hartmannii were aligned with P. schwartzii and P. kofoidii but was not observed in the alignment between P. hartmannii and P. lebourae. Using scanning electron microscopy, several morphological features previously not reported for P. hartmannii were observed: a ventral groove located in the sulcus, a deep arc-like apical concavity within the area of apical groove, scale-like vesicles, and a shallow, completely enclosed, loop-like apical groove. Resting cysts with arrow-like surface spines were produced heterothallically by crossing clonal isolates and germinated single gymnoid cells. Finally, filtered and unfiltered bloom water from

the Forge River and clonal cultures of P. hartmannii exhibited acute ichthyotoxicity to juvenile sheepshead minnows (Cyprinodon variegates) and aeration did not mitigate this effect, suggesting P. hartmannii buy HKI-272 is an ichthyotoxic, harmful alga. “
“The preference of phytoplankton for ammonium over nitrate has traditionally been explained by the greater metabolic

cost of reducing oxidized forms of nitrogen. This “metabolic cost hypothesis” implies that there should be a growth disadvantage on nitrate compared to ammonium or other forms of reduced nitrogen such as urea, especially when light limits growth, but in a variety of phytoplankton taxa, this predicted difference has not been observed. Our experiments with three strains of marine Synechococcus (WH7803, WH7805, and WH8112) did not reveal consistently faster growth (cell division) on ammonium or urea as compared to nitrate. Urease and glutamine synthetase (GS) activities varied with nitrogen source in a manner consistent with regulation AZD6244 in vitro by cellular nitrogen status via NtcA (rather than by external availability of nitrogen) in all three strains and indicated that each strain experienced some degree of nitrogen insufficiency during growth MCE公司 on nitrate. At light intensities that strongly limited growth, the composition (carbon, nitrogen, and pigment quotas) of WH7805 cells using nitrate was indistinguishable

from that of cells using ammonium, but at saturating light intensities, cellular carbon, nitrogen, and pigment quotas were significantly lower in cells using nitrate than ammonium. These and similar results from other phytoplankton taxa suggest that a limitation in some step of nitrate uptake or assimilation, rather than the extra cost of reducing nitrate per se, may be the cause of differences in growth and physiology between cells using nitrate and ammonium. “
“The last two decades have witnessed increasing episodes of lesser flamingo die-offs in East Africa. Based on data on phytoplankton composition, biomass, and flamingo population density in three alkaline-saline lakes of Kenya (Bogoria, Nakuru, and Oloidien) in 2001–2010, this study explored the link between sudden flamingo deaths and fluctuations in algal food quantity and quality. The phytoplankton biomass ranged from 13 to 768 mg · L−1.

05), but there was no significant differences exsist between pre treatment and post treatment in SAP patients (P > 0.05). Conclusion: CRP probably will predict the prognosis and the severity of patients with SAP early, and can be used as the prognosis Bortezomib index at the same time. It is worth to popularized and applicated. Key Word(s): 1. Acute pancreatitis; 2. C reactive protein; 3. Diagnostic value; 4. prognosis; Presenting Author: ZHAOBAO MIN Additional Authors: GUBING QUAN, LING XIAO, CHEN XI Corresponding

Author: ZHAOBAO MIN Affiliations: The Fourth Military Medical University; The Fourth Military Medical University Objective: To investigate the effect of genistein derived from soybean on rats with acute pancreatitis. Methods: 45 SD rats were randomly divided into 3 groups: three groups adopt arginine (2-amino-5-guanidinovaleric acid) acute pancreatitis model was induced by intraperitoneal injection, 3-Methyladenine in vitro Control group were intragastric administration through the mouth in 100 g/kg soybean protein three times every day; Model groups were intragastric administration by in 2 ml in normal saline; Genistein groups was given 5, 7, 4′-triatomic isoflavone intragastric administration through the mouth in 100 mg/kg. Observation rat survival and death within 72 h of situation; Detecting survival rats 24 h, 48 h, 72 h of serum amylase levels, pancreatic tissue pathological index score

is calculated. Results: Soybean protein group 6 h mortality rates is highest at 53%; Three hydroxyl groups of isoflavones 6 h cumulative mortality rate is only 6.7%, to 24 h for peak mortality (33.3%), compared with soybean protein group was significantly delayed, mortality in both groups had significant difference (p < 0.01). Three hydroxyl groups of isoflavones survival rats 24 h, 48 h, 72 h serum amylase activity was significantly lower than soybean protein group (1830 + 325 vs. 2667 + 262 U/L, p < 0.01), (1744 + 321 vs. 2935 + 301 U/L, p < 0.01), (1319 + 338 vs.

2725 + 235 U/L, p < 0.05). Conclusion: Through stomach perfusion genistein can delay the peak of death of rats with acute pancreatitis, improve the survival rate of rats, and inhibit the serum pancreatic amylase activity, probably by reduce pancreatic inflammation and play an important role. Key Word(s): 1. 上海皓元 Acute pancreatitis; 2. Genistein; 3. Soybean protein; 4. Rats; Presenting Author: LI HONG-YU Additional Authors: ZHANG NINGNING, LIU XU, LIU WEI-WEI, ZHANG YAN-LIN, GUO XIAO-ZHONG Corresponding Author: GUO XIAO-ZHONG Affiliations: General Hospital of Shenyang Military Area Command Objective: To investigate the reasons why serum amylase did not drop in the patients with mild acute pancreatitis, and provide reference for prevention and treatment of mild acute pancreatitis. Methods: The clinical data of 307 cases with mild acute pancreatitis in our hospital were retrospectively analyzed.

05), but there was no significant differences exsist between pre treatment and post treatment in SAP patients (P > 0.05). Conclusion: CRP probably will predict the prognosis and the severity of patients with SAP early, and can be used as the prognosis Doramapimod concentration index at the same time. It is worth to popularized and applicated. Key Word(s): 1. Acute pancreatitis; 2. C reactive protein; 3. Diagnostic value; 4. prognosis; Presenting Author: ZHAOBAO MIN Additional Authors: GUBING QUAN, LING XIAO, CHEN XI Corresponding

Author: ZHAOBAO MIN Affiliations: The Fourth Military Medical University; The Fourth Military Medical University Objective: To investigate the effect of genistein derived from soybean on rats with acute pancreatitis. Methods: 45 SD rats were randomly divided into 3 groups: three groups adopt arginine (2-amino-5-guanidinovaleric acid) acute pancreatitis model was induced by intraperitoneal injection, selleck chemical Control group were intragastric administration through the mouth in 100 g/kg soybean protein three times every day; Model groups were intragastric administration by in 2 ml in normal saline; Genistein groups was given 5, 7, 4′-triatomic isoflavone intragastric administration through the mouth in 100 mg/kg. Observation rat survival and death within 72 h of situation; Detecting survival rats 24 h, 48 h, 72 h of serum amylase levels, pancreatic tissue pathological index score

is calculated. Results: Soybean protein group 6 h mortality rates is highest at 53%; Three hydroxyl groups of isoflavones 6 h cumulative mortality rate is only 6.7%, to 24 h for peak mortality (33.3%), compared with soybean protein group was significantly delayed, mortality in both groups had significant difference (p < 0.01). Three hydroxyl groups of isoflavones survival rats 24 h, 48 h, 72 h serum amylase activity was significantly lower than soybean protein group (1830 + 325 vs. 2667 + 262 U/L, p < 0.01), (1744 + 321 vs. 2935 + 301 U/L, p < 0.01), (1319 + 338 vs.

2725 + 235 U/L, p < 0.05). Conclusion: Through stomach perfusion genistein can delay the peak of death of rats with acute pancreatitis, improve the survival rate of rats, and inhibit the serum pancreatic amylase activity, probably by reduce pancreatic inflammation and play an important role. Key Word(s): 1. medchemexpress Acute pancreatitis; 2. Genistein; 3. Soybean protein; 4. Rats; Presenting Author: LI HONG-YU Additional Authors: ZHANG NINGNING, LIU XU, LIU WEI-WEI, ZHANG YAN-LIN, GUO XIAO-ZHONG Corresponding Author: GUO XIAO-ZHONG Affiliations: General Hospital of Shenyang Military Area Command Objective: To investigate the reasons why serum amylase did not drop in the patients with mild acute pancreatitis, and provide reference for prevention and treatment of mild acute pancreatitis. Methods: The clinical data of 307 cases with mild acute pancreatitis in our hospital were retrospectively analyzed.

05), but there was no significant differences exsist between pre treatment and post treatment in SAP patients (P > 0.05). Conclusion: CRP probably will predict the prognosis and the severity of patients with SAP early, and can be used as the prognosis selleck screening library index at the same time. It is worth to popularized and applicated. Key Word(s): 1. Acute pancreatitis; 2. C reactive protein; 3. Diagnostic value; 4. prognosis; Presenting Author: ZHAOBAO MIN Additional Authors: GUBING QUAN, LING XIAO, CHEN XI Corresponding

Author: ZHAOBAO MIN Affiliations: The Fourth Military Medical University; The Fourth Military Medical University Objective: To investigate the effect of genistein derived from soybean on rats with acute pancreatitis. Methods: 45 SD rats were randomly divided into 3 groups: three groups adopt arginine (2-amino-5-guanidinovaleric acid) acute pancreatitis model was induced by intraperitoneal injection, Roxadustat molecular weight Control group were intragastric administration through the mouth in 100 g/kg soybean protein three times every day; Model groups were intragastric administration by in 2 ml in normal saline; Genistein groups was given 5, 7, 4′-triatomic isoflavone intragastric administration through the mouth in 100 mg/kg. Observation rat survival and death within 72 h of situation; Detecting survival rats 24 h, 48 h, 72 h of serum amylase levels, pancreatic tissue pathological index score

is calculated. Results: Soybean protein group 6 h mortality rates is highest at 53%; Three hydroxyl groups of isoflavones 6 h cumulative mortality rate is only 6.7%, to 24 h for peak mortality (33.3%), compared with soybean protein group was significantly delayed, mortality in both groups had significant difference (p < 0.01). Three hydroxyl groups of isoflavones survival rats 24 h, 48 h, 72 h serum amylase activity was significantly lower than soybean protein group (1830 + 325 vs. 2667 + 262 U/L, p < 0.01), (1744 + 321 vs. 2935 + 301 U/L, p < 0.01), (1319 + 338 vs.

2725 + 235 U/L, p < 0.05). Conclusion: Through stomach perfusion genistein can delay the peak of death of rats with acute pancreatitis, improve the survival rate of rats, and inhibit the serum pancreatic amylase activity, probably by reduce pancreatic inflammation and play an important role. Key Word(s): 1. MCE Acute pancreatitis; 2. Genistein; 3. Soybean protein; 4. Rats; Presenting Author: LI HONG-YU Additional Authors: ZHANG NINGNING, LIU XU, LIU WEI-WEI, ZHANG YAN-LIN, GUO XIAO-ZHONG Corresponding Author: GUO XIAO-ZHONG Affiliations: General Hospital of Shenyang Military Area Command Objective: To investigate the reasons why serum amylase did not drop in the patients with mild acute pancreatitis, and provide reference for prevention and treatment of mild acute pancreatitis. Methods: The clinical data of 307 cases with mild acute pancreatitis in our hospital were retrospectively analyzed.

Unsupervised hierarchical clustering analysis revealed two main branches. All eight cluster-A ICC samples were grouped with epithelial cell adhesion molecule (EpCAM)+AFP+ HCC cases previously identified having a stem cell-like gene expression trait, whereas all eight cluster-B ICC samples were grouped with EpCAM−AFP−

HCC cases with a mature hepatocyte-like gene expression trait (Fig. S2A).9 Similar results were obtained when ICC/CHC cases were compared to a second group of 23 randomly selected HCC cases (Fig. S2B). Seven CHC cases were split among two clusters. For the convenience of keeping track of these ICC samples, we refer to ICC cases in cluster-A as HpSC-ICC (i.e., hepatic stem cell-like ICC) and those in cluster-B as MH-ICC (i.e., mature hepatocyte-like ICC).

These results indicate that both ICC and HCC are heterogeneous and their Selleckchem Kinase Inhibitor Library subgroups share similar gene expression profiles. Next, we performed a class comparison analysis and identified 636 genes that are differentially expressed between eight HpSC-ICC and eight MH-ICC cases (univariate P < Everolimus research buy 0.01; false discovery rate [FDR] <0.2) (Table S2). We then tested whether this 636 ICC-specific gene signature could independently classify HCC cases based on HpSC-like or MH-like features. We tested the robustness of the signature to discriminate HpSC-HCC from MH-HCC cases by examining 61 well-defined extreme HCC cases or x-HCC, i.e., those with top quartile EpCAM expression in 上海皓元医药股份有限公司 HCC tissues and with >1,000 ng/mL of serum alpha-fetoprotein (AFP) levels versus those with bottom quartile EpCAM expression and with <20 ng/mL of serum AFP levels (Table S1). Hierarchical clustering analysis revealed that the 636 ICC-specific genes could nicely divide x-HpSC and x-MH HCC cases (Fig. 1C) and were associated with HCC survival (Fig. 1D). This 636 ICC-specific gene signature was also associated with survival in 139 remaining unstratified HCC cases from the original 246 HCC cases after

excluding 46 randomly selected HCC cases and 61 extreme HCC cases used in the initial clustering analysis (Fig. S2C). Venn diagram analysis indicated that 158 of 636 ICC-specific genes (25%) overlapped with previously identified stem-like HCC genes (Fig. 1E). Consistent with the data in Fig. 1C, 158 overlapping genes could significantly discriminate stem-like HCC cases from mature hepatocyte-like HCC cases (P < 0.0001) and was associated with HCC survival (P = 0.031) (Fig. S3). The above data indicate that ICC cases could be classified into two main subtypes that are associated with stem-like or mature hepatocyte like gene expression traits, respectively, and that ICC and HCC may share common gene expression profiles reflecting their cellular origins. We used the NanoString nCounter microRNA Expression Assay platform to independently examine gene expression profiles of the same 23 ICC and CHC samples used above.

Disclosures: Velimir A. Luketic – Grant/Research Support: Intercept, Merck, Idenix, Vertex, Gilead, BMS, Novartis, abbvie, Genfit, Takeda Joseph A. Odin – Advisory Committees or Review Panels: Bristol Meyers Squibb, AbbVie Kris V. Kowdley – Advisory Committees or Review Panels: AbbVie, Gilead, Merck, Novartis, Trio Health, Boeringer Ingelheim, Ikaria, Janssen; Grant/Research Support: AbbVie, Beckman, Boeringer Ingelheim, BMS, Gilead Sciences, Ikaria, Janssen, Merck, Mochida, Vertex Gideon M. Hirschfield – Advisory Committees or Review Panels: Centocor/J&J, Medigene, Intercept, Falk Pharma ; Consulting: Lumena, Intercept

Naga P. Chalasani – Consulting: Salix, Abbvie, Lilly, Boerhinger-Ingelham, Aege-rion; Grant/Research Support: MLN8237 in vitro Intercept, Lilly, Gilead, Cumberland, Galectin The following people have nothing to disclose: John E. Eaton, Brian D. Juran, Elizabeth J. Atkinson, Erik M. Schlicht, Selleckchem OSI-906 Xiao Xie, Mariza de Andrade, Craig Lammert, Ayman A. Koteish, Kapil B. Chopra, Konstantinos Lazaridis Background: Effective medical therapies for PSC are needed. Moderate dose UDCA improves serum biochemistry but does not change the disease course. ATRA can activate FXR (farnesoid X receptor) and RXR (retinoid X receptor) and repress CYP7A1 and bile acid synthesis in human hepatocytes.

In animal models of biliary injury ATRA improved hepatic inflammation and fibrosis when combined with UDCA (He et al. Hepatology 2011; Cai MCE公司 et al. J. Pharm. Exp. Ther. 2014). Aim: To determine if ATRA + UDCA improve serum parameters of cholestasis in PSC patients with alkaline phosphatase (AP) >1.5xULN despite moderate-dose UDCA for ≥6 months. Methods: Patients were enrolled at Yale and Mayo Liver Clinics. ATRA capsules were compounded and dosed at 45 mg/m2/ day divided b.i.d.. Combination therapy was given for 12 weeks followed by a 12-week washout. Baseline labs were compared to the end-of-treatment and to washout. Results: Twenty-one subjects were screened and 19 enrolled. Mean age was 45±11 years, 74% Caucasian and 74% male; 63% had large duct vs. 37% with small-duct PSC, 79% had IBD and median Mayo PSC Risk Score was −0.03±0.7. Mean UDCA

dose was 18±6 mg/kg/day. Fifteen subjects completed 12 weeks of therapy. Mean AP significantly declined (356±209 vs. 318±225 U/L, p=0.046); 20% achieved ≥30% reduction. Interestingly, mean alanine aminotransferase (ALT) also declined (94±55 vs. 56±32 U/L, p=0.007) along with serum bile acid levels (41±52 vs. 28±45 umol/L, p=0.04). Mean LDL (131±60 vs. 155±51 mg/dL, p=0.055) and triglyceride (86±31 vs. 145±45 mg/dL, p=0.003) levels increased while HDL decreased (61±21 vs. 41±11 mg/dL, p=0.01). Mean serum levels of bile acid intermediate 7a-hydroxy-4-cholesten-3-one (C4) significantly decreased (17±19 vs. 9±11 ng/mL, p=0.04) indicating that ATRA inhibited bile acid synthesis. There was no difference in bilirubin or peripheral regulatory T cell frequency.

Disclosures: Velimir A. Luketic – Grant/Research Support: Intercept, Merck, Idenix, Vertex, Gilead, BMS, Novartis, abbvie, Genfit, Takeda Joseph A. Odin – Advisory Committees or Review Panels: Bristol Meyers Squibb, AbbVie Kris V. Kowdley – Advisory Committees or Review Panels: AbbVie, Gilead, Merck, Novartis, Trio Health, Boeringer Ingelheim, Ikaria, Janssen; Grant/Research Support: AbbVie, Beckman, Boeringer Ingelheim, BMS, Gilead Sciences, Ikaria, Janssen, Merck, Mochida, Vertex Gideon M. Hirschfield – Advisory Committees or Review Panels: Centocor/J&J, Medigene, Intercept, Falk Pharma ; Consulting: Lumena, Intercept

Naga P. Chalasani – Consulting: Salix, Abbvie, Lilly, Boerhinger-Ingelham, Aege-rion; Grant/Research Support: PLX3397 mouse Intercept, Lilly, Gilead, Cumberland, Galectin The following people have nothing to disclose: John E. Eaton, Brian D. Juran, Elizabeth J. Atkinson, Erik M. Schlicht, Olaparib Xiao Xie, Mariza de Andrade, Craig Lammert, Ayman A. Koteish, Kapil B. Chopra, Konstantinos Lazaridis Background: Effective medical therapies for PSC are needed. Moderate dose UDCA improves serum biochemistry but does not change the disease course. ATRA can activate FXR (farnesoid X receptor) and RXR (retinoid X receptor) and repress CYP7A1 and bile acid synthesis in human hepatocytes.

In animal models of biliary injury ATRA improved hepatic inflammation and fibrosis when combined with UDCA (He et al. Hepatology 2011; Cai medchemexpress et al. J. Pharm. Exp. Ther. 2014). Aim: To determine if ATRA + UDCA improve serum parameters of cholestasis in PSC patients with alkaline phosphatase (AP) >1.5xULN despite moderate-dose UDCA for ≥6 months. Methods: Patients were enrolled at Yale and Mayo Liver Clinics. ATRA capsules were compounded and dosed at 45 mg/m2/ day divided b.i.d.. Combination therapy was given for 12 weeks followed by a 12-week washout. Baseline labs were compared to the end-of-treatment and to washout. Results: Twenty-one subjects were screened and 19 enrolled. Mean age was 45±11 years, 74% Caucasian and 74% male; 63% had large duct vs. 37% with small-duct PSC, 79% had IBD and median Mayo PSC Risk Score was −0.03±0.7. Mean UDCA

dose was 18±6 mg/kg/day. Fifteen subjects completed 12 weeks of therapy. Mean AP significantly declined (356±209 vs. 318±225 U/L, p=0.046); 20% achieved ≥30% reduction. Interestingly, mean alanine aminotransferase (ALT) also declined (94±55 vs. 56±32 U/L, p=0.007) along with serum bile acid levels (41±52 vs. 28±45 umol/L, p=0.04). Mean LDL (131±60 vs. 155±51 mg/dL, p=0.055) and triglyceride (86±31 vs. 145±45 mg/dL, p=0.003) levels increased while HDL decreased (61±21 vs. 41±11 mg/dL, p=0.01). Mean serum levels of bile acid intermediate 7a-hydroxy-4-cholesten-3-one (C4) significantly decreased (17±19 vs. 9±11 ng/mL, p=0.04) indicating that ATRA inhibited bile acid synthesis. There was no difference in bilirubin or peripheral regulatory T cell frequency.

81; Fig. 5). Owing to the limited number of studies that disclosed data about the NAFLD traits associated with disease severity and metabolic syndrome intermediate phenotypes, meta-regression analysis of these variables with BMI, homeostasis model assessment

of insulin resistance (HOMA-IR), fasting glucose, or fasting insulin was not possible. The evaluation of the risk associated with heterozygosity for the variant and liver disease severity showed that the effect when carrying only one G allele does not differ from the GG genotype (Fig. 7), suggesting that carrying two G alleles does not lead to a large change on the risk of severe histological features (details in Supporting Table 1). ALT was significantly RAD001 mw associated with the rs738409 variant in 11 heterogeneous studies (P < 0.001, I2: 86.5),1, 2, 5, 6, 15, 17-21, 24 including 5,366 individuals; fixed effect P < 1 × 10−9, and

random effect P < 0.0009, without evidence of publication bias (two-tailed P = 0.30); details of the association stratified by ethnicity are shown in Supporting Fig. 5. Subjects see more were stratified by age (Fig. 6), ethnicity, study design, and associated disease condition, but the heterogeneity remained significant. The heterogeneity did not disappear even after removing the outlier studies.5, 18, 19, 21 Nevertheless, the effect estimate seems to be robust because similar and significant results (standard 上海皓元医药股份有限公司 deviation between 0.32 and 0.45, P < 1 × 10−8) still remained after excluding one study at a time. The analysis of the heterozygosity for the

variant showed that ALT levels were significantly associated with the rs738409 G allele when the reference genotype (CC) was compared with the CG genotype, suggesting again an additive genetic effect (details in Supporting Table 1). Additional information about the NAFLD-associated insulin resistance phenotype was available in six studies that reported data on HOMA-IR,2, 5, 6, 20, 21, 24 including 1,404 subjects; in seven studies that reported data on fasting insulin levels,2, 6, 18-21, 24 including 1,721 subjects; and in nine studies that reported data on fasting glucose levels,1, 2, 5, 6, 18-21, 24 including 4160 subjects (Supporting Table 2). Interestingly, no significant association with the variant was found for HOMA-IR and fasting glucose or insulin levels. Neither was the trait obesity, as measured by BMI, associated with the variant (Supporting Table 2) in 4,141 subjects included in 10 heterogeneous studies.1, 2, 6, 15, 18, 19, 21, 22 The median impact factor for all the included studies was 7.81 (range, 2.84-34.28). In conclusion, we observed that the data we have included in the analysis were published in leading journals with a high impact factor.

81; Fig. 5). Owing to the limited number of studies that disclosed data about the NAFLD traits associated with disease severity and metabolic syndrome intermediate phenotypes, meta-regression analysis of these variables with BMI, homeostasis model assessment

of insulin resistance (HOMA-IR), fasting glucose, or fasting insulin was not possible. The evaluation of the risk associated with heterozygosity for the variant and liver disease severity showed that the effect when carrying only one G allele does not differ from the GG genotype (Fig. 7), suggesting that carrying two G alleles does not lead to a large change on the risk of severe histological features (details in Supporting Table 1). ALT was significantly find more associated with the rs738409 variant in 11 heterogeneous studies (P < 0.001, I2: 86.5),1, 2, 5, 6, 15, 17-21, 24 including 5,366 individuals; fixed effect P < 1 × 10−9, and

random effect P < 0.0009, without evidence of publication bias (two-tailed P = 0.30); details of the association stratified by ethnicity are shown in Supporting Fig. 5. Subjects selleck products were stratified by age (Fig. 6), ethnicity, study design, and associated disease condition, but the heterogeneity remained significant. The heterogeneity did not disappear even after removing the outlier studies.5, 18, 19, 21 Nevertheless, the effect estimate seems to be robust because similar and significant results (standard 上海皓元医药股份有限公司 deviation between 0.32 and 0.45, P < 1 × 10−8) still remained after excluding one study at a time. The analysis of the heterozygosity for the

variant showed that ALT levels were significantly associated with the rs738409 G allele when the reference genotype (CC) was compared with the CG genotype, suggesting again an additive genetic effect (details in Supporting Table 1). Additional information about the NAFLD-associated insulin resistance phenotype was available in six studies that reported data on HOMA-IR,2, 5, 6, 20, 21, 24 including 1,404 subjects; in seven studies that reported data on fasting insulin levels,2, 6, 18-21, 24 including 1,721 subjects; and in nine studies that reported data on fasting glucose levels,1, 2, 5, 6, 18-21, 24 including 4160 subjects (Supporting Table 2). Interestingly, no significant association with the variant was found for HOMA-IR and fasting glucose or insulin levels. Neither was the trait obesity, as measured by BMI, associated with the variant (Supporting Table 2) in 4,141 subjects included in 10 heterogeneous studies.1, 2, 6, 15, 18, 19, 21, 22 The median impact factor for all the included studies was 7.81 (range, 2.84-34.28). In conclusion, we observed that the data we have included in the analysis were published in leading journals with a high impact factor.

4, 95% confidence interval [CI] 1.5–12.8); the presence of the V617F-JAK2 mutation (HR 2.4, 95% CI 1.3–4.7);

duration of anticoagulation therapy (HR 1.01, 95% CI 1.001–1.007); splenic vein obstruction (HR 4, 95% CI 1.6–10.1); and superior mesenteric vein obstruction (HR 3, 95% CI 1.3–6). Factors predicting recanalization were familial history of venous thrombosis (HR 2.3, 95% CI 1.1–5). Erlotinib datasheet The outcome did not differ according to the type or number of thrombotic risk factors or the timing of anticoagulation treatment from first symptoms (heparin-based treatment initiated within 7 days in 26 patients, or between 7 and 30 days in 58 patients). The only independent factors found at multivariate analysis were ascites (assessed clinically or at imaging) (HR 3.8, 95% CI 1.3–11.1) and splenic vein obstruction (HR 3.5, 95% CI 1.4–8.9). Figure 4 shows that recanalization did not occur in any of the 19 patients with both splenic vein obstruction and ascites. Figure 3 shows that the 1-year recanalization rate was 61% for the superior mesenteric

vein, and 54% for the splenic vein. There was no apparent plateau in recanalization over time for these two veins. Patient characteristics find more were not significantly different in those with recanalization and those without (data not shown). Among the 13 patients in whom recanalization of the mesenteric vein was documented to occur after 6 months, nine were still on anticoagulation. Among the eight patients MCE who had recanalization of the splenic vein documented after 6 months, five were still on anticoagulation. Two patients did not receive anticoagulation therapy. One of these patients had acute pancreatitis as the only cause of portal vein obstruction; he fully recovered

with a patent portal venous system. The other patient had the lupus anticoagulant and had persisting occlusion of the left portal vein at the end of follow-up. One patient receiving only antiplatelet therapy did not recanalize. Among the four patients who had anticoagulation initiated 34 to 76 days after diagnosis; none recanalized the portal vein. Partial recanalization was observed in only one of these four patients: he had portal, mesenteric and right portal branch obstruction, was treated 65 days after diagnosis, and recanalized the mesenteric vein and the right portal branch. Bleeding occurred in nine of the 95 patients (gastrointestinal or nasal in seven, intra-abdominal in one, bone marrow biopsy-related hematoma in one). Bleeding required transfusion or a prolonged hospital stay in five patients. There were no bleeding-related mortalities. Two patients who developed mesenteric infarction 6 and 12 days after beginning anticoagulation underwent 140-cm-long and 40-cm-long intestinal resection, respectively. Both patients survived with good clinical outcome.