Low fecal calprotectin predicts clinical remission in Crohn's disease patients: the simple answer to a challenging question

Background and aim: Fecal calprotectin (FC) is a noninvasive marker of intestinal inflammation. Predicting relapses in Crohn’s disease (CD) patients can allow earlier changes in therapy. The aim of this study was to evaluate the role of FC in predicting relapse in CD patients in clinical remission within six months follow-up.

Methods: Patients with CD who were in clinical remission at least ≥3 months were included in this study. The first FC sample during the remission period was evaluated and was used as the baseline value. Relapse was defined as an unexpected escalation in therapy, hospitalization or need for surgery for active CD. The accuracy and optimal cutoff FC values for predicting clinical relapse at six months were assessed by the area under the ROC curve (AUC).

Results: One hundred and forty-four patients were evaluated, with mean age of 38.4 years. Of these, 13 (9%) had a relapse during the follow-up period. The mean FC value was significantly lower for non-relapsers (203.2?μg/g) than for relapsers (871.3?μg/g), p?<?.001. The AUC for predicting relapse by using FC values was 0.924. The optimal cutoff FC value to predict relapse was 327?μg/g; with values of sensitivity, specificity, negative predictive value and positive predictive value were 92.3%, 82.4%, 99.1% and 34.3%, respectively.

Conclusions: FC is more useful in predicting remission maintenance than relapse in patients with CD in clinical remission. Values of FC ≤327?μg/g can exclude relapse at least at six months follow-up period.     

Activation of CD3+ T cells by Helicobacter pylori DNA vaccines in potential immunotherapy of gastric carcinoma

Most of gastric carcinoma (GC) is attributed to infection by Helicobacter pylori (H. pylori) but there is increasing evidence that the positive H. pylori status correlates with better prognosis in GC. The H. pylori-induced cellular immune response may suppress cancer and in this work, recombinant pcDNA3 plasmids encoding various fragments of H. pylori virulence genes of cagA, vacA and babA are constructed and combined into groups to immunize BALB/c mice. The activated splenic CD3⁺ T cells are purified and the anticancer effects are investigated in vitro and in vivo. The H. pylori DNA vaccines induce a shift in the response from Th1 to Th2 that mimicks the immune status in patients of GC with chronic H. pylori infection. The stimulated CD3⁺ T cells inhibit the growth of human GC cells in vitro and adoptive transfusions of the CD3⁺ T cells suppress the growth of GC xenograft in vivo. The effects may be caused by the larger ratios of infiltrated CD8⁺/CD4⁺ T cells, reduced infiltration of regulatory FOXP3⁺ T cells, and enhanced apoptosis induced by upregulation of Caspase-9/Caspase-3 and downregulation of Survivin. Our results reveal the potential immunotherapeutic value of H. pylori vaccine-activated CD3⁺ T cells in those with advanced GC.     

Application of non-invasive detection of peripheral vascular dysfunction in ovarian hyperstimulation syndrome (OHSS): A pilot study of clinical relevance

ObjectiveThe current study tested the hypothesis that vascular endothelial function, as reflected by the reactive hyperemia index (RHI), and biochemical factors, including VEGF, TNFα, CRP, inhibin A, and inhibin B, were involved in the pathogenesis of ovarian hyperstimulation syndrome (OHSS).Materials and methodsThis study was conducted between June 2010 and June 2012, enrolling 15 patients with OHSS and 6 healthy control subjects <45 years of age. Detailed clinical parameters were reviewed, including serum VEGF, TNFα, CRP, inhibin A, inhibin B, and hematocrit. RHI assessed by novel automatic peripheral arterial tonography was used to evaluate the vascular endothelial function.ResultsTwenty-one subjects were evaluated. There was no significant difference between patients with OHSS and control subjects with respect to VEGF, TNFα, CRP, inhibin A and inhibin B. The RHI was not significantly different between patients with OHSS and control subjects (mean, 1.8 ± 0.4 vs. 1.7 ± 0.2). The hematocrit was significantly different between patients with OHSS and control subjects.ConclusionsOur preliminary data did not reveal direct evidence of vascular endothelial dysfunction in patients with OHSS. To identify whether RHI could reflect vascular endothelial dysfunction in patients with OHSS, more cases with different severities of OHSS should be recruited in the future study.     

Pulmonary artery pulsatility index predicts prolonged inotrope/pulmonary vasodilator use after implantation of continuous flow left ventricular assist device

Objective: Predictors of right ventricle (RV) dysfunction after continuous‐flow left ventricular assist device (CF‐LVAD) implantation in children are not well described. We explored the association of preimplantation Pulmonary Artery Pulsatility index (PAPi) and other hemodynamic parameters as predictors of prolonged postoperative inotropes/pulmonary vasodilator use after CF‐LVAD implantation.
Design: Retrospective chart review.
Setting: Single tertiary care pediatric referral center.
Patients: Patients who underwent CF‐LVAD implantation from January 2012 to October 2017.
Interventions: Preimplantation invasive hemodynamic parameters were analyzed to evaluate the association with post‐CF‐LVAD need for prolonged (>72 hours) use of inotropes/pulmonary vasodilators.
Measurements and main results: Preimplantation cardiac catheterization data was available for 12 of 44 patients who underwent CF‐LVAD implant during the study period. Median (IQR) age and BSA of the cohort were 15.3 years (10.2, 18) and 1.74 m2 (0.98, 2.03). Group 1 (n = 6) included patients with need for prolonged inotropes/pulmonary vasodilator use after CF‐LVAD implantation and Group 2 (n = 6) included those without. Baseline demographic parameters, cardiopulmonary bypass time, and markers of RV afterload (pulmonary vascular resistance, PA compliance and elastance) were similar among the two groups. PAPi was significantly lower in group 1 compared to group 2 (0.96 vs 3.6, respectively; P = .004). Post‐LVAD stay in the intensive care unit was longer for patients in group 1 (46 vs 23 days, P = .52). Brain natriuretic peptide was significantly higher at 3 months after implantation in group 1; P = .01.
Conclusions: The need for inotropes/pulmonary vasodilators in the postoperative period can be predicted by the preimplantation intrinsic RV contractile reserve as assessed by PAPi rather than the markers of RV afterload. Further investigation and correlation with clinical outcomes is needed.     

胃癌组织C19orf28蛋白表达的预后价值

目的：探讨C19orf28是否可以预测胃癌（gastriccancer,GC）患者的预后。方法：采用免疫组化染色法检测141例胃癌组织及其癌旁组织（距癌组织5cm）中C19orf28蛋白表达水平。结果：C19orf28蛋白在胃癌组织中的表达显著高于癌旁组织（P<0.05）。C19orf28高表达患者（n=43）的临床病理学特征与C19orf28低表达患者（n=98）的临床病理学特征差异无统计学意义。C19orf28高表达患者总生存期（overallsurvival,OS）短于C19orf28低表达患者OS（P=0.0003）。C19orf28高表达患者平均生存期（23.40个月）短于C19orf28低表达患者平均生存期（38.35个月），差异有统计学意义（P<0.01）。Cox多因素风险回归模型分析显示，C19orf28表达（HR=2.34,P=0.005,95%CI1.30～4.21）是胃癌患者不良预后的独立预测因子。结论：胃癌组织C19orf28蛋白表达水平与患者不良预后相关，在预测胃癌患者预后中有潜在应用价值。     

Low-dose l-isoproterenol versus salbutamol in hospitalized pediatric patients with severe acute exacerbation of asthma: A double-blind,randomized controlled trial

BackgroundAlthough the guidelines in most countries do not recommend continuous inhalation of l-isoproterenol to treat pediatric patients with acute severe exacerbation of asthma, lower dose of l-isoproterenol has been widely used in Japan. To determine whether the efficacy of low-dose l-isoproterenol was superior to that of salbutamol, we conducted a double-blind, randomized controlled trial.MethodsHospitalized patients aged 1–17 years were eligible if they had severe asthma exacerbation defined by the modified pulmonary index score (MPIS). Patients were randomly assigned (1:1) to receive inhalation of l-isoproterenol (10 μg/kg/h) or salbutamol (500 μg/kg/h) for 12 hours via a large-volume nebulizer with oxygen. The primary outcome was the change in MPIS from baseline to 3 hours after starting inhalation. Trial registration number UMIN000001991.ResultsFrom December 2009 to October 2013, 83 patients (42 in the l-isoproterenol group and 41 in the salbutamol group) were enrolled into the study. Of these, one patient in the l-isoproterenol group did not receive the study drug and was excluded from the analysis. Compared with salbutamol, l-isoproterenol reduced MPIS more rapidly. Mean (SD) changes in MPIS at 3 hours were −2.9 (2.5) in the l-isoproterenol group and −0.9 (2.3) in the salbutamol group (difference −2.0, 95% confidence interval −3.1 to −0.9; P < 0.001). Adverse events occurred in 1 (2%) and 11 (27%) patients in the l-isoproterenol and salbutamol groups, respectively (P = 0.003). Hypokalemia and tachycardia occurred only in the salbutamol group.ConclusionsLow-dose l-isoproterenol has a more rapid effect with fewer adverse events than salbutamol.