. Patients were followed clinically and radiologically with sequential abdominal magnetic resonance imaging (MRI). Clinical characteristics and laboratory data were related to changes in estimated glomerular filtration rate (eGFR) and total kidney volume (TKV). A linear regression model was developed to analyze the factors which determine eGFR and TKV changes.ResultsThe age range of this unselected cohort ranged from 4 to 77 years. Median follow-up time was 14.3±10.6 months. Although inter-individual differences in eGFR and TKV were large, there was a consistent link between these two parameters. Baseline log10-transformed TKV and urinary protein/creatinine ratio were identified as the major predictors for a faster eGFR decline and were associated with a higher TKV growth rate. Interestingly, a lower thrombocyte count correlated significantly with lower eGFR (r = 0.222) and higher TKV (r = 0.134).ConclusionsThis large cohort of Chinese patients with ADPKD provides unique epidemiological data for comparison with other cohorts of different ethnicity. In Chinese patients we identified a lower thrombocyte count as a significant predictor of disease progression. These results are important for the design of future clinical trials to retard polycystic kidney disease progression.

External validation and clinical evaluation of the International Prognostic Score of Thrombosis for Essential Thrombocythemia (IPSET‐thrombosis) in a large cohort of Chinese patients

In patients with essential thrombocythemia (ET), vascular complications contribute to both morbidity and mortality. To better predict the occurrence of thrombotic events, an International Prognostic Score of thrombosis for ET (IPSET-thrombosis) was recently developed. We hereby presented an external validation and analysis of this model in a large Cohort of Chinese Patients. We retrospectively evaluated the characteristics and risk factors for thrombosis in 970 Chinese patients with ET and estimated the clinical implications of the IPSET-thrombosis model. The median follow-up was 49months (range, 0-360). Chinese ET patients had similar clinical characteristics as Caucasian patients. Similar to the IPSET-thrombosis study, our multivariate analysis revealed age >60 (HR=1.949), previous thrombosis (HR=2.484), JAK2V617F mutation (HR=1.719), and cardiovascular risk factors (HR=1.877) as independent risk factors for thrombosis. We confirmed that the above risk factors in IPSET-thrombosis, when compared with traditional risk factors (e.g., age ≥60 and previous thrombotic events), were more predictive of thrombotic events (C-index 0.714 vs. 0.647). Classification by IPSET-thrombosis risk groups revealed different cumulative thrombosis-free survival (P<0.001). For treatment, patients in the intermediate- and high-risk group derived clinical benefit from cytoreductive agents (P<0.05), but those in the low-risk group did not (P=0.446). The lower risk of thrombosis on cytoreductive therapy was related to decrease in leukocyte count during the disease course. We validate the reproducibility of IPSET-thrombosis in Chinese ET patients and provide key clinical implications.

GW24-e3969 The common genotypes of long QT syndrome and the role of ECG prediction the China experience

ObjectivesLong QT syndrome (LQTS) is an inherited cardiac disorder characterised by QT prolongation and increased risks of torsade de pointes and sudden death. To date, mutations in 13 genes, including...

Mutation Spectrum in a Large Cohort of Unrelated Chinese Patients With Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HC) is a hereditary heterogeneous cardiovascular disorder. Existing data have been of predominantly Caucasian samples, and a large study is needed in Chinese population. The present study was intended to explore the genetic basis and clinical characteristics correlated with different genotypes in a large cohort of Chinese patients. Direct gene sequencing of β-myosin heavy chain (MYH7), myosin binding protein-C (MYBPC3), and cardiac troponin T (TNNT2) was performed in 136 unrelated Chinese HC patients. Clinical evaluations were conducted. In total, 32 mutations were identified in 36 patients (27%), including 10 novel ones. Distribution of mutations was 56% (MYBPC3), 31% (MYH7), and 13% (TNNT2), respectively. Double mutations were identified in 3% patients. The occurrence of HC-associated sarcomeric mutations was associated with an earlier age of onset, increased left ventricular hypertrophy, a higher incidence of syncope, previous family history, and sudden cardiac death. No statistical difference was identified in patients carrying MYBPC3 and MYH7 mutations with regard to clinical characteristics and outcomes. Patients with double mutations were associated with malignant progression in the study. In conclusion, MYBPC3 is the most predominant gene in HC. Multiple mutations are common in MYH7, MYBPC3, and TNNT2. The present study suggests a large diversity of HC and a prognostic role of genotype.

Hepatocellular carcinoma diameter and blood platelet levels in a large cohort of Chinese patients in Taiwan.

e15157 Background: Cirrhosis is often associated with thrombocytopenia and predisposes to HCC. Platelets are known to produce several HCC growth factors. Methods: A cohort of 4,139 Chinese HCC patients from Taiwan was interrogated for baseline clinical, tumor and liver function characteristics in relation to blood platelet counts. Results: Trichotomization of the cohort by tumor size after log-linearization, revealed significant relationships of tumor size to blood platelet, AFP and GGTP levels. Patients with higher platelets had larger tumors, more tumor nodules and higher AFP and GGTP levels than those with lower platelet levels. 80% of patients with larger tumors had normal platelet counts, compared to 50% of patients with smaller tumors. Analysis of the cohort according to platelet sub-sets, revealed significant relationships of platelet counts to tumor size and AFP levels. By Spearman’s correlation coefficient, platelet counts correlated moderately with tumor size (rho=0.411), but weakly with tumor numbers, PVT, AST or AFP levels. Sub-set analysis of the cohort according to platelet levels showed that 38% of patients had thrombocytopenia and they had the smallest tumors, lowest tumor numbers, lowest percent with PVT and lowest AFP levels. Conclusions: There was a significant correlation between HCC size and blood platelet counts; patients with larger tumors had higher platelet levels.

RAS mutation analysis in a large cohort of Chinese patients with acute myeloid leukemia

ObjectiveWe examined RAS mutational status and correlated this with presenting morphology, cytogenetics, clinical outcome and other gene aberrations in a large cohort of Chinese acute myeloid leukemia (AML) patients. Designs and methodsN-RAS and K-RAS were screened for mutations at hot-spot codons 12, 13 and 61 using high resolution melting analysis (HRMA) and direct DNA sequencing in 504 Chinese AML patients and their clinical relevance was analyzed. ResultsThe frequencies of mutations of N-RAS and K-RAS were 9.7% (49/504) and 2.9% (15/504), respectively. c.35G>A (rs121913237: G>A; p.Gly12Asp and rs121913529: G>A; p.Gly12Asp) and c.38G>A (rs121434596: G>A; p.Gly13Asp and rs112445441: G>A; p.Gly13Asp) were the most common base substitutions (46% in N-RAS and 60% in K-RAS, respectively). AML patients with RAS mutations presented significantly higher white blood cell count (WBC) at diagnosis than those without mutations (p<0.001). RAS mutations were underrepresented in patients with t(15;17) (2.9%, p=0.01), while overrepresented in cases with abn11q23 (50%, p=0.002) and inv(16) (66.6%, p=0.04). In the FAB subtypes M4 and M5, RAS mutations were more frequent (21.6% and 20.6%, respectively) than they were in other subtypes (7.5%, p=0.006 and 0.005, respectively). FLT3-ITD and RAS mutation were rarely coexistent (p=0.03). RAS mutation didn't influence overall survival (OS) either in the entire cohort or within some defined subgroups. ConclusionsRAS mutations are associated with some biologically specific subtypes of AML but don't impact clinical outcome in Chinese patients.

A clinicopathological analysis in a large cohort of Chinese patients with renal amyloid light-chain amyloidosis

The aim of the study is to investigate the association between clinical and pathological features in a large cohort of Chinese patients with renal immunoglobulin light-chain amyloidosis (AL). A series of 186 patients with renal AL amyloidosis diagnosed between 1990 and 2011 were retrospectively reviewed. The extent of amyloid deposition in glomeruli, blood vessels and tubulointerstitium were evaluated semiquantitatively. The renal amyloid load was defined by the sum of glomerular, vascular and interstitial deposits. The associations between the clinical manifestations and pathological features were analyzed. The extent of glomerular amyloid deposition was positively correlated with the level of proteinuria. Patients with codeposition of amyloid and immune complexes (ICs) in glomeruli had higher levels of proteinuria than those without ICs. Advanced glomerular amyloid deposition was an independent pathological factor associated with renal insufficiency at diagnosis. The degree of vascular amyloid (VA) deposition was positively correlated with cardiac involvement and hepatic involvement. Patients with AL-κ showed a higher prevalence of hepatic involvement and more severe VA deposition than patients with AL-λ. High renal amyloid load independently predicted the increased risk for overall death after adjusting for recognized confounders. The degree and localization of amyloid deposits in the kidney of AL patients were associated with the degree of proteinuria and renal insufficiency, as well as extrarenal organs involvement. There were some differences between AL-κ and AL -λ in clinical and pathological characteristics. The renal amyloid load was an independent predictor for overall mortality.

Validation of contemporary stroke and bleeding risk stratification scores in non-anticoagulated Chinese patients with atrial fibrillation

Risk stratification schemes assessing stroke and thromboembolism (stroke/TE) and bleeding relating to atrial fibrillation (AF) have largely been derived and validated in Western populations. We assessed risk factors that constitute scores for assessing stroke/TE (CHADS2, CHA2DS2-VASc) and bleeding (HAS-BLED), and the predictive value of these scores in a large cohort of Chinese patients with AF. We studied 1034 AF patients (27.1% female, median age 75; 85.6% non-anticoagulated) with mean follow-up of 1.9 years. On multivariate analysis, vascular disease was independently associated with stroke/TE in non-anticoagulated patients (p=0.04). In patients with a CHADS2 or CHA2DS2-VASc score=1, the rate of stroke/TE was 2.9% and 0.9% respectively, but in patients at "high risk" (scores ≥ 2), this rate was 4.6% and 4.5%, respectively. The c-statistics for predicting stroke/TE with CHADS2 and CHA2DS2-VASc were 0.58 (p=0.109) and 0.72 (p<0.001), respectively. Compared to CHADS2, the use of CHA2DS2-VASc would result in a Net Reclassification Improvement (NRI) of 16.6% (p=0.009) and an Integrated Discrimination Improvement (IDI) of 1.1% (p=0.002). Cumulative survival of the patients with a CHA2DS2-VASc score≥2 was decreased compared to those with a CHA2DS2-VASc score 0-1 (p<0.001), but the CHADS2 was not predictive of mortality. There was an increased risk of major bleeding with increasing HAS-BLED score (c-statistic 0.61, 95% CI: 0.51-0.71, p=0.042). Vascular disease was a strong independent predictor of stroke/TE in Chinese patients with AF. The CHA2DS2-VASc score performed better than CHADS2 in predicting stroke/TE in this Chinese AF population. Cumulative survival of the patients at high risk with the CHA2DS2-VASc score (but not using CHADS2) was significantly decreased.

Stroke risk and suboptimal thromboprophylaxis in Chinese patients with atrial fibrillation: Would the novel oral anticoagulants have an impact?

BackgroundThe risk of stroke associated with atrial fibrillation (AF) is higher in Far Eastern population than in Western population, and warfarin use suboptimal. There is uncertainty whether the novel oral anticoagulants (NOACs) would have a major impact on stroke prevention in Far Eastern populations with AF. ObjectivesWe investigated current antithrombotic therapy use on stroke and bleeding risk, determinants of warfarin use and performed a modeling analysis of the net clinical benefit of the NOACs (apixaban, dabigatran) in a large cohort of Chinese patients with AF. MethodsWe studied 1034 Chinese patients (27.1% female, median age 75years, interquartile range [IQR]: 63–83) with AF who were followed-up for an average of 1.9years (IQR: 1.43–2.64). Stroke/thromboembolism (TE), and major bleeding associated to antithrombotic treatment were investigated. A modeling analysis was performed for the net clinical benefit balancing major bleeding against stroke/TE for dabigatran 110mg bid, dabigatran 150mg bid and apixaban, using their respective recent clinical trial outcome data. ResultsUsing a Cox proportional hazard model, the Hazard Ratio [HR (95% confidence interval, CI)] for stroke/TE compared to no-antithrombotic therapy (no ATT) was 1.27 (0.65–2.50) on aspirin, 1.40 (0.35–3.57) on clopidogrel, 1.52 (0.72–3.23) on dual antiplatelets and 1.65 (0.76–3.57) on warfarin. The risk for major bleeding was 0.35 (0.14–0.85) on aspirin, 0.74 (0.24–2.29) on clopidogrel, 0.35 (0.11–1.10) on dual antiplatelets, and 0.88 (0.36–2.17) on warfarin. Binary logistic regression analysis showed persistent/permanent AF (Odds Ratio, OR, 2.03 [95%CI 1.05–3.92], p=0.035) was associated with warfarin use, but age ≥75years (0.26 [0.16–0.42], p<0.001), aspirin (0.18 [0.12–0.27], p<0.001) and clopidogrel (0.17 [0.08–0.33], p<0.001) were independent determinants of non-use of warfarin.On modeling net clinical benefit (per 100 person-years [95% CI]), apixaban use compared to antiplatelet agents or no ATT was 3.29 (2.15–4.30) using Singer's method and 2.08 (1.18–3.21) with Connolly's method amongst high-risk patients. The use of dabigatran 110mg bid and 150mg bid compared to antiplatelet agents could reduce an additional 18.1 stroke/TE and 24.3 stroke/TE events, respectively. Compared to warfarin, dabigatran 150mg bid had the best net clinical benefit. ConclusionsThere was suboptimal stroke prevention with no difference between antiplatelet and OAC treated patients, perhaps reflecting an inappropriate Target INR range. On modeling analyses, the use of the NOACs (apixaban and dabigatran) could provide better stroke prevention compared to antiplatelet (or warfarin) use in this Chinese AF population, with a positive net clinical benefit.

Diagnostic Value of Anti-Sa and Anticitrullinated Protein Antibodies in Rheumatoid Arthritis

To determine the diagnostic value of anticitrullinated protein antibodies, second generation (ACPA2), by electrochemiluminescent immunoassay (ECLIA) and anti-Sa by ELISA in a large cohort of Chinese patients with early rheumatoid arthritis (RA). One hundred ninety-eight patients with early RA (< 1 yr duration), 112 with other rheumatic diseases, and 60 healthy individuals were studied. The combination of anti-Sa and ACPA2 positivity had the highest specificity (99.42%), but it had a rather low sensitivity (50.0%). The combination of anti-rheumatoid factor (RF) and ACPA2 showed the highest sensitivity (80.30%), with specificity of 95.93%. The mean titer of ACPA2 and RF was significantly higher in the anti-Sa-positive group compared to the negative group (ACPA2, p <0.001; RF, p = 0.007). The 28-joint Disease Activity Scores of the anti-Sa-positive patients were significantly higher than those of the negative group (p = 0.01). The anti-Sa had no significant correlation with age, sex, antinuclear antibody, SSA, SSB, erythrocyte sedimentation rate, C-reactive protein, immunoglobulin A (IgA), IgG, IgM, C3, and C4. Our results come from a newly developed ECLIA for detection of ACPA2 and the anti-Sa-antibody-based ELISA system. The combined application of ACPA2 and anti-Sa tests can improve the laboratory diagnosis of early RA.

Predicting Progression of IgA Nephropathy: New Clinical Progression Risk Score

IgA nephropathy (IgAN) is a common cause of end-stage renal disease (ESRD) in Asia. In this study, based on a large cohort of Chinese patients with IgAN, we aim to identify independent predictive factors associated with disease progression to ESRD. We collected retrospective clinical data and renal outcomes on 619 biopsy-diagnosed IgAN patients with a mean follow-up time of 41.3 months. In total, 67 individuals reached the study endpoint defined by occurrence of ESRD necessitating renal replacement therapy. In the fully adjusted Cox proportional hazards model, there were four baseline variables with a significant independent effect on the risk of ESRD. These included: eGFR [HR = 0.96(0.95–0.97)], serum albumin [HR = 0.47(0.32–0.68)], hemoglobin [HR = 0.79(0.72–0.88)], and SBP [HR = 1.02(1.00–1.03)]. Based on these observations, we developed a 4-variable equation of a clinical risk score for disease progression. Our risk score explained nearly 22% of the total variance in the primary outcome. Survival ROC curves revealed that the risk score provided improved prediction of ESRD at 24th, 60th and 120th month of follow-up compared to the three previously proposed risk scores. In summary, our data indicate that IgAN patients with higher systolic blood pressure, lower eGFR, hemoglobin, and albumin levels at baseline are at a greatest risk of progression to ESRD. The new progression risk score calculated based on these four baseline variables offers a simple clinical tool for risk stratification.

Combination of anti-C1q and anti-dsDNA antibodies is associated with higher renal disease activity and predicts renal prognosis of patients with lupus nephritis

Although nephritogenic autoantibodies are considered to play a central role in the initiation of lupus nephritis, whether these autoantibodies are associated with renal clinical and pathological activity or renal outcome is still controversial. Here, we investigated the associations of certain serum autoantibodies with renal disease activity and renal outcome in a large cohort of Chinese patients with lupus nephritis. One hundred and thirty-six Chinese patients with biopsy-proven lupus nephritis and with long-term follow up data were studied. Sera at renal biopsy were tested for a panel of autoantibodies, including anti-nuclear antibodies, anti-double-stranded DNA (anti-dsDNA) antibodies, anti-extractable nuclear antigen antibodies, anti-C-reactive protein antibodies, anti-C1q antibodies, anti-cardiolipin antibodies and anti-β2-glycoprotein I antibodies. Associations of these autoantibodies with clinical features, laboratory findings, histopathological data and renal outcomes were further investigated. Among the various autoantibodies, anti-dsDNA and anti-C1q antibodies were better than other antibodies to evaluate the renal disease activity. Anti-dsDNA antibodies were correlated with higher incidence of leukocyturia (P< 0.05), total pathological activity index (AI) score (P< 0.05), endocapillary hypercellularity (P< 0.05), subendothelial hyaline deposits (P< 0.05) and leukocyte infiltration (P< 0.05). Anti-C1q antibodies were correlated with leukocyturia (P< 0.01), hematuria (P< 0.003) and the majority of the histopathological AIs including total AI score (P< 0.003), endocapillary hypercellularity (P< 0.003), cellular crescents (P< 0.05), karyorrhexis/fibrinoid necrosis (P< 0.003), subendothelial hyaline deposits (P< 0.003) and leukocyte infiltration (P< 0.01). Patients with both anti-dsDNA and anti-C1q antibodies had higher renal disease activity and poorer renal outcome (log-rank test: P= 0.048) compared with those without the two antibodies. In univariate survival analysis of renal prognosis, neither the presence of anti-C1q nor the presence of anti-dsDNA antibodies was a risk factor of renal survival. However, the combination of the two antibodies predicted renal prognosis (hazard ratio 4.40, 95% confidence interval: 1.268-15.269, P= 0.02). Anti-C1q antibodies are more closely correlated with renal disease activity than the other autoantibodies. The combination of anti-C1q and anti-dsDNA autoantibodies indicates higher renal disease activity and predicts poor renal outcome.

Long-term Prognosis in Hepatocellular Carcinoma Patients after Hepatectomy

The hepatocellular carcinoma is very common in China. Our aim in this report was to investigate clinical and pathological factors based on the current decade data that could influence prognosis of HCC patients after hepatectomy. Between 2002 and 2009, all patients undergoing hepatectomy for HCC were followed up and reviewed retrospectively. Prognostic factors were studied by univariate and multivariate analysis, with Kaplan-Meier and Cox multivariate survival analyses. Complete clinicopathologic and follow-up data were available for 114 patients. The estimated cumulative survival rates at 1, 3, and 5 yr were 84.6%, 60.2% and 51.8%, respectively. On univariate analysis, key prognostic factors were AFP level, GGT level, tumor size, number of tumors, portal vein invasion, liver cirrhosis status and TNM stage. In the multivariate analysis, tumor size, GGT level, liver cirrhosis status and portal vein invasion were significantly associated with patients' prognosis. Through follow-up of a relatively large cohort of Chinese patients, tumor size, GGT level, liver cirrhosis status, portal vein invasion were revealed as important factors for long-term survival after hepatectomy. Early diagnosis for tumor and the improvement of liver function before surgery are important ways to improve the prognosis.

Autoantibodies to CCL3 are of low sensitivity and specificity for the diagnosis of type 1 diabetes

Type 1 diabetes (T1D) is a T cell-dependent tissue-specific autoimmune disease, characterized by the selective destruction of the β cells of the pancreatic islets of Langerhans. Recently, contradictory findings have been reported about the relationship of autoantibodies to CC chemokine 3 (CCL3) and T1D, which need to be confirmed by more investigations in larger cohorts. The aim of our research was to investigate whether autoantibodies to CCL3 are useful markers for T1D in a large cohort of Chinese patients. We analyzed autoantibodies to CCL3, glutamic acid decarboxylase(GADA), insulinoma-associated protein-2 (IA-2A), and zinc transporter-8 (ZnT8A) by a radioimmunoprecipitation assay in 290 T1D subjects, 200 subjects with type 2 diabetes (T2D), 210 subjects with other diseases, and 178 healthy control subjects. Results showed that the frequencies of autoantibodies to CCL3 in subjects with T1D, T2D, and healthy control subjects were similar [3.10% (9/290), 2.50% (5/200), and 0.56% (1/178), respectively, P = 0.189]. Autoantibodies to CCL3 were not significantly different between T1D patients with or without GADA, IA-2A, or ZnT8A antibodies (2.7% vs. 3.9%, P = 0.725). In contrast, patients with systemic lupus erythematosus and rheumatoid arthritis showed higher positivity for autoantibodies to CCL3 than healthy control subjects [15.6% (5/32) and 12.5% (8/64) vs. 0.56% (1/178), all P = 0.000], and higher titer of autoantibodies to CCL3 than T1D patients (median 0.9633 and 0.4095 vs. 0.0873, P = 0.012 and P = 0.034, respectively). We conclude that autoantibodies to CCL3 are of low sensitivity and specificity for T1D and cannot be used in the diagnosis of T1D.

Value of muscle enzyme measurement in evaluating different neuromuscular diseases

Background Muscle enzymes sometimes can provide clues for many similar neuromuscular disorders. However literatures that described and compared the muscle enzyme levels among these diseases are few. We described their changes in a group of Chinese patients. Methods We reviewed creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST) levels and CK/lDH in Chinese patients with Duchene/Becker muscular dystrophy (DMD/BMD), facioscapulohumeral muscular dystrophy (FSHD), limb-girdle muscular dystrophy (LGMD), polymyositis (PM), lipid storage myopathy (LSM), motor neuron disease (MND) and spinal muscular atrophy (SMA). The diagnosis of DMD/BMD, FSHD, LSM and SMA was confirmed by genetic analysis. Comparisons between groups were tested by One-Way ANOVA analysis and LSD test. Results CK: DMD/BMD > PM > LGMD > LSM > FSHD > MND > SMA. LDH and AST: DMD/BMD > LSM > PM > LGMD > FSHD > SMA > MND. For MND, logCK in PMA is the highest. For SMA, logCK value in type III is the highest. LDH disproportionately elevates in LSM and SMA. Conclusion This investigation described muscle enzyme profiles in a large cohort of Chinese patients with neuromuscular diseases. Muscle enzyme values may have some implications for making decision when the diagnosis is hard.

Acute kidney injury in Chinese patients with lupus nephritis: a large cohort study from a single center

In this study we assess clinicopathologic characteristics, treatment and prognosis of acute kidney injury (AKI) in a large cohort of Chinese patients with lupus nephritis. The clinical, laboratory, renal histopathology, treatment and outcome data were retrospectively collected and compared between lupus nephritis patients with and without AKI. The impact of AKI on renal outcome was evaluated. Among 322 patients with renal biopsy-proven lupus nephritis, 66 (20.5%) were identified as AKI. Male predominance was observed in patients with AKI (p < 0.001). In comparison with the non-AKI group, patients with AKI had significantly higher proportions of serositis (p < 0.001), neurologic disorder (p = 0.026), anemia (p < 0.001), thrombocytopenia (p = 0.013) and nephrotic syndrome (p = 0.011), but significant lower serum C3 (p < 0.001). The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, renal pathological activity indices and chronicity indices were significantly higher in the AKI group (p < 0.001 in all cases). Regarding outcome, the AKI group had a significantly poorer renal outcome compared with non-AKI group (p < 0.001). In the AKI group, patients with crescentic glomerulonephritis and thrombotic microangiopathy had the worst renal outcome. AKI was an independent risk factor for renal outcome (hazard ratio [HR] = 5.819, 95% confidence interval 2.411-14.044, p < 0.001). AKI is common in lupus nephritis and is an independent risk factor for renal outcome.

Renal involvement in a large cohort of Chinese patients with Castleman disease

The association of kidney disease with Castleman disease (CD) is uncommon. To date, most studies have been based on single-case reports. Here, we describe renal involvement in CD in a large Chinese cohort. Seventy-six CD patients were identified in one clinical center. Clinical and pathological characteristics of patients with renal involvement were described, which were also compared with cases identified through a systematic literature review. Nineteen patients (25%) exhibited renal involvement. Patients with multicentric clinical type (59 versus 0%) or plasma cell (PC)/mixed cellularity histological variant (61.5 versus 6%) were more likely to have renal involvement (P < 0.001). Proteinuria (with 7/19 reaching nephrotic range) and acute renal failure (12/19, 63%) were the main clinical presentations. Kidney biopsy revealed various glomerular diseases (10/11) and interstitial nephritis (1/11), while with 'thrombotic microangiopathy-like' lesions were the most common pathological characteristics (6/11, 55%). This contrasted significantly with the literature in which amyloidosis was the most reported. Renal outcomes responded well to chemotherapy. Nine (9/12, 75%) patients with acute renal failure recovered completely, one recovered partially. Overall, only three (3/19, 16%) patients progressed to end-stage kidney disease. Renal involvement did not influence survival rate (log-rank test, P = 0.73) in the follow-up. CD with multicentric type and PC or mixed cellularity variant are often associated with renal complications. Thrombotic microangiopathy-like lesions are the most common pathological characteristics. Chemotherapy can reverse kidney damage in most cases.

Genotypic resistance profile of hepatitis B virus (HBV) in a large cohort of nucleos(t)ide analogue‐experienced Chinese patients with chronic HBV infection

Summary. The study investigated the hepatitis B virus (HBV) genotypic resistance profile in 1803 nucleos(t)ide analogue (NA)‐experienced Chinese patients with chronic HBV infection. Serum HBV DNA was extracted, and the reverse transcriptase region was analysed by a high‐sensitive direct PCR sequencing and verified by clonal sequencing if necessary. Drug‐resistant mutations were detected in 560 of the 1803 patients, including 214 of 490 patients who received lamivudine (LAM), 35 of 428 patients who received adefovir (ADV), five of 18 patients who received telbivudine and 306 of 794 patients who received various sequential/combined NA therapies. ADV‐resistant mutations were detected in 36 of 381 patients who received LAM and then switched‐to ADV in contrast to one of 82 patients who received ADV add‐on LAM. Entecavir (ETV)‐resistant mutations were detected not only in LAM‐ and ETV‐treated patients but also in LAM‐treated ETV‐naïve patients. Double mutations rtM204I and rtL180M were detected more frequently in genotype C than in genotype B virus, and patients infected with this mutant had higher alanine transaminase levels than those infected with mutant containing the rtM204I substitution alone. Multidrug‐resistant HBV strains were identified in eight patients, including two novel strains with mutational patterns rtL180M + A181V + S202G + M204V + N236T and rtL180M + S202G + M204V + N236T. The results provide new information on HBV genotypic resistance profiles in a large cohort of Chinese patients with chronic HBV infection and may have important clinical implication for HBV drug resistance management in China.