Progression In Chinese Patients Research Articles

The average 30-minute post-prandial C-peptide predicted diabetic retinopathy progress: a retro-prospective study

BackgroundThe conclusion between Connecting peptide (C-peptide) and diabetic chronic complication was controversial. The purpose of this study is to explore the possible association between average C-peptide with diabetic retinopathy (DR) progression in Chinese patients with type 2 diabetes.MethodsThis is a retro-prospective study. 622 patients with type 2 diabetes were included. DR was evaluated using non-mydriatic fundus photography and DR progression was defined as any deterioration of either eye. Fasting and postprandial c-peptide levels were assayed at baseline and follow-up period. Differences between continuous variables were compared using the Mann–Whitney U test; and categorical variables were analyzed by the chi-square test. Correlation between parameters and 30-minute postprandial C-peptide were determined by Spearman correlation test. The relationship between C-peptide and DR progression was evaluated by multivariable binary logistic regression. Two-tailed P-values < 0.05 were regarded as statistically significant.ResultsDR was present in 162 (26.0%) patients at baseline, and 26.4% of patients were found progression of DR at follow-up. Patients with progression of DR had lower average levels of 30-minute postprandial C-peptide (2.01 ng/ml vs. 2.6 ng/ml, p = 0.015) and 120-minute postprandial C-peptide (3.17 ng/ml vs. 3.92 ng/ml, p < 0.029), as well as average increment of 30-minute (0.41 ng/ml vs. 0.64 ng/ml, p = 0.015) and 120-minute postprandial C-peptide (1.48 ng/ml vs. 1.93 ng/ml, p < 0.017), than those without DR aggravation. Multivariate logistic regression analysis determined that 30-minute postprandial C-peptide and its increment were related to reduced odds ratios for DR progression (odds ratios [OR] = 0.83 and 0.74, respectively).ConclusionOur results suggest that the Average 30-minute post-prandial C-peptide and increment were negatively correlated with DR progression, which further demonstrates the importance to preserve β-cell residual function in the prevention for DR progression.Trial registrationNot applicable.

Circulating AFABP, FGF21, and PEDF Levels as Prognostic Biomarkers of Sight-threatening Diabetic Retinopathy.

Adipocyte fatty acid-binding protein (AFABP), fibroblast growth factor 21 (FGF21), and pigment epithelium-derived factor (PEDF) are 3 diabetes-related biomarkers whose circulating levels had been shown to associate with nephropathy progression in Chinese patients with type 2 diabetes. Here, we evaluated and compared their prospective associations with the development of sight-threatening DR (STDR), another important diabetic microvascular complication. Baseline serum AFABP, PEDF, and FGF21 levels were measured in 4760 Chinese individuals with type 2 diabetes and without STDR at baseline. The associations of these biomarkers with incident STDR were analyzed using Cox regression analysis. Among these 4760 participants (mean diabetes duration of 11 years and ≥ 50% with nonproliferative DR at baseline), 172 participants developed STDR over a median follow-up of 8.8 years. Participants with incident STDR had comparable baseline serum FGF21 levels but significantly higher baseline serum AFABP and PEDF levels (both P < .001) than those without. However, in multivariable Cox regression analysis, only serum AFABP remained independently associated with incident STDR (hazard ratio 1.28; 95% CI, 1.05-1.55; P = .013). The addition of serum AFABP to a clinical model of conventional STDR risk factors including diabetes duration, glycemic control, albuminuria, and baseline DR status significantly improved the c statistics (P < .001), net reclassification index (P = .0027), and integrated discrimination index (P = .033) in predicting incident STDR among participants without DR or with mild DR at baseline. Among the 3 diabetes-related biomarkers, serum AFABP level appeared to be a more clinically useful biomarker for predicting incident STDR in type 2 diabetes.

Clinical and Pathological Features of Chinese Patients with Type 2 Diabetes, Biopsy-Proven Diabetic Kidney Disease, and Rapid eGFR Decline.

ObjectiveThe rate of kidney function decline in patients with diabetic kidney disease (DKD) is known to differ. This study analyzed the clinicopathologic features and related risk factors affecting long-term renal survival in Chinese type 2 diabetic patients with rapid estimated glomerular filtration rate (eGFR) decline.MethodsIn this retrospective descriptive study, 191 DKD patients were first classified as rapid eGFR decliners and slow eGFR decliners on the basis of the median eGFR slope value (−8.0 mL/min/1.73 m2/year). In total, 96 patients with rapid eGFR decline were included in the analyses and subsequently allocated to end-stage renal disease (ESRD) and non-ESRD groups. Baseline clinicopathological data of rapid eGFR decliners were collected. Cox proportional hazard analysis was performed to calculate the hazard ratios (HRs) for progression to ESRD.ResultsDuring a median follow-up of 25 months, 52 (54.2%) rapid eGFR decliners progressed to ESRD. These 52 rapid eGFR decliners had poorer renal function, lower hemoglobin and albumin concentrations, higher total cholesterol and baseline proteinuria levels, and more severe interstitial inflammation than those who did not progress to ESRD. After adjustment for age, gender, baseline eGFR, proteinuria, hemoglobin level, serum albumin concentration, and histopathologic parameters, multivariate Cox proportional hazard analysis revealed that eGFR (HR 0.973, 95% CI 0.956–0.989) and proteinuria (HR 1.125, 95% CI 1.030–1.228) were associated with the increased risk of progression to ESRD.ConclusionHigher proteinuria and lower eGFR were independent risk factors for renal progression in Chinese patients with type 2 diabetes and rapid eGFR decline.

Plasma Exo-miRNAs Correlated with AD-Related Factors of Chinese Individuals Involved in Aβ Accumulation and Cognition Decline

Numerous studies have investigated the risk factors of Alzheimer’s disease (AD); however, AD-risk factors related miRNAs were rarely reported. In this study, AD-risk factor related miRNAs of 105 Chinese individuals (45 AD patients and 60 cognitively normal controls) were investigated. The results showed that Hsa-miR-185-5p, Hsa-miR-20a-5p, and Hsa-miR-497-5p were related to AD and education, Hsa-miR-185-5p, Hsa-miR-181c-5p, Hsa-miR-664a-3p, Hsa-miR-27a-3p, Hsa-miR-451a, and Hsa-miR-320a were related to AD and depression. Target prediction of above miRNAs showed that these miRNAs were involved in the generation and clearance of amyloid-beta (Aβ), important molecules related to cognition, and disease-activated microglia response to AD. It is worth noting that Hsa-miR-185-5p was related to both education and depression, whose decreased expression pattern in AD patients was alleviated by education and enhanced by depression, and participates in Aβ generation and accumulation. Our results indicated that certain education and depression factors can contribute to AD progression by modulating miRNA expression, implying that preventive interventions might alter AD progression in Chinese patients.

CRF07_BC is associated with slow HIV disease progression in Chinese patients

HIV subtypes convey important epidemiological information and possibly influence the rate of disease progression. In this study, HIV disease progression in patients infected with CRF01_AE, CRF07_BC, and subtype B was compared in the largest HIV molecular epidemiology study ever done in China. A national data set of HIV pol sequences was assembled by pooling sequences from public databases and the Beijing HIV laboratory network. Logistic regression was used to assess factors associated with the risk of AIDS at diagnosis ([AIDSAD], defined as a CD4 count < 200 cells/µL) in patients with HIV subtype B, CRF01_AE, and CRF07_BC. Of the 20,663 sequences, 9,156 (44.3%) were CRF01_AE. CRF07_BC was responsible for 28.3% of infections, followed by B (13.9%). In multivariable analysis, the risk of AIDSAD differed significantly according to HIV subtype (OR for CRF07_BC vs. B: 0.46, 95% CI 0.39─0.53), age (OR for ≥ 65 years vs. < 18 years: 4.3 95% CI 1.81─11.8), and transmission risk groups (OR for men who have sex with men vs. heterosexuals: 0.67 95% CI 0.6─0.75). These findings suggest that HIV diversity in China is constantly evolving and gaining in complexity. CRF07_BC is less pathogenic than subtype B, while CRF01_AE is as pathogenic as B.

Effects of a multicomponent intervention to slow mild cognitive impairment progression: A randomized controlled trial

BackgroundMild cognitive impairment affects 36% of people aged ≥65 years in China, around 50% of whom will develop dementia within 3 years. Early intervention can slow disease progression and delay the onset of dementia; however, whether a multicomponent intervention can decelerate the progression of mild cognitive impairment remains unknown. ObjectiveTo evaluate the effects of a multicomponent intervention to slow mild cognitive impairment progression in Chinese patients. DesignRandomized controlled trial. Setting(s) and participantsThis study was conducted in two large regional communities in Guangzhou, China. Patients aged ≥ 65 years diagnosed with mild cognitive impairment were included. MethodsA total of 112 eligible participants were assigned to receive either a 6-month multicomponent intervention or usual care from September 2019 until January 2021. Data were collected at the beginning of the study and at 1, 3, and 6 months thereafter. The primary outcomes were cognitive function, comprehensive physical capacity, depression, and quality of life. Analysis followed the intention-to-treat principle. A generalized estimating equation was used to determine intervention effects. ResultsAt baseline, clinical characteristics did not differ significantly between groups. Significant interaction effects between time and group were detected (p < 0.001), indicating that the scores of five outcomes (cognitive function, short physical performance battery, timed up and go test, quality of life, and depression) of intervention and control groups changed differently over time. Participants in the intervention group were found to have a significantly greater improvement in cognitive function, physical function, quality of life, and fewer depression symptoms compared with the control group at baseline and follow-up periods. ConclusionsThis study demonstrates the beneficial effects of a multicomponent intervention on cognitive function, physical function, depression symptoms, and quality of life in people with mild cognitive impairment in the East Asia region. The effectiveness and feasibility of this intervention program suggest that its application should be promoted in community settings to delay the progression of disease in people with mild cognitive impairment.Registration number:ChiCTR1900026042Tweetable abstract: The multicomponent intervention improves cognitive/physical function, depression, and quality of life, slowing cognitive impairment progression.

Epidemiology and risk factors for progression in Chinese patients with IgA nephropathy

BackgroundIgA nephropathy (IgAN) is one of the main causes of primary glomerulonephritis worldwide, and it is also the main primary disease leading to chronic kidney disease. The purpose of this study is to evaluate the epidemiology and risk factors for progression in Chinese patients with IgAN. MethodsIn this retrospective study, 246 patients with renal biopsy-proven IgAN were enrolled from January 2012 to June 2018. The patients’ data were divided into two groups according to eGFR at the end of follow-up: a high-eGFR group (eGFR≥60ml/min) and a low-eGFR group (eGFR<60ml/min). ResultsAt the end of the study, we identified 49 (19.92%) patients with low-eGFR from 246 IgAN patients. Renal function, represented by serum creatinine, urea nitrogen and cystatin-C, was significantly decreased in the low-eGFR group (P<0.001 for all) at the time of renal biopsy. Compared with the high-eGFR group, the age, mean arterial blood pressure (MAP), proteinuria, cholesterol, triglycerides and serum uric acid were significantly higher (P<0.05 for all). According to the Oxford evaluation, the proportion of S1-2 (59.2%) and T1-2 (65.3%) was significantly increased (P<0.001 for both) and the proportion that had a MEST-C score ≥3 was statistically increased in the low-eGFR group (83.7%, P=0.001). ConclusionsMale, MAP, haematuria, Scr, cholesterol, hemoglobin, Lee classification more than 3 and C1-2 are independent risk factors for low-eGFR in Chinese IgAN patients.

\u201cHot cross bun\u201d is a potential imaging marker for the severity of cerebellar ataxia in MSA-C

To evaluate the correlation between “hot cross bun” sign (HCBs) and disease severity in multiple system atrophy (MSA). We recruited patients with probable and possible MSA with parkinsonism (MSA-P) or the cerebellar ataxia (MSA-C) subtypes. Clinical and imaging characteristics were collected and comparison was performed between MSA-C and MSA-P cases. Spearman test was used to evaluate the correlation between HCBs and other variables. Curve estimate and general linear regression was performed to evaluate the relationship between HCBs and the Scale for Assessment and Rating of Ataxia (SARA). Unified Multiple System Atrophy Rating Scale (UMSARS) IV was used to assess the severity of disease. Multinomial ordered logistic regression was used to confirm the increased likelihood of disability for the disease. Eighty-one MSA with HCBs comprising of 50 MSA-C and 31 MSA-P were recruited. We demonstrated that the severity of HCBs showed a positive linear correlation with SARA scores in MSA-C. Multinomial ordered logistic regression test revealed that the increase in the HCBs grade may be associated with an increased likelihood of disability for the disease severity in MSA, especially in those with cerebellar ataxia subtype. We demonstrated that HCBs is a potential imaging marker for the severity of cerebellar ataxia. The increase in the HCBs grade may be associated with an increased likelihood of disability in MSA-C, but not MSA-P cases, suggesting that it may be a useful imaging indicator for disease progression in Chinese patients with MSA-C.

Prediction of long-term disability in Chinese patients with multiple sclerosis: A prospective cohort study

BackgroundMuch information about outcomes of multiple sclerosis (MS) has been studied in Caucasian cohorts. However, little is known about the predictors of long-term disability in Chinese patients with MS. The aim of this prospective, observational study is to identify the prognostic factors associated with long-term disability progression (expanded disability status scale, EDSS=6.0) in Chinese patients with relapsing-onset MS. MethodsBased on data from the MSNMOBase registry within the neurology department of Peking Union Medical College Hospital (PUMCH) in China, this hospital-based cohort study was conducted to estimate the median time of attaining disability endpoint (EDSS = 6.0) by Kaplan-Meier curves, and identify factors that associated with disability progression by Cox proportional regression analysis. ResultsA total of 415 consecutive, eligible patients with MS were registered in the MSNMOBase of PUMCH and prospectively followed from 2011 to 2019. Of these patients, 365 patients with relapsing-onset MS were analyzed. The median time to reach an EDSS of 6.0 was 22.0 (95% CI 16.5-27.5) years. Age at disease onset greater than 50 years (HR 3.846, 95% CI 1.240–11.932, P=0.020), incomplete recovery from first attack (HR 2.107, 95% CI 1.168–3.800, P=0.013), and ≥2 relapses during the first 2 years after onset (HR 2.217, 95% CI 1.148–4.281, P=0.018) significantly associated with a higher hazard ratio to reach an EDSS of 6.0. ConclusionsOur results confirm the importance of age at onset, recovery from the first attack, and number of relapses during the first 2 years after disease onset as predictors of disability progression in Chinese patients with relapsing-onset MS.

Epidemiology and risk factors for progression in Chinese patients with IgA nephropathy

BackgroundIgA nephropathy (IgAN) is one of the main causes of primary glomerulonephritis worldwide, and it is also the main primary disease leading to chronic kidney disease. The purpose of this study is to evaluate the epidemiology and risk factors for progression in Chinese patients with IgAN. MethodsIn this retrospective study, 246 patients with renal biopsy-proven IgAN were enrolled from January 2012 to June 2018. The patients’ data were divided into two groups according to eGFR at the end of follow-up: a high-eGFR group (eGFR≥60ml/min) and a low-eGFR group (eGFR<60ml/min). ResultsAt the end of the study, we identified 49 (19.92%) patients with low-eGFR from 246 IgAN patients. Renal function, represented by serum creatinine, urea nitrogen and cystatin-C, was significantly decreased in the low-eGFR group (P<0.001 for all) at the time of renal biopsy. Compared with the high-eGFR group, the age, mean arterial blood pressure (MAP), proteinuria, cholesterol, triglycerides and serum uric acid were significantly higher (P<0.05 for all). According to the Oxford evaluation, the proportion of S1-2 (59.2%) and T1-2 (65.3%) was significantly increased (P<0.001 for both) and the proportion that had a MEST-C score ≥3 was statistically increased in the low-eGFR group (83.7%, P=0.001). ConclusionsMale, MAP, haematuria, Scr, cholesterol, hemoglobin, Lee classification more than 3 and C1-2 are independent risk factors for low-eGFR in Chinese IgAN patients.

Genetic Modifiers of Duchenne Muscular Dystrophy in Chinese Patients.

Background: Duchenne muscular dystrophy (DMD) is a fatal, X-linked recessive muscle disorder characterized by heterogeneous progression and severity. We aimed to study the effects of single nucleotide polymorphisms (SNPs) in SPP1 and LTBP4 on DMD progression in Chinese patients.Methods: We genotyped LTBP4 haplotypes and the SPP1 promoter SNPs rs28357094, rs11730582, and rs17524488 in 326 patients registered in the neuromuscular database of The First Affiliated Hospital of Sun Yat-sen University. Kaplan-Meier curves and log-rank tests were used to estimate and compare median age at loss of ambulation, while Cox proportional hazard regression models were used as to analyze the effects of glucocorticoids treatments, DMD genotype, and SPP1/LTBP4 SNPs on loss of ambulation.Results: The CC/CT genotype at rs11730582 was associated with a 1.33-year delay in ambulation loss (p = 0.006), with hazard ratio 0.63 (p = 0.008), in patients with truncated DMD genotype and undergoing steroid treatment. On the other hand, rs17524488 in SPP1 and the IAAM/IAAM haplotype in LTBP4 were not associated with time to ambulation loss.Conclusions: SPP1 rs11730582 is a genetic modifier of the long-term effects of steroid treatment in Chinese DMD patients. Thus, any future clinical study in DMD should adjust for glucocorticoids use, DMD genotype, and SPP1 polymorphisms.

Obesity, clinical, and genetic predictors for glycemic progression in Chinese patients with type 2 diabetes: A cohort study using the Hong Kong Diabetes Register and Hong Kong Diabetes Biobank.

BackgroundType 2 diabetes (T2D) is a progressive disease whereby there is often deterioration in glucose control despite escalation in treatment. There is significant heterogeneity to this progression of glycemia after onset of diabetes, yet the factors that influence glycemic progression are not well understood. Given the tremendous burden of diabetes in the Chinese population, and limited knowledge on factors that influence glycemia, we aim to identify the clinical and genetic predictors for glycemic progression in Chinese patients with T2D.Methods and findingsIn 1995–2007, 7,091 insulin-naïve Chinese patients (mean age 56.8 ± 13.3 [SD] years; mean age of T2D onset 51.1 ± 12.7 years; 47% men; 28.4% current or ex-smokers; median duration of diabetes 4 [IQR: 1–9] years; mean HbA1c 7.4% ± 1.7%; mean body mass index [BMI] 25.3 ± 4.0 kg/m2) were followed prospectively in the Hong Kong Diabetes Register. We examined associations of BMI and other clinical and genetic factors with glycemic progression defined as requirement of continuous insulin treatment, or 2 consecutive HbA1c ≥8.5% while on ≥2 oral glucose-lowering drugs (OGLDs), with validation in another multicenter cohort of Hong Kong Diabetes Biobank. During a median follow-up period of 8.8 (IQR: 4.8–13.3) years, incidence of glycemic progression was 48.0 (95% confidence interval [CI] 46.3–49.8) per 1,000 person-years with 2,519 patients started on insulin. Among the latter, 33.2% had a lag period of 1.3 years before insulin was initiated. Risk of progression was associated with extremes of BMI and high HbA1c. On multivariate Cox analysis, early age at diagnosis, microvascular complications, high triglyceride levels, and tobacco use were additional independent predictors for glycemic progression. A polygenic risk score (PRS) including 123 known risk variants for T2D also predicted rapid progression to insulin therapy (hazard ratio [HR]: 1.07 [95% CI 1.03–1.12] per SD; P = 0.001), with validation in the replication cohort (HR: 1.24 [95% CI 1.06–1.46] per SD; P = 0.008). A PRS using 63 BMI-related variants predicted BMI (beta [SE] = 0.312 [0.057] per SD; P = 5.84 × 10−8) but not glycemic progression (HR: 1.01 [95% CI 0.96–1.05] per SD; P = 0.747). Limitations of this study include potential misdiagnosis of T2D and lack of detailed data of drug use during follow-up in the replication cohort.ConclusionsOur results show that approximately 5% of patients with T2D failed OGLDs annually in this clinic-based cohort. The independent associations of modifiable and genetic risk factors allow more precise identification of high-risk patients for early intensive control of multiple risk factors to prevent glycemic progression.

Clinical Characteristics and Factors Associated with Disease Progression in Chinese Patients with Connective Tissue Disease and Pulmonary Arterial Hypertension

Abstract Objective To clarify the characteristics, survival, and predictors of mortality in Chinese patients with pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD). Methods This single-cohort study involved 67 CTD-PAH patients who visited Shanghai Renji Hospital between January 2011 and January 2019. Baseline clinical features and hemodynamic parameters were recorded. Logistic regression was used to determine the independent factors associated with mPAP improvement. Results SLE was the major underlying CTD, affecting 70% of PAH patients, whereas systemic sclerosis was less common (6%). Modern PAH drug use was associated with a favorable outcome and mPAP improvement. Conclusion The majority of the CTD-PAH population in China suffers from SLE in contrast to the CTD-PAH patients in the USA and Europe. Pulmonary vasodilation treatment has improved the mPAP in these patients.

Evening exercise is associated with lower odds of visual field progression in Chinese patients with primary open angle glaucoma

BackgroundExercise is widely known to lower intraocular pressure and increase ocular blood flow, which may be beneficial for glaucoma management. However, there are few studies that have reported on the relationship between exercise and glaucoma progression. The aim of our study was to investigate the exercise habits of those with primary open angle glaucoma (POAG) and its association with the progression of visual field (VF) loss.MethodsDaily physical activity (PA) was monitored by an accelerometer (ActiGraph wGT3x-BT) which patients wore for more than 10 h of being awake on their right wrists for 1 week.ResultsSeventy-one non-progressive and 27 progressive patients were enrolled in the study. 24-h moderate to vigorous physical activity (MVPA) exercise showed that POAG patients had similar variation trends consisting of 3 wave peaks and 2 wave hollows. Minutes spent in MVPA was 19.89 ± 15.81 and 21.62 ± 15.10 during 07:00–09:00 h (p = 0.204), 15.40 ± 14.49 and 15.67 ± 12.43 during 15:00–17:00 h (p = 0.822) and 17.26 ± 21.11 and 11.42 ± 11.58 during 18:00–20:00 h (p = 0.001) in the non-progressive and progressive group, respectively. Univariate analysis indicated that 10 min of MVPA (18:00–20:00 h) [odds ratio, OR (95% CI) = 0.82 (0.73, 0.92)], average mean arterial pressure [OR (95% CI) = 0.96 (0.94, 0.98)], age [OR (95% CI) = 1.06 (1.03, 1.08)], male [OR (95% CI) = 0.67 (0.48, 0.96)], spherical equivalent [OR (95% CI) = 1.14 (1.07, 1.22)] and IOP-lowering medications [OR (95% CI) = 1.54 (1.16, 2.05)] were significantly correlated with having progressive VF damage. Multivariable analysis showed that 10 min of MVPA (18:00–20:00 h) [OR (95% CI) = 0.85 (0.75, 0.97)] was associated with progressive VF loss even after adjusting for other risk factors.ConclusionsEvening exercise may lower the odds of VF progression, suggesting that exercise habits possibly play an important role in glaucoma progression.

Long-Term Natural Course of Pathologic Myopia in Chinese Patients.

Purpose To investigate the natural progression in Chinese patients with pathological myopia (PM) and its associated factors. Methods The medical records of 28 patients with PM (worse than −6 diopter), including 31 eyes of 21 children and 12 eyes of 7 adults, were studied. All of the patients underwent a complete ophthalmologic examination at least twice over 3-year period, including the measurement of refractive error (shown as spherical equivalent, SE), axial length (AL), intraocular pressure, visual acuity (uncorrected visual acuity, UCVA, and best-corrected visual acuity, BCVA), and dilated fundus examination. Results The median AL of adults increased significantly from 29.8 mm to 31.43 mm over 5.4 years follow-up (P=0.0037), accompanied with the median SE progressing significantly from −16.4 D to −18.94 D (P=0.0005). Similarly, the median AL of children increased significantly from 26.13 mm to 27.81 mm over 3.9 years (P=0.0001). However, the improvements of UCVA and BCVA in children were significant (P=0.0304, 0.0001), and they had a negative correlation with age (P=0.0010, 0.0005). Also, UCVA and BCVA in children with bilateral PM were significantly better than those with unilateral PM (P=0.0385, 0.0210). Conclusions Fundus degenerations in children with pathological myopia may lead its way since the age of 10 years. Besides, children with bilateral pathological myopia can have parallel development in visual acuity.

EORTC risk tables are more suitable for Chinese patients with nonmuscle-invasive bladder cancer than AUA risk stratification

Background:Patients with non-muscle-invasive bladder cancer (NMIBC) need accurate estimations of the risk of recurrence and progression. Physicians can offer individualized therapy after identifying high-risk tumors. In our study, we compared the applicability of European Organization for Research and Treatment of Cancer (EORTC) risk tables and American Urological Association (AUA) risk stratification in Chinese patients with NMIBC.Methods:We retrospectively studied 301 patients with NMIBC who underwent transurethral resection of bladder tumor (TURBT) between October 2000 and July 2009 at Huashan Hospital of Fudan University and analyzed their parameters. The recurrence and progression rates at 1 and 5 years postoperatively were calculated along with 95% confidence intervals. We compared them with results obtained from the EORTC risk tables and AUA risk stratification. P values <.05 were considered statistically significant.Results:The median patient age was 67 years (21–92 years) and the median follow-up duration was 46 months (2–151 months). We used EORTC risk tables to classify patients into 3 groups, depending on whether they suffered recurrence or progression after TURBT. Kaplan–Meier curves showed significant differences among the 3 recurrence-free survival (RFS) levels (P < .0001, log-rank test) and among the 3 progression-free survival (PFS) levels (P < .0001, log-rank test). AUA risk stratification showed the same results. Both classifications were suitable to predict recurrence and progression in Chinese patients. However, for high-risk patients in both series, Kaplan–Meier curves showed significant differences between RFS levels (P < .0001, log-rank test) and between PFS levels (P < .0001, log-rank test). EORTC risk tables were stricter and AUA was more sensitive in assigning patients to a high-risk group.Conclusion:EORTC risk tables are better than AUA risk stratification for predicting recurrence and progression in Chinese patients with NMIBC, especially among high-risk patients.

Annual Change in FIB-4, but not in APRI, was a Strong Predictor for Liver Disease Progression in Chinese Patients with Chronic Hepatitis C

Background: Previous studies showed a significant prognostic value of 3-year and 5-year evolution of noninvasive fibrosis tests in European chronic hepatitis C (CHC) patients with or without HIV. It is uncertain whether this conclusion can be extrapolated to Chinese patients and whether the assessment of noninvasive fibrosis tests in a shorter time interval still has a prognostic value. Objectives: The study aimed to assess the prognostic value of changes of aspartate aminotransferase-to-platelet ratio (APRI) and fibrosis-4 (FIB-4) in consecutive years in Chinese CHC patients. Methods: There were 173 CHC patients enrolled in 2 centers in this retrospective study. APRI and FIB-4 were calculated every 12 ± 2 months. The average difference between 2 adjacent calculations was defined as an annual change (AC). Risk factors were evaluated by Cox proportional regression models. Results: Cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver-related death developed in 29 patients during the median follow-up of 47.0 (29.5 - 72.0) months. Baseline FIB-4 and APRI, Child-Pugh class C, non-sustained virologic response (SVR) to interferon (IFN) or Pegylated IFN plus ribavirin, and AC of FIB-4 were significantly associated with liver disease progression. AC of FIB-4 (P 3.25 and AC of FIB-4 > 0.22, or non-SVR and AC of FIB-4 > 0.22 had the highest cumulative incidence of liver disease progression among the 4 groups identified according to baseline FIB-4 and AC of FIB-4, or SVR and AC of FIB-4. Conclusions: An increased FIB-4 over time is an independent risk factor of liver disease development in Chinese CHC patients. Monitoring FIB-4 annually may help physicians to predict prognosis in CHC patients.

Toll like receptor7 polymorphisms in relation to disease susceptibility and progression in Chinese patients with chronic HBV infection

Toll-like receptors (TLRs) play a key role in innate and adaptive immunity, protecting the host from viral pathogens. We studied the effect of TLR7 polymorphisms on disease susceptibility and progression of chronic hepatitis B (CHB) infection in Chinese adults. Blood samples were taken from 612 patients with confirmed CHB, hepatitis B virus (HBV)-related liver cirrhosis (LC) or hepatocellular carcinoma (HCC) and 293 controls. TLR7 polymorphisms (rs179010-C > T, rs2074109-T > C, and rs179009-A > G) were analyzed by PCR-based sequencing. A significantly higher frequency of TLR7 rs179010 C allele was found in male CHB patients than in controls (74.8% vs 59.5%, P = 0.002). The frequency of rs179009 G allele was markedly increased with disease progression when male patients with CHB, LC and HCC were compared (P = 0.012). The haplotype CTA was significantly associated with an increased susceptibility to CHB among male patients (P = 0.000). Frequency of the haplotype CTG was higher in male patients with HCC than CHB (P = 0.005). No such differences in these allele frequencies were found between female patients and controls. Our results indicated that TLR7 polymorphisms play an important role in disease susceptibility and the progression of CHB infections in Chinese adults, and may partly explain the high incidence of HBV related diseases in Chinese men.

Polymorphism of TLR5 rs5744174 is associated with disease progression in Chinese patients with chronic HBV infection.

Toll-like receptors (TLRs) play a crucial role in innate and adaptive immunity, protecting the host from viral pathogens. Studies have implicated that TLR5 is associated with various diseases such as autoimmune and inflammation related diseases. However, little is known about the relationship between TLR5 and hepatitis B virus (HBV) infection. We studied the effect of TLR5 gene polymorphisms on susceptibility to and disease progression of chronic hepatitis B (CHB) infection in Chinese. Blood samples were taken from 636 patients with CHB, HBV-related liver cirrhosis (LC) or hepatocellular carcinoma (HCC) and 273 controls. Polymorphisms of TLR5 (1775A>G rs2072493 and 1846T>C rs5744174) were analyzed by PCR-based sequencing. No difference in genotypic and allelic frequencies of TLR5 rs2072493 and rs5744174 was observed between patients and controls. Significant difference was found in frequency of TLR5 rs5744174 TT genotype between men with CHB and LC (p=0.035). Frequency of TT genotype of TLR5 rs5744174 in patients positive for HBeAg was increased from 53.2% in patients with CHB to 74.1% in those with HCC (p=0.024). Our results indicate that in Chinese genetic variation of TLR5 may be not a determinant of susceptibility to HBV-related diseases but may play a role in development of HBV-related severe liver diseases.

Clinical benefit of continuing crizotinib therapy after initial disease progression in Chinese patients with advanced ALK-rearranged non-small-cell lung cancer.

PurposeAlthough most patients with ALK-positive non?small-cell lung cancer (NSCLC) who benefit from treatment with crizotinib ultimately develop progressive disease (PD), continuing crizotinb beyond the initial PD (CBPD) in these patients may be beneficial. In this study, we investigated whether Chinese patients with advanced ALK-positive NSCLC benefit from CBPD, and whether any factors are predictive of a longer post-initial progression-free survival time (PFS2).Materials and MethodsData on 33 patients with ALK-positive NSCLC who achieved disease control with crizotinib were analyzed retrospectively. The impact of continued crizotinib therapy on the patients’ PFS2 time was assessed after adjusting for potential confounding factors.ResultsWith initial crizotinib therapy, the objective response rate (ORR) and median PFS time (PFS1) in the 33 patients were 63.6% and 8.6 months, respectively. With continued crizotinib therapy after documentation of PD, the median PFS2 for all 33 patients was 16 weeks, and in those with CNS progression but systemic disease control it was 30 weeks. Patients who received local therapy after disease progression had a significantly longer PFS2 compared with those who did not (P = 0.039). Multivariable Cox regression analysis showed that the PFS1 with initial crizotinib treatment and local therapy were independent predictors of PFS2.DiscussionThis study provides further evidence of the benefit of continuing crizotinib therapy in Chinese patients with progressive ALK-positive NSCLC. Patients with a longer PFS1 and those who received local brain therapy would have a longer period of continuing crizotinib.