A prognostic nomogram in patients with distant metastasis of pancreatic neuroendocrine tumors: a population-based study.

Aim: Prognostic factors in patients with distant metastatic pancreatic neuroendocrine tumors (PNETs) remain uncertain. The purpose of our study is to establish a nomogram to predict survival outcomes in patients with metastatic PNETs. Methods: A total of 878 patients diagnosed with PNETs in the Surveillance, Epidemiology and End Results database between 2004 and 2016 were retrospectively identified. The Kaplan-Meier survival analysis with log-rank test was used to analyze survival outcomes. The nomogram was established after a univariate and multivariate Cox analysis. Results: The independent prognostic variables, including age, tumor grade and primary site surgery were applied to develop a nomogram. The original concordance index was 0.773 (95% CI: 0.751-0.795), and the bias-corrected concordance index was 0.769 (95% CI: 0.748-0.791). The internal calibration curves showed well consistency and veracity in predicting cancer-specific survival probabilities. Conclusion: A nomogram was constructed and verified to predict survival outcomes in patients with distant-stage PNETs.

Stress-Induced Hyperglycemia and Remote Diffusion-Weighted Imaging Lesions in Primary Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Stress-induced hyperglycemia (SIH) is the relative transient increase in glucose during a critical illness such as intracerebral hemorrhage (ICH) and is likely to play an important role in the pathogenesis of remote diffusion-weighted imaging (DWI) lesion (R-DWIL) in primary ICH. We sought to determine the association between SIH and the occurrence of R-DWILs. METHODS: We prospectively enrolled primary ICH patients within 14 days after onset from November 2016 to May 2018. In these patients, cerebral magnetic resonance imaging was performed within 14 days after ICH onset. R-DWIL was defined as a hyperintensity signal in DWI with corresponding hypointensity in apparent diffusion coefficient, and at least 20 mm apart from the hematoma. SIH was measured by stress-induced hyperglycemia ratio (SHR). SHR was calculated by fasting blood glucose (FBG) divided by estimated average glucose derived from glycosylated hemoglobin. The included patients were dichotomized into two groups by the 50th percentile of SHR, and named as SHR (-P50) group and SHR (P50+) group, respectively. We evaluated the association between SHR and R-DWIL occurrence using multivariable logistic regression modeling adjusted for potential confounders. RESULTS: Among the 288 patients enrolled, forty-six (16.0%) of them had one or more R-DWILs. Compared with the patients in the lower 50% of SHR (SHR [-P50]), the odds ratio (OR) [95% confidence interval (CI)] for the higher 50% of SHR (SHR [P50+]) group for R-DWIL occurrence was 3.13 (1.39-7.07) in the total population and 6.33 (2.19-18.30) in population absent of background hyperglycemia after adjusting for potential covariates. Similar results were observed after further adjusted for FBG. CONCLUSIONS: Our study demonstrated that SIH was associated with the occurrence of R-DWILs in patients with primary ICH within 14 days of symptom onset.

Reduced field-of-view diffusion-weighted imaging (DWI) in patients with gastric cancer: Comparison with conventional DWI techniques at 3.0T: A preliminary study.

To evaluate the qualitative image quality and quantitative apparent diffusion coefficient (ADC) value of reduced field-of view (rFOV) and full field-of-view (fFOV) diffusion-weighted imaging (DWI) sequences at 3.0 T in patients with gastric cancer.Fifty-three patients (37 males, 16 females; mean age, 63.3 ±â€Š10.3 years) with 60 lesions with gastric cancer who underwent magnetic resonance (MR) scans, including both rFOV-DWI and fFOV-DWI, were retrospectively analyzed. Two observers subjectively evaluated image quality for both the fFOV-DWI and rFOV-DWI sequences regarding the anatomic details, distortion, lesion conspicuity, artifacts, and overall image quality. The mean ADC values of gastric cancer were calculated. The Wilcoxon test and paired samples t test were used. Interobserver agreement was assessed using kappa statistics.The mean scores based on the 2 observers demonstrated significant differences in image quality in terms of anatomic details, distortion, lesion conspicuity, artifacts and overall image quality at both b values between rFOV-DWI and fFOV-DWI (P < .05) in the whole gastric area. rFOV-DWI yielded significantly better scores in image quality at b = 800 seconds/mm (P < .05) in patients with esophagogastric junction cancers, but there were no significant differences in the gastric corpus and gastric antrum region. The mean tumor ADC values of rFOV-DWI were significantly lower than those of fFOV-DWI (1.237 ±â€Š0.228 × 10-3 mm/second vs 1.683 ±â€Š0.322 × 10-3 mm/second, P < .001).rFOV-DWI yielded significantly better image quality (anatomic details, distortion, lesion conspicuity, artifacts, overall image quality) and more accurate ADC measurements than fFOV-DWI did.

Early elevated neutrophil-to-lymphocyte ratio associated with remote diffusion-weighted imaging lesions in acute intracerebral hemorrhage.

AIMS: To explore the relationship between the circulating neutrophil-to-lymphocyte ratio (NLR) and the remote diffusion-weighted imaging lesions (R-DWILs) after spontaneous intracerebral hemorrhage (ICH). METHODS: Consecutive patients with spontaneous ICH were prospectively collected from November 2016 to May 2018 and retrospectively analyzed. We included subjects who presented within 24 hours after symptom onset and were free of detectable infections on admission or in hospital. Blood samples were obtained at 24-48 hours after ICH ictus, while all complete MRI scans were performed at 5-8 days. R-DWILs were defined as focal hyperintensities remote from the site of the ICH or the peri-hematoma regions. NLR was calculated by dividing the absolute neutrophil counts by the absolute lymphocyte counts. Multivariate binary logistic regression models were generated to evaluate the relationship between NLR and R-DWILs. RESULTS: One hundred sixty-three subjects met eligibility criteria (age 62.3 ± 13.6 years, 60.7% males), of whom 31(19.0%) experienced R-DWILs. Higher circulating NLR was documented in patients with R-DWILs. With the best cutoff value of 6.01, elevated NLR was independently associated with the presence of R-DWILs (OR = 3.170, 95% CI 1.306-7.697, P = .011) in the bivariate logistic regression analysis with adjustment for age, sex, atrial fibrillation, previous ischemic stroke/TIA, SBP on admission, hematoma volume, and IVH. CONCLUSIONS: This study provides significant evidence of the association between circulating NLR and R-DWILs in spontaneous ICH patients. Patients with NLR > 6.01 at 24-48 hours after ICH ictus should be paid more attention to when evaluating R-DWILs.

Fluorocitrate, an inhibitor of glial metabolism, inhibits the up-regulation of NOS expression, activity and NO production in the spinal cord induced by formalin test in rats.

Previous experiments have suggested that nitric oxide plays an important role in nociceptive transmission in the spinal cord. In order to explore the involvement of glia in the NO-mediated nociceptive transmission, the present study was undertaken to investigate the effect of fluorocitrate (FC), an inhibitor of glial metabolism, on NOS expression and activity and NO production in the spinal cord during the process of peripheral inflammatory pain and hyperalgesia induced by formalin test in rats. Sixty adult male Sprague-Dawley rats were randomly assigned into sham, formalin, formalin + normal saline (NS), and formalin + FC groups. The NOS expression, NOS activity and NO production was detected by NADPH-d histochemistry staining, NOS and NO assay kit, respectively. It was found that formalin test significantly up-regulated NOS expression and activity and NO production in the laminae I-II of the dorsal horn and the grey matter around the central canal in the lumbar spinal cord at 1 h after the formalin test. Selective inhibition of glia metabolism with intrathecal administration of FC (1 nmol) significantly inhibited the up-regulation in NOS expression and activity and NO production normally induced by the formalin test, which was represented with decreases in the number and density of the NADPH-d positive cells in the dorsal horn and grey matter around the central canal, and decrease in density of NADPH-d positive neuropil in the dorsal horn in formalin + FC group compared with formalin group. The results suggested that glia may be involved in the NO-mediated nociceptive transmission in the spinal cord.

[Antisense oligodeoxynucleotides of glial glutamate transporter-1 inhibits the neuro-protection of cerebral ischemic preconditioning in rats].

The present study was undertaken to investigate the role of glial glutamate transporter-1 (GLT-1) in the brain ischemic tolerance induced by cerebral ischemic preconditioning (CIP) by observing the effect of GLT-1 antisense oligodeoxynucleotides (AS-ODNs) on the neuro-protection of CIP against brain ischemic insult in rats. Wistar rats with permanently occluded bilateral vertebral arteries were randomly assigned to 7 groups: (1) Sham group: the bilateral common carotid arteries (BCCA) were separated, but without occluding the blood flow; (2) CIP group: the BCCA were clamped for 3 min; (3) Brain ischemic insult group: the BCCA were clamped for 8 min; (4) CIP+brain ischemic insult group: 3 min CIP was preformed 2 d prior to 8 min ischemic insult; (5) Double distilled water group: 5 muL double distilled water was injected into the right lateral cerebral ventricle 12 h before, 12 h and 36 h after the BCCA was separated (but without occluding the blood flow), respectively; (6) AS-ODNs group: 5 microL AS-ODNs solution was injected into the right lateral cerebral ventricle 12 h before, 12 h and 36 h after the BCCA was separated (but without occluding the blood flow), respectively. This group was further divided into 9 nmol and 18 nmol subgroups according to the doses of AS-ODNs; (7) AS-ODNs+CIP+brain ischemic insult group: 5 microL AS-ODNs solution was injected into the right lateral cerebral ventricle 12 h before, 12 h and 36 h after CIP, respectively. This group was also further divided into 9 nmol and 18 nmol subgroups according to the doses of AS-ODNs. The other treatments were the same as those in CIP+brain ischemic insult group. The effect of the AS-ODNs on the expression of GLT-1 was assayed by using Western blot analysis. The profile of delayed neuronal death (DND) of pyramidal neurons in the CA1 hippocampus was evaluated by using thionin staining under light microscope by determining the neuronal density (ND) and histological grade (HG). Western blot analysis showed that AS-ODNs injected into the lateral cerebroventricle inhibited the expression of GLT-1 in the CA1 hippocampus in a dose-dependent manner. Neuropathological evaluation showed that there was no apparent DND in sham and CIP groups. Obvious DND of pyramidal neurons was found in brain ischemic insult group, which was represented by an increase in HG and a decrease in ND. CIP effectively protected the pyramidal neurons in the CA1 hippocampus against DND normally induced by ischemic insult, which indicating that CIP induced ischemic tolerance on the pyramidal neurons in the CA1 hippocampus. However, the injection of AS-ODNs into the lateral cerebroventricle blocked the neuro-protection of CIP against DND induced by brain ischemic insult. These results further proved the role of GLT-1 in the brain ischemic tolerance induced by CIP in rats.

Association of Renal Dysfunction With Remote Diffusion-Weighted Imaging Lesions and Total Burden of Cerebral Small Vessel Disease in Patients With Primary Intracerebral Hemorrhage.

Objective: Remote diffusion-weighted imaging (DWI) lesions (R-DWIL) found in intracerebral hemorrhage (ICH) patients are considered as an additional marker of cerebral small vessel disease (cSVD). This study aimed to investigate the association of renal dysfunction and R-DWIL, as well as the total burden of cSVD on magnetic resonance imaging among patients with primary ICH. Methods: One hundred and twenty-six consecutive patients were prospectively enrolled. R-DWIL on DWI, as well as other imaging markers of cSVD, including lacunes, white matter lesions, cerebral microbleeds, and enlarged perivascular spaces were rated using validated scales. Renal dysfunction was evaluated either by reduced estimated glomerular filtration rate (eGFR) or the presence of proteinuria or increased cystatin C. Results: After adjustments for potential confounders by logistic regression, impaired eGFR [odds ratio (OR) 6.00, 95% confidence interval (CI) 1.73-20.78], proteinuria (OR 3.07, 95% CI 1.25-7.54) and increased cystatin C (OR 2.73, 95% CI 1.11-6.72) were correlated with presence of R-DWIL. A similar association was also found between cystatin C levels (OR 3.16, 95% CI 1.39-7.19), proteinuria (OR 2.79, 95% CI 1.34-5.83) and the comprehensive cSVD burden. Conclusions: Renal dysfunction are associated with the presence of R-DWIL, and total burden of cSVD in patients with primary ICH.

Factors Associated With Remote Diffusion-Weighted Imaging Lesions in Spontaneous Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Remote diffusion-weighted imaging lesions (R-DWILs) have been detected in patients with spontaneous intracerebral hemorrhage (ICH) and may be correlated with clinical outcome. However, the mechanisms and characteristics of R-DWILs have not been fully elucidated. In this study, we sought to demonstrate the clinical characteristics of R-DWILs in spontaneous ICH. METHODS: We prospectively collected data with spontaneous ICH patients from November 2016 to December 2017. In these patients, cerebral magnetic resonance imaging was performed within 28 days after ICH onset. R-DWIL was defined as a hyperintensity signal in diffusion-weighted imaging with corresponding hypointensity in apparent diffusion coefficient, and at least 20 mm apart from the hematoma. We compared two groups of patients with or without R-DWIL with the demographic and clinical characteristics, laboratory parameters, and imaging characteristics, by using univariate and multivariate analysis. RESULTS: Of the 222 patients enrolled, a total of 75 R-DWILs were observed in 41 patients (18.5%). Among these lesions, the cortical and subcortical areas were the predominant locations with a proportion of 77.3%. The median diameter of R-DWILs was 7 mm (range 2-20 mm). Twelve patients were found having more than one lesion, with five among which showed R-DWILs in multiple cerebral arterial territories. In multivariate modeling, higher fasting glucose (OR 1.231; 95% CI 1.035-1.465; p = 0.019) and more severe white matter hyperintensity (WMH) (OR 6.589; 95% CI 2.975-14.592; p < 0.001) were independent factors related to the presence of R-DWILs. CONCLUSION: In our study, approximately one-fifth of ICH patients showed coexistence of R-DWIL. Higher fasting glucose and more severe WMH were associated with R-DWIL occurrence in spontaneous ICH.

The PI3K-AKT-mTOR pathway activates recovery from general anesthesia.

We investigated roles of PI3K-AKT-mTOR pathway in recovery from general anesthesia. Sprague-Dawley rats divided into five groups: saline+artificial cerebrospinal fluid (ACSF; Group A), ketamine+ACSF (Group B), ketamine+IGF-1 (Group C), ketamine+PI3K inhibitor (Group D), and PI3K/Akt agonists (Group E). Proportion of δ waves on ECoGs was recorded. Rats were tested for duration of loss of righting reflex (LORR), ataxic period and behavior in Morris water maze. mRNA and protein expression of members of PI3K-AKT-mTOR pathway were measured by RT-qPCR and Western blots. Histopathologic changes in hippocampal tissues observed by HE staining. We found that the proportion of δ waves decreased in Group C, while increased in Group D compared with Group B; the durations of LORR and ataxic period were shorter in Group C, but longer in Group D. In Morris water maze, escape latency (EL) and duration and frequency of staying on platform was shorter in Group C and longer in Group D than in Group B. Group A exhibited low expression of proteins in PI3K-AKT-mTOR pathway, while p-AKT, p-mTOR and p-P70S6K expression increased in cerebral cortex, brain stem, and thalamus in Group C. By contrast, expression of those proteins was lower in Group D than Group B. Those proteins expressions were higher in Group E than in Group A. HE staining showed that anesthesia may induce cell apoptosis in rat hippocampal CA1 areas, and PI3K/Akt agonists could inhibit apoptosis. Our results suggest that activation of PI3K-AKT-mTOR pathway may promote recovery from general anesthesia and enhance spatial learning and memory.