Proteomic characterization identifies clinically relevant subgroups of soft tissue sarcoma.

Soft tissue sarcoma is a broad family of mesenchymal malignancies exhibiting remarkable histological diversity. We portray the proteomic landscape of 272 soft tissue sarcomas representing 12 major subtypes. Hierarchical classification finds the similarity of proteomic features between angiosarcoma and epithelial sarcoma, and elevated expression of SHC1 in AS and ES is correlated with poor prognosis. Moreover, proteomic clustering classifies patients of soft tissue sarcoma into 3 proteomic clusters with diverse driven pathways and clinical outcomes. In the proteomic cluster featured with the high cell proliferation rate, APEX1 and NPM1 are found to promote cell proliferation and drive the progression of cancer cells. The classification based on immune signatures defines three immune subtypes with distinctive tumor microenvironments. Further analysis illustrates the potential association between immune evasion markers (PD-L1 and CD80) and tumor metastasis in soft tissue sarcoma. Overall, this analysis uncovers sarcoma-type-specific changes in proteins, providing insights about relationships of soft tissue sarcoma.

ASSESS-IE: a Novel Risk Score for Patients with Infective Endocarditis.

Mortality in patients with infective endocarditis (IE) remains high. The existing risk scores are relatively complex with limited clinical application. This study was conducted to establish a new risk model to predict in-hospital and 6-month mortality in IE patients. A total of 1549 adult patients with definite IE admitted to Guangdong Provincial People's Hospital (n=1354) or Xiamen Cardiovascular Hospital (n=195) were included. The derivation cohort consisted of 1141 patients. The score was developed using the multivariate stepwise logistic regression analysis for in-hospital death. Bootstrap analysis was used for validation. Discrimination and calibration were evaluated by the receiver operating characteristic curve and the Hosmer-Lemeshow goodness-of-fit test. Six risk factors were used as score parameters (1 point for each): aortic valve affected, previous valve replacement surgery, severe heart failure, elevated serum direct bilirubin, moderate-severe anemia and acute stage. The predictive value and calibration of the ASSESS-IE score for in-hospital death were excellent in the derivation (area under the curve [AUC]=0.781, p<0.001; Hosmer-Lemeshow p=0.948) and validation (AUC=0.779, p<0.001; Hosmer-Lemeshow p=0.520) cohorts. The score remained excellent in bootstrap validation (AUC=0.783). The discriminatory ability of the ASSESS-IE score for in-hospital (AUC: 0.781 vs. 0.799, p=0.398) and 6-month mortality (AUC: 0.778 vs. 0.814, p=0.040) were similar with that of Park's score which comprised 14 variables. The ASSESS-IE risk score is a new and robust risk-stratified tool for patients with IE, which might further facilitate clinical decision-making.

Proteogenomics of diffuse gliomas reveal molecular subtypes associated with specific therapeutic targets and immune-evasion mechanisms.

Diffuse gliomas are devastating brain tumors. Here, we perform a proteogenomic profiling of 213 retrospectively collected glioma tumors. Proteogenomic analysis reveals the downstream biological events leading by EGFR-, IDH1-, TP53-mutations. The comparative analysis illustrates the distinctive features of GBMs and LGGs, indicating CDK2 inhibitor might serve as a promising drug target for GBMs. Further proteogenomic integrative analysis combined with functional experiments highlight the cis-effect of EGFR alterations might lead to glioma tumor cell proliferation through ERK5 medicates nucleotide synthesis process. Proteome-based stratification of gliomas defines 3 proteomic subgroups (S-Ne, S-Pf, S-Im), which could serve as a complement to WHO subtypes, and would provide the essential framework for the utilization of specific targeted therapies for particular glioma subtypes. Immune clustering identifies three immune subtypes with distinctive immune cell types. Further analysis reveals higher EGFR alteration frequencies accounts for elevation of immune check point protein: PD-L1 and CD70 in T-cell infiltrated tumors.

Proteogenomic characterization of cholangiocarcinoma.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is a highly heterogeneous cancer with limited understanding and few effective therapeutic approaches. We aimed at providing a proteogenomic CCA characterization to inform biological processes and treatment vulnerabilities. APPROACH AND RESULTS: Integrative genomic analysis with functional validation uncovered biological perturbations downstream of driver events including DPCR1 , RBM47 mutations, SH3BGRL2 copy number alterations, and FGFR2 fusions in CCA. Proteomic clustering identified three subtypes with distinct clinical outcomes, molecular features, and potential therapeutics. Phosphoproteomics characterized targetable kinases in CCA, suggesting strategies for effective treatment with CDK and MAPK inhibitors. Patients with CCA with HBV infection showed increased antigen processing and presentation (APC) and T cell infiltration, conferring a favorable prognosis compared with those without HBV infection. The characterization of extrahepatic CCA recommended the feasible application of vascular endothelial-derived growth factor inhibitors. Multiomics profiling presented distinctive molecular characteristics of the large bile duct and the small bile duct of intrahepatic CCA. The immune landscape further revealed diverse tumor immune microenvironments, suggesting immune subtypes C1 and C5 might benefit from immune checkpoint therapy. TCN1 was identified as a potential CCA prognostic biomarker, promoting cell growth by enhancing vitamin B12 metabolism. CONCLUSIONS: We characterized the proteogenomic landscape of 217 CCAs with 197 paired normal adjacent tissues and identified their subtypes and potential therapeutic targets. The multiomics analyses with other databases and some functional validations have indicated strategies regarding the clinical, biological, and therapeutic approaches to the management of CCA.

Integrated proteogenomic characterization across major histological types of pituitary neuroendocrine tumors.

Pituitary neuroendocrine tumor (PitNET) is one of the most common intracranial tumors. Due to its extensive tumor heterogeneity and the lack of high-quality tissues for biomarker discovery, the causative molecular mechanisms are far from being fully defined. Therefore, more studies are needed to improve the current clinicopathological classification system, and advanced treatment strategies such as targeted therapy and immunotherapy are yet to be explored. Here, we performed the largest integrative genomics, transcriptomics, proteomics, and phosphoproteomics analysis reported to date for a cohort of 200 PitNET patients. Genomics data indicate that GNAS copy number gain can serve as a reliable diagnostic marker for hyperproliferation of the PIT1 lineage. Proteomics-based classification of PitNETs identified 7 clusters, among which, tumors overexpressing epithelial-mesenchymal transition (EMT) markers clustered into a more invasive subgroup. Further analysis identified potential therapeutic targets, including CDK6, TWIST1, EGFR, and VEGFR2, for different clusters. Immune subtyping to explore the potential for application of immunotherapy in PitNET identified an association between alterations in the JAK1-STAT1-PDL1 axis and immune exhaustion, and between changes in the JAK3-STAT6-FOS/JUN axis and immune infiltration. These identified molecular markers and alternations in various clusters/subtypes were further confirmed in an independent cohort of 750 PitNET patients. This proteogenomic analysis across traditional histological boundaries improves our current understanding of PitNET pathophysiology and suggests novel therapeutic targets and strategies.

Incremental value of combinatorial contrast echocardiography and 18F-fluorodeoxyglucose positron emission tomography/computed tomography in giant right atrial myxomas.

Although several studies have shown that myocardial contrast echocardiography and 18-FDG PET/CT can differentiate between benign and malignant intracardiac masses, it is rarely used in practice to evaluate myxoma. This case describes the contrast echocardiography and 18-FDG PET/CT findings of a giant myxoma with an atypical location and subclinical symptoms.

Impact of Body Composition During Neoadjuvant Chemoradiotherapy on Complications, Survival and Tumor Response in Patients With Locally Advanced Rectal Cancer.

BACKGROUND: To explore the impact of body composition before neoadjuvant chemoradiotherapy (pre-NCRT) and after neoadjuvant chemoradiotherapy (post-NCRT) on complications, survival, and tumor response in patients with locally advanced rectal cancer (LARC). METHODS: Patients with LARC who underwent radical surgery after NCRT between Ja 22nuary 2012 and March 2019 were studied. Body composition parameters, including skeletal muscle area (SMA), muscle density (MD), visceral fat area (VFA), total abdominal fat area (TAFA), and subcutaneous fat area (SFA), was identified at the third lumbar vertebra level on computed tomography (CT). The patients were divided into two groups based on the sex-specific quartile values of SMA, MD, VFA, TAFA, SFA, and body composition change. Patient characteristics, short- and long-term postoperative complications, survival, and tumor response were analyzed. RESULTS: A total of 122 eligible patients were enrolled. Body composition parameters, except MD, were strongly correlated with BMI (p < 0.001). Pre-NCRT low MD (p = 0.04) and TAFA loss (p = 0.02) were significantly correlated with short- and long-term ileus, respectively. Pre-NCRT low SMA was a significant prognostic factor for both disease-free survival (DFS) (HR 2.611, 95% CI 1.129-6.040, p = 0.025) and cancer-specific survival (CSS) (HR 3.124, 95% CI 1.030-9.472, p = 0.044) in the Cox regression multivariate analysis. Multivariate logistic regression analysis identified post-NCRT SFA (OR 3.425, 95% CI 1.392-8.427, p = 0.007) and SFA loss (OR 3.358, 95% CI 1.214-9.289, p = 0.02) as independent risk factors for tumor regression grade (TRG) and downstaging, respectively. CONCLUSION: Pre-NCRT low MD and TAFA loss were related to a high incidence of short- and long-term ileus, respectively. Pre-NCRT low SMA was a significant prognostic factor for CSS and DFS. Post-NCRT SFA and SFA loss were independent risk factors for TRG and downstaging, respectively.

The relationship between pre-procedural elevated arterial lactate and contrast-induced nephropathy following primary percutaneous coronary intervention.

BACKGROUND: Risk stratification has been one of the main steps in preventing contrast-induced nephropathy (CIN), which is a common complication after percutaneous coronary intervention (PCI). Elevated arterial lactate is a biomarker indicating severe disease condition and post-intervention complications. The relationship between lactate and CIN has not been established. This study is performed to investigate the relationship between elevated arterial lactate level and contrast-induced nephropathy (CIN). METHODS: Patients diagnosed with ST-segment elevated myocardial infarction (STEMI) were prospectively enrolled, with lactate measured within 0.5-1 hours before primary percutaneous coronary intervention (PCI). Patients with cardiopulmonary resuscitation, any forms of severe anaerobic condition, or end-stage renal disease undergoing dialysis were excluded. CIN was defined as an increase in serum creatinine ≥0.5 mg/dL or 25% within 72 hours after PCI. The Mehran Risk Score (MRS) is widely regarded as a classic risk model for CIN and the risk factors of MRS were applied in our multivariate regression analysis. RESULTS: Of the 227 enrolled patients, 47 (20.7%) developed CIN according to the definition. The mean lactate level was higher in the CIN group than in the non-CIN group (2.68±2.27 vs. 1.74±1.94, P<0.001). The arterial lactate level ≥2.0 mmol/L had 57.5% sensitivity and 75.6% specificity in predicting CIN. The performance of the lactate level in discriminating CIN was similar to that of the MRS (AUClac =0.707 vs. AUCMRS =0.697, P=0.86). After adjusting for other risk factors, lactate ≥2.0 mmol/L still significantly predicted CIN (odds ratio =3.77, 95% CI, 1.77-7.99, P=0.001). CONCLUSIONS: An arterial lactate level of ≥2.0 mmol/L is associated with CIN in STEMI patients after primary PCI.

HSVtk/GCV system on hepatoma carcinoma cells: Construction of the plasmid pcDNA3.1­pAFP-TK and targeted killing effect.

Previous studies demonstrated that herpes simplex virus thymidine kinase (HSVtk) could phosphorylate non­toxic gancyclovir (GCV) efficiently to produce phosphorylated products that result in cell apoptosis, to kill tumor cells. The present study aimed to construct a plasmid vector, pcDNA3.1­pAFP­TK, carrying the suicide gene driven by the alpha­fetoprotein (AFP) promoter, to investigate the cytotoxicity of HSVtk/GCV suicide gene system on hepatoma carcinoma cells. Reverse transcription­polymerase chain reaction and western blotting results demonstrated that the HSVtk gene was effectively expressed in HepG2 hepatoma carcinoma cells transfected with pcDNA3.1­pAFP­TK plasmid, whereas HSVtk gene expression was not detected in normal HL­7702 liver cells. In addition, MTT assays indicated that cell viability of HepG2 cells with the plasmid pcDNA3.1­pAFP­TK decreased in a dose­dependent manner following treatment with GCV for 48 h. Flow cytometry also revealed that the cell apoptosis rate and mitochondrial membrane potential reduction rate in the HepG2 cells treated with HSVtk/GCV suicide gene system were significantly higher than in the control group. Apoptosis rates in the control group and the pcDNA3.1­pAFP­TK group were (1.00±0.62%) and (38.70±6.03%), respectively. Mitochondrial membrane potential reduction rates in the control group and the pcDNA3.1-pAFP-TK group were (0.57±0.11%) and (22.84±5.79%), respectively. Caspase­3 staining demonstrated that activated caspase­3 increased significantly in the HepG2 cells treated with HSVtk/GCV suicide gene system, whereas in the control group activated caspase­3 increase was not observed. The results of the present study, therefore, indicated that HSVtk suicide gene was obviously expressed in the HepG2 cells and that the HSVtk/GCV system was effective at killing HepG2 hepatoma carcinoma cells.

Atorvastatin protects against contrast-induced nephropathy via anti-apoptosis by the upregulation of Hsp27 in vivo and in vitro.

Contrast-induced nephropathy (CIN) is an iatrogenic acute renal failure occurring following the intravascular injection of iodinated radiographic contrast medium. However, the regulatory mechanisms for CIN remain to be fully elucidated. The present study aimed to investigate whether atorvastatin protects against CIN via anti­apoptotic effects by the upregulation of Hsp27 in vivo and in vitro. To determine whether atorvastatin attenuated CIN, the inflammatory response and apoptosis in vivo and in vitro, a rat model of iopamidol­induced CIN was used, and human embryonic proximal tubule (HK2) cell damage was assessed. The rats were assigned into four groups (n=10 per group), as follows: Control rats; rats+atorvastatin; rats + iopamidol; rats+iopamidol+atorvastatin. In vitro, the HK2 cells were treated with iopamidol in the presence or absence of atorvastatin, heat shock protein (Hsp)27 small interfering (si)RNA or pcDNA3.1­Hsp27. The renal tissues were examined histopathologically and collected for western blot analysis. The results showed that atorvastatin ameliorated the apoptosis and deterioration of renal function (P<0.05). Furthermore, atorvastatin reduced the iopamidol­induced activity of B cell lymphoma­2 (Bcl­2)­associated X protein (Bax)/caspase­3 and increased the expression of Bcl­2 in vivo and in vitro. Notably, following treatment with Hsp27 siRNA or pcDNA3.1­Hsp27, it was found that iopamidol enhanced or weakened the upregulation of Bax/caspase­3 and downregulation of Bcl­2 in the HK2 cells, respectively. The results of the present study suggested that atorvastatin protected against contrast­induced renal tubular cell apoptosis through the upregulation of Hsp27 in vivo and in vitro.

Preprocedural High-Sensitivity C-Reactive Protein Predicts Contrast-Induced Nephropathy and Long-Term Outcome After Coronary Angiography.

We investigated whether high-sensitivity C-reactive protein (hsCRP) levels were associated with contrast-induced nephropathy (CIN) and long-term mortality after coronary angiography (CAG). Patients (N = 2133) undergoing CAG with preprocedural hsCRP were consecutively enrolled. High-sensitivity C-reactive protein was measured before angiography. Median follow-up was 2.3 years. The overall incidence of CIN was 2.77% (59 of 2133). There was a positive trend of hsCRP quartiles (Q) with rates of CIN: 0.9% for Q1 (<1.6 mg/L), 0.9% for Q2 (1.6-3.9 mg/L), 2.4% for Q3 (4.0-11.3mg/L), and 6.8% for Q4 (>11.3 mg/L; P < .05). The receiver operating characteristic (ROC) analysis showed that the cutoff point of hsCRP was 7.3 mg/L for predicting CIN with a 72.7% sensitivity and a 67.0% specificity (area under the curve [AUC] = 0.742, 95% confidence interval [CI] 0.672-0.810; P < .05). The predictive value of hsCRP was similar to the Mehran score for CIN (AUChsCRP = 0.742 vs AUCMehran = 0.801; P = .228). After adjustment for other potential risk factors, hsCRP >7.3 mg/L still was an independent predictor of CIN (odds ratio [OR] = 2.83, 95% CI: 1.44-5.58; P = .003). Furthermore, hsCRP >7.3 mg/L was associated with higher mortality (OR = 2.04, 95% CI: 1.30-3.19; P = .002).

Excessively High Hydration Volume May Not Be Associated With Decreased Risk of Contrast-Induced Acute Kidney Injury After Percutaneous Coronary Intervention in Patients With Renal Insufficiency.

BACKGROUND: No well-defined protocols currently exist regarding the optimal rate and duration of normal saline administration to prevent contrast-induced acute kidney injury (CI-AKI) in patients with renal insufficiency. METHODS AND RESULTS: Hydration volume ratios (hydration volume/weight; HV/W) were calculated in 1406 patients with renal insufficiency (estimated glomerular filtration rate [eGFR], <90 mL/min per 1.73 m(2)) undergoing percutaneous coronary intervention (PCI) with routine speed hydration (1 or 0.5 mL/kg per hour). We investigated the relationship between hydration volume, risk of CI-AKI (increase in serum creatinine ≥0.5 mg/dL or 25% within 48-72 hours), and prognosis. Mean follow-up duration was 2.85±0.88 years. Individuals with higher HV/W were more likely to develop CI-AKI (quartiles: Q1, Q2, Q3, and Q4: 4.3%, 6.6%, 10.9%, and 15.0%, respectively; P<0.001). After adjusting 12 confounders, including age, sex, eGFR, anemia, emergent PCI, diabetes mellitus, chronic heart failure, diuretics, contrast volume, lesions, smoking status, and number of stents, multivariate analysis showed that a higher HV/W ratio was not associated with a decreased CI-AKI risk (Q2 vs Q1: adjusted odds ratio [OR], 1.13; Q3 vs Q1: adjusted OR, 1.51; Q4 vs Q1: adjusted OR, 1.87; all P>0.05) and even increased CI-AKI risk (HV/W >25 mL/kg: adjusted OR, 2.11; 95% CI, 1.24-3.59; P=0.006). Additionally, higher HV/W was significantly associated with an increased risk of death (Q4 vs Q1: adjusted hazard ratio, 3.44; 95% CI, 1.20-9.88; P=0.022). CONCLUSIONS: Excessively high hydration volume at routine speed might be associated with increased risk of CI-AKI and death post-PCI in patients with renal insufficiency.

Relationship Between the Urine Flow Rate and Risk of Contrast-Induced Nephropathy After Emergent Percutaneous Coronary Intervention.

A low urine flow rate is a marker of acute kidney injury. However, it is unclear whether a high urine flow rate is associated with a reduced risk of contrast-induced nephropathy (CIN) in high-risk patients. We conducted this study to evaluate the predictive value of the urine flow rate for the risk of CIN following emergent percutaneous coronary intervention (PCI). We prospectively examined 308 patients undergoing emergent PCI who provided consent. The predictive value of the 24-hour postprocedural urine flow rate, adjusted by weight (UR/W, mL/kg/h) and divided into quartiles, for the risk of CIN was assessed using multivariate logistic regression analysis. The cumulative incidence of CIN was 24.4%. In particular, CIN was observed in 29.5%, 19.5%, 16.7%, and 32.0% of cases in the UR/W quartile (Q)-1 (≤0.94  mL/kg/h), Q2 (0.94-1.30  mL/kg/h), Q3 (1.30-1.71  mL/kg/h), and Q4 (≥1.71  mL/kg/h), respectively. Moreover, in-hospital death was noted in 7.7%, 3.9%, 5.1%, and 5.3% of patients in Q1, Q2, Q3, and Q4, respectively. After adjusting for potential confounding predictors, multivariate analysis indicated that compared with the moderate urine flow rate quartiles (Q2 + Q3), a high urine flow rate (Q4) (odds ratio [OR], 2.69; 95% confidence interval [CI], 1.27-5.68; P = 0.010) and low urine flow rate (Q1) (OR, 2.23; 95% CI, 1.03-4.82; P = 0.041) were significantly associated with an increased risk of CIN. Moreover, a moderate urine flow rate (0.94-1.71  mL/kg/h) was significantly associated with a decreased risk of mortality. Our data suggest that higher and lower urine flow rates were significantly associated with an increased risk of CIN after emergent PCI, and a moderate urine flow rate (0.94-1.71  mL/kg/h) may be associated with a decreased risk of CIN with a good long-term prognosis after emergent PCI.

Safe limits of contrast vary with hydration volume for prevention of contrast-induced nephropathy after coronary angiography among patients with a relatively low risk of contrast-induced nephropathy.

BACKGROUND: Few studies have investigated the safe limits of contrast to prevent contrast-induced nephropathy (CIN) based on hydration data. We aimed to investigate the relative safe maximum contrast volume adjusted for hydration volume in a population with a relatively low risk of CIN. METHODS AND RESULTS: The ratios of contrast volume-to-creatinine clearance (V/CrCl) and hydration volume to body weight (HV/W) were determined in patients undergoing cardiac catheterization. Receiver-operator characteristic curve analysis based on the maximum Youden index was used to identify the optimal cutoff for V/CrCl in all patients and in HV/W subgroups. Eighty-six of 3273 (2.6%) patients with mean CrCl 71.89±27.02 mL/min developed CIN. Receiver-operator characteristic curve analysis indicated that a V/CrCl ratio of 2.44 was a fair discriminator for CIN in all patients (sensitivity, 73.3%; specificity, 70.4%). After adjustment for other confounders, V/CrCl >2.44 continued to be significantly associated with CIN (adjusted odds ratio, 4.12; P<0.001) and the risk of death (adjusted hazard ratio, 2.62; P<0.001). The mean HV/W was 12.18±7.40. We divided the patients into 2 groups (HV/W ≤12 and >12 mL/kg). The best cutoff value for V/CrCl was 1.87 (sensitivity, 67.9%; specificity, 64.4%; adjusted odds ratio, 3.24; P=0.011) in the insufficient hydration subgroup (HV/W, ≤12 mL/kg; CIN, 1.32%) and 2.93 (sensitivity, 69.0%; specificity, 65.0%; adjusted odds ratio, 3.04; P=0.004) in the sufficient hydration subgroup (HV/W, >12 mL/kg; CIN, 5.00%). CONCLUSIONS: The V/CrCl ratio adjusted for HV/W may be a more reliable predictor of CIN and even long-term outcomes after cardiac catheterization. We also found a higher best cutoff value for V/CrCl to predict CIN in patients with a relatively sufficient hydration status, which may be beneficial during decision-making about contrast dose limits in relatively low-risk patients with different hydration statuses.

Contrast-induced nephropathy following chronic total occlusion percutaneous coronary intervention in patients with chronic kidney disease.

OBJECTIVES: Contrast-induced nephropathy (CIN) has not been systematically studied in high-risk patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). METHODS: We prospectively observed 515 consecutive patients with CKD undergoing PCI. Patients were divided into three groups: patients who underwent attempted PCI for CTO (group A, n = 85), patients who did not receive PCI for CTO (group B, n = 45) and patients without CTO (group C, n = 385). RESULTS: CIN developed in 55 patients (10.68 %). Group A patients received a larger CM dose than group B or group C (p = 0.024). The intravenous hydration volume, age and CIN Mehran score were not significantly different between the three groups. The incidence of CIN was 9.4 % for group A, 6.7 % for group B and 11.4 % for group C (p = 0.344). In-hospital mortality and required renal replacement therapy (p = 0.325) were not significantly different between the groups. Multivariate analysis showed that after adjusting for potential confounding factors, the odds ratio for CIN was 1.03 (p = 0.944) for group A and 0.64 for group B (p = 0.489) compared to group C. CONCLUSIONS: Attempts to achieve recanalization of CTO in patients with CKD might not increase the risk of CIN if appropriate preventative measures are taken. KEY POINTS: • Contrast-induced nephropathy can increase morbidity and mortality • Chronic kidney disease patients are at the greatest risk of CIN • Patients with CKD undergoing CTO-PCI are common • Incidence of CIN has not been reported in CKD patients • CTO-PCI in CKD patients might not increase the risk of CIN.

Preprocedural N-terminal pro-brain natriuretic peptide (NT-proBNP) is similar to the Mehran contrast-induced nephropathy (CIN) score in predicting CIN following elective coronary angiography.

BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) has been associated with important risk factors for contrast-induced nephropathy (CIN). However, few studies have investigated the predictive value of NT-proBNP itself. This study investigated whether levels of preprocedural NT-proBNP could predict CIN after elective coronary angiography as effectively as the Mehran CIN score. METHODS AND RESULTS: We retrospectively observed 2248 patients who underwent elective coronary angiography. The predictive value of preprocedural NT-proBNP for CIN was assessed by receiver operating characteristic and multivariable logistic regression analysis. The 50 patients (2.2%) who developed CIN had higher Mehran risk scores (9.5 ± 5.1 versus 4.8 ± 3.8), and higher preprocedural levels of NT-proBNP (5320 ± 7423 versus 1078 ± 2548 pg/mL, P<0.001). Receiver operating characteristic analysis revealed that NT-proBNP was not significantly different from the Mehran CIN score in predicting CIN (C=0.7657 versus C=0.7729, P=0.8431). An NT-proBNP cutoff value of 682 pg/mL predicted CIN with 78% sensitivity and 70% specificity. Multivariable analysis suggested that, after adjustment for other risk factors, NT-proBNP >682 pg/mL was significantly associated with CIN (odds ratio: 4.007, 95% CI: 1.950 to 8.234; P<0.001) and risk of death (hazard ratio: 2.53; 95% CI: 1.49 to 4.30; P=0.0006). CONCLUSIONS: Preprocedural NT-proBNP >682 pg/mL was significantly associated with the risk of CIN and death. NT-proBNP, like the Mehran CIN score, may be another useful and rapid screening tool for CIN and death risk assessment, identifying subjects who need therapeutic measures to prevent CIN.

[The relationship between hyperuricemia and contrast-induced nephropathy in patients with chronic kidney disease undergoing percutaneous coronary intervention].

OBJECTIVE: To investigate the relationship between hyperuricemia and contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI). METHODS: A total of 446 consecutive patients with CKD undergoing PCI in Guangdong general hospital were enrolled in this study. Patients were divided into hyperuricemic group (n = 205) and normouricemic group (n = 241).Hyperuricemia was defined as serum uric acid > 420 µmol/L for male, > 357 µmol/L for female. CIN was defined as ≥ 44.2 µmol/L or ≥ 25% increase from baseline Serum creatinine within 48-72 hours after contrast medium exposure, and that was not attributable to other causes.In hospital incidences of CIN and the major adverse cardiac events were compared between the two groups. The relationship between the incidence of CIN and hyperuricemia was evaluated by multivariate logistic regression analysis. RESULTS: CIN occurred in 16.6% (74/446) of patients, and incidence of CIN was significantly higher in the hyperuricemic group than in the normouricemic group [23.9% (49/446) vs. 10.4% (25/446) , P = 0.000]. Patients who developed CIN had higher in hospital mortality [14.9% (11/74) vs. 1.3% (5/372), P = 0.000]. Need for renal replacement therapy, acute heart failure, intra-aortic balloon pump use and the hypotension after PCI were significantly higher in the hyperuricemic group compared with normouricemic group (P < 0.01 or P < 0.05) . Multivariate analysis indicates that hyperuricemia (OR = 1.9, 95%CI:1.1-3.5, P = 0.037), age > 75 years (OR = 3.2, 95%CI:1.8-5.7, P = 0.000) , emergent PCI (OR = 2.9, 95%CI:1.6-5.1, P = 0.000) and anemia (OR = 2.1, 95%CI:1.2-3.8, P = 0.012) were predictors of CIN in patients with CKD. CONCLUSION: Hyperuricemia is the independent risk predictor of CIN in patients with CKD undergoing PCI.

[Association between high-sensitivity C-reactive protein and contrast-induced nephropathy after primary percutaneous coronary intervention].

OBJECTIVE: To explore the association between high-sensitivity C-reactive protein (hs-CRP) and contrast-induced nephropathy (CIN) in patients with ST-segment elevated myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) . METHODS: A total of 220 STEMI patients undergoing primary PCI from Guangdong general hospital were recruited. Patients were divided into four groups according to the quartile of hs-CRP (Q1 group:hs-CRP < 6.26 mg/L,Q2 group:6.26-14.44 mg/L, Q3 group:14.45-33.08 mg/L, Q4 group:hs-CRP > 33.08 mg/L) . Baseline data, CIN incidence and other in-hospital outcomes were compared among groups. CIN was defined as an increase in serum creatinine of more than 5 mg/L from baseline within 48-72 hours after contrast media exposure. Receiver operator characteristics (ROC) curves and multivariate logistic regression were used to assessed the correlation between hs-CRP and CIN. RESULTS: CIN occurred in 21 (9.8%) patients. CIN incidence of hs-CRP quartitles were 1.8%(1/55), 1.8% (1/55), 14.5% (8/55) and 20.0% (11/55) (P-trend < 0.01), respectively. In-hospital death (P-trend > 0.05) , required renal replace therapy (P-trend > 0.05) were similar among groups. ROC analysis revealed that the optimal cutoff value of hs-CRP to predict the onset of CIN was 16.85 mg/L (sensitivity: 81.0%, specificity: 61.8%, AUC: 0.748). Univariate logistic analysis showed that hs-CRP was strongly related with CIN incidence (OR = 6.88,95%CI:2.23-21.21, P < 0.01). Multivariate logistic regression analysis showed that after adjusting other traditional risk factors including female gender, anemia, ACEI/ARB use, IABP support, LVEF < 40%, age > 75 years, baseline eGFR and diabetes, hs-CRP > 16.85 mg/L was still a significant independent predictor of CIN in patients with STEMI undergoing primary PCI. Additionally, age > 75 years (OR = 7.27,95%CI:1.85-28.63, P < 0.01), eGFR (OR = 6.38,95% CI:1.48-27.41, P < 0.05) were also independent risk factors of CIN. CONCLUSIONS: hs-CRP is positively correlated with CIN incidence. STEMI patients with higher hs-CRP level post PCI is at higher risk of developing CIN.

[Quantitation of HTLV-I proviral load using real-time quantitative PCR with Taqman MGB probe].

A quantitative real-time PCR assay was developed to measure the proviral load of human T-lymphotropic virus type I (HTLV-I) in peripheral blood. The technology utilizes special primers and Taqman MGB fluorescence probe to measure amplification products from the gag-pro-pol polyprotein gene of HTLV-I. HTLV-I copy number was normalized to the amount of cellular DNA by quantitation of the beta-actin gene, The amplification system was sensitive to detect 5 copy/microL. The standard curve had a good linearity when the quantity for the gene was between 10(3) and 10(7) copy/microL (R2 = 0.999). Good reproducibility was observed in each intra- and inter-assay. We also measured proviral load in peripheral blood in 12 HTLV-I seropositive former blood donors. Proviral load for HTLV-I infected donors ranged from 0.015 to 12.819 copy/cell in WBC with the mean of 3.116 copy/cell.

[Genetic polymorphisms of interferon-gamma and interleukin-8 in patients with nasopharyngeal carcinoma].

OBJECTIVE: To investigate the distribution of genotype and allele frequencies of the genetic polymorphisms of IFN-gamma and IL-8 in patients with nasopharyngeal carcinoma (NPC) and analyze the relationship between the genetic polymorphisms of IFN-gamma and IL-8 and NPC. METHODS: A total of 105 NPC patients and 109 healthy people were recruited in this study. The polymorphism of IL-8-251 locus was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The IFN-gamma CA-repeat polymorphism was determined by polymerase chain reaction and polyacrylamide gel electrophoresis with silver staining. The relationship between the polymorphisms of the two loci and NPC was analyzed. RESULTS: There was no statistically significant difference in IL-8-251(A/T) genotype and allele frequencies between the NPC patients and the healthy people (P < 0.05). The frequency of IFN-gamma 13 times CA repeats in the NPC patients was significantly lower than that of the healthy people (chi2 = 5.878, P = 0.015). A significant difference in the distribution of the genotype of (CA)13+ / (CA)13+, (CA)13+ / (CA)13- and (CA)13- / (CA)13- between the NPC patients and the healthy people was also found (chi2 = 15.181, P = 0.001). CONCLUSION: The IFN-gamma 13 times CA-repeat polymorphism is associated with the onset of NPC. But no association between the polymorphism of IL-8-251 (A/T) locus and NPC is evident. The IFN-gamma CA-repeat polymorphism might play an important role in determining the susceptibility to nasopharyngeal carcinoma.