Long-term prognosis and its associated predictive factors in patients with eosinophilic gastroenteritis.

BACKGROUND: Eosinophilic gastroenteritis (EGE) is a chronic recurrent disease with abnormal eosinophilic infiltration in the gastrointestinal tract. Glucocorticoids remain the most common treatment method. However, disease relapse and glucocorticoid dependence remain notable problems. To date, few studies have illuminated the prognosis of EGE and risk factors for disease relapse. AIM: To describe the clinical characteristics of EGE and possible predictive factors for disease relapse based on long-term follow-up. METHODS: This was a retrospective cohort study of 55 patients diagnosed with EGE admitted to one medical center between 2013 and 2022. Clinical records were collected and analyzed. Kaplan-Meier curves and log-rank tests were conducted to reveal the risk factors for long-term relapse-free survival (RFS). RESULTS: EGE showed a median onset age of 38 years and a slight female predominance (56.4%). The main clinical symptoms were abdominal pain (89.1%), diarrhea (61.8%), nausea (52.7%), distension (49.1%) and vomiting (47.3%). Forty-three (78.2%) patients received glucocorticoid treatment, and compared with patients without glucocorticoid treatments, they were more likely to have elevated serum immunoglobin E (IgE) (86.8% vs 50.0%, P = 0.022) and descending duodenal involvement (62.8% vs 27.3%, P = 0.046) at diagnosis. With a median follow-up of 67 mo, all patients survived, and 56.4% had at least one relapse. Six variables at baseline might have been associated with the overall RFS rate, including age at diagnosis < 40 years [hazard ratio (HR) 2.0408, 95% confidence interval (CI): 1.0082-4.1312, P = 0.044], body mass index (BMI) > 24 kg/m2 (HR 0.3922, 95%CI: 0.1916-0.8027, P = 0.014), disease duration from symptom onset to diagnosis > 3.5 mo (HR 2.4725, 95%CI: 1.220-5.0110, P = 0.011), vomiting (HR 3.1259, 95%CI: 1.5246-6.4093, P = 0.001), total serum IgE > 300 KU/L at diagnosis (HR 0.2773, 95%CI: 0.1204-0.6384, P = 0.022) and glucocorticoid treatment (HR 6.1434, 95%CI: 2.8446-13.2676, P = 0.003). CONCLUSION: In patients with EGE, younger onset age, longer disease course, vomiting and glucocorticoid treatment were risk factors for disease relapse, whereas higher BMI and total IgE level at baseline were protective.

The remodeling of metabolic brain pattern in patients with extracranial diffuse large B-cell lymphoma.

BACKGROUND: Owing to the advances in diagnosis and therapy, survival or remission rates for lymphoma have improved prominently. Apart from the lymphoma- and chemotherapy-related somatic symptom burden, increasing attention has been drawn to the health-related quality of life. The application of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) has been routinely recommended for the staging and response assessment of FDG-avid lymphoma. However, up till now, only a few researches have investigated the brain metabolic impairments in patients with pre-treatment lymphoma. The determination of the lymphoma-related metabolic brain pattern would facilitate exploring the tailored therapeutic regimen to alleviate not only the physiological, but also the psychological symptoms. In this retrospective study, we aimed to establish the diffuse large B-cell lymphoma-related pattern (DLBCLRP) of metabolic brain network and investigate the correlations between DLBCLRP and several indexes of the staging and response assessment. RESULTS: The established DLBCLRP was characterized by the increased metabolic activity in bilateral cerebellum, brainstem, thalamus, striatum, hippocampus, amygdala, parahippocampal gyrus and right middle temporal gyrus and by the decreased metabolic activity in bilateral occipital lobe, parietal lobe, anterior cingulate gyrus, midcingulate cortex and medial frontal gyrus. Significant difference in the baseline expression of DLBCLRP was found among complete metabolic response (CMR), partial metabolic response (PMR) and progressive metabolic disease (PMD) groups (P < 0.01). DLBCLRP expressions were also significantly or tended to be positively correlated with international prognostic index (IPI) (rs = 0.306, P < 0.05), lg(total metabolic tumor volume, TMTV) (r = 0.298, P < 0.05) and lg(total lesion glycolysis, TLG) (r = 0.233, P = 0.064). Though no significant correlation of DLBCLRP expression was found with Ann Arbor staging or tumor SUVmax (P > 0.05), the post-treatment declines of DLBCLRP expression were significantly positively correlated with Ann Arbor staging (rs = 0.284, P < 0.05) and IPI (rs = 0.297, P < 0.05). CONCLUSIONS: The proposed DLBCLRP would lay the foundation for further investigating the cerebral dysfunction related to DLBCL itself and/or treatments. Besides, the expression of DLBCLRP was associated with the tumor burden of lymphoma, implying a potential biomarker for prognosis.

Autoimmune pancreatitis associated with inflammatory bowel diseases: A retrospectively bidirectional case-control study in China.

OBJECTIVES: Autoimmune pancreatitis (AIP) is a rare and enigmatic immune-mediated inflammatory disease. We aimed to investigate the prevalence, characteristics, and associated factors of AIP-inflammatory bowel disease (IBD) in China. METHODS: A retrospective bidirectional case-control study was performed. The diagnoses of IBD and AIP were made based on the European Crohn's and Colitis Organization guidelines and the International Consensus Diagnostic Criteria. IBD controls were matched by age, sex, and IBD type at a ratio of 1:4, while AIP controls were matched by AIP types. RESULTS: The age-standardized prevalence of AIP-IBD patients in the IBD and AIP population were 292.0 and 8151.93 per 100 000 population, respectively. IBD patients had a higher risk of AIP compared to non-IBD patients (odds ratio 8.4, 95% confidence interval 4.7-14.9, P < 0.0001), and AIP patients had a higher risk of developing IBD compared to the general population in China. The mean age at diagnosis of IBD and AIP was 34.83 years and 40.42 years. IBD was diagnosed before AIP in seven cases. The median total IBD and AIP duration was 43.5 months and 13.5 months. Use of mesalamine and tuberculosis were associated with AIP in IBD patients (P = 0.031). And fecal occult blood test was associated with IBD in AIP patients (P = 0.008). CONCLUSIONS: Most AIP-IBD patients had ulcerative colitis and type 2 AIP. IBD patients are more likely to develop AIP compared to the general population, and vice versa. Use of mesalamine and tuberculosis infection were associated with AIP, and fecal occult blood test was associated with IBD.

Age-matched control or age-specific template, which is essential for voxel-wise analysis of cerebral metabolism abnormality in pediatric patients with epilepsy?

The aim of this study was to explore the influences of age-matched control and/or age-specific template on voxel-wise analysis of brain 18 F-fluorodeoxyglucose positron emission tomography (18 F-FDG PET) data in pediatric epilepsy patients. We, retrospectively, included 538 pediatric (196 females; age range of 12 months to 18 years) and 35 adult subjects (18 females; age range of 20-50 years) without any cerebral pathology as pediatric and adult control group, respectively, as well as 109 pediatric patients with drug-resistant epilepsy (38 females; age range of 13 months to 18 years) as epilepsy group. Statistical parametric mapping (SPM) analysis for 18 F-FDG PET data of each epilepsy patients was performed in four types of procedures, by using age-matched controls with age-specific template, age-matched controls with adult template, adult controls with age-specific template or adult controls with adult template. The numbers of brain regions affected by artifacts among these four types of SPM analysis procedures were further compared. Any template being adopted, the artifacts were significantly less in SPM analysis procedures using age-matched controls than those using adult controls in each age range (p < .001 in each comparison), except in the age range of 15-18 (p > .05 in each comparison). No significant difference was found in artifacts, when compared procedures using the identical control group with different templates (p = 1.000 in each comparison). In conclusion, the age stratification for age-matched control should be divided as many layers as possible for the SPM analysis of brain 18 F-FDG PET images, especially in pediatric patients ≤14-year-old, while age-specific template is not mandatory.

The Anti-Inflammatory Effect of Preventive Intervention with Ketogenic Diet Mediated by the Histone Acetylation of mGluR5 Promotor Region in Rat Parkinson's Disease Model: A Dual-Tracer PET Study.

Materials and Methods: The neuroprotective effect of ketosis state prior to the onset of PD (preventive KD, KDp) was compared with that receiving KD after the onset (therapeutic KD, KDt) in the lipopolysaccharide- (LPS-) induced rat PD model. A total of 100 rats were randomly assigned to the following 4 groups: sham, LPS, LPS + KDp, and LPS + KDt groups. Results: Significant dopamine deficient behaviors (rotational behavior and contralateral forelimb akinesia), upregulation of proinflammatory mediators (TNF-α, IL-1ß, and IL-6), loss of dopaminergic neurons, reduction of mGluR5+ microglia cells, increase of TSPO+ microglia cells, reduction of H3K9 acetylation in the mGluR5 promoter region and mGluR5 mRNA expression, and decline in the phosphorylation levels of Akt/GSK-3ß/CREB pathway were observed after the intervention of LPS (P < 0.01). TSPO and DAT PET imaging revealed the increased uptake of 18F-DPA-714 in substantia nigra and decreased uptake of 18F-FP-CIT in substantia nigra and striatum in LPS-treated rats (P < 0.001). These impairments were alleviated by the dietary intervention of KD, especially with the strategy of KDp (P < 0.05). Conclusions: The anti-inflammatory effect of KD on PD was supposed to be related to the modulation of Akt/GSK-3ß/CREB signaling pathway mediated by the histone acetylation of mGluR5 promotor region. The KD intervention should be initiated prior to the PD onset in high-risk population to achieve a more favorable outcome.

External validation of the Paddington International Virtual Electronic ChromoendoScopy ScOre as a good endoscopic score to define mucosal healing and predict long-term clinical outcomes in ulcerative colitis.

OBJECTIVES: To define endoscopic and histological remission in ulcerative colitis (UC) accurately, several scoring systems have been established. A novel virtual electronic chromoendoscopy score, the Paddington International Virtual ChromoendoScopy ScOre (PICaSSO), was developed, validated, and reproduced to assess inflammation grade and predict patient prognosis. We externally verified and validated the clinical value of PICaSSO in UC patients. METHODS: This prospective study enrolled 63 UC patients. The Mayo endoscopic score (MES), UC Endoscopic Index of Severity (UCEIS), and PICaSSO were adopted for endoscopic evaluation. All biopsy samples were scored using the Robarts histological index (RHI), Nancy histological index (NHI), and "Extent, Chronicity, Activity, Plus additional findings" (ECAP) score. Patients with an endoscopic MES of 0-1 at baseline were followed up during a median time of 23.5 months. RESULTS: PICaSSO was strongly correlated with other endoscopic and histological scoring systems. PICaSSO ≤3 had advantages in assessing histological remission (HR), with the highest accuracy of 88.9% for ECAP-HR. Relapse-free survival rates were significantly different between patients with MES 0 and MES 1 and patients with PICaSSO ≤3 and >3 (P = 0.010 and 0.018, respectively). CONCLUSIONS: PICaSSO was externally validated with strong correlations with other endoscopic and histological scoring systems in UC, and PICaSSO-ER might potentially predict a better long-term clinical outcome in UC patients.

Lateralization of the crossed cerebellar diaschisis-associated metabolic connectivities in cortico-ponto-cerebellar and cortico-rubral pathways.

This study aimed to explore the glucose metabolic profile of extrapyramidal system in patients with crossed cerebellar diaschisis (CCD). Furthermore, the metabolic connectivities in cortico-ponto-cerebellar and cortico-rubral pathways associated with CCD were also investigated. A total of 130 CCD positive (CCD+) and 424 CCD negative (CCD-) patients with unilateral cerebral hemisphere hypometabolism on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) were enrolled. Besides, the control group consisted of 56 subjects without any brain structural and metabolic abnormalities. Apart from the "autocorrelation", metabolic connectivity pattern of right or left affected cerebellar hemisphere involved unilateral (left or right, respectively) caudate, pallidum, putamen, thalamus and red nucleus, in CCD+ patients with left or right supratentorial lesions, respectively (Puncorrected < 0.001, cluster size > 200). CCD+ group had significantly lower asymmetry index (AI) in cortico-ponto-cerebellar pathway (including ipsilateral cerebral white matter, ipsilateral pons, contralateral cerebellum white matter and contralateral cerebellum exterior cortex) and cortico-rubral pathway (including ipsilateral caudate, thalamus proper, pallidum, putamen, ventral diencephalon and red nucleus) than those of both CCD- and control groups (all P < 0.05). AI in contralateral cerebellum exterior cortex was significantly positively correlated with that in ipsilateral caudate, putamen, pallidum, thalamus proper, ventral diencephalon, red nucleus and pons among CCD+ group (all P < 0.01), but only with that in ipsilateral caudate and putamen among CCD- group (both P < 0.001). These results provide additional insight into the involvement of both cortico-ponto-cerebellar and cortico-rubral pathways in the presence of CCD, underlining the need for further investigation about the role of their aberrant metabolic connectivities in the associated symptoms of CCD.

The genomic landscape of Cronkhite-Canada syndrome: Possible clues for pathogenesis.

OBJECTIVES: Cronkhite-Canada syndrome (CCS) is a rare hamartomatous polyposis syndrome with a proposed association with chronic autoimmune inflammation. To date, genetic background of patients with CCS remains less investigated. In this study we aimed to explore the genomic landscape of CCS. METHODS: Whole exome sequencing was performed on peripheral blood samples extracted from 18 patients with CCS. Potential function-impacting germline variants were filtered by R software. Through systematic data analysis, a number of genetic variants were identified. Enrichment analysis was performed using the R package ClusterProfiler. RESULTS: Overall, 3960 low-frequency (<0.05 or not reported in the Exome Aggregation Consortium East Asian, 1000 Genomes, or ESP6500 database) potentially function-impacting germline variants were identified, with 18 genes (FDFT1, LOC400863, MUC3A, MUC4, ZNF806, GXYLT1, MUC6, PABPC3, PSPH, ZFPM1, CIC, LOC283710, ARSD, GOLGA6L2, LOC388282, SLC25A5, TMEM247, WDR89) involved over half the patients. Functional enrichment of these genes revealed several biological processes in relation to innate immune responses and glycosylation. Only one likely pathogenic germline variant of an hamartomatous polyposis syndrome-associated gene, PTCH1, was detected in one patient. CONCLUSIONS: CCS has genomic alteration patterns completely distinct from those of traditional hamartomatous polyposis syndrome. The germline mutation landscape indicates potential roles of innate immune responses and glycosylation in the pathogenesis of CCS.

Voxel-based analysis of the metabolic asymmetrical and network patterns in hypermetabolism-associated crossed cerebellar diaschisis.

Crossed cerebellar diaschisis (CCD) has been widely investigated in patients with supratentorial hypometabolism, however, the available evidence about the metabolic feature of CCD in patients with contralateral supratentorial hypermetabolism is lacking. This study aimed to assess the metabolic asymmetrical profile, network pattern and predisposing factors for the hypermetabolism-associated CCD, by using voxel-based asymmetry index (AI) and brain network analyses. Seventy CCD positive (CCD+) and 99 CCD negative (CCD-) patients with unilateral supratentorial hypermetabolism were introduced. Among different brain regions with AImax or AImin, striatum & thalamus was accompanied by the highest positive rate of CCD (85.7% or 70.1%, respectively). CCD+ group had significantly greater AImax (median [IQR], 0.62 [0.44-0.84] vs. 0.47 [0.35-0.61]), supratentorial hypermetabolic volume (1183.5 [399.3-3026.8] vs. 386.0 [152.0-1193.0]) and hypometabolic volume (37796.5 [24741.8-53278.0] vs. 3337.0 [1020.0-17193.0]), and lower AImin (-0.85 [-1.05--0.73] vs. -0.49 [-0.68--0.35]) compared with CCD- group (all P < 0.001). Logistic regression analysis manifested that patients with AImin located at striatum & thalamus were 16.4 times more likely to present CCD than those at frontal lobe (OR = 16.393; 95% CI, 4.463-60.207; P < 0.001), and the occurrence of CCD was also associated with AImax (OR = 49.594; 95% CI, 5.519-445.653; P < 0.001) and AImin (OR = 3.133 × 10-4, 95% CI, 1.693 × 10-5-5.799 × 10-3, P < 0.001). Brain network analysis indicated that the relative hypermetabolism in the contralateral supplementary motor cortex (SMC) and precuneus gyrus were constant in the CCD related patterns. These results demonstrated that the greater AImax, lower AImin and AImin located at striatum & thalamus should be predisposing factors for CCD in patients with unilateral supratentorial hypermetabolism. Relative increased activities in the contralateral SMC and precuneus gyrus might be attributed to a compensatory mechanism for the abnormal brain network related to CCD.

Use of isotope differential derivatization for simultaneous determination of thiols and oxidized thiols by liquid chromatography tandem mass spectrometry.

Here we report a new isotopic pair of derivatization reagents, ω-bromoacetonylquinolinium bromide (BQB) and d(7)-ω-bromoacetonylquinolinium bromide (d(7)-BQB). BQB and d(7)-BQB both rapidly and selectively reacted with thiols in acidic medium within 3min with the aid of a microwave. Reduced thiols and total thiols in urine were labeled with BQB and d(7)-BQB, respectively. The BQB- and d(7)-BQB-labeled urine samples were then mixed and separated on a HILIC (hydrophilic interaction chromatography) column followed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) detection. The new strategy, which we have named isotope differential derivatization, allows us to simultaneously determine thiols and oxidized thiols in a single run. Compared with positive mode ESI detection of unlabeled thiols, the positive mode ESI-MS signal intensities of BQB-labeled thiols were found to increase by 10-, 20-, and 40-fold for cysteine (Cys), homocysteine (HCys), and glutathione (GSH), respectively (unlabeled N-acetylcysteine (Nac) is difficult to detect by ESI-MS in positive mode due to its low ionization efficiency). The detection limits calculated at a signal-to-noise ratio of 3 were found to be 8.02, 1.56, 0.833, and 3.27nmol/L for Cys, HCys, Nac, and GSH, respectively. Recoveries of thiols and disulfides from spiked urine samples were between 80% and 105%. The method was successfully used to determine thiols and oxidized thiols in urine samples of 25 healthy volunteers.

Hybrid organic-inorganic silica monolith with hydrophobic/strong cation-exchange functional groups as a sorbent for micro-solid phase extraction.

A hybrid organic-inorganic silica monolith with hydrophobic and strong cation-exchange functional groups was prepared and used as a sorbent for micro-solid phase extraction (micro-SPE). The hybrid silica monolith functionalized with octyl and thiol groups was conveniently synthesized by hydrolysis and polycondensation of a mixture of tetraethoxysilane (TEOS), n-octyltriethoxysilane (C8-TEOS) and 3-mercaptopropyltrimethoxysilane (MPTMS) via a two-step catalytic sol-gel process. Due to the favorable chemical reactivity of mercapto pendant moieties, the obtained hybrid monolith was oxidized using hydrogen peroxide (30%, w/w) to yield sulfonic acid groups, which provided strong cation-exchange sites. The obtained hybrid monolith was characterized by diffused infrared spectroscopy, elemental analysis, scanning electron microscopy and mercury intrusion porosimetry. The results show that the resulting monolith contains much higher carbon (31.6%) and sulfur (4.8%) contents than traditionally bonded silica materials. The extraction performance of the hybrid monolith was evaluated using sulfonamides as testing analytes by micro-SPE on-line coupled to HPLC. The results show that the hybrid monolith with hydrophobic and strong cation-exchange functional groups exhibits high extraction efficiency towards the testing analytes. The column-to-column RSD values were 1.3-9.8% for the extraction of SAs investigated. The extraction performance of the hybrid silica monolith remained practically unchanged after treated with acid (pH 1.0) and basic solutions (pH 10.5). Finally, the application of the hybrid monolith was demonstrated by micro-SPE of sulfonamide residues from milk followed by HPLC-UV analysis. The limits of detection (S/N=3) for eight SAs were found to be 1.0-3.0ng/mL in milk. The recoveries of eight SAs spiked in milk sample ranged from 80.2% to 115.6%, with relative standard deviations less than 11.8%.

Evaluating polymer monolith in-tube solid-phase microextraction coupled to liquid chromatography/quadrupole time-of-flight mass spectrometry for reliable quantification and confirmation of quinolone antibacterials in edible animal food.

A simple, rapid, and sensitive method is presented to determine seven trace quinolone antibacterials simultaneously in milk, egg, chicken and fish. This method is based on the combination of polymer monolith in-tube solid-phase microextraction with liquid chromatography and electrospray ionization quadrupole time-of-flight mass spectrometry (LC/ESI-QTOF-MS). LC/ESI-QTOF-MS offers the capability of unequivocal identification of target compounds from complex matrices, as well as the possibility of quantitation at low-level concentrations in real samples. The extraction was performed with a poly(methacrylic acid-ethylene glycol dimethacrylate) monolithic column. Under the optimized extraction conditions, good extraction efficiencies for the targets were obtained with no matrix interference in the subsequent LC/ESI-QTOF-MS. Good linearities were obtained for seven quinolones with the correlation coefficients (R) above 0.9951. The limits of detection (S/N=3) for seven quinolones were found to be 0.3-1.2 ng/g in egg, 0.2-3.0 ng/mL in milk, 0.2-0.7 ng/g in chicken and 0.2-1.0 ng/g in fish. The recoveries of quinolones spiked in four different matrices ranged from 80.2 to 115.0%, with relative standard deviations less than 14.5%. The developed method was applied for the determination of quinolone residues in animal-producing food, and the positive samples were confirmed with high number of identification points (IPs) according to the IP system defined by the European Union (Commission Decision 2002/657/EC).

Determination of chlorine in atmosphere by kinetic spectrophotometry.

A kinetic method for determination of chlorine in air was described in the present work. The method based on fading of methyl orange (MO) containing solution in air absorption process. A determination limit of 2.64 microg L(-1) was found. With the present method, chlorine concentration could be determined in several minutes with convenient manipulation. As concentration variation of methyl orange in the absorption solution did not affect the experimental results, fabrication and preservation of the stock absorption is also convenient. The present method is promising in monitoring chlorine concentration in atmosphere.