Controlling Nutritional Status (CONUT) as a Novel Postoperative Prognostic Marker in Breast Cancer Patients: A Retrospective Study.

Purpose: This investigation seeks to elucidate the potential prognostic significance as well as the clinical utility of the controlling nutritional status (CONUT) score in breast cancer patients. Methods: Breast cancer patients managed in our center between January 2010 and December 2016 were recruited for our study. They comprised 187 patients who did not undergo neoadjuvant chemotherapy and 194 who did. A receiver operating characteristic curve (ROC) was utilized in identifying the ideal cut-off CONUT value. This cut-off score was then used to reclassify patients into those with high CONUT scores (≥1) and low CONUT scores (<1). The outcomes were analyzed by statistical methods. Results: Univariate and multivariate Cox regression survival analyses revealed that a CONUT score cut-off of 1 was able to significantly predict duration of disease-free survival (DFS) (p < 0.001; hazard ratio [HR]: 3.184; 95% CI: 1.786-5.677; and p < 0.001; HR: 2.465; 95% CI: 1.642-3.700) and overall survival (OS) (p < 0.001; HR: 2.326; 95% CI: 1.578-3.429; and p < 0.001; HR: 2.775; 95% CI: 1.791-4.300). The mean DFS and OS in those with lower CONUT scores were 41.59 (95% CI: 37.66-45.51 months) and 77.34 months (95% CI: 71.79-82.90 months), respectively. On the other hand, the average DFS and OS for all individuals in the raised CONUT score group were 39.18 (95% CI: 34.41-43.95 months) and 71.30 months (95% CI: 65.47-77.12 months), respectively. Moreover, Kaplan-Meier survival analysis revealed that those in the raised CONUT score cohort had remarkably worse DFS and OS survival rates compared to individuals in the low CONUT score cohort (Log-rank test, DFS: χ 2 = 12.900, p = 0.0003, and OS: χ 2 = 16.270, p < 0.0001). Conclusion: The survival times of breast cancer patients may be reliably predicted using the CONUT score. This score is an easy, convenient, readily accessible, and clinically significant means of prognosticating patients with breast cancer.

A ketogenic diet attenuates proliferation and stemness of glioma stem­like cells by altering metabolism resulting in increased ROS production.

Abnormal metabolism serves a critical role in the development and progression of different types of malignancies including glioblastoma (GBM), and may therefore serve as a promising target for treatment of cancer. Preclinical studies have indicated that a ketogenic diet (KD) may exhibit beneficial effects in patients with GBM; however, the underlying mechanisms remain incompletely understood. The aim of the present study was to evaluate the effects of a KD on glioma stem­like cells (GSCs), by culturing patient­derived primary GSCs as well as a GSC cell line in glucose­restricted, ß­hydroxybutyrate­containing medium (BHB­Glow) which was used to mimic clinical KD treatment. GSCs cultured in BHB­Glow medium exhibited reduced proliferation and increased apoptosis compared with cells grown in the control medium. Furthermore, decreased expression of stem cell markers, diminished self­renewal in vitro, and reduced tumorigenic capacity in vivo, providing evidence that the stemness of GSCs was compromised. Mechanistically, culturing in BHB­Glow medium reduced glucose uptake and inhibited glycolysis in GSCs. Furthermore, culturing in the BHB­Glow medium resulted in morphological and functional disturbances to the mitochondria of GSCs. These metabolic changes may have reduced ATP production, promoted lactic acid accumulation, and thus, increased the production of reactive oxygen species (ROS) in GSCs. The expression levels and activation of mammalian target of rapamycin, hypoxia­inducible factor 1 and B­cell lymphoma 2 were decreased, consistent with the reduced proliferation of GSCs in BHB­Glow medium. ROS scavenging reversed the inhibitory effects of a KD on GSCs. Taken together, the results demonstrate that treatment with KD inhibited proliferation of GSCs, increased apoptosis and attenuated the stemness in GSCs by increasing ROS production.

Serum human epididymis protein 4 is a predictor for developing nephritis in patients with systemic lupus erythematosus: A prospective cohort study.

BACKGROUND: It has been demonstrated that serum human epididymis protein 4 (HE4) is a useful biomarker for differentiating lupus nephritis (LN) from systemic lupus erythematosus (SLE). However, it remains unclear whether HE4 can be used to predict the development of LN. METHODS: A total of 74 SLE patients without LN were recruited between August 2008 and September 2013. Serum HE4 concentrations were measured by enzyme-linked immunosorbent assay. These patients were followed up from the date of SLE diagnosis to LN development or the end of the study. The receiver operating characteristics (ROC) curve was drawn to assess the predictive value of HE4 for the incidence of LN. In addition, Kaplan-Meier and Cox regression analyses were used to determine the prognostic factors for the incidence of LN. RESULTS: Serum HE4 levels significantly increased in patients who are positive for anti-dsDNA antibody, low C3 and the incidence LN (P < 0.05), and these were closely correlated with age, erythrocyte sedimentation rate (ESR) and the SLE disease activity index (SLEDAI) (P < 0.05). During the follow-up, 44 patients developed LN. The ROC curve revealed that for HE4 levels, the predictive performance for LN with 64.8 pM as an optimal cutoff yielded an AUC of 0.714, with a 95% confidence interval of 0.597-0.831, and a sensitivity and specificity of 81.8% and 53.3%, respectively. The Kaplan-Meier analysis revealed that LN occurred in 72% of high-HE4 patients and 33.3% of low-HE4 patients (P = 0.036). The univariate analysis revealed that anti-dsDNA antibody, low C3, SLEDAI and HE4 were significantly associated with the incidence of LN (P < 0.05). Multivariate Cox regression revealed that only SLEDAI and HE4 were independently associated with the incidence of LN. CONCLUSION: Elevated serum HE4 is significantly associated with a higher risk of incidence for LN, and may be a useful predictor for developing LN.

Establishment of reference interval for the tumour marker serum CYFRA 21-1 in healthy Chinese Han ethnic adults.

BACKGROUND: Our aim was to establish the reference interval (RI) for serum CYFRA 21-1 in healthy Chinese Han ethnic adults, since there has been no report about it. METHODS: After screening, 9954 healthy Chinese Han adults (age range 18-95 years) were recruited, including 6639 (66.7%) males and 3315 (33.3%) females. Electrochemiluminescence immunoassay was used to measure serum CYFRA21-1. The RI was defined by nonparametric 95% percentile interval. RESULTS: The distribution for serum CYFRA21-1 level was non-Gaussian. The RI for healthy Chinese Han adults calculated by nonparametric method was 0-4.47 ng/ml in this study, higher than that recommended by Roche Diagnostics GmbH (≤3.3 ng/ml). The reference values were higher in males than females before 50 years of age, although the difference was hardly seen after 50 years of age. The reference value increased with age in both males and females. Of slight difference, the increase of male reference value was obvious at 60-69 and more than 80 years of age, while that of female obvious at 50-69 and more than 80 years of age. CONCLUSIONS: We establish the RI for serum CYFRA21-1 in healthy Chinese Han population, which is higher than that recommended by Roche Diagnostics GmbH. Furthermore, our study suggests that it is necessary to establish the age- and sex-specific RIs for serum CYFRA21-1.

Comparisons of neutrophil-, monocyte-, eosinophil-, and basophil- lymphocyte ratios among various systemic autoimmune rheumatic diseases.

This study was aimed to evaluate levels of neutrophil- (NLR), monocyte- (MLR), eosinophil- (ELR), and basophil-lymphocyte ratio (BLR) and their association with inflammatory markers in systemic autoimmune rheumatic diseases (SARDs). A total of 1139 SARD patients and 170 healthy individuals were enrolled. Clinical and laboratory data were extracted. NLR and MLR were significantly increased, but BLR decreased in most SARD patients (p < 0.05). ELR were significantly decreased in systemic lupus erythematosus (SLE) patients, but increased in those with other SARDs (p < 0.001). In SLE patients, C-reactive protein (CRP) showed positive correlation with NLR, MLR, and BLR. IgG negatively correlated with NLR, and did positively with ELR. IgM negatively correlated with NLR and MLR. In those with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and osteoarthritis (OA), NLR and MLR positively correlated with erythrocyte sedimentation rate (ESR) and CRP. In primary Sjögren's syndrome (pSS) patients, ESR showed positive correlation with NLR and MLR. IgA had positive correlation with BLR. In polymyositis/dermatomyositis (PM/DM) patients, ESR and CRP positively correlated with NLR. Additionally, significant correlations were also found between CRP and BLR, IgG and ELR, IgM and ELR. In systemic sclerosis (SSc) patients, clear correlations were only observed between CRP and NLR or MLR. In mixed connective tissue disease (MCTD) patients, NLR positively correlated with ESR and CRP, while NLR and MLR did negatively with IgM. In polymyalgia rheumatic (PMR) patients, MLR positively correlated with CRP, while ELR did negatively with IgG. This study demonstrated increased NLR and MLR and deceased BLR in most SARDs, decreased ELR in SLE and increased ELR in other SARDs. Furthermore, NLR and MLR may be useful tools to reflect inflammatory status of SARDs.

Prevalence of systemic autoimmune rheumatic diseases and clinical significance of ANA profile: data from a tertiary hospital in Shanghai, China.

It is necessary and useful to explore prevalence of various systemic autoimmune rheumatic diseases (SARDs) in patients with suspicion of having SARDs and to characterize antinuclear antibodies (ANA) profile for identifying different populations (SARDs and non-SARDs). A total of 5024 consecutive patients with available medical records were investigated, whose sera had been tested for ANA profile, including ANA, anti-dsDNA and anti-extractable nuclear antigen (ENA) antibodies, between 31 January 2012 and 26 March 2014. Only 594 (11.8%) patients were diagnosed with SARDs of those suspected with SARDs. The prevalence of systemic lupus erythematosus (SLE) was highest (3.2%), followed by rheumatoid arthritis (RA) (2.5%), primary Sjögren's syndrome (pSS) (1.7%), ankylosing spondylitis (AS) (1.5%), etc. Of females, SLE also showed the highest prevalence (6%), while of males, AS showed the highest prevalence (1.9%). The prevalence of most SARDs was closely associated with age, except mixed connective tissue disease (MCTD), and the variation characteristics among different age groups were different among various SARDs. The prevalence of ANA was significantly increased in most SARD patients [especially in SLE, systemic sclerosis (SSc) and MCTD]. For anti-ENA antibodies, in contrast to some autoantibodies associated with multiple SARDs (e.g. anti-SSA, SSB, nRNP), others were relatively specific for certain diseases, such as anti-dsDNA, Sm, histone, nucleosome and Rib-P for SLE, anti-SCL-70 for SSc and anti-Jo-1 for polymyositis/dermatomyositis (PM/DM). Of note, ANA profile appeared to be of little significance for AS, ANCA-associated vasculitis (AAV), polymyalgia rheumatic (PMR), adult-onset Still's disease (ASD) and Behcet's disease (BD). The younger were more likely to have the presence of anti-dsDNA, Sm, histone or Rib-P for SLE, and anti-SSA for RA or MCTD. No significant differences for frequencies of ANA and anti-ENA autoantibodies were found between sexes in most SARDs, with the exception of RA and AS. The present study suggests that, of patients with SARDs-like clinical manifestations, the proportion of those with true SARDS is small, for most of whom tests for autoantibodies are necessary and useful to help make a prompt and precise diagnosis.