Long-term and short-term prognostic value of the prognostic nutritional index in cancer: a narrative review.

OBJECTIVE: To perform a narrative review of the prognostic value of prognostic nutritional index (PNI) in cancers. BACKGROUND: Prognostic estimation greatly determines the treatment approach in various cancers. The PNI, calculated using the serum albumin level and total lymphocyte count, is a useful indicator to assess nutritional and immunological conditions. The PNI represents a low-cost, easy-to-perform, noninvasive, rapid, and standardized tool for estimating the prognosis of cancer. Many studies have aimed to clarify the prognostic value of PNI for various types of cancer. METHODS: We summarize the studies, particularly the systematic reviews and meta-analyses, that have examined the prognostic value of PNI in common cancers. CONCLUSIONS: The relevant studies indicate that low PNI is an independent prognostic factor for decreasing overall survival in many types of cancers. Disease-free survival and progression-free survival were also associated with PNI in some types of cancer including lung cancer and renal cell carcinoma. Therefore, we suggest that the measurement of PNI is a useful method to identify cancer patients that have a worse prognosis and that the treatment strategy for these patients be adjusted accordingly. We hypothesize that maintaining good nutritional status during treatment may improve outcomes of various cancers.

The diagnostic utility of pleural markers for tuberculosis pleural effusion.

Tuberculosis pleural effusion (TPE) is common in clinical practice, and its diagnosis remains a challenge for clinicians. Ziehl-Neelsen staining, PE Mycobacterium tuberculosis culture, and biopsy are the gold standards for TPE diagnosis; however, they are time-consuming, invasive, observer-dependent, and insensitive. PE markers represent a rapid, low-cost, and non-invasive objective diagnostic tool for TPE. In the past decades, several PE biomarkers have been developed, and their diagnostic accuracy has been evaluated in many studies. Here, we reviewed the literature to summarize the diagnostic accuracy of these biomarkers, especially using the evidence from systematic review and meta-analysis. The current research strongly suggests that adenosine deaminase (ADA), interferon-gamma (IFN-γ), and interleukin 27 (IL-27) have extremely higher diagnostic accuracy for TPE, while the diagnostic accuracy of interferon gamma release assays (IGRAs), tumor necrosis factor-α (TNF-α), and interferon-γ-induced protein 10 kDa (IP-10) is moderate. Although some evidence supports C-X-C motif chemokine ligand 9 (CXCL9), CXCL11, CXCL12, sFas ligand, angiotensin-converting enzyme (ACE), calpain-1, spectrin breakdown products (SBDP), matrix metalloproteinase-1 (MMP-1), soluble CD26 (sCD26), soluble interleukin 2 receptor (sIL-2R) as useful diagnostic markers for TPE, more support is needed to validate their diagnostic accuracy. Finally, nucleic acid amplification tests (NAATs) have extremely high diagnostic specificity, but their sensitivity is low. Taken together, ADA is the preferred marker for TPE because its low cost and suitability for standardization.

Predictive accuracy of serum total calcium for both critically high and critically low ionized calcium in critical illness.

BACKGROUND: The accuracy of total calcium and its corrected value for predicting critically high and critically low ionized calcium in critical illness is controversial. The aim of this study was to investigate whether the concentration of total serum calcium, either corrected for albumin or not, could predict critically high or low values in critical illness. METHODS: This report describes a retrospective study using the Medical Information Mart for Intensive Care (MIMIC) III database. Test panels that contained serum albumin, total calcium, and ionized calcium (named ATI panels) with order time intervals of less than one hour were extracted. The predictive accuracy of total calcium, either corrected for albumin or not, was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 12 118 ATIs with 103 critically low and 92 critically high ionized calcium results were extracted. The areas under ROC curves (AUCs) of corrected and uncorrected total calcium for predicting critically low ionized calcium were 0.69 (95% CI: 0.61-0.76) and 0.70 (95% CI: 0.63-0.78), respectively. For predicting critically high ionized calcium, the AUCs were 0.98 (95% CI: 0.97-1.00) and 0.97 (95% CI: 0.95-1.00), respectively. With positive predictive values (PPVs) of 0.05 and 0.10, the sensitivities (both corrected and uncorrected) were approximately 0.50 for predicting critically low ionized calcium and 0.95 for predicting critically high ionized calcium. CONCLUSIONS: Total calcium, either corrected for albumin or not, is not a reliable test to predict critically low ionized calcium in critical illness. Total calcium's predictive accuracy for critically high ionized calcium is high.

UVB induces apoptosis via downregulation of CALML3-dependent JNK1/2 and ERK1/2 pathways in cataract.

The aim of the current study was to understand the mechanisms of apoptosis occurring in cultured human lens epithelial cells (HLECs) following ultraviolet B (UVB) irradiation. The investigations intended to confirm the presence of apoptosis and to reveal the roles of oxidative stress, calcium (Ca2+), c­Jun NH2­terminal kinase (JNK)1/2, and extracellular signal­regulated kinase (ERK)1/2 signaling pathway in these progresses. Cell apoptosis, ROS generation and intracellular Ca2+ concentration was measured by flow cytometry. The expression of CALML3, caspase-3, Bax, Bcl-2, p-JNK1/2, JNK1/2, p-ERK1/2 and ERK1/2 was measured by RT-qPCR and western blot analysis. Annexin V­fluorescein isothiocyanate/propidium iodide staining demonstrated that UVB irradiation increased the apoptotic rate, reactive oxygen species (ROS) production and intracellular Ca2+ concentration of HLECs in dose­ and time­dependent manners. Overexpression of calmodulin like 3 (CALML3) reversed the effects of UVB irradiation on apoptosis, ROS production and Ca2+ concentration of HLECs, and decreased expressions of caspase­3 and Bax, with increased expressions of Bcl­2. Notably, silencing of CALML3 had similar effects to UVB irradiation and inhibited the activation JNK1/2 and ERK1/2 pathways. Nimodipine, a Ca2+­channel antagonist, significantly attenuated the damages induced by CALML3 downregulation. In conclusion, UVB irradiation induced increase in apoptosis, ROS production and Ca2+ concentration of HLECs, in part, by downregulating the expression of CALML3 and involved oxidative stress, Ca2+, JNK1/2 and ERK1/2 signaling pathways, suggesting that investigating CALML3 may useful for developing cataract treatment.

Red blood cell distribution width and neutrophil to lymphocyte ratio are correlated with disease activity of dermatomyositis and polymyositis.

BACKGROUND: Previous studies indicated that both red blood cell distribution width (RDW) and neutrophil to lymphocyte ratio (NLR) were useful indices in assessing the disease activity of autoimmune diseases. However, the evidence for the association between RDW, NLR and dermatomyositis (DM) and polymyositis (PM) is limited. The aim of this study is to investigate the association between the disease activity of PM/DM and both RDW and NLR. METHODS: Medical records of 114 PM/DM patients and 114 healthy controls were retrospectively reviewed, and their RDW, NLR and myositis disease activity assessment visual analogue scale (MYOACT) on admission were extracted. The correlations between RDW, NLR and MYOACT were analyzed using the Spearman approach and multivariable model. RESULTS: PM/DM patients had significantly higher RDW and NLR. Increased RDW in PM/DM patients was not completely attributed to decreased hemoglobin or therapeutic agents. Both RDW and NLR are independently and positively correlated MYOACT. CONCLUSION: Both RDW and NLR are useful indices in assessing the disease activity of PM/DM.

Red blood cell distribution width and neutrophil to lymphocyte ratio are associated with outcomes of adult subarachnoid haemorrhage patients admitted to intensive care unit.

Background Red blood cell distribution width (RDW) and neutrophil to lymphocyte ratio (NLR) have been reported to be associated with outcomes of acute cerebral infarction. However, their prognostic value in patients with subarachnoid haemorrhage (SAH) remains largely unknown. The aim of this study was to investigate the prognostic value of RDW and NLR in SAH patients. Methods Medical records of adult SAH patients admitted to intensive care unit (ICU) were extracted from Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC II, version 2.6), a publicly accessible ICU database. Prognostic value of RDW and NLR was analysed using logistic regression model, Kaplan-Meier curve analysis and Cox regression model. Results A total of 274 SAH patients were included. Patients died in hospital had significantly higher RDW and NLR. RDW and NLR were significantly associated with hospital death, with adjusted odds ratios of 1.39 (95% CI, 1.06-1.82) and 1.04 (95% CI, 1.00-1.08), respectively. Furthermore, increased RDW and NLR were associated with higher one-year mortality, with an adjusted hazard ratio of 1.20 (95% CI, 1.02-1.41) for per 1% increased RDW and 1.03 (95% CI, 1.00-1.05) for per 1 increased NLR. Conclusion RDW and NLR are useful indices to evaluate the outcomes of ICU admitted patients with SAH.

Lower mean corpuscular hemoglobin concentration is associated with poorer outcomes in intensive care unit admitted patients with acute myocardial infarction.

BACKGROUND: Accumulated studies have shown that hematological parameters [e.g., red blood cell distribution width (RDW), hemoglobin, platelet count] and serum potassium level can impact the prognosis of patients with acute myocardial infarction (AMI). However, no previous study has evaluated the prognostic values of these laboratory tests simultaneously. METHODS: This study is based on an intensive care unit (ICU) database named Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC II). Adult patients with AMI were included, and their hematological parameters and serum ion levels on admission were extracted. The relationships between these laboratory tests and hospital mortality were evaluated using a logistic regression model and receiver operating characteristic (ROC) curve analysis. The effects of these laboratory tests on 1-year mortality were evaluated using a Cox hazard regression model and Kaplan-Meier curve analysis. RESULTS: In univariable analysis, increased white blood cell (WBC), neutrophil percentage, mean corpuscular volume (MCV), RDW, potassium and decreased red blood cell (RBC), hemoglobin, mean corpuscular hemoglobin concentration (MCHC), hematocrit and percentage of lymphocyte, monocyte, basophil and eosinophil were significantly associated with hospital mortality. In multivariable analyses, basophil percentage, potassium, WBC and MCHC were independently associated with hospital morality, while WBC, RDW, MCHC, potassium and percentages of neutrophil and lymphocyte were associated with 1-year mortality. CONCLUSIONS: Hematological parameters and serum potassium can provide prognostic information in AMI patients. MCHC is an independent prognostic factor for both short and long term outcomes of AMI.

Prognostic value of neutrophil to lymphocyte ratio for gastric cancer.

BACKGROUND: Although the prognostic value of the neutrophil to lymphocyte ratio (NLR) in gastric cancer (GC) patients has been investigated by many studies, the results are heterogeneous. The objective of this systematic review is to ascertain the prognostic value of NLR in GC patients. METHODS: PubMed and Embase were retrieved to identify potential studies published before 8 June, 2014. Newcastle-Ottawa Scale (NOS) for cohort study was used to assess the quality of all eligible studies. RESULTS: Of the 20 studies included in this systematic review, 17 studies investigated the effect of NLR on overall survival (OS), 11 studies reported that NLR negatively affected OS in their multivariante analysis, and 16 studies reported that NLR negatively affected OS in univariate analysis. Three studies investigated the effect of NLR on progression-free survival (PFS), reporting that increased NLR was associated with worse PFS. Four studies investigated the effect of NLR on disease-free survival (DFS), two of which reported that increased NLR was associated with worse DFS. Two studies investigated the effect of NLR on disease special survival (DSS), but neither observed any significant association between NLR and DSS. The major design deficiencies of the studies available were retrospective data collection, inadequacy of follow-up cohorts, and unavailability of the method used for outcome assessment. CONCLUSIONS: Based on the above findings, we conclude that NLR may be a useful prognostic index (PI) for GC. In addition, future studies with prospective design, long-term follow-up and fully adjusted confounding factors are needed to rigorously assess the prognostic value of NLR for GC.

Diagnostic accuracy of cytokeratin-19 fragment (CYFRA 21-1) for bladder cancer: a systematic review and meta-analysis.

Previous studies have evaluated the accuracy of serum and urinary measurements of cytokeratin-19 fragment (CYFRA 21-1) for the diagnosis of bladder cancer; however, the results have been inconsistent. The aim of this study was to evaluate the overall accuracy of CYFRA 21-1 for the diagnosis of bladder cancer. We performed a search for English-language publications reporting on the detection of CYFRA21-1 levels for the diagnosis of bladder cancer through November 2, 2014, using public medical databases, including EMBASE, Web of Science, and Medline. The quality of the studies was assessed by revised QUADAS tools. The performance characteristics were pooled and analyzed using a bivariate model. Publication bias was explored with the Deek's test. Sixteen studies, with a total 1,262 bladder-cancer patients and 1,233 non-bladder-cancer patients, were included in the study. The pooled sensitivities for serum and urine CYFRA 21-1 were 0.42 (95 % confidence interval (CI), 0.33-0.51) and 0.82 (95 % CI, 0.70-0.90), respectively. The corresponding specificities were 0.94 (95 % CI, 0.90-0.96) and 0.80 (95 % CI, 0.73-0.86), respectively. The areas under the summary receiver-operating-characteristic curves for serum and urine CYFRA 21-1 were 0.88 (95 % CI, 0.85-0.91) and 0.87 (95 % CI, 0.84-0.90), respectively. The major design deficiencies of the included studies were participant-selection bias, potential review, and verification bias. Therefore, we concluded that both serum and urine CYFRA 21-1 served as efficient indexes for bladder-cancer diagnosis. Additional, well-designed studies should be performed to rigorously evaluate the diagnostic value of CYFRA 21-1 for bladder cancer.

Red blood cell distribution width and neutrophil/lymphocyte ratio are positively correlated with disease activity in primary Sjögren's syndrome.

OBJECTIVE: The red blood cell distribution width (RDW) and neutrophil/lymphocyte ratio (NLR) are increased in various inflammation related diseases, but their clinical significance in primary Sjögren's syndrome (pSS) has not been reported. The aim of the present study was to investigate the clinical significance of RDW and NLR in pSS patients. METHODS: The medical records of pSS patients who were admitted to Changhai Hospital of the Second Military Medical University between April 2012 and December 2013 were retrospectively reviewed. Correlations between RDW, NLR and the patient clinical characteristics were analyzed using the Spearman approach and the multiple linear regression model. RESULTS: Fifty-two pSS patients and 58 healthy controls were enrolled. RDW and NLR were increased in pSS patients and positively correlated with the Sjögren's syndrome disease activity index (SSDAI). CONCLUSION: RDW and NLR may prove to be useful indices to estimate pSS disease activity.

Prognostic value of red blood cell distribution width for patients with heart failure: a systematic review and meta-analysis of cohort studies.

AIMS: Multiple studies have investigated the prognostic role of red blood cell distribution width (RDW) for patients with heart failure (HF), but the results have been inconsistent. The aim of the present study was to estimate the impact of RDW on the prognosis of HF by performing a systematic review and meta-analysis. METHODS AND RESULTS: The Embase, PubMed, and Web of Science databases were searched up to November 16, 2013 to identify eligible cohort studies. The quality of each study was assessed using the Newcastle-Ottawa Scale (NOS). The association between RDW, either on admission or at discharge, and HF outcomes (all-cause mortality [ACM], heart transplantation, cardiovascular mortality, and rehospitalization, etc.) were reviewed. The overall hazard ratio (HR) for the effect of RDW on ACM was pooled using a random-effects model, and the publication bias was evaluated using funnel plots and Eggers' tests. Seventeen studies, with a total of 18288 HF patients, were included for systematic review. All eligible studies indicated that RDW on admission and RDW at discharge, as well as its change during treatment, were of prognostic significance for HF patients. The HR for the effect of a 1% increase in baseline RDW on ACM was 1.10 (95% confidence interval: 1.07-1.13), based on pooling of nine studies that provided related data. However, publication bias was observed among these studies. CONCLUSIONS: HF patients with higher RDW may have poorer prognosis than those with lower RDW. Further studies are needed to explore the potential mechanisms underlying this association.

Diagnostic accuracy of anti-alpha-fodrin antibodies for primary Sjögren's syndrome.

OBJECTIVES: To estimate the diagnostic accuracy of anti-alpha-fodrin antibodies for primary Sjögren's syndrome (pSS). METHODS: Sixty-four pSS subjects and 108 non-pSS patients were prospectively enrolled in this study. Serum anti-alpha-fodrin IgA and IgG were detected by ELISA in a blind fashion. The diagnostic accuracy of anti-alpha-fodrin antibodies was assessed by receiver operating characteristic (ROC) curve analysis. Logistic regression was used to investigate whether anti-alpha-fodrin antibodies could improve the accuracy of pSS diagnosis if used in addition to anti-SSA and anti-SSB. RESULTS: The areas under the ROC curves for anti-alpha-fodrin IgG and IgA were 0.69 (95% confidence interval (CI): 0.60-0.77) and 0.63 (95% CI: 0.54-0.72), respectively (P < 0.01 for both). The optimal diagnostic thresholds for anti-fodrin IgG and IgA were 11.75 U/ml and 9.75 U/ml, respectively, with a sensitivity of 0.59 and 0.55, and a specificity of 0.75 and 0.73, respectively. Anti-alpha-fodrin IgG and IgA antibodies were associated with pSS after adjustment for anti-SSA and anti-SSB. CONCLUSIONS: Anti-alpha-fodrin IgG and IgA antibodies are useful diagnostic markers which may improve the accuracy of pSS diagnosis.

Red blood cell distribution width is a potential index to assess the disease activity of systemic lupus erythematosus.

BACKGROUND: General population-based investigations have revealed that red blood cell distribution width (RDW) is associated with inflammatory indexes such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Chronic inflammation is one of the major components of many autoimmune diseases and RDW may reflect the severity of these autoimmune diseases as well. Therefore, the objective of this study was to investigate the correlation between RDW and disease activity of systemic lupus erythematosus (SLE). METHODS: The medical records of 131 SLE patients were retrospectively analyzed. Correlations between RDW and disease activity or other inflammatory indexes were analyzed. The effect of glucocorticoid treatment for three months on RDW was estimated in 3 newly diagnosed SLE cases. RESULTS: Increased RDW was observed in SLE patients. RDW was positively correlated with serum IgM, CRP, ESR, and SLE Disease Activity Index 2000 (SLEDAI-2K). Glucocorticoid treatment decreased both SLEDAI-2K and RDW. CONCLUSION: RDW may be a useful index to estimate the disease activity of SLE.

Value of baseline platelet count for prediction of complications in primary biliary cirrhosis patients treated with ursodeoxycholic acid.

BACKGROUND: Decreased platelet count has been observed in various liver diseases, but its significance in primary biliary cirrhosis (PBC) remains unknown. The present study aimed to evaluate the predictive value of the platelet count at diagnosis for PBC-related complications in patients newly diagnosed with PBC and treated with ursodeoxycholic acid (UDCA). METHODS: Ninety-six PBC patients without complications treated with UDCA immediately after diagnosis were retrospectively reviewed. All hematologic and chemical parameters, Mayo risk score and PBC-related complications including upper gastrointestinal hemorrhage, presence of ascites, serum bilirubin concentration > 102.6 µmol/L and onset of hepatic encephalopathy were extracted. The associations between these parameters at diagnosis and complications were determined and the prognostic value of the platelet count was evaluated by receiver operating characteristics (ROC) analysis, Kaplan-Meier method and Cox proportional hazard model with the hazard ratio (HR) and 95% confidence interval (CI) calculated. RESULTS: Patients with PBC-related complications had significantly decreased platelet count and serum bilirubin concentration, prolonged prothrombin time, and increased Mayo risk score compared to those without complications. A platelet count of ≤ 132.5 × 10(9)/L was associated with the occurrence of complications, with an area under the ROC curve of 0.74 (95% CI: 0.64-0.85). The association remained even after adjustment for Mayo risk score (HR: 2.85; 95% CI: 1.46-5.54; p < 0.01), as shown in the Cox proportional hazard model. CONCLUSIONS: Decreased platelet count is a predictive factor for PBC-related complications. A cut-off value of ≤ 132.5 × 10(9)/L is recommended for the baseline platelet count to predict complications in patients newly diagnosed with PBC and treated with UDCA.

Angiogenesis and clinicopathologic characteristics in different hepatocellular carcinoma subtypes defined by EpCAM and α-fetoprotein expression status.

Recently, two hepatic lineage markers epithelial cell adhesion molecule (EpCAM) and α-fetoprotein (AFP) were used to classify hepatocellular carcinoma (HCC) into four subtypes with prognostic implication. In the present study, we further evaluated the clinicopathologic and angiogenic characteristics among these HCC subtypes. EpCAM expression was investigated by immunohistochemistry in 115 HCC primary tumors. Based on EpCAM immunostaining and serum AFP levels, 115 HCC cases were classified into four subtypes: EpCAM+AFP+ (26.1%), EpCAM-AFP+ (20.0%), EpCAM+AFP- (20.8%), and EpCAM-AFP- (33.1%). EpCAM+AFP+ and EpCAM-AFP+ HCC were associated with late TNM stages and high frequencies of venous invasion, whereas EpCAM+AFP- and EpCAM-AFP- subtypes were associated with early TNM stages and low frequencies of venous invasion. Furthermore, EpCAM+AFP+ HCC had a significantly higher microvessel density (MVD) and higher level of VEGF (Vascular epithelial growth factor) expression than the other three subtypes. In conclusion, our study indicated that subtype classification of HCC based on EpCAM and AFP status had clinicopathologic and biologic implications in aggressive phenotype and angiogenesis. We also suggest that the EpCAM+AFP+ HCC patients might be potential therapeutic candidates for anti-angiogenesis therapy.