Role of growth differentiation factor 15 in cancer cachexia (Review).

Growth differentiation factor 15 (GDF15), a member of the transforming growth factor-ß family, is a stress-induced cytokine. Under normal circumstances, the expression of GDF15 is low in most tissues. It is highly expressed during tissue injury, inflammation, oxidative stress and cancer. GDF15 has been established as a biomarker in patients with cancer, and is associated with cancer cachexia (CC) and poor survival. CC is a multifactorial metabolic disorder characterized by severe muscle and adipose tissue atrophy, loss of appetite, anemia and bone loss. Cachexia leads to reductions in quality of life and tolerance to anticancer therapy, and results in a poor prognosis in cancer patients. Dysregulated GDF15 levels have been discovered in patients with CC and animal models, where they have been found to be involved in anorexia and weight loss. Although studies have suggested that GDF15 mediates anorexia and weight loss in CC through its neuroreceptor, glial cell-lineage neurotrophic factor family receptor α-like, the effects of GDF15 on CC and the potential regulatory mechanisms require further elucidation. In the present review, the characteristics of GDF15 and its roles and molecular mechanisms in CC are elaborated. The targeting of GDF15 as a potential therapeutic strategy for CC is also discussed.

Development and Verify of Survival Analysis Models for Chinese Patients With Systemic Lupus Erythematosus.

Background: The aim of this study is to develop survival analysis models of hospitalized systemic lupus erythematosus (h-SLE) patients in Jiangsu province using data mining techniques to predict patient survival outcomes and survival status. Methods: In this study, based on 1999-2009 survival data of 2453 hospitalized SLE (h-SLE) patients in Jiangsu Province, we not only used the Cox proportional hazards model to analyze patients' survival factors, but also used neural network models to predict survival outcomes. We used semi-supervised learning to label the censored data and introduced cost-sensitivity to achieve data augmentation, addressing category imbalance and pseudo label credibility. In addition, the risk score model was developed by logistic regression. Results: The overall accuracy of the survival outcome prediction model exceeded 0.7, and the sensitivity was close to 0.8, and through the comparative analysis of multiple indicators, our model outperformed traditional classifiers. The developed survival risk assessment model based on logistic regression found that there was a clear threshold, i.e., a survival threshold indicating the survival risk of patients, and cardiopulmonary and neuropsychiatric involvement, abnormal blood urea nitrogen levels and alanine aminotransferase level had the greatest impact on patient survival time. In addition, the study developed a graphical user interface (GUI) integrating survival analysis models to assist physicians in diagnosis and treatment. Conclusions: The proposed survival analysis scheme identifies disease-related pathogenic and prognosis factors, and has the potential to improve the effectiveness of clinical interventions.

Predictors of improvement in disease activity in first hospitalized patients with systemic lupus erythematosus: a multicenter retrospective study of a Chinese cohort.

OBJECTIVES: To analyze the relative factors of improvement in disease activity (IDA) after first hospitalized treatment based on the systemic lupus erythematosus disease activity index (SLEDAI). METHODS: A total of 1069 adult systemic lupus erythematosus (SLE) patients who were hospitalized for the first time in 26 hospitals in Jiangsu Province from 1999 to 2009 were retrospectively analyzed. SLEDAI decrease ≥ 4 during hospitalization was identified as IDA. Relative factors of IDA were assessed by univariate and multivariate logistic regression. RESULTS: A total of 783 (73.2%) adult SLE patients showed IDA after the first hospitalization, while the remaining patients (n = 286) were in the non-IDA group. The IDA group had higher SLEDAI at admission; fewer patients had SLICC/ACR damage index (SDI) ≥ 1, comorbidities at admission, especially Sjögren's syndrome, abnormal serum creatinine, and glomerular filtration rate. More patients had mucocutaneous and musculoskeletal involvements, leukopenia, increased C-reactive protein, anti-dsDNA antibody positive, and hypocomplementemia at admission and were treated with methotrexate and leflunomide during hospitalization. After multivariate logistic regression analysis, SDI ≥ 1 (P = 0.005) and combined with Sjögren's syndrome (P < 0.001) at admission had negative association with IDA. Musculoskeletal involvement (P < 0.001), anti-dsDNA antibody positive (P = 0.012), hypocomplementemia (P = 0.001), and use of leflunomide (P = 0.030) were significantly related with IDA. CONCLUSION: Organ damage or comorbidities at admission were adverse to SLE improvement. Anti-dsDNA antibody positive, hypocomplementemia, musculoskeletal involvements, and leflunomide treatment had positive association with IDA of SLE. Key Points • Organ damage or comorbidities at admission were negatively correlated with SLE improvement. • Anti-dsDNA antibody positivity, hypocomplementemia, musculoskeletal involvements, and leflunomide treatment were positively associated with SLE improvement.

Clinical and laboratorial outcome of different age-onset systemic lupus erythematosus patients in Jiangsu, China: a multicentre retrospective study.

Studies on clinical features of systemic lupus erythematosus among different age-onset patients are lacking in China. This multicentre study aimed to systemically compare clinical manifestations, comorbidities, organ involvement, and laboratory findings among 797 Chinese juvenile-onset, adult-onset, and late-onset SLE (JSLE, ASLE, and LSLE) patients. They were classified into JSLE, ASLE, and LSLE groups if first diagnosed at < 18, 18-50, and > 50 years old, respectively. Chi-square test and analysis of variance were employed for categorical and continuous variables respectively. In younger-onset patients, the SLE Disease Activity Index 2000 score was significantly higher (JSLE vs. ASLE vs. LSLE = 17.43 ± 9.139 vs. 16.34 ± 8.163 vs. 14.08 ± 6.474, p = 0.031). Mucocutaneous symptoms (79.5% vs. 73.4% vs. 62.0%, p = 0.042), especially malar rash (76.1% vs. 66.1% vs. 53.5%, p = 0.011) occurred more frequently, and proteinuria rate was higher (54.5% vs. 56.3% vs. 36.6%, p = 0.007). In later-onset patients, cardiopulmonary involvement increased (11.4% vs. 24.3% vs. 29.6%, p = 0.012). In ASLE, hypoalbuminemia rate elevated (46.6% vs. 59.9% vs. 47.9%, p = 0.015). Our study demonstrated in a Chinese population that JSLE may be more active and suffer mucocutaneous disorders, while LSLE tended to suffer cardiopulmonary involvement at-onset. These findings may help identify treatment priorities when facing different age-onset SLE patients.

Impact of diabetes mellitus developing after kidney transplantation on patient mortality and graft survival: a meta-analysis of adjusted data.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) occurs in 10-30% of kidney transplant recipients. However, its impact on mortality and graft survival is still ambiguous. Therefore, the current study aimed to analyze if PTDM increases mortality and graft failure by pooling multivariable-adjusted data from individual studies. METHODS: PubMed, Embase, and CENTRAL, and Google Scholar were searched for studies comparing mortality and graft failure between PTDM and non-diabetic patients. Multivariable-adjusted hazard ratios (HR) were pooled in a random-effects model. RESULTS: Fourteen retrospective studies comparing 9872 PTDM patients with 65,327 non-diabetics were included. On pooled analysis, we noted a statistically significant increase in the risk of all-cause mortality in patients with PTDM as compared to non-diabetics (HR: 1.67 95% CI 1.43, 1.94 I2 = 57% p < 0.00001). The meta-analysis also indicated a statistically significant increase in the risk of graft failure in patients with PTDM as compared to non-diabetics (HR: 1.35 95% CI 1.15, 1.58 I2 = 78% p = 0.0002). Results were stable on sensitivity analysis. There was no evidence of publication bias on funnel plots. CONCLUSION: Kidney transplant patients developing PTDM have a 67% increased risk of all-cause mortality and a 35% increased risk of graft failure. Further studies are needed to determine the exact cause of increased mortality and the mechanism involved in graft failure.

The relationship of polluted air and drinking water sources with the prevalence of systemic lupus erythematosus: a provincial population-based study.

Environmental exposures interact with genetic factors has been thought to influence susceptibility of systemic lupus erythematosus (SLE) development. To evaluate the effects of environmental exposures on SLE, we conducted a population-based cohort study across Jiangsu Province, China, to examine the associations between the living environment including air and water pollution, population density, economic income level, etc. and the prevalence and mortality of hospitalized SLE (h-SLE) patients. A total of 2231 h-SLE patients were retrieved from a longitudinal SLE database collected by the Jiangsu Lupus Collaborative Group from 1999 to 2009. The results showed that: It existed regional differences on the prevalence of h-SLE patients in 96 administrative districts; The distribution of NO2 air concentration monitored by atmospheric remote sensors showed that three of the ultra-high-prevalence districts were located in the concentrated chemical industry emission area; h-SLE patient prevalence was positively correlated with the excessive levels of nitrogen in drinking water; The positive ratio of pericarditis and proteinuria was positively correlated with the prevalence of h-SLE patients and pollution not only induced a high h-SLE patient prevalence but also a higher mortality rate, which might be attributed to NOx pollution in the air and drinking water. In summary, our data suggested that NOx in air and drinking water may be one of the important predispositions of SLE, especially for patients with renal involvement.

Prognosis for Hospitalized Patients with Systemic Lupus Erythematosus in China: 5-Year Update of the Jiangsu Cohort.

OBJECTIVE: To identify early signs associated with poor prognosis in Chinese patients with systemic lupus erythematosus (SLE) through a large population-based follow-up study. METHODS: Medical records of > 2,500 SLE patients that first hospitalized between 1999-2009 were collected from 26 centers across Jiangsu province, China, and entered into a database. These patients were followed-up for 5 to 15 years, and those remained contact and had known survival status in 2015 were assessed for the association of factors presented at the initial hospitalization with mortality at two time points (≤1year and > 1year). The independency of mortality factors was evaluated using multivariate Cox regression analysis. RESULTS: Among 1,372 patients we assessed, 92.3% were women and 17.2% were deceased in 2015. The main causes of death were infection (30.1%), neuropsychiatric impairment (14.8%), renal failure (14.4%) and cardiopulmonary involvement (8.5%). Hazard ratios (HR) of independent predictors for mortality (≤1year and > 1year, respectively) included hospital presentation of neuropsychiatric involvement (2.03 and 1.91), cardiopulmonary involvement (1.94 and 1.61) and increased serum creatinine (2.52 and 2.58). Patients older than 45 years and with disease durations more than 2 years at admission had unfavorable short-term outcome (HR 1.76 and 1.79), while the presence of anti-dsDNA and anti-Sm antibodies indicated diverse prognosis after 1 year (HR 1.60 and 0.45). Treatment with cyclophosphamide was beneficial for patient's first-year outcome (HR 0.50), and anti-malarial drugs significantly reduced the risk of mortality over different time points (HR 0.48 and 0.54). SLEDAI score, proteinuria or hypocomplementemia was not independently associated with the outcome in this cohort. CONCLUSION: SLE patients presented with vital organ damages rather than active disease at initial hospitalization are likely to have a poor outcome, especially for those with neuropsychiatric, cardiopulmonary involvements and renal insufficiency. Early and effective intervention with the use of anti-malarial drugs may decrease mortality.

[Low concentration of iodixanol used in CT angiography of lower extremity arteriosclerosis obliterans].

OBJECTIVE: To evaluate the clinical diagnostic value of low concentration of iodixanol used in CT angiography (CTA) of lower extremity arteriosclerosis obliterans (LEASO). METHODS: 42 patients which were suspect diagnosed with LEASO were divided to A group (270 mgI/ml iodixanol, tube voltage 100 kV) and B group (350 mgI/ml iohexol, tube voltage 120 kV), 21 patients in each group. Measure the body mass index (BMI) before the CTA of lower extremity. CTA results were analyzed with the digital subtraction angiography (DSA) as the "gold standard". RESULTS: There were no statistical difference of age, gender, BMI and CT value of the bifurcation of profunda femoral artery and superficial femoral artery, upper segment of anterior tibial artery and posterior tibial artery between A and B group. The diagnostic sensitivity and specificity of A and B groups of CTA were 97.0%, 99.1% and 98.3%, 99.5% for occlusion. Regard artery more than moderate stenosis (include moderate stenosis) as the overall statistics, the diagnostic sensitivity and specificity of A and B groups of CTA were 99.2%, 99.3% and 99.1%, 99.3%, the accuracy were 92.9% and 93.0%, the positive predictive and negative predictive value were 96.9%, 99.3% and 96.6%, 99.3%, respectively. The kappa value of A and B groups of CTA and DSA consistency test were 0.930 and 0.927, respectively. CONCLUSION: The CTA with low concentration of iodixanol combine with low tube voltage can achieve superior conventional scanning imaging features, and has great clinical value in the diagnosis of LEASO, also is an effective method for the inspection, evaluation and follow-up.