Disease Progression In Chinese Patients Research Articles

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.

\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.

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.

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.

P3.02a-021 Clinical Benefit of Continuing Crizotinib Therapy after Initial Disease Progression in Chinese Patients with Advanced ALK -Rearranged NSCLC: Topic: ALK Clinical

Although 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 retrospective study, we investigated whether Chinese patients with advanced ALK-positive NSCLC benefit from CBPD, including patients with CNS progression and those who had received local therapy, and whether any factors are predictive of a longer post-initial progression-free survival time (PFS2). Data on 33 patients with ALK-positive NSCLC who had achieved disease control with initial crizotinib therapy were studied. The impact of continued crizotinib therapy (defined as >3 weeks of crizotinib treatment after the first documentation of PD) on the patients’ PFS2 time was assessed after adjusting for potential confounding factors. With initial crizotinib therapy, the objective response rate (ORR) and median PFS time (PFS1) in the 33 patients studied were 63.6% and 8.6 months, respectively (Figure 1). The brain was the most commonly involved disease progression site (n = 20; 60.6%); 14 patients (42.4%) received local therapy before and after crizotinib. With continued crizotinib therapy after the first documentation of PD, the median PFS2 time for all 33 patients was 16 weeks (Figure 1), 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 time compared with those who did not (p = 0.039). Multivariable Cox regression analysis showed that the PFS1 time with initial crizotinib treatment and local therapy were independent predictors of PFS2. This 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 had better survival with continued crizotinib therapy.

Lack of association between anemia and renal disease progression in Chinese patients with type 2 diabetes.

Anemia has a close interaction with renal dysfunction in diabetes patients. More proof is still awaited on the relationship between anemia and the progression of renal disease in this population. In the present longitudinal study, 1,645 Chinese type2 diabetes patients without end-stage renal disease were included in the analysis in Nanjing, China, during January 2006 and December 2012. All patients were managed by staged diabetes management protocol, and clinical parameters were collected at each visit. The end-point of progression of renal disease was evaluated during the follow up. Cox regression analysis was used to estimate the risk of anemia on renal disease progression. On recruitment, 350 (21.3%) patients had anemia, which was more common among those with older ages, longer diabetes duration, lower estimated glomerular filtration rate or more albuminura. On median follow up of 49months (range 28-62months), 37 patients (2.2%) developed the defined renal end-point. Compared with those without anemia, patients with anemia had a higher risk of renal disease progression. However, multivariate analysis showed that anemia lost its statistical significance once estimated glomerular filtration rate was added into the model. Although the incidence of renal disease progression markedly increased by anemia status in patients of estimated glomerular filtration rate <60mL/min/1.73m(2), anemia was still not an independent risk factor for renal disease progression in this subgroup. Anemia was a common finding in Chinese type2 diabetes patients. Anemia was a risk factor for renal disease progression, but lost its significance once baseline renal function was adjusted.

Responsiveness to reduced dosage of rituximab in Chinese patients with neuromyelitis optica

To determine the effect of a lower dose of rituximab in depleting B lymphocytes, maintaining low B-cell counts, and relapse in patients with neuromyelitis optica (NMO) and NMO spectrum disorders. We treated 5 Chinese patients with deteriorating NMO and NMO spectrum disorders with a 100-mg IV infusion of rituximab once a week for 3 consecutive weeks, followed by additional infusion of the same dosage depending on circulating B-cell repopulation. This reduced dosage of rituximab was sufficient to deplete B cells and maintain low B-cell counts. None of the treated patients experienced relapse, and all patients exhibited stabilized or improved neurologic function during the 1-year follow-up period. MRI revealed the absence of new lesions, no enhancement in spinal cord and brain, a significant shrinkage of spinal cord segments, and a reduction/disappearance of previous brain lesions. A lower dosage of rituximab may be sufficient in depleting B cells, maintaining low B-cell counts, and preventing disease progression in Chinese patients with NMO.

TOSO is overexpressed and correlated with disease progression in Chinese patients with chronic lymphocytic leukemia

Recently, a gene named TOSO was identified as being overexpressed and associated with the anti-apoptotic characteristic of chronic lymphocytic leukemia (CLL). However, the association of TOSO expression with clinical features of CLL has not been fully described, especially in Chinese patients. TOSO expression was detected by quantitative RT-PCR in CD19+ sorted cells in a cohort of 81 untreated patients with CLL. The results showed that the expression of TOSO in CLL was significantly higher than that in healthy controls (p = 0.027) and other B-cell lymphoproliferative diseases (p = 0.033). The expression level of TOSO was significantly correlated with Binet staging, IGVH mutation status, age, and time to treatment in CLL. A negative correlation was observed between age and TOSO expression (Spearman's, p = 0.025). No correlation was observed between the expression of TOSO and CD38 or ZAP-70. Cox regression analysis indicated that high expression of TOSO (more than 8.4) was an independent indicator for shorter treatment-free survival in CLL. We conclude that TOSO is specifically overexpressed and associated with progressive disease, and might be an important prognostic factor in CLL.

Accelerating Effect of Human Leukocyte Antigen-Bw6 Homozygosity on Disease Progression in Chinese HIV-1-Infected Patients

Most HIV-1-infected individuals progress to AIDS within 8 to 10 years after seroconversion. Less than 5% of them, however, remain asymptomatic, although their CD4 T-cell counts stay normal. In this study, our polymerase chain reaction sequence-specified primer (PCR-SSP) based human leukocyte antigen (HLA)-B genotyping of 28 typical progressors (TPs) and 15 long-term nonprogressors (LTNPs) revealed some evidence that an HLA-B locus polymorphism can influence the rate of disease progression in Chinese HIV-1-infected individuals: 12 of 28 TPs (43%) were HLA-Bw6 homozygotes. Only 1 of 15 LTNPs (6.7%) was homozygous for the polymorphism (P = 0.013), suggesting that HLA-Bw6 homozygosity is associated with accelerated disease progression. In contrast, 3 of 15 LTNPs (20%) were HLA-Bw4 homozygotes, whereas none of the 28 TPs were homozygotes (P = 0.037), supporting the conclusion that HLA-Bw4 homozygosity may have a protective role. Interestingly, the frequency of the HLA-B*15 allele was extremely high in the TP group (23.2%), which may be associated with faster disease progression in Chinese patients.