Predicting progression to AIDS

This study evaluated the predictive validity of two clinical staging systems for HIV infection (the Rabeneck and Royce systems) using data obtained from the Department of Veterans Affairs Cooperative Study Number 298, a randomized clinical trial involving 335 symptomatic patients with CD4 counts of 200 to 500/mm³. The relation between the HIV clinical stages and progression to AIDS was examined using Kaplan-Meier estimates, and Cox models were used to determine if the stages remained predictive after controlling for CD4 count. Both systems were significant independent predictors of progression to AIDS. This work demonstrates that simple, valid staging systems for HIV infection can be developed that provide greater prognostic distinction than the CD4 count alone.     

Nonalcoholic fatty liver disease in relation to the remission and progression along the glycemic continuum

BackgroundThe study aimed to explore the associations of nonalcoholic fatty liver disease (NAFLD) with the remission and progression along the glycemic continuum.MethodsThis prospective cohort study was performed among the general population in 2010–2015. NAFLD was defined as ultrasound‐detected hepatic steatosis with absence of excessive alcohol consumption and other hepatic diseases. Remission of type 2 diabetes referred to glycated hemoglobin <6.5% without hypoglycemic agents for ≥3 months. Prediabetes remission referred to normalization of blood glucose. Multivariable logistic analysis was applied to identify the risk of glycemic metabolic transition.ResultsDuring a median follow‐up of 4.3 years, participants with NAFLD had a significantly higher risk of progressing from normal glucose tolerance to diabetes (3.36 [1.60–7.07]) and lower likelihood of diabetes remission (0.48 [0.30–0.78]). Associations in participants with overweight or obesity and higher probability of hepatic fibrosis remained consistent. Results related to the effect of NAFLD on the specific glucose parameters were generally in line with the changes of glycemic status. NAFLD improvement decreased the risk of prediabetes progressing to diabetes (0.50 [0.32–0.80]) and increased the probability of prediabetes remission (2.67 [1.49–4.79]). NAFLD tended to show the most significant association with glycemic progression and decreased the likelihood in remission of prediabetes and diabetes.ConclusionsPresence of NAFLD increased risk of glycemic progression and decreased likelihood of remission. NAFLD improvement mitigated glycemic deterioration, whereas NAFLD progression impeded the chance of remission. The results emphasized joint management of NAFLD and diabetes and further focused on liver‐specific subgroups of diabetes to tailor early intervention.     

Development and progression of atherosclerotic disease in relation to insulin resistance and hyperinsulinemia.

It is unclear whether the role of insulin resistance in the development of atherosclerotic cardiovascular disease is similar in populations in which the incidence of atherosclerotic diseases significantly differs from that in Western countries. The aim of this study was to determine the relationship between insulin resistance and the development of cardiovascular disease in the Japanese population. We conducted 75 g-oral glucose tolerance tests (OGTTs) on 1,928 inhabitants of two towns in Hokkaido, Japan. Subjects using antihypertensive agents and known diabetic patients were excluded from the study. Data from the remaining 1,227 subjects (540 males and 687 females; mean age 56.0 +/- 10.8 years) were used for the analysis, and 1,051 subjects were seen in a follow-up care setting for a period of 8 years. The presence of insulin resistance was defined according to the guidelines reported our previous study: insulin levels of 64.0 mU/l or higher 2 h after the 75 g-OGTT. The insulin-resistant (IR) group had several risk factors such as hypertension, diabetes, treated or untreated hypercholesterolemia, hypertriglyceridemia, low high-density-lipoprotein (HDL) cholesterol levels, and obesity. During the follow-up period of 8 years, the incidence of coronary artery disease, which was adjusted for age, body mass index, sex, systolic blood pressure, fasting plasma glucose, total cholesterol, triglyceride, and HDL cholesterol was significantly (3.2 times) higher in the IR group than in the insulin non-resistant group. The results suggested that insulin resistance is an independent risk factor for coronary artery disease in Japanese subjects, as has also been demonstrated in the case of individuals in Europe and USA.     

Cytokine profile in Egyptian hepatitis C virus genotype-4 in relation to liver disease progression

AIM: To observe the imbalance between T helper cell Th1 and Th2 cytokines in several chronic hepatitis disease at different stages of disease progression. METHODS: We measured the cytokine levels of Thl (IL-2 and IL-2R), Th2 (IL-10) and the pro-inflammatory cytokines (IL-6 and IL-6R and TNF and TNF-RI and Ⅱ) by the ELISA technique in the sera of 33 hepatocellular carcinoma (HCC) patients and 20 chronic liver disease (CLD) patients. In addition, 20 asymptomatic hepatitis C virus carriers and 20 healthy subjects negative for hepatitis C virus(HCV) markers served as controls. RESULTS: Anti-HCV antibodies were found to be positive in 94% of HCC cases and 75% of CLD cases. On the other hand, HCV viremia was detected using RT-PCR in 67% of HCC cases and 65% of CLD cases. HBsAg was positive in 9% of HCC cases and 30% of CLD cases. Also bilharzial-Ab was positive in 55% of HCC cases, 65% of CLD cases and in 70% of asymptomatic carriers (ASC). HCC patients had significantly higher values of IL-2R, TNF-RⅡ (P<0.001), and TNF-RI (P>0.05), but lower TNFα (P<0.001) and IL-6 (P = 0.032) in comparison to ASC. But, in comparison to non-cancer controls, HCC patients had higher values of IL-2R, IL-6R, TNF-RI and TNF-RⅡ, but lower TNF-α (P<0.001). CLD patients had higher IL-2R, TNF-RI, and TNF-RⅡ (P<0.001) than ASC. But, in comparison to non-cancer controls, CLD patients had higher values of IL-2R, TNF-RI and TNF- RⅡ, but lower TNF-α (P<0.001). IL-10 was higher (though not significantly) in HCC and CLD patients than in symptomatic carriers and non-cancer controls. CONCLUSION: Liver disease progression from CLD to HCC due to HCV genotype-4 infection is associated with an imbalance between Thl and Th2 cytokines. IL-2R, TNF-RI, and TNF-RⅡ could be used as potential markers.     

Progression to AIDS and predictors of AIDS in seroprevalent and seroincident cohorts of homosexual men

As part of an ongoing prospective study of seropositive homosexual men in Vancouver, Canada, a seroprevalent cohort of 246 subjects (i.e. duration of infection unknown) and a seroincident cohort of 102 subjects (i.e. duration of infection known) were followed a median of 63 and 45 months, respectively. Follow-up with validation utilizing record linkage with the Canadian Federal Centre for AIDS registry revealed 58 and nine cases of AIDS in the seroprevalent and seroincident cohorts, respectively, through July 1988. These data yield product limit estimates of the cumulative progression rates to AIDS at 60 months of 23.0% for the seroprevalent cohort, 13.0% for the seroincident cohort, and 21.0% for the combined groups. Univariate analyses revealed the following to be statistically and clinically significant predictors of AIDS progression: low CD4 counts, low CD4/CD8 ratios, elevated immune complexes, elevated immunoglobulin G (IgG) and immunoglobulin A (IgA) levels, and low platelet counts. Cox regression revealed that elevated IgA levels, low CD4 counts, elevated immune complexes, two or more symptoms, and more than 20 male sexual partners in high-risk areas in the 5 years prior to enrollment were independent predictors of progression to AIDS over the subsequent 5 years. A multivariate risk function based on the latter five variables delineated low-, medium- and high-risk groups whose 5-year progression rates to AIDS were 6.7, 15.6 and 64.4%, respectively. The high-risk group contained 75% of all subjects who progressed to AIDS. Only 6% of the high-risk group would have qualified for zidovudine therapy under current guidelines at the beginning of the observation period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interruption of combination antiretroviral therapy and risk of clinical disease progression to AIDS or death

Objectives

The aim of the study was to compare incidence rates (IRs) of AIDS/death in patients with and without treatment interruption (TI) of combination antiretroviral therapy (cART) for periods of 3 months or more for different categories of CD4 cell count and viral load, and to determine risk factors for clinical progression to AIDS/death.

Methods

Patients starting cART with a CD4 cell count and a viral load available within 6 months of starting cART were included in the study. The IR and risk factors of TI were determined. We assessed the incidence rate ratios (IRRs) for TI and AIDS/death events using Poisson regression models.

Results

Of 3811 patients included in the study, 26% were ART‐naïve prior to cART. The median date of starting cART was July 1997, the median CD4 cell count was 226 cells/μL and the median viral load was 4.36 log₁₀ HIV‐1 RNA copies/mL. We observed 1243 interruptions and 403 AIDS‐events/deaths. The IR of AIDS/death was higher in patients with lower CD4 cell counts or higher viral loads, regardless of TI. After adjusting for baseline factors, the IR of AIDS/death was significantly higher in the TI group than in the non‐TI group [IRR 2.63; 95% confidence interval (CI) 2.01–3.44; P<0.0001]; this could be explained by current CD4 cell counts and viral loads, as the CD4 cell count‐ and viral load‐adjusted IRR was 1.14 (95% CI 0.86–1.51; P=0.37). Within the TI group, patients with a current CD4 cell count of <200 cells/μL had a 3‐fold higher risk of AIDS/death than those with a CD4 cell count of 200–350 cells/μL, whereas patients with a current CD4 cell count of >350 cells/μL had a 4‐fold lower risk of disease progression.

Conclusions

TI is common in clinical practice. The risk of AIDS/death increased more than 2‐fold for patients stopping all cART regimen drugs for 3 months or more. Among patients experiencing a TI, those with low CD4 cell counts, high viral loads or prior AIDS had an increased risk of AIDS/death. Hence, TI should be discouraged and closely monitored if it occurs.

     

Abatacept in rheumatoid arthritis-associated interstitial lung disease: short-term outcomes and predictors of progression

Clinical Rheumatology - Interstitial lung disease in rheumatoid arthritis (RA-ILD) is an extra-articular involvement that impairs the prognosis and for which there is still no well-coded treatment....     

KISS1 methylation and expression as predictors of disease progression in colorectal cancer patients

AIM:To examine the effect of aberrant methylation of the KISS1 promoter on the development of colorectal cancer(CRC)and to investigate reversing aberrant methylation of the KISS1 promoter as a potential therapeutic target.METHODS:KISS1 promoter methylation,mRNA expression and protein expression were detected by methylation-specific polymerase chain reaction(PCR),real-time quantitative PCR and Western blotting,respectively,in 126 CRC tissues and 142 normal colorectal tissues.Human CRC cells with KISS1 promoter hypermethylation and poor KISS1 expression were treated in vitro with 5-aza-2’-deoxycytidine(5-Aza-CdR).After treatment,KISS1 promoter methylation,KISS1 mRNA and protein expression and cell migration and invasion were evaluated.RESULTS:Hypermethylation of KISS1 occurred frequently in CRC samples(83.1%,105/126),but was infrequent in normal colorectal tissues(6.34%,9/142).Moreover,KISS1 methylation was associated with tumor differentiation,the depth of invasion,lymph node metastasis and distant metastasis(P<0.001).KISS1methylation was also associated with low KISS1 expression(P<0.001).Furthermore,we observed re-expression of the KISS1 gene and decreased cell migration after 5-Aza-CdR treatment in a CRC cell line.CONCLUSION:These data suggest that KISS1 is down-regulated in cancer tissues via promoter hypermethylation and therefore may represent a candidate target for treating metastatic CRC.     

Psychosocial factors and disease progression in simian AIDS: a preliminary report

Infection of macaques by the simian immunodeficiency virus (SIV), like HIV infection in humans, results in a variable time course to clinical disease. Developmental studies of macaques have shown that psychosocial disruption, including social separations, can result in both immediate and long-term immunological consequences. Using colony records on a subset of rhesus macaques (Macaca mulatta) inoculated with SIV at the California Primate Research Center, Davis, California, USA, we constructed regression equations to determine whether the animals' psychosocial histories could explain any of the variability observed in measures of disease progression. After controlling for dosage, age at inoculation, sex, and previous inoculation history, psychosocial variables were found to be significantly associated with several indicators of disease, including latencies to display leukopenia and lymphopenia, weight loss, and survival. We believe these preliminary results suggest an important role for psychosocial processes in affecting disease progression in SIV infection in macaques.