AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived f...AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD).展开更多
BACKGROUND Duodenal biopsies are commonly obtained during esophagogastroduodenoscopy(EGD) but are very often histopathologically normal. Therefore, a more strategic method for evaluating the duodenal mucosa and avoidi...BACKGROUND Duodenal biopsies are commonly obtained during esophagogastroduodenoscopy(EGD) but are very often histopathologically normal. Therefore, a more strategic method for evaluating the duodenal mucosa and avoiding unnecessary biopsies is needed.AIM To examine the clinical utility of narrow band imaging(NBI) for evaluating duodenal villous morphology.METHODS We performed a prospective cohort study of adult patients at Mayo Clinic Rochester from 2013-2014 who were referred for EGD with duodenal biopsies. A staff endoscopist scored, in real-time, the NBI-based appearance of duodenal villi into one of three categories(normal, partial villous atrophy, or complete villous atrophy), captured ≥ 2 representative duodenal NBI images, and obtained mucosal biopsies therein. Images were then scored by an advanced endoscopist and gastroenterology fellow, and biopsies(gold standard) by a pathologist, in a masked fashion using the same three-category classification. Performing endoscopist, advanced endoscopist, and fellow NBI scores were compared to histopathology to calculate performance characteristics [sensitivity, specificity,positive and negative, negative predictive value(NPV), and accuracy]. Inter-rater agreement was assessed with Cohen's kappa.RESULTS112 patients were included. The most common referring indications were dyspepsia(47%), nausea(23%), and suspected celiac disease(14%). Duodenal histopathology scores were: 84% normal, 11% partial atrophy, and 5% complete atrophy. Performing endoscopist NBI scores were 79% normal, 14% partial atrophy, and 6% complete atrophy compared to 91%, 5%, and 4% and 70%, 24%,and 6% for advanced endoscopist and fellow, respectively. NBI performed favorably for all raters, with a notably high(92%-100%) NPV. NBI score agreement was best between performing endoscopist and fellow(κ = 0.65).CONCLUSION NBI facilitates accurate, non-invasive evaluation of duodenal villi. Its high NPV renders it especially useful for foregoing biopsies of histopathologically normal duodenal mucosa.展开更多
Chronic denervation is one of the key factors that affect nerve regeneration.Chronic axotomy deteriorates the distal nerve stump,causes protein changes,and renders the microenvironment less permissive for regeneration...Chronic denervation is one of the key factors that affect nerve regeneration.Chronic axotomy deteriorates the distal nerve stump,causes protein changes,and renders the microenvironment less permissive for regeneration.Some of these factors/proteins have been individually studied.To better delineate the comprehensive protein expression profiles and identify proteins that contribute to or are associated with this detrimental effect,we carried out a proteomic analysis of the distal nerve using an established delayed rat sciatic nerve repair model.Four rats that received immediate repair after sciatic nerve transection served as control,whereas four rats in the experimental group(chronic denervation)had their sciatic nerve repaired after a 12-week delay.All the rats were sacrificed after 16 weeks to harvest the distal nerves for extracting proteins.Twenty-five micrograms of protein from each sample were fractionated in SDS-PAGE gels.NanoLC-MS/MS analysis was applied to the gels.Protein expression levels of nerves on the surgery side were compared to those on the contralateral side.Any protein with a P value of less than 0.05 and a fold change of 4 or higher was deemed differentially expressed.All the differentially expressed proteins in both groups were further stratified according to the biological processes.A PubMed search was also conducted to identify the differentially expressed proteins that have been reported to be either beneficial or detrimental to nerve regeneration.Ingenuity Pathway Analysis(IPA)software was used for pathway analysis.The results showed that 709 differentially expressed proteins were identified in the delayed repair group,with a bigger proportion of immune and inflammatory process-related proteins and a smaller proportion of proteins related to axon regeneration and lipid metabolism in comparison to the control group where 478 differentially expressed proteins were identified.The experimental group also had more beneficial proteins that were downregulated and more detrimental proteins that were upregulated.IPA revealed that protective pathways such as LXR/RXR,acute phase response,RAC,ERK/MAPK,CNTF,IL-6,and FGF signaling were inhibited in the delayed repair group,whereas three detrimental pathways,including the complement system,PTEN,and apoptosis signaling,were activated.An available database of the adult rodent sciatic nerve was used to assign protein changes to specific cell types.The poor regeneration seen in the delayed repair group could be associated with the down-regulation of beneficial proteins and up-regulation of detrimental proteins.The proteins and pathways identified in this study may offer clues for future studies to identify therapeutic targets.展开更多
AIM: To assess whether metformin, which has a chemopreventive effect in chronic liver disease, has any chemotherapeutic effect in hepatocellular carcinoma.
AIM To determine the frequency and risk factors for colorectal cancer(CRC) development among individuals with resected advanced adenoma(AA)/traditional serrated adenoma(TSA)/advanced sessile serrated adenoma(ASSA). ME...AIM To determine the frequency and risk factors for colorectal cancer(CRC) development among individuals with resected advanced adenoma(AA)/traditional serrated adenoma(TSA)/advanced sessile serrated adenoma(ASSA). METHODS Data was collected from medical records of 14663 subjects found to have AA, TSA, or ASSA at screening or surveillance colonoscopy. Patients with inflammatory bowel disease or known genetic predisposition for CRC were excluded from the study. Factors associated with CRC developing after endoscopic management of high risk polyps were calculated in 4610 such patients who had at least one surveillance colonoscopy within 10 years following the original polypectomy of the incident advanced polyp. RESULTS84/4610(1.8%) patients developed CRC at the polypectomy site within a median of 4.2 years(mean 4.89 years), and 1.2%(54/4610) developed CRC in a region distinct from the AA/TSA/ASSA resection site within a median of 5.1 years(mean 6.67 years). Approximately, 30%(25/84) of patients who developed CRC at the AA/TSA/ASSA site and 27.8%(15/54) of patients who developed CRC at another site had colonoscopy at recommended surveillance intervals. Increasing age; polyp size; male sex; right-sided location; high degree of dysplasia; higher number of polyps resected; and piecemeal removal were associated with an increased risk for CRC developmentat the same site as the index polyp. Increasing age; right-sided location; higher number of polyps resected and sessile endoscopic appearance of the index AA/TSA/ASSA were significantly associated with an increased risk for CRC development at a different site. CONCLUSION Recognition that CRC may develop following AA/TSA/ASSA removal is one step toward improving our practice efficiency and preventing a portion of CRC related morbidity and mortality.展开更多
AIM: To describe the dietary recommendations of experienced endoscopists for patients who have undergone endoscopic retrograde cholangiopancreatography (ERCP) and the factors that influence these recommendations. METH...AIM: To describe the dietary recommendations of experienced endoscopists for patients who have undergone endoscopic retrograde cholangiopancreatography (ERCP) and the factors that influence these recommendations. METHODS: Selected U.S. endoscopists with ERCP experience were surveyed by e-mail. A questionnaire with three hypothetical ERCP cases of patients at low, medium and high risk for development of post-ERCP pancreatitis (PEP) was shown. For each scenario, respondents were asked to recommend a post-procedure diet and time to first oral intake. Respondents were also asked about the effect of various clinical factors on their recommendations, including risk of PEP.RESULTS: 97/187 selected ASGE members (51.9%) responded. When risk of PEP was either low, medium or high, 53%, 88% and 96% recommended a diet of clear liquids/NPO respectively, and 2%, 5% and 18% recommended delaying first oral intake until the following day. About 88% of respondents gave the same type of diet to patients at high as those with moderate-risk of PEP (P = 0.04). However, 37% and 43% of respondents gave different types of diet to patients at low vs moderate-risk and low-risk vs high-risk of PEP respectively (P < 0.001). No statistically significant associations were found regarding the effect of other clinical factors or respondent demographics.CONCLUSION: Most experienced endoscopists limit diet to NPO/clear liquids after ERCP for patients at high or moderate risk of post-ERCP pancreatitis. About half allow a low-fat or regular diet in patients at low risk.展开更多
BACKGROUND： Fibromyalgia is a syndrome characterized by chronic pain, fatigue, depression, and sleep disturbances. Its primary cause is unclear. Several studies have reported decreased intracellular magnesium levels ...BACKGROUND： Fibromyalgia is a syndrome characterized by chronic pain, fatigue, depression, and sleep disturbances. Its primary cause is unclear. Several studies have reported decreased intracellular magnesium levels in patients with fibromyalgia and have found negative correlation between magnesium levels and fibromyalgia symptoms.OBJECTIVE： To gather preliminary data on whether transdermal magnesium can improve quality of life for women who have fibromyalgia. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： This is a patient questionnaires and survey in a fibremyalgia clinic at a tertiary medical center. Forty female patients with the diagnosis of fibremyalgia were enrolled. Each participant was provided a spray bottle containing a transdermal magnesium chloride solution and asked to apply 4 sprays per limb twice daily for 4 weeks. Participants were asked to complete the Revised Fibromyalgia Impact Questionnaire, SF-36v2 Health Survey, and a quality-of-life analog scale at baseline, week 2, and week 4. MAIN OUTCOME MEASURE： Questionnaire and survey scores, evaluated through intent-to-treat and per-protocol analyses. RESULTS： Twenty-four patients completed the study （mean [SD] age, 57.2 [7.6] years; white, 95%; mean body mass index, 31.3 kg/m2）. With intention-to-treat analysis, Revised Fibromyalgia Impact Questionnaire subscale and total scores were significantly improved at week 2 and week 4 （total score, P = 0.001）. Per-protocol analysis results were similar： all subscales of the Revised Fibremyalgia Impact Questionnaire were significantly improved at week 2 and week 4 （total score, P = 0.001）. CONCLUSION： This pilot study suggests that transdermal magnesium chloride applied on upper and lower limbs may be beneficial to patients with fibromyalgia.展开更多
AIM To characterize isolated non-obstructive sinusoidal dilatation(SD) by identifying associated conditions, laboratory findings, and histological patterns. METHODS Retrospectively reviewed 491 patients with SD betwee...AIM To characterize isolated non-obstructive sinusoidal dilatation(SD) by identifying associated conditions, laboratory findings, and histological patterns. METHODS Retrospectively reviewed 491 patients with SD between 1995 and 2015. Patients with obstruction at the level of the small/large hepatic veins, portal veins, or right-sided heart failure were excluded along with history of cirrhosis, hepatic malignancy, liver transplant, or absence of electrocardiogram/cardiac echocardiogram. Liver histology was reviewed for extent of SD, fibrosis, red blood cell extravasation, nodular regenerative hyperplasia, hepaticpeliosis, and hepatocellular plate atrophy(HPA). RESULTS We identified 88 patients with non-obstructive SD. Inflammatory conditions(32%) were the most common cause. The most common pattern of liver abnormalities was cholestatic(76%). Majority(78%) had localized SD to Zone Ⅲ. Medication-related SD had higher proportion of portal hypertension(53%), ascites(58%), and median AST(113 U/L) and ALT(90 U/L) levels. Nineteen patients in our study died within one-year after diagnosis of SD, majority from complications related to underlying diseases.CONCLUSION Significant proportion of SD and HPA exist without impaired hepatic venous outflow. Isolated SD on liver biopsy, in the absence of congestive hepatopathy, requires further evaluation and portal hypertension should be rule out.展开更多
The increase in health care costs is not sustainable and has heightened the need for innovative low cost effective strategies for delivering patient care.Remote monitoring holds great promise for preventing or shorten...The increase in health care costs is not sustainable and has heightened the need for innovative low cost effective strategies for delivering patient care.Remote monitoring holds great promise for preventing or shortening duration of hospitalization even while improving quality of care.We therefore conducted a proof of concept study to examine the quality of electrocardiograph(ECG)recordings obtained remotely and to test its potential utility in detecting harmful rhythms such as atrial fibrillation.We tested a novel adhesive strip ECG monitor and assessed the ECG quality in ambulatory individuals.2630 ECG strips were analyzed and classified as:Sinus,atrial fibrillation(AF),indeterminate,or other.Four readers independently rated ECG quality:0:Noise;1:QRS complexes seen,but P-wave indeterminate;2:QRS complexes seen,P-waves seen but poor quality;and 3:Clean QRS complexes and P-waves.The combined average rating was:Noise 12%;R-R,no P-wave 10%;R-R,no PR interval 18%;and R-R with PR interval 60%(if Sinus).If minimum diagnostic quality was a score of 1,88%of strips were diagnostic.There was moderate to high agreement regarding quality(weighted Kappa statistic values;0.58 to 0.76)and high level of agreement regarding ECG diagnosis(ICC=0.93).A highly variable RR interval(HRV≥7)predicted AF(AUC=0.87).The monitor acquires and transmits diagnostic high quality ECG data and permits characterization of AF.展开更多
Migraine is a complex trait in which multiple genetic loci, as well as environmental factors, likely contribute to its clinical manifestation. Many genetic associations reported in previous studies either have not bee...Migraine is a complex trait in which multiple genetic loci, as well as environmental factors, likely contribute to its clinical manifestation. Many genetic associations reported in previous studies either have not been replicated to date or showed only marginal statistical significance, possibly due to the genetic heterogeneity of the common forms of migraine. One major phenotypic and possibly genetically identifiable migraine subgroup consists of women whose attacks are influenced by fluctuation in gonadal hormones. We hypothesized that for these women, the association between migraine attacks and the menstrual cycle might be attributable to an increased prevalence of genetic polymorphisms in the hypothalamic-pituitary-gonadal axis. We selected 21 such polymerphisms previously reported to be associated with the common forms of migraine and genotyped 1740 individuals (1132 migraineurs) to determine whether any of these selected polymorphisms occurred more frequently in females with hormonally modulated migraine. We were able to confirm the association of migraine with 3 genetic polymorphisms seen in previous studies (rs4680 [COMT], rs2283265 [DRD2], and rs7131056 [DRD2]). Interestingly, we found 2 additional genetic polymorphisms (rs2070762 [TH] and rs6356 [TH]) to be associated with migraine when defining the phenotype as hormonally modulated migraine.展开更多
We determined whether telavancin is as active in experimental immunocompetent murine pneumococcal pneumonia as is vancomycin or ceftriaxone. Experimental murine pneumonia was established by intratracheal administratio...We determined whether telavancin is as active in experimental immunocompetent murine pneumococcal pneumonia as is vancomycin or ceftriaxone. Experimental murine pneumonia was established by intratracheal administration of Streptococcus pneumoniae. Four groups of animals were studied, untreated and treated with vancomycin (110 mg/kg, bid, SQ), telavancin (40 mg/kg, bid, SQ), or ceftriaxone (50 mg/kg, bid, SQ) for 2 days. The untreated animals had a mean of 6.54 ± 0.82 log10 cfu/g lung. The vancomycin-, telavancin-, and ceftriaxone-treated animals had means of 2.01 ± 0.02, 2.00 ± 0.00, and 2.00 ± 0.01 log10 cfu/g lung, respectively (p-values < 0.0001 for each treatment group versus the untreated group). In the model studied, telavancin was as active as vancomycin and ceftriaxone in treating experimental pneumococcal pneumonia in mice.展开更多
Background:Human epidermal growth factor receptor(EGFR)is an oncogenic gene and one of top targets of precision therapy in lung cancer with EGFR mutations.Although there are many reports for some individual cancers,co...Background:Human epidermal growth factor receptor(EGFR)is an oncogenic gene and one of top targets of precision therapy in lung cancer with EGFR mutations.Although there are many reports for some individual cancers,comprehensive profiling of EGFR mutations,overexpression,amplification,DNA methylation,and their clinical associations across many different cancers simultaneously was not available.This study aimed to fill the gap and provide insights to the alteration spectrum of EGFR and its therapeutic and prognostic implications.Methods:The Cancer Genome Atlas(TCGA)datasets for 32 cancer types involving 11,314 patients were analyzed for alterations(mutations and amplification/deletion),abnormal expression and DNA methylation in EGFR gene.Mutation frequency,genomic location distribution,functional impact,and clinical targeted therapy implication were compared among different cancer types,and their associations with patient survival were analyzed.Results:EGFR alteration frequency,mutation sites across functional domains,amplification,overexpression,and DNA methylation patterns differed greatly among different cancer types.The overall mutation frequency in all cancers combined was relatively low.Targetable mutations,mainly in lung cancer,were primarily found in the Pkinase_Tyr domain.Glioblastoma multiforme had the highest rate of alterations,but it was dominated by gene amplification and most mutations were in the Furin-like domain where targeted therapy was less effective.Low-grade glioma often had gene amplification and increased EGFR expression which was associated with poor outcome.Colon and pancreatic adenocarcinoma had very few EGFR mutations;however,high EGFR expression was significantly associated with short patient survival.Squamous cell carcinoma regardless of their sites(the head and neck,lung,or esophagus)exhibited similar characteristics with an alteration frequency of about 5.0%,was dominated by gene amplification,and had increased EGFR expression generally associated with short patient survival.DNA methylation was highly associated with EGFR expression and patient outcomes in some cancers.Conclusions:EGFR aberration type,frequency,distribution in functional domains,and expression vary from cancer to cancer.While mutations in the Pkinase_Tyr domain are more important for treatment selection,increased expression from amplification or deregulation affects more tumor types and leads to worse outcome,which calls for new treatment strategies for these EGFR-driven tumors.展开更多
Background Food composition and style is changing dramatically now, which causes inappropriate secretion of hormones from brain, gastrointestinal and endo-pancreas, may be related to unbalance of glucose in blood. The...Background Food composition and style is changing dramatically now, which causes inappropriate secretion of hormones from brain, gastrointestinal and endo-pancreas, may be related to unbalance of glucose in blood. The aim of this study was to explore the fast response of C-peptide, glucagon-like peptide-1 （GLP-1）, ghrelin and endomorphin-1 （EM-1） to the eastern and western style meals in patients with type 2 diabetes mellitus. Methods The study enrolled 57 patients with type 2 diabetes （20 men and 37 women, mean age （67.05±8.26） years）. Eastern style meal （meal A） and western style meal （meal B） were designed to produce the fullness effect. C-peptide, GLP-1, ghrelin and EM-1 were assessed before （0 hour） and after （2 hours） each diet. Results The delta （2h-0h） of C- peptide in meal A was significantly lower than that in meal B （P=0.0004）. C-peptide, GLP-1, ghrelin and EM-1 were obviously higher before meal B than those before meal A （P 〈0.0001, 〈0.0001, =0.001, =0.0004 respectively）. Blood glucose 2 hours and 3 hours after meal B were higher than those after meal A （P=0.0005, 0.0079 respectively）. Correlations between GLP-1 and ghrelin were strongly positive before both meals and 2 hours after both meals and also in relation to the delta of meal A and meal B （rA0h=0.7838, rB05=0.9368, rA25=0.7615, rB2h=0.9409, r A（2h-0h）=0.7531, rB（2h 05）=0.9980, respectively, P 〈0.0001）. Conclusion Western style meal （high fat and protein food） could make more response of C-peptide than eastern style meal, and could stimulate more gut hormones （GLP-1, ghrelin） and brain peptide （EM-1） at the first phase of digestion.展开更多
Background:Capsule endoscopy(CE)is frequently hindered by intra-luminal debris.Our aim was to determine whether a combination bowel preparation would improve small-bowel visualization,diagnostic yield,and the completi...Background:Capsule endoscopy(CE)is frequently hindered by intra-luminal debris.Our aim was to determine whether a combination bowel preparation would improve small-bowel visualization,diagnostic yield,and the completion rate of CE.Methods:Single-blind,prospective randomized–controlled study of outpatients scheduled for CE.Bowel-preparation subjects ingested 2 L of polyethylene glycol solution the night prior to CE,5mL simethicone and 5mg metoclopramide 20 minutes prior to CE and laid in the right lateral position 30 minutes after swallowing CE.Controls had no solid food after 7 p.m.the night prior to CE and no liquids 4 hours prior to CE.Participants completed a satisfaction survey.Capsule readers completed a small-bowel-visualization assessment.Results:Fifty patients were prospectively enrolled(56%female)with a median age of 54.4 years and 44 completed the study(23 patients in the control group and 21 in the preparation group).There was no significant difference between groups on quartile-based small-bowel visualization(all P>0.05).There was no significant difference between groups in diagnostic yield(P=0.69),mean gastric(P=0.10)or small-bowel transit time(P=0.89).The small-bowel completion rate was significantly higher in the preparation group(100%vs 78%;P=0.02).Bowel-preparation subjects reported significantly more discomfort than controls(62%vs 17%;P=0.01).Conclusions:Combined bowel preparation did not improve small-bowel visualization but did significantly increase patient discomfort.The CE completion rate improved in the preparation group but the diagnostic yield was unaffected.Based on our findings,a bowel preparation prior to CE does not appear to improve CE performance and results in decreased patient satisfaction(ClinicalTrials.gov,No.NCT01243736).展开更多
Peripheral artery disease(PAD)results from the buildup of atherosclerotic plaque in the arterial wall,can progress to severe ischemia and lead to tissue necrosis and limb amputation.We evaluated a means of assessing P...Peripheral artery disease(PAD)results from the buildup of atherosclerotic plaque in the arterial wall,can progress to severe ischemia and lead to tissue necrosis and limb amputation.We evaluated a means of assessing PAD mechanics ex vivo using ten human peripheral arteries with PAD.Pressure-inflation testing was performed at six physiological pressure intervals ranging from 10 to 200 mmHg.These vessels were imaged with IVUS-VH to determine plaque composition and change in vessel structure with pressure.Statistical analysis was performed to determine which plaque structures and distributions of these structures had the greatest influence on wall deformation.We found that fibrous plaque,necrotic core,and calcification had a statistically significant effect on all variables(p<0.05).The presence of large concentrations of fibrous plaque was linked to reduced vessel compliance and ellipticity,which could lead to stent fractures and restenosis.For the plaque distribution we found that clustered necrotic core increased overall compliance while clustered calcification decreased overall compliance.The effect of plaque distribution on vessel wall deformation must be considered equally important to plaque concentration.展开更多
non-invasive chronic rhinosinusitis(CRS)following liver or kidney transplant and determine factors associated with disease-related complications,selection of endoscopic sinus surgery(ESS),and disease resolution in thi...non-invasive chronic rhinosinusitis(CRS)following liver or kidney transplant and determine factors associated with disease-related complications,selection of endoscopic sinus surgery(ESS),and disease resolution in this population.Study design:Retrospective chart review.Setting:An academic tertiary care center(Mayo Clinic,Rochester,Minnesota).Subjects and methods:Liver and kidney transplant recipients evaluated by Mayo Clinic otolaryngologists for CRS between 1998 and 2018 were identified.Univariate and multivariate logistic regression analyses were used to determine patient factors and treatment modalities associated with developing complications,selection of ESS,and disease resolution.Results:Fifty-seven patients met inclusion criteria.No patients developed intraorbital or intracranial complications of their CRS.Multivariate modeling demonstrated that the presence of polyps(P=0.036)was associated with undergoing ESS within one year of presentation.A higher Lund-Mackay(LM)computed tomography score(P=0.023)and older age(P=0.018)were significantly associated with decreased disease resolution.No other factors were significantly associated with the use of endoscopic sinus surgery within one year of otolaryngology presentation or resolution of CRS in this cohort.Conclusion:The risk of developing CRS-related intraorbital or intracranial complications in this immunecompromised patient cohort may be lower than originally thought.For liver-and kidney-recipients stable on immunosuppressive medication for many years,prognostic factors for CRS may mirror those for immunocompetent patients.展开更多
In shotgun proteomics, database search algorithms rely on fragmentation models to pre- dict fragment ions that should be observed for a given peptide sequence. The most widely used strat- egy （Naive model） is oversi...In shotgun proteomics, database search algorithms rely on fragmentation models to pre- dict fragment ions that should be observed for a given peptide sequence. The most widely used strat- egy （Naive model） is oversimplified, cleaving all peptide bonds with equal probability to produce fragments of all charges below that of the precursor ion. More accurate models, based on fragmen- tation simulation, are too computationally intensive for on-the-fly use in database search algorithms. We have created an ordinal-regression-based model called Basophile that takes fragment size and basic residue distribution into account when determining the charge retention during CID/higher- energy collision induced dissociation （HCD） of charged peptides. This model improves the accuracy of predictions by reducing the number of unnecessary fragments that are routinely predicted for highly-charged precursors. Basophile increased the identification rates by 26% （on average） over the Naive model, when analyzing triply-charged precursors from ion trap data. Basophile achieves simplicity and speed by solving the prediction problem with an ordinal regression equation, which can be incorporated into any database search software for shotgun proteomic identification.展开更多
基金Mayo Clinic Center for Clinical and Translational Science(CCATS)No.NCATS 1UL1TR002377-01+1 种基金Mayo Clinic Center for Cell Signaling in Gastroenterology,No.NIDDK P30DK084567-09Wako Life Sciences,Inc
文摘AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD).
基金the National Institutes of Health,No.T32DK007198 in part during the study period
文摘BACKGROUND Duodenal biopsies are commonly obtained during esophagogastroduodenoscopy(EGD) but are very often histopathologically normal. Therefore, a more strategic method for evaluating the duodenal mucosa and avoiding unnecessary biopsies is needed.AIM To examine the clinical utility of narrow band imaging(NBI) for evaluating duodenal villous morphology.METHODS We performed a prospective cohort study of adult patients at Mayo Clinic Rochester from 2013-2014 who were referred for EGD with duodenal biopsies. A staff endoscopist scored, in real-time, the NBI-based appearance of duodenal villi into one of three categories(normal, partial villous atrophy, or complete villous atrophy), captured ≥ 2 representative duodenal NBI images, and obtained mucosal biopsies therein. Images were then scored by an advanced endoscopist and gastroenterology fellow, and biopsies(gold standard) by a pathologist, in a masked fashion using the same three-category classification. Performing endoscopist, advanced endoscopist, and fellow NBI scores were compared to histopathology to calculate performance characteristics [sensitivity, specificity,positive and negative, negative predictive value(NPV), and accuracy]. Inter-rater agreement was assessed with Cohen's kappa.RESULTS112 patients were included. The most common referring indications were dyspepsia(47%), nausea(23%), and suspected celiac disease(14%). Duodenal histopathology scores were: 84% normal, 11% partial atrophy, and 5% complete atrophy. Performing endoscopist NBI scores were 79% normal, 14% partial atrophy, and 6% complete atrophy compared to 91%, 5%, and 4% and 70%, 24%,and 6% for advanced endoscopist and fellow, respectively. NBI performed favorably for all raters, with a notably high(92%-100%) NPV. NBI score agreement was best between performing endoscopist and fellow(κ = 0.65).CONCLUSION NBI facilitates accurate, non-invasive evaluation of duodenal villi. Its high NPV renders it especially useful for foregoing biopsies of histopathologically normal duodenal mucosa.
基金supported by Helene Houle Career Development Award in Neurologic Surgery Research and Fund for Mayo Clinic Center for Regenerative Medicine Program Director,Neuroregenerative Medicine,Mayo Clinic College of Medicine and Science.SG was supported by the Chinese Scholarship Council.
文摘Chronic denervation is one of the key factors that affect nerve regeneration.Chronic axotomy deteriorates the distal nerve stump,causes protein changes,and renders the microenvironment less permissive for regeneration.Some of these factors/proteins have been individually studied.To better delineate the comprehensive protein expression profiles and identify proteins that contribute to or are associated with this detrimental effect,we carried out a proteomic analysis of the distal nerve using an established delayed rat sciatic nerve repair model.Four rats that received immediate repair after sciatic nerve transection served as control,whereas four rats in the experimental group(chronic denervation)had their sciatic nerve repaired after a 12-week delay.All the rats were sacrificed after 16 weeks to harvest the distal nerves for extracting proteins.Twenty-five micrograms of protein from each sample were fractionated in SDS-PAGE gels.NanoLC-MS/MS analysis was applied to the gels.Protein expression levels of nerves on the surgery side were compared to those on the contralateral side.Any protein with a P value of less than 0.05 and a fold change of 4 or higher was deemed differentially expressed.All the differentially expressed proteins in both groups were further stratified according to the biological processes.A PubMed search was also conducted to identify the differentially expressed proteins that have been reported to be either beneficial or detrimental to nerve regeneration.Ingenuity Pathway Analysis(IPA)software was used for pathway analysis.The results showed that 709 differentially expressed proteins were identified in the delayed repair group,with a bigger proportion of immune and inflammatory process-related proteins and a smaller proportion of proteins related to axon regeneration and lipid metabolism in comparison to the control group where 478 differentially expressed proteins were identified.The experimental group also had more beneficial proteins that were downregulated and more detrimental proteins that were upregulated.IPA revealed that protective pathways such as LXR/RXR,acute phase response,RAC,ERK/MAPK,CNTF,IL-6,and FGF signaling were inhibited in the delayed repair group,whereas three detrimental pathways,including the complement system,PTEN,and apoptosis signaling,were activated.An available database of the adult rodent sciatic nerve was used to assign protein changes to specific cell types.The poor regeneration seen in the delayed repair group could be associated with the down-regulation of beneficial proteins and up-regulation of detrimental proteins.The proteins and pathways identified in this study may offer clues for future studies to identify therapeutic targets.
基金Supported by National Institutes of Health,No.NCI CA165076Mayo Clinic Center for Cell Signaling in Gastroenterology,No.NIDDK P30DK084567+1 种基金Mayo Clinic Cancer Center,No.NCI CA15083Mayo Clinic Center for Clinical and Translational Science,No.NCATS UL1 TR000135
文摘AIM: To assess whether metformin, which has a chemopreventive effect in chronic liver disease, has any chemotherapeutic effect in hepatocellular carcinoma.
基金Supported by the National Cancer Institute,No.CA170357the Mayo Clinic Center for Cell Signaling in Gastroenterology,NIDDK Mo.P30DK084567
文摘AIM To determine the frequency and risk factors for colorectal cancer(CRC) development among individuals with resected advanced adenoma(AA)/traditional serrated adenoma(TSA)/advanced sessile serrated adenoma(ASSA). METHODS Data was collected from medical records of 14663 subjects found to have AA, TSA, or ASSA at screening or surveillance colonoscopy. Patients with inflammatory bowel disease or known genetic predisposition for CRC were excluded from the study. Factors associated with CRC developing after endoscopic management of high risk polyps were calculated in 4610 such patients who had at least one surveillance colonoscopy within 10 years following the original polypectomy of the incident advanced polyp. RESULTS84/4610(1.8%) patients developed CRC at the polypectomy site within a median of 4.2 years(mean 4.89 years), and 1.2%(54/4610) developed CRC in a region distinct from the AA/TSA/ASSA resection site within a median of 5.1 years(mean 6.67 years). Approximately, 30%(25/84) of patients who developed CRC at the AA/TSA/ASSA site and 27.8%(15/54) of patients who developed CRC at another site had colonoscopy at recommended surveillance intervals. Increasing age; polyp size; male sex; right-sided location; high degree of dysplasia; higher number of polyps resected; and piecemeal removal were associated with an increased risk for CRC developmentat the same site as the index polyp. Increasing age; right-sided location; higher number of polyps resected and sessile endoscopic appearance of the index AA/TSA/ASSA were significantly associated with an increased risk for CRC development at a different site. CONCLUSION Recognition that CRC may develop following AA/TSA/ASSA removal is one step toward improving our practice efficiency and preventing a portion of CRC related morbidity and mortality.
文摘AIM: To describe the dietary recommendations of experienced endoscopists for patients who have undergone endoscopic retrograde cholangiopancreatography (ERCP) and the factors that influence these recommendations. METHODS: Selected U.S. endoscopists with ERCP experience were surveyed by e-mail. A questionnaire with three hypothetical ERCP cases of patients at low, medium and high risk for development of post-ERCP pancreatitis (PEP) was shown. For each scenario, respondents were asked to recommend a post-procedure diet and time to first oral intake. Respondents were also asked about the effect of various clinical factors on their recommendations, including risk of PEP.RESULTS: 97/187 selected ASGE members (51.9%) responded. When risk of PEP was either low, medium or high, 53%, 88% and 96% recommended a diet of clear liquids/NPO respectively, and 2%, 5% and 18% recommended delaying first oral intake until the following day. About 88% of respondents gave the same type of diet to patients at high as those with moderate-risk of PEP (P = 0.04). However, 37% and 43% of respondents gave different types of diet to patients at low vs moderate-risk and low-risk vs high-risk of PEP respectively (P < 0.001). No statistically significant associations were found regarding the effect of other clinical factors or respondent demographics.CONCLUSION: Most experienced endoscopists limit diet to NPO/clear liquids after ERCP for patients at high or moderate risk of post-ERCP pancreatitis. About half allow a low-fat or regular diet in patients at low risk.
基金Supported by Taiwan’s SBIR promoting program from the De-partment of Industrial Technology of the Ministry of Economic Affairs,Advpharma,Incthe National Defense Medical Cen-ter(NDMC),Bureau of Military Medicine,Ministry of Defense,Taiwan
文摘AIM: Optimal molecular markers for detecting colorectal cancer (CRC) in a blood-based assay were evaluated.
文摘BACKGROUND： Fibromyalgia is a syndrome characterized by chronic pain, fatigue, depression, and sleep disturbances. Its primary cause is unclear. Several studies have reported decreased intracellular magnesium levels in patients with fibromyalgia and have found negative correlation between magnesium levels and fibromyalgia symptoms.OBJECTIVE： To gather preliminary data on whether transdermal magnesium can improve quality of life for women who have fibromyalgia. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： This is a patient questionnaires and survey in a fibremyalgia clinic at a tertiary medical center. Forty female patients with the diagnosis of fibremyalgia were enrolled. Each participant was provided a spray bottle containing a transdermal magnesium chloride solution and asked to apply 4 sprays per limb twice daily for 4 weeks. Participants were asked to complete the Revised Fibromyalgia Impact Questionnaire, SF-36v2 Health Survey, and a quality-of-life analog scale at baseline, week 2, and week 4. MAIN OUTCOME MEASURE： Questionnaire and survey scores, evaluated through intent-to-treat and per-protocol analyses. RESULTS： Twenty-four patients completed the study （mean [SD] age, 57.2 [7.6] years; white, 95%; mean body mass index, 31.3 kg/m2）. With intention-to-treat analysis, Revised Fibromyalgia Impact Questionnaire subscale and total scores were significantly improved at week 2 and week 4 （total score, P = 0.001）. Per-protocol analysis results were similar： all subscales of the Revised Fibremyalgia Impact Questionnaire were significantly improved at week 2 and week 4 （total score, P = 0.001）. CONCLUSION： This pilot study suggests that transdermal magnesium chloride applied on upper and lower limbs may be beneficial to patients with fibromyalgia.
文摘AIM To characterize isolated non-obstructive sinusoidal dilatation(SD) by identifying associated conditions, laboratory findings, and histological patterns. METHODS Retrospectively reviewed 491 patients with SD between 1995 and 2015. Patients with obstruction at the level of the small/large hepatic veins, portal veins, or right-sided heart failure were excluded along with history of cirrhosis, hepatic malignancy, liver transplant, or absence of electrocardiogram/cardiac echocardiogram. Liver histology was reviewed for extent of SD, fibrosis, red blood cell extravasation, nodular regenerative hyperplasia, hepaticpeliosis, and hepatocellular plate atrophy(HPA). RESULTS We identified 88 patients with non-obstructive SD. Inflammatory conditions(32%) were the most common cause. The most common pattern of liver abnormalities was cholestatic(76%). Majority(78%) had localized SD to Zone Ⅲ. Medication-related SD had higher proportion of portal hypertension(53%), ascites(58%), and median AST(113 U/L) and ALT(90 U/L) levels. Nineteen patients in our study died within one-year after diagnosis of SD, majority from complications related to underlying diseases.CONCLUSION Significant proportion of SD and HPA exist without impaired hepatic venous outflow. Isolated SD on liver biopsy, in the absence of congestive hepatopathy, requires further evaluation and portal hypertension should be rule out.
文摘The increase in health care costs is not sustainable and has heightened the need for innovative low cost effective strategies for delivering patient care.Remote monitoring holds great promise for preventing or shortening duration of hospitalization even while improving quality of care.We therefore conducted a proof of concept study to examine the quality of electrocardiograph(ECG)recordings obtained remotely and to test its potential utility in detecting harmful rhythms such as atrial fibrillation.We tested a novel adhesive strip ECG monitor and assessed the ECG quality in ambulatory individuals.2630 ECG strips were analyzed and classified as:Sinus,atrial fibrillation(AF),indeterminate,or other.Four readers independently rated ECG quality:0:Noise;1:QRS complexes seen,but P-wave indeterminate;2:QRS complexes seen,P-waves seen but poor quality;and 3:Clean QRS complexes and P-waves.The combined average rating was:Noise 12%;R-R,no P-wave 10%;R-R,no PR interval 18%;and R-R with PR interval 60%(if Sinus).If minimum diagnostic quality was a score of 1,88%of strips were diagnostic.There was moderate to high agreement regarding quality(weighted Kappa statistic values;0.58 to 0.76)and high level of agreement regarding ECG diagnosis(ICC=0.93).A highly variable RR interval(HRV≥7)predicted AF(AUC=0.87).The monitor acquires and transmits diagnostic high quality ECG data and permits characterization of AF.
文摘Migraine is a complex trait in which multiple genetic loci, as well as environmental factors, likely contribute to its clinical manifestation. Many genetic associations reported in previous studies either have not been replicated to date or showed only marginal statistical significance, possibly due to the genetic heterogeneity of the common forms of migraine. One major phenotypic and possibly genetically identifiable migraine subgroup consists of women whose attacks are influenced by fluctuation in gonadal hormones. We hypothesized that for these women, the association between migraine attacks and the menstrual cycle might be attributable to an increased prevalence of genetic polymorphisms in the hypothalamic-pituitary-gonadal axis. We selected 21 such polymerphisms previously reported to be associated with the common forms of migraine and genotyped 1740 individuals (1132 migraineurs) to determine whether any of these selected polymorphisms occurred more frequently in females with hormonally modulated migraine. We were able to confirm the association of migraine with 3 genetic polymorphisms seen in previous studies (rs4680 [COMT], rs2283265 [DRD2], and rs7131056 [DRD2]). Interestingly, we found 2 additional genetic polymorphisms (rs2070762 [TH] and rs6356 [TH]) to be associated with migraine when defining the phenotype as hormonally modulated migraine.
文摘We determined whether telavancin is as active in experimental immunocompetent murine pneumococcal pneumonia as is vancomycin or ceftriaxone. Experimental murine pneumonia was established by intratracheal administration of Streptococcus pneumoniae. Four groups of animals were studied, untreated and treated with vancomycin (110 mg/kg, bid, SQ), telavancin (40 mg/kg, bid, SQ), or ceftriaxone (50 mg/kg, bid, SQ) for 2 days. The untreated animals had a mean of 6.54 ± 0.82 log10 cfu/g lung. The vancomycin-, telavancin-, and ceftriaxone-treated animals had means of 2.01 ± 0.02, 2.00 ± 0.00, and 2.00 ± 0.01 log10 cfu/g lung, respectively (p-values < 0.0001 for each treatment group versus the untreated group). In the model studied, telavancin was as active as vancomycin and ceftriaxone in treating experimental pneumococcal pneumonia in mice.
基金China Scholarship Council,Grant/Award Number:201806015028Chinese National Natural Science Foundation,Grant/Award Numbers:81101998,81872018,81372292+1 种基金Chinese Ministry of Science and Technology,Grant/Award Number:2017YFC0110200Mayo Clinic Center for Individualized Medicine。
文摘Background:Human epidermal growth factor receptor(EGFR)is an oncogenic gene and one of top targets of precision therapy in lung cancer with EGFR mutations.Although there are many reports for some individual cancers,comprehensive profiling of EGFR mutations,overexpression,amplification,DNA methylation,and their clinical associations across many different cancers simultaneously was not available.This study aimed to fill the gap and provide insights to the alteration spectrum of EGFR and its therapeutic and prognostic implications.Methods:The Cancer Genome Atlas(TCGA)datasets for 32 cancer types involving 11,314 patients were analyzed for alterations(mutations and amplification/deletion),abnormal expression and DNA methylation in EGFR gene.Mutation frequency,genomic location distribution,functional impact,and clinical targeted therapy implication were compared among different cancer types,and their associations with patient survival were analyzed.Results:EGFR alteration frequency,mutation sites across functional domains,amplification,overexpression,and DNA methylation patterns differed greatly among different cancer types.The overall mutation frequency in all cancers combined was relatively low.Targetable mutations,mainly in lung cancer,were primarily found in the Pkinase_Tyr domain.Glioblastoma multiforme had the highest rate of alterations,but it was dominated by gene amplification and most mutations were in the Furin-like domain where targeted therapy was less effective.Low-grade glioma often had gene amplification and increased EGFR expression which was associated with poor outcome.Colon and pancreatic adenocarcinoma had very few EGFR mutations;however,high EGFR expression was significantly associated with short patient survival.Squamous cell carcinoma regardless of their sites(the head and neck,lung,or esophagus)exhibited similar characteristics with an alteration frequency of about 5.0%,was dominated by gene amplification,and had increased EGFR expression generally associated with short patient survival.DNA methylation was highly associated with EGFR expression and patient outcomes in some cancers.Conclusions:EGFR aberration type,frequency,distribution in functional domains,and expression vary from cancer to cancer.While mutations in the Pkinase_Tyr domain are more important for treatment selection,increased expression from amplification or deregulation affects more tumor types and leads to worse outcome,which calls for new treatment strategies for these EGFR-driven tumors.
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 81070677）. Conflict of interest： None.
文摘Background Food composition and style is changing dramatically now, which causes inappropriate secretion of hormones from brain, gastrointestinal and endo-pancreas, may be related to unbalance of glucose in blood. The aim of this study was to explore the fast response of C-peptide, glucagon-like peptide-1 （GLP-1）, ghrelin and endomorphin-1 （EM-1） to the eastern and western style meals in patients with type 2 diabetes mellitus. Methods The study enrolled 57 patients with type 2 diabetes （20 men and 37 women, mean age （67.05±8.26） years）. Eastern style meal （meal A） and western style meal （meal B） were designed to produce the fullness effect. C-peptide, GLP-1, ghrelin and EM-1 were assessed before （0 hour） and after （2 hours） each diet. Results The delta （2h-0h） of C- peptide in meal A was significantly lower than that in meal B （P=0.0004）. C-peptide, GLP-1, ghrelin and EM-1 were obviously higher before meal B than those before meal A （P 〈0.0001, 〈0.0001, =0.001, =0.0004 respectively）. Blood glucose 2 hours and 3 hours after meal B were higher than those after meal A （P=0.0005, 0.0079 respectively）. Correlations between GLP-1 and ghrelin were strongly positive before both meals and 2 hours after both meals and also in relation to the delta of meal A and meal B （rA0h=0.7838, rB05=0.9368, rA25=0.7615, rB2h=0.9409, r A（2h-0h）=0.7531, rB（2h 05）=0.9980, respectively, P 〈0.0001）. Conclusion Western style meal （high fat and protein food） could make more response of C-peptide than eastern style meal, and could stimulate more gut hormones （GLP-1, ghrelin） and brain peptide （EM-1） at the first phase of digestion.
文摘Background:Capsule endoscopy(CE)is frequently hindered by intra-luminal debris.Our aim was to determine whether a combination bowel preparation would improve small-bowel visualization,diagnostic yield,and the completion rate of CE.Methods:Single-blind,prospective randomized–controlled study of outpatients scheduled for CE.Bowel-preparation subjects ingested 2 L of polyethylene glycol solution the night prior to CE,5mL simethicone and 5mg metoclopramide 20 minutes prior to CE and laid in the right lateral position 30 minutes after swallowing CE.Controls had no solid food after 7 p.m.the night prior to CE and no liquids 4 hours prior to CE.Participants completed a satisfaction survey.Capsule readers completed a small-bowel-visualization assessment.Results:Fifty patients were prospectively enrolled(56%female)with a median age of 54.4 years and 44 completed the study(23 patients in the control group and 21 in the preparation group).There was no significant difference between groups on quartile-based small-bowel visualization(all P>0.05).There was no significant difference between groups in diagnostic yield(P=0.69),mean gastric(P=0.10)or small-bowel transit time(P=0.89).The small-bowel completion rate was significantly higher in the preparation group(100%vs 78%;P=0.02).Bowel-preparation subjects reported significantly more discomfort than controls(62%vs 17%;P=0.01).Conclusions:Combined bowel preparation did not improve small-bowel visualization but did significantly increase patient discomfort.The CE completion rate improved in the preparation group but the diagnostic yield was unaffected.Based on our findings,a bowel preparation prior to CE does not appear to improve CE performance and results in decreased patient satisfaction(ClinicalTrials.gov,No.NCT01243736).
基金This work was funded by NIH grant R01EB018965.Human subjects research was conducted with Mayo Clinic Institutional Review Board approval(IRB 14-009261).
文摘Peripheral artery disease(PAD)results from the buildup of atherosclerotic plaque in the arterial wall,can progress to severe ischemia and lead to tissue necrosis and limb amputation.We evaluated a means of assessing PAD mechanics ex vivo using ten human peripheral arteries with PAD.Pressure-inflation testing was performed at six physiological pressure intervals ranging from 10 to 200 mmHg.These vessels were imaged with IVUS-VH to determine plaque composition and change in vessel structure with pressure.Statistical analysis was performed to determine which plaque structures and distributions of these structures had the greatest influence on wall deformation.We found that fibrous plaque,necrotic core,and calcification had a statistically significant effect on all variables(p<0.05).The presence of large concentrations of fibrous plaque was linked to reduced vessel compliance and ellipticity,which could lead to stent fractures and restenosis.For the plaque distribution we found that clustered necrotic core increased overall compliance while clustered calcification decreased overall compliance.The effect of plaque distribution on vessel wall deformation must be considered equally important to plaque concentration.
文摘non-invasive chronic rhinosinusitis(CRS)following liver or kidney transplant and determine factors associated with disease-related complications,selection of endoscopic sinus surgery(ESS),and disease resolution in this population.Study design:Retrospective chart review.Setting:An academic tertiary care center(Mayo Clinic,Rochester,Minnesota).Subjects and methods:Liver and kidney transplant recipients evaluated by Mayo Clinic otolaryngologists for CRS between 1998 and 2018 were identified.Univariate and multivariate logistic regression analyses were used to determine patient factors and treatment modalities associated with developing complications,selection of ESS,and disease resolution.Results:Fifty-seven patients met inclusion criteria.No patients developed intraorbital or intracranial complications of their CRS.Multivariate modeling demonstrated that the presence of polyps(P=0.036)was associated with undergoing ESS within one year of presentation.A higher Lund-Mackay(LM)computed tomography score(P=0.023)and older age(P=0.018)were significantly associated with decreased disease resolution.No other factors were significantly associated with the use of endoscopic sinus surgery within one year of otolaryngology presentation or resolution of CRS in this cohort.Conclusion:The risk of developing CRS-related intraorbital or intracranial complications in this immunecompromised patient cohort may be lower than originally thought.For liver-and kidney-recipients stable on immunosuppressive medication for many years,prognostic factors for CRS may mirror those for immunocompetent patients.
基金supported by the National Library of Medicine training grant (Grant No. 5T15LM007450-10)
文摘In shotgun proteomics, database search algorithms rely on fragmentation models to pre- dict fragment ions that should be observed for a given peptide sequence. The most widely used strat- egy （Naive model） is oversimplified, cleaving all peptide bonds with equal probability to produce fragments of all charges below that of the precursor ion. More accurate models, based on fragmen- tation simulation, are too computationally intensive for on-the-fly use in database search algorithms. We have created an ordinal-regression-based model called Basophile that takes fragment size and basic residue distribution into account when determining the charge retention during CID/higher- energy collision induced dissociation （HCD） of charged peptides. This model improves the accuracy of predictions by reducing the number of unnecessary fragments that are routinely predicted for highly-charged precursors. Basophile increased the identification rates by 26% （on average） over the Naive model, when analyzing triply-charged precursors from ion trap data. Basophile achieves simplicity and speed by solving the prediction problem with an ordinal regression equation, which can be incorporated into any database search software for shotgun proteomic identification.
