Balanced Solution versus Normal Saline in Predicted Severe Acute Pancreatitis: A Stepped Wedge Cluster Randomized Trial.

OBJECTIVE: To compare the effect of balanced multielectrolyte solutions(BMES) versus normal saline(NS) for intravenous fluid on chloride levels and clinical outcomes.in patients with predicted severe acute pancreatitis (pSAP). SUMMARY BACKGROUND DATA: Isotonic crystalloids are recommended for initial fluid therapy in acute pancreatitis, but whether the use of BMES in preference to NS confers clinical benefits is unknown. METHODS: In this multicenter, stepped-wedge, cluster-randomized trial, we enrolled patients with pSAP (APACHE II score ≥8 and C-reactive protein >150 mg/L) admitted within 72 hours of the advent of symptoms. The study sites were randomly assigned to staggered start dates for one-way crossover from the NS phase (NS for intravenous fluid) to the BMES phase(Sterofudin for intravenous fluid). The primary endpoint was the serum chloride concentration on trial day3. Secondary endpoints included a composite of clinical and laboratory measures. RESULTS: Overall, 259 patients were enrolled from eleven sites to receive NS(n=147) or BMES(n=112). On trial day3, the mean chloride level was significantly lower in patients who received BMES(101.8 mmol/L(SD4.8) versus 105.8 mmol/L(SD5.9), difference -4.3 mmol/L [95%CI -5.6 to -3.0 mmol/L];P<0.001). For secondary endpoints, patients who received BMES had less systemic inflammatory response syndrome(19/112,17.0% versus 43/147,29.3%, P=0.024) and increased organ failure-free days (3.9 d(SD2.7) versus 3.5days(SD2.7), P<0.001) by trial day7. They also spent more time alive and out of ICU(26.4 d(SD5.2) versus 25.0days(SD6.4), P=0.009) and hospital(19.8 d(SD6.1) versus16.3days(SD7.2), P<0.001) by trial day30. CONCLUSIONS: Among patients with pSAP, using BMES in preference to NS resulted in a significantly more physiological serum chloride level, which was associated with multiple clinical benefits(Trial registration number: ChiCTR2100044432).

The Impact of Normal Saline or Balanced Crystalloid on Plasma Chloride Concentration and Acute Kidney Injury in Patients With Predicted Severe Acute Pancreatitis: Protocol of a Phase II, Multicenter, Stepped-Wedge, Cluster-Randomized, Controlled Trial.

Introduction/aim: The supraphysiologic chloride concentration of normal saline may contribute to acute kidney injury (AKI). Balanced crystalloids can decrease chloride concentration and AKI in critically ill patients. We aim to test the hypothesis that, in patients with predicted severe acute pancreatitis (pSAP), compared with saline, fluid therapy with balanced crystalloids will decrease plasma chloride concentration. Methods/Design: This is a multicenter, stepped-wedge, cluster-randomized, controlled trial. All eligible patients presenting to the 11 participating sites across China during the study period will be recruited. All sites will use saline for the first month and sequentially change to balanced crystalloids at the pre-determined and randomly allocated time point. The primary endpoint is the plasma chloride concentration on day 3 of enrollment. Secondary endpoints will include major adverse kidney events on hospital discharge or day 30 (MAKE 30) and free and alive days to day 30 for intensive care admission, invasive ventilation, vasopressors, and renal replacement therapy. Additional endpoints include daily serum chloride and sequential organ failure assessment (SOFA) score over the first seven days of enrollment. Discussion: This study will provide data to define the impact of normal saline vs. balanced crystalloids on plasma chloride concentration and clinical outcomes in pSAP patients. It will also provide the necessary data to power future large-scale randomized trials relating to fluid therapy. Ethics and Dissemination: This study was approved by the ethics committee of Jinling Hospital, Nanjing University (2020NZKY-015-01) and all the participating sites. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences. Trial registration: The trial has been registered at the Chinese Clinical Trials Registry (ChiCTR2100044432).

RGL2 as an age-dependent factor regulates colon cancer progression.

Colon cancer is the fourth leading cause of cancer-related death, and exhibited clinical differences among patients of different ages, including malignancy, metastasis, and mortality rate. Few studies, however, focus on the communications between aging and colon cancer. Here we identified age-dependent differentially expressed genes (DEGs) in colon cancer using TCGA transcriptome data. Through analyzing multi-omics high throughput data, including ATAC-Seq, DNaseI-Seq and ChIP-Seq, we obtained six age-dependent transcription factors in colon cancer, and their age-dependent targets, significantly affecting patients' overall survivals. Transcription factor ETS1 potentially functioned in both aging process and colon cancer progression through regulating its targets, RGL2 and SLC2A3. In addition, comparing with its relative lower expression levels in elderly patients, higher levels of RGL2 were detected in young patients, and significantly associated with larger tumor size, higher metastasis, and invasions of colon cancer, consistent with the clinical traits that young patients' colon cancer exhibited late stages with more aggressiveness. Thus, these elements may serve as keys linking aging and colon cancer, and providing new insights and basis for mechanism researches, as well as diagnosis and therapies of colon cancer, especially in young patients.

Alterations of coagulation and fibrinolysis in patients with blunt splenic injury after splenic artery embolization.

BACKGROUND: Thrombotic complications following splenectomy have been documented. However, there has been sparse literature regarding thrombotic complications following splenic artery embolization (SAE).The objective of this study was to determine changes in coagulation and fibrinolysis and assess the thrombotic risk after SAE in patients with blunt splenic injury (BSI). METHODS: This study included 38 BSI patients who were hemodynamically stable on admission. SAE was performed if the splenic injury was classed as grade III or greater and had no requirement of immediate surgery. Platelet (PLT), fibrinogen (FIB), D-dimers (D-D), fibrinogen/fibrin degradation products (FDP), antithrombin III (AT III), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), hemoglobin (Hb), and hematocrit (Hct) were measured before SAE procedures and then 1d, 3d, and 7d after SAE. RESULTS: The technical success rate of SAE and the splenic salvage rate were 100%. There was no mortality. Compared with pre-SAE values, the levels of PLT, FIB, D-D, and FDP increased significantly at 3 days and 7 days after SAE (p < 0.05). However, AT III, PT, APTT, TT, Hb, and Hct showed no statistically significant difference at 1d, 3d, and 7d after SAE (p > 0.05). CONCLUSION: Alterations in PLT and hemostatic parameters might contribute to the increased risk of thrombotic complications in BSI patients undergoing SAE. Thromboembolism following SAE should be considered and thrombotic prophylaxis should be recommended.

Hepatocellular Carcinoma-propagating Cells are Detectable by Side Population Analysis and Possess an Expression Profile Reflective of a Primitive Origin.

The recent identification of "Side Population" (SP) cells in a number of unrelated human cancers has renewed interests in the hypothesis of cancer stem cells. Here we isolated SP cells from HepG2 cells and 18 of the 21 fresh hepatocellular carcinoma (HCC) tissue samples. These SP cells have higher abilities of forming spheroids, invasion and migration. Tumors could generate only from SP, not non-SP (NSP), cells in a low dose of subcutaneous injection to the NOD/SCID mice (5 × 102 cells/mouse). The mRNA microarray analysis of the SP vs. NSP cells isolated from HepG2 cells revealed that the SP cells express higher levels of pluripotency- and stem cell-associated transcription factors including Klf4, NF-Ya, SALL4 and HMGA2. Some of the known hepatobiliary progenitor/stem cell markers, such as Sox9 was also up-regulated. RT-qPCR analysis of the gene expression between SP cells and NSP cells isolated from both HepG2 cells and HCC tissue samples showed that most of the tested mRNAs' changes were in consistent with the microarray data, including the general progenitor/stem cells markers such as Klf4, NF-Ya, SALL4 and HMGA2, which were up-regulated in SP cells. Our data indicates that HCC cancer stem cells exist in HepG2 and HCC fresh tissue samples and can be isolated by SP assay.

High-level expression of periostin is closely related to metastatic potential and poor prognosis of hepatocellular carcinoma.

Periostin (PN) is a kind of secreted glycoprotein, which is closely related to the metastatic potential and prognosis of many kinds of tumors in recent studies. However, the expression level of PN in hepatocellular carcinoma (HCC) and its correlation with tumor angiogenesis and prognosis remain unclear. Here Immunohistochemistry assay was used to determine the expression of PN in HCC and corresponding adjacent tissues from 71 patients. VEGF and CD34 were only examined in HCC tissues of patients mentioned above. Immunohistochemically, the expression of PN in HCC was judged to be positive in 73.2 % (52/71) compared with 19.7 % (14/71) in corresponding adjacent tissues, and it was associated with tumor nodules (P = 0.070), microvascular invasion (P = 0.013), Edmondson grade (P = 0.003), tumor capsula (P = 0.038) and TNM stage (P = 0.000); besides, tumors with PN-positive group expressed higher VEGF (82.7 vs. 26.3 %, χ (2) = 20.195, P = 0.000) and had higher MVD (80.5 ± 36.5 vs. 24.0 ± 19.9, t = -6.395, P = 0.000) than those in PN-negative group. Kaplan-Meier method was used for survival analysis, and Cox regression model was performed for multivariate survival analysis. In particular, the expression of PN was found to be an independent factor for predicting overall and disease-free survival of HCC. It is possible that the expression level of PN in HCC is associated with tumor metastatic potential and angiogenesis. Its abnormal expression could be a predictive factor to anticipate HCC patient's prognosis after surgery.