[Occurrence and prediction on post-contrast acute kidney injury following endovascular interventions].

Objective: To investigate the incidence, risk factors and prognosis of post-contrast acute kidney injury (PC-AKI) and to evaluate the usefulness of serum cystatin C (sCysC) and serum creatinine (sCr) for the prediction of PC-AKI after endovascular interventions. Methods: The clinical data of 404 patients who underwent endovascular procedures from August 2014 to October 2018 in the Sixth People's Hospital South Campus, Shanghai Jiao Tong University were retrospectively analyzed. All patients received 0.9% sodium chloride through an angiographic catheter during the procedure. Patients with an estimated GFR (eGFR)<60 ml/(min·1.73m2) received a continuous intravenous hydration with isotonic saline from 6 hours before to 12 hours after an endovascular procedure. The level of sCr, eGFR and sCysC were measured at 1-2 days pre-procedure and at 48, 72 h, and 7 days post-procedure. Univariate and multivariate logistic regression analyses were used to identify risk factors of PC-AKI. A receiver operator characteristic (ROC) curve was used to evaluate the usefulness of various factors for the prediction of PC-AKI. Kaplan-Meier method was used for survival analysis. Results: Thirteen patients (3.2%) developed PC-AKI. All patients were divided into PC-AKI group and no PC-AKI group for statistical comparison. Wilcoxon signed rank sum test revealed that sCr levels at 7 days post-procedure [63.0 (56.0, 74.0) µmol/L] were significantly lower than pre-procedure sCr levels [65.6 (56.2, 77.0) µmol/L] in patients without PC-AKI (P<0.05). Meanwhile, eGFR levels were significantly higher at 72 h [114.9 (96.3, 135.0) ml/(min·1.73m2)] and 7 days [116.7 (98.5, 139.9) ml/(min·1.73m2)] post-procedure than eGFR levels before endovascular procedures [112.3 (94.1, 133.5) ml/(min·1.73m2)] in patients without PC-AKI (P<0.05). However, there was an increase in sCysC at 48 h [0.9 (0.8, 1.1) mg/L] after endovascular procedures than pre-operative sCysC [0.9 (0.8, 1.1) mg/L] in patients without PC-AKI (P<0.05). SCr, sCysC, levels were significantly increased at 48 h [108.0 (95.3, 125.0) µmol/L, 1.5 (1.2, 2.0) mg/L] and 72 h [123.4 (91.3, 143.0) µmol/L, 1.6 (1.1, 2.0) mg/L] post-procedure than SCr, sCysC, levels before endovascular procedures [81.6 (63.1, 111.0) µmol/L, 1.1 (1.0,1.7) mg/L] and eGFR levels were significantly decreased at 48 h [55.8 (48.9, 77.6) ml/(min·1.73m2)] and 72 h [52.7 (47.7, 63.9) ml/(min·1.73m2)] after endovascular procedures than eGFR levels before exposure to CM [88.8 (65.6, 100.7) ml/(min·1.73m2)] in patients with PC-AKI (P<0.05). SCr, sCysC and eGFR in PC-AKI group tended to levels before an endovascular procedure within 7 days. The receiver operator characteristic curve (ROC) analysis showed that preoperative sCysC and sCr levels had high discriminatory power for evaluating the risk of PC-AKI after an endovascular procedure. ROC analysis showed that sCysC before endovascular procedures was useful to predict the risk of PC-AKI with a satisfactory sensitivity of 69.2% (9/13), specificity of 77.5% (300/387), positive predictive value (PPV) of 9.3% (9/96) and negative predictive value (NPV) of 98.7% (300/304). The incidence of PC-AKI was low in patients with a pre-procedure sCysC<1.09 mg/L. The sCr was predictive of PC-AKI with a satisfactory sensitivity of 69.2% (9/13), specificity of 76.7% (300/391), PPV of 9.0% (9/100) and NPV of 98.7% (300/304). The incidence of PC-AKI was low in patients with a pre-procedure sCr<77.6 µmol/L. Results of univariate analysis and multiple logistic regression analysis indicated that sCysC before endovascular procedures was an risk factor for PC-AKI (OR=13.917, 95%CI:1.666-116.237, P=0.015). The one-year, three-year and five-year survival rate for patients diagnosed with PC-AKI was 50%, 30% and 30% respectively. The median survival time was 6 (0-26) months. Conclusions: The sCysC before endovascular procedures is an independent risk factor of PC-AKI. SCysC and SCr before an endovascular procedure with a cut-off value of 1.09 mg/L and 77.6 µmol/L may help to rule out patients at lower risk of PC-AKI.

Infiltrating immune cells and gene mutations in pancreatic ductal adenocarcinoma.

BACKGROUND: The aim of this study was to assess the immune profile within the microenvironment of pancreatic ductal adenocarcinoma (PDAC), and to investigate the prognostic value of intratumoral infiltrating immune/inflammatory cells (IICs) in patients after surgery. METHODS: Eighteen phenotypic markers representing 11 types of IIC and the protein products of genes TP53, CDKN2A/p16 and SMAD4/DPC4 were assessed by immunohistochemistry of specimens from patients with pancreatic cancer. The expression of IICs and the mutational status of the genes were correlated with tumour recurrence and survival, and results were validated in an independent cohort. RESULTS: CD15+ neutrophils, CD20+ B cells and CD206+ tumour-associated macrophages were seen frequently in tumours, and their presence was associated with reduced survival in a cohort of 79 patients. Expression of CD4+ T helper cells, CD8+ cytotoxic T lymphocytes and CD117+ mast cells was associated with a favourable prognosis. A weighted Cox regression recurrence-predictive model was constructed that showed good correlation of IICs and gene mutations. A combination of CD15, CD206, CD117 and Smad4 expression was independently associated with overall (hazard ratio (HR) 3·63, 95 per cent c.i. 2·18 to 6·04; P < 0·001) and recurrence-free (HR 2·93, 1·81 to 4·75; P < 0·001) survival. These findings were validated in an independent cohort (151 patients) and in 54 tissue samples obtained by preoperative endoscopic ultrasound-guided fine-needle aspiration. CONCLUSION: PDAC has a unique immunosuppressive phenotype that is associated with characteristic gene mutations, disease recurrence and survival after pancreatectomy. Surgical relevance The immune microenvironment plays a critical role in the development of pancreatic ductal adenocarcinoma (PDAC). PDAC is associated with mutations in major driver genes, including KRAS, TP53, CDKN2A/p16 and SMAD4/DPC4. This study shows that the microenvironment of PDAC has a unique immunosuppressive phenotype, which may be driven by oncogene mutations. Patients with PDAC with a highly immunosuppressive profile tended to have poor postoperative survival. A model including three intratumoral infiltrating immune markers (CD15+, CD206+ and CD117+) and a SMAD4 mutation can be used to predict recurrence and survival in patients after surgery for PDAC.

Solid state 27Al NMR investigation of Knight shift tensors of LnAl2 (Ln = Y, La and Lu) and correlation with DFT calculations.

The atomic and electronic structures of LnAl(2) (Ln=Y, La and Lu) on Al sites were characterized by (27)Al solid state NMR spectroscopy. (27)Al isotropic metallic shifts have been determined in these cubic laves phases under both static and magic angle spinning (MAS) conditions. Based on band structure calculations, we found a strong correlation of (27)Al isotropic metallic shifts and s character of the density of states at the Fermi level on Al sites. We also found tetrahedral distortion of Al centered clusters, which can be well characterized by quadruple coupling constants and Knight shift anisotropy.

NMR signature of evolution of ductile-to-brittle transition in bulk metallic glasses.

The mechanical properties of monolithic metallic glasses depend on the structures at atomic or subnanometer scales, while a clear correlation between mechanical behavior and structures has not been well established in such amorphous materials. In this work, we find a clear correlation of (27)Al NMR isotropic shifts with a microalloying induced ductile-to-brittle transition at ambient temperature in bulk metallic glasses, which indicates that the (27)Al NMR isotropic shift can be regarded as a structural signature to characterize plasticity for this metallic glass system. The study provides a compelling approach for investigating and understanding the mechanical properties of metallic glasses from the point of view of electronic structure.