A good drug or drug candidate should not only interact with its target molecule effectively and specifically,but also be absorbed into the body,distributed to the right location,metabolized into right compounds,and el...A good drug or drug candidate should not only interact with its target molecule effectively and specifically,but also be absorbed into the body,distributed to the right location,metabolized into right compounds,and eliminated out of the body in proper manner.The processes of drug getting into and out of the body involve Absorption,Distribution,Metabolism,and Excretion（ADME）,展开更多
Objective: To investigate the clinical effect of rituximab (RTX) in the management of progressive rheumatoid arthritis related interstitial lung disease (RA-ILD). Methods: A total of 10 patients with progressive RA-IL...Objective: To investigate the clinical effect of rituximab (RTX) in the management of progressive rheumatoid arthritis related interstitial lung disease (RA-ILD). Methods: A total of 10 patients with progressive RA-ILD were enrolled into this 48-week, open-label treatment study. Treatment was with RTX at 1000 mg at day 1, day 15, and again at weeks 24 and 26, with concomitant methotrexate therapy. Results: The study included 4 men and 6 women. Of 7 evaluable patients at week 48, the diffusing capacity to carbon monoxide had worsened by at least 15% in 1 patient, was stable in 4 patients, and increased by >15% of baseline value in 2 patients. The forced vital capacity declined by at least 10% in 1 patient, was stable in 4 patients, and increased by at least 10% in 2 patients. High resolution computed tomo-graphy of the chest showed improvement in 1 patient, and was unchanged in 5. Three patients were withdrawn, one who had an infusion reaction at week 0, one at week 5 who was hospitalized for congestive heart failure at week 5 and who later died at week 32 of complications following a traumatic hip fracture, and one died at week 6 of possible pneumonia. Conclusions: In this pilot study of 10 patients with RA-ILD treated with RTX, measures of lung disease remained stable in the majority of study completers. Further research is needed to clarify whether this treatment has a role in management of RA-ILD.展开更多
Objective:The artificial urinary sphincter(AUS)is the gold standard for severe male stress urinary incontinence,though evaluations of specific predictors for device outcomes are sparse.We sought to compare outcomes be...Objective:The artificial urinary sphincter(AUS)is the gold standard for severe male stress urinary incontinence,though evaluations of specific predictors for device outcomes are sparse.We sought to compare outcomes between primary and revision AUS surgery for non-infectious failures.Methods:We identified 2045 consecutive AUS surgeries at Mayo Clinic(Rochester,MN,USA)from 1983 to 2013.Of these,1079 were primary AUS implantations and 281 were initial revision surgeries,which comprised our study group.Device survival rates,including overall and specific rates for device infection/erosion,urethral atrophy and mechanical failure,were compared between primary AUS placements versus revision surgeries.Patient follow-up was obtained through office examination,written correspondence,or telephone correspondence.Results:During the study period,1079(79.3%)patients had a primary AUS placement and 281(20.7%)patients underwent a first revision surgery for mechanical failure or urethral atrophy.Patients undergoing revision surgery were found to have adverse 1-and 5-year AUS device survival on Kaplan-Meier analysis,90%vs.85% and 74%vs.61%,respectively(p<0.001).Specifically,revision surgery was associated with a significantly increased cumulative incidence of explantation for device infection/urethral erosion(4.2%vs.7.5%at 1 year;p=0.02),with similar rates of repeat surgery for mechanical failure(p=0.43)and urethral atrophy(p=0.77).Conclusions:Our findings suggest a significantly higher rate of overall device failure following revision AUS surgery,which is likely secondary to an increased rate of infection/urethral erosion events.展开更多
Purpose: Hip arthroscopy is a surgery with favorable outcomes to treat labral tears of the hip. This retrospective review was conducted to identify an optimal anesthetic technique for hip arthroscopy to minimize posto...Purpose: Hip arthroscopy is a surgery with favorable outcomes to treat labral tears of the hip. This retrospective review was conducted to identify an optimal anesthetic technique for hip arthroscopy to minimize postoperative pain and decrease opioid consumption. Methods: A retrospective analysis was performed for 92 patients who underwent hip arthroscopy for femoroacetabular impingement (FAI) with labral tear under general anesthesia (G) with fascia-iliaca block (64 patients) or regional anesthesia (R) with fascia-iliaca block (28 patients) from March 9, 2016 to April 9, 2018. Data collected included: demographics, diagnosis, ASA status, time in surgery, medications administered, type of anesthesia administered, pain scores, use of straight catheter, and time in PACU. Results: Patients who underwent hip arthroscopy under regional anesthesia reported significantly less first (G: 3.4 (3.9), R: 1.3 (3.0), p = 0.0085) and average (G: 3.8 (2.5), R: 2.0 (2.2), p = 0.0038) pain post-operatively. Patients under regional anesthesia also received less total morphine milligram equivalents (MME) intraoperatively and post-operatively (G: 40.8 (21.7) MME, R: 24.9 (17.8), p = 0.004 MME). Patients under regional anesthesia had a significantly higher incidence of urinary retention (G: 3.1%, R: 28.6%, p = 0.009) and increased time spent in PACU (G = 181.9 (86.3), R: 251.4 (80.4), p = 0.0001). Conclusions: The administration of regional anesthesia resulted in significantly lower pain scores and perioperative opioid consumption compared to general anesthesia in patients undergoing hip. This may be the optimal anesthetic technique for pain control;however, incidence of urinary retention and time to discharge are significantly increased. Prospective randomized control trials are needed to compare general anesthesia and regional anesthesia for hip arthroscopy.展开更多
AIM: To investigate the survival of individuals with colorectal cancer (CRC) with inflammatory bowel disease (IBD-associated CRC) compared to that of individuals without IBD diagnosed with CRC. METHODS: Epidemiologic,...AIM: To investigate the survival of individuals with colorectal cancer (CRC) with inflammatory bowel disease (IBD-associated CRC) compared to that of individuals without IBD diagnosed with CRC. METHODS: Epidemiologic, clinical, and follow-up data were obtained from the Colon Cancer Family Registry (Colon CFR). IBD-associated cases were identified from self-report of physician diagnosis. For a subset of participants, medical records were examined to confirm self-report of IBD. Cox proportional hazards regression was applied to estimate adjusted hazard ratios (aHR) and 95%CI of mortality, comparing IBD-associated to non-IBD-associated CRC, adjusted for age at CRC diagnosis, sex, Colon CFR phase, and number of prior endoscopies. Following imputation to complete CRC stage information, adjustment for CRC stage was examined. RESULTS: A total of 7202 CRC cases, including 250 cases of IBD-associated CRC, were analyzed. Over a twelve year follow-up period following CRC diagnosis, 2013 and 74 deaths occurred among non-IBD associated CRC and IBD-associated CRC patients, respectively. The difference in survival between IBD-associated and non-IBD CRC cases was not statistically significant (aHR = 1.08; 95%CI: 0.85-1.36). However, the assumption of proportional hazards necessary for valid inference from Cox regression was not met over the entire follow-up period, and we therefore limited analyses to within five years after CRC diagnosis when the assumption of proportional hazards was met. Over this period, there was evidence of worse prognosis for IBD-associated CRC (aHR = 1.36; 95%CI: 1.05-1.76). Results were similar when adjusted for CRC stage, or restricted to IBD confirmed in medical records. CONCLUSION: These results support the hypothesis that IBD-associated CRC has a worse prognosis than non-IBD-associated CRC.展开更多
In the current biomedical data movement, numerous efforts have been made to convert and normalize a large number of traditional structured and unstructured data (e.g., EHRs, reports) to semi-structured data (e.g., RDF...In the current biomedical data movement, numerous efforts have been made to convert and normalize a large number of traditional structured and unstructured data (e.g., EHRs, reports) to semi-structured data (e.g., RDF, OWL). With the increasing number of semi-structured data coming into the biomedical community, data integration and knowledge discovery from heterogeneous domains become important research problem. In the application level, detection of related concepts among medical ontologies is an important goal of life science research. It is more crucial to figure out how different concepts are related within a single ontology or across multiple ontologies by analysing predicates in different knowledge bases. However, the world today is one of information explosion, and it is extremely difficult for biomedical researchers to find existing or potential predicates to perform linking among cross domain concepts without any support from schema pattern analysis. Therefore, there is a need for a mechanism to do predicate oriented pattern analysis to partition heterogeneous ontologies into closer small topics and do query generation to discover cross domain knowledge from each topic. In this paper, we present such a model that predicates oriented pattern analysis based on their close relationship and generates a similarity matrix. Based on this similarity matrix, we apply an innovated unsupervised learning algorithm to partition large data sets into smaller and closer topics and generate meaningful queries to fully discover knowledge over a set of interlinked data sources. We have implemented a prototype system named BmQGen and evaluate the proposed model with colorectal surgical cohort from the Mayo Clinic.展开更多
Introduction: Hepatic magnetic resonance elastography (MRE) allows for noninvasive assessment of liver fibrosis. The purpose of this study was to evaluate the usefulness of MRE in detecting and quantifying liver fibro...Introduction: Hepatic magnetic resonance elastography (MRE) allows for noninvasive assessment of liver fibrosis. The purpose of this study was to evaluate the usefulness of MRE in detecting and quantifying liver fibrosis in patients with rheumatoid arthritis (RA) who have received methotrexate (MTX). Methods: The association between mean liver stiffness value as determined by MRE and variables of interest was determined. The decision for a liver biopsy in participants with an abnormal liver stiffness was made based on clinical judgment. Results: Sixty-five RA patients were enrolled. Mean liver stiffness value by MRE was abnormal in 7 patients, suggestive of hepatic injury. As a result of findings from the MRE, biopsies were performed in 5 patients and all correlated with elevated liver stiffness values. Elevated mean liver stiffness values were associated with body mass index (BMI) (OR = 1.18 per 1 kg/m2;95% CI: 1.03, 1.36;p = 0.017). Neither the total MTX dose nor the duration of MTX treatment was associated with mean liver stiffness value (p = 0.51 and P = 0.20, respectively). Conclusion: MRE provides a reliable, non-invasive assessment of liver fibrosis in patients with RA receiving MTX. Patients with RA receiving MTX who have an elevated BMI may be at increased risk for chronic hepatic injury, regardless of MTX cumulative dose or duration of treatment.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
Objective: To investigate the association of Parkinson disease (PD) with education and occupations using a case-control study design. Methods: The authors used the medical records-linkage system of the Rochester Epide...Objective: To investigate the association of Parkinson disease (PD) with education and occupations using a case-control study design. Methods: The authors used the medical records-linkage system of the Rochester Epidemiology Project to identify all subjects who developed PD in Olmsted County, MN, from 1976 through 1995. Each incident case was matched by age (±1 year) and sex to a general population control. The authors collected information about education and occupations using two independent sources of data: a review of the complete medical records in the system and a telephone interview. Occupations were coded using the 1980 Standard Occupational Classification. Results: Subjects with 9 or more years of education were at increased risk of PD (OR = 2.0; 95%CI = 1.1 to 3.6; p = 0.02), and there was a trend of increasing risk with increasin g education (test for linear trend, p = 0.02; medical records data). Physicians were at significantly increased risk of PD using both sources of occupational data. By contrast, four occupational groups showed a significantly decreased risk of PD using one source of data: construction and extractive workers (e.g., miner s, oil well drillers), production workers (e.g., machine operators, fabricators), metal workers, and engineers. These associations with increased or decreased risk did not change noticeably after adjustment for education. Conclusion: Subjects with higher education and physicians have an increased risk of Parkinson disease (PD), while subjects with some occupations presumed to involve high physical activity have a decreased risk of PD.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
Objective To assess the relationship between ovarian hyperstimulation syndrome(OHSS)and adverse outcomes using population-based data in the United States.The hypothesis is that patients with OHSS were more likely to d...Objective To assess the relationship between ovarian hyperstimulation syndrome(OHSS)and adverse outcomes using population-based data in the United States.The hypothesis is that patients with OHSS were more likely to deliver preterm and more likely to have hypertensive disorders.Methods This retrospective cohort study identified 94 patients with OHSS and 183 matched referents in eight counties in Minnesota.Data were collected regarding pregnancy history,infertility treatment,and pregnancy outcomes.Using the Rochester Epidemiology Project,study subjects were identified from female patients,aged 18 to 49 years,who were diagnosed with infertility from January 2,1995 to December 1,2017,and had a pregnancy greater than 20 weeks'gestation.The primary outcome was preterm delivery or hypertensive disorder of pregnancy incidence in the OHSS group when compared with control patients.Chi-squared test,t test,and multivariate logistic models were used where appropriate.Results Patients with OHSS were more likely to deliver preterm(odds ratio,2.14;95%confidence interval,1.26–3.65;P<0.01),and their neonates were more likely to be small for gestational age(odds ratio,4.78;95%confidence interval,1.61–14.19;P<0.01).No significant differences between the groups were observed in any other outcome.Patients with OHSS are more likely to deliver preterm if they undergo fresh transfer compared with a freeze all and subsequent frozen transfer(odds ratio,3.03,95%confidence interval,1.20–7.66,P=0.02).Conclusion OHSS may lead to preterm birth and small-for-gestational-age neonates,which changes patient counseling and leads to arranging specialized obstetrical care for these patients with OHSS.展开更多
Background:Freezing of gait(FoG)is a common and debilitating condition in Parkinson’s disease(PD)associated with executive dysfunction.A subtype of FoG does not respond to dopaminergic therapy and may be related to n...Background:Freezing of gait(FoG)is a common and debilitating condition in Parkinson’s disease(PD)associated with executive dysfunction.A subtype of FoG does not respond to dopaminergic therapy and may be related to noradrenergic deficiency.This pilot study explores the effects of atomoxetine on gait in PD patients with dopaunresponsive FoG using a novel paradigm for objective gait assessment.Findings:Ten patients with PD and dopa-unresponsive FoG were enrolled in this eight-week open label pilot study.Assessments included an exploratory gait analysis protocol that quantified spatiotemporal parameters during straight-away walking and turning,while performing a dual task.Clinical,and subjective assessments of gait,quality of life,and safety were also administered.The primary outcome was a validated subjective assessment for FoG(FOG-Q).Atomoxetine was well tolerated,however,no significant change was observed in the primary outcome.The gait analysis protocol correlated well with clinical scales,but not with subjective assessments.DBS patients were more likely to increase gait velocity(p=0.033),and improved in other clinical assessments.Conclusions:Objective gait analysis protocols assessing gait while dual tasking are feasible and useful for this patient population,and may be superior correlates of FoG severity than subjective measures.These findings can inform future trials in this population.展开更多
Functional genomics employs dozens of OMICs technologies to explore the functions of DNA, RNA and protein regulators in gene regulation processes. Despite each of these technologies being powerful tools on their own, ...Functional genomics employs dozens of OMICs technologies to explore the functions of DNA, RNA and protein regulators in gene regulation processes. Despite each of these technologies being powerful tools on their own, fike the parable of blind men and an elephant, any one single technology has a limited ability to depict the complex regulatory system. Integrative OMICS approaches have emerged and become an important area in biology and medicine. It provides a precise and effective way to study gene regulations. Results： This article reviews current popular OMICs technologies, OMICs data integration strategies, and bioinformatics tools used for multi-dimensional data integration. We highlight the advantages of these methods, particularly in elucidating molecular basis of biological regulatory mechanisms. Conclusions： To better understand the complexity of biological processes, we need powerful bioinformatics tools to integrate these OMICs data. Integrating multi-dimensional OMICs data will generate novel insights into system-level gene regulations and serves as a foundation for further hypothesis-driven research.展开更多
Intrahepatic cholangiocarcinoma(iCCA)is an often-fatal malignancy,with an annual incidence rate that closely approximates the mortality rate(1,2).The poor prognosis of these cancers is due in part to their nonspecific...Intrahepatic cholangiocarcinoma(iCCA)is an often-fatal malignancy,with an annual incidence rate that closely approximates the mortality rate(1,2).The poor prognosis of these cancers is due in part to their nonspecific clinical presentation and the often-late stage at diagnosis—which is not amenable to curative treatment.While understanding the underlying biology of iCCA is important for early detection and therapy development,there is also a need to ascertain the temporal trends of the disease incidence and mortality.A thorough appraisal of trends in iCCA incidence and mortality would inform strategies for the prevention and identification of high-risk populations for screening and surveillance.Many studies have shown that the incidence and mortality rates of iCCA have increased in the US over the last few decades(1-6),but while some of these studies suggest that the increase in iCCA incidence appears to have plateaued(2,5),others show continuous rise of both the incidence and mortality of iCCA in the US(3,4,6).展开更多
Background.Patients increasingly use asynchronous communication platforms to converse with care teams.Natural language processing(NLP)to classify content and automate triage of these messages has great potential to en...Background.Patients increasingly use asynchronous communication platforms to converse with care teams.Natural language processing(NLP)to classify content and automate triage of these messages has great potential to enhance clinical efficiency.We characterize the contents of a corpus of portal messages generated by patients using NLP methods.We aim to demonstrate descriptive analyses of patient text that can contribute to the development of future sophisticated NLP applications.Methods.We collected approximately 3,000 portal messages from the cardiology,dermatology,and gastroenterology departments at Mayo Clinic.After labeling these messages as either Active Symptom,Logistical,Prescription,or Update,we used NER(named entity recognition)to identify medical concepts based on the UMLS library.We hierarchically analyzed the distribution of these messages in terms of departments,message types,medical concepts,and keywords therewithin.Results.Active Symptom and Logistical content types comprised approximately 67%of the message cohort.The“Findings”medical concept had the largest number of keywords across all groupings of content types and departments.“Anatomical Sites”and“Disorders”keywords were more prevalent in Active Symptom messages,while“Drugs”keywords were most prevalent in Prescription messages.Logistical messages tended to have the lower proportions of“Anatomical Sites,”,“Disorders,”,“Drugs,”,and“Findings”keywords when compared to other message content types.Conclusions.This descriptive corpus analysis sheds light on the content and foci of portal messages.The insight into the content and differences among message themes can inform the development of more robust NLP models.展开更多
基金supported by the Natural Science Foundation ofChina(Nos.30873159 and 31271405)
文摘A good drug or drug candidate should not only interact with its target molecule effectively and specifically,but also be absorbed into the body,distributed to the right location,metabolized into right compounds,and eliminated out of the body in proper manner.The processes of drug getting into and out of the body involve Absorption,Distribution,Metabolism,and Excretion（ADME）,
文摘Objective: To investigate the clinical effect of rituximab (RTX) in the management of progressive rheumatoid arthritis related interstitial lung disease (RA-ILD). Methods: A total of 10 patients with progressive RA-ILD were enrolled into this 48-week, open-label treatment study. Treatment was with RTX at 1000 mg at day 1, day 15, and again at weeks 24 and 26, with concomitant methotrexate therapy. Results: The study included 4 men and 6 women. Of 7 evaluable patients at week 48, the diffusing capacity to carbon monoxide had worsened by at least 15% in 1 patient, was stable in 4 patients, and increased by >15% of baseline value in 2 patients. The forced vital capacity declined by at least 10% in 1 patient, was stable in 4 patients, and increased by at least 10% in 2 patients. High resolution computed tomo-graphy of the chest showed improvement in 1 patient, and was unchanged in 5. Three patients were withdrawn, one who had an infusion reaction at week 0, one at week 5 who was hospitalized for congestive heart failure at week 5 and who later died at week 32 of complications following a traumatic hip fracture, and one died at week 6 of possible pneumonia. Conclusions: In this pilot study of 10 patients with RA-ILD treated with RTX, measures of lung disease remained stable in the majority of study completers. Further research is needed to clarify whether this treatment has a role in management of RA-ILD.
文摘Objective:The artificial urinary sphincter(AUS)is the gold standard for severe male stress urinary incontinence,though evaluations of specific predictors for device outcomes are sparse.We sought to compare outcomes between primary and revision AUS surgery for non-infectious failures.Methods:We identified 2045 consecutive AUS surgeries at Mayo Clinic(Rochester,MN,USA)from 1983 to 2013.Of these,1079 were primary AUS implantations and 281 were initial revision surgeries,which comprised our study group.Device survival rates,including overall and specific rates for device infection/erosion,urethral atrophy and mechanical failure,were compared between primary AUS placements versus revision surgeries.Patient follow-up was obtained through office examination,written correspondence,or telephone correspondence.Results:During the study period,1079(79.3%)patients had a primary AUS placement and 281(20.7%)patients underwent a first revision surgery for mechanical failure or urethral atrophy.Patients undergoing revision surgery were found to have adverse 1-and 5-year AUS device survival on Kaplan-Meier analysis,90%vs.85% and 74%vs.61%,respectively(p<0.001).Specifically,revision surgery was associated with a significantly increased cumulative incidence of explantation for device infection/urethral erosion(4.2%vs.7.5%at 1 year;p=0.02),with similar rates of repeat surgery for mechanical failure(p=0.43)and urethral atrophy(p=0.77).Conclusions:Our findings suggest a significantly higher rate of overall device failure following revision AUS surgery,which is likely secondary to an increased rate of infection/urethral erosion events.
文摘Purpose: Hip arthroscopy is a surgery with favorable outcomes to treat labral tears of the hip. This retrospective review was conducted to identify an optimal anesthetic technique for hip arthroscopy to minimize postoperative pain and decrease opioid consumption. Methods: A retrospective analysis was performed for 92 patients who underwent hip arthroscopy for femoroacetabular impingement (FAI) with labral tear under general anesthesia (G) with fascia-iliaca block (64 patients) or regional anesthesia (R) with fascia-iliaca block (28 patients) from March 9, 2016 to April 9, 2018. Data collected included: demographics, diagnosis, ASA status, time in surgery, medications administered, type of anesthesia administered, pain scores, use of straight catheter, and time in PACU. Results: Patients who underwent hip arthroscopy under regional anesthesia reported significantly less first (G: 3.4 (3.9), R: 1.3 (3.0), p = 0.0085) and average (G: 3.8 (2.5), R: 2.0 (2.2), p = 0.0038) pain post-operatively. Patients under regional anesthesia also received less total morphine milligram equivalents (MME) intraoperatively and post-operatively (G: 40.8 (21.7) MME, R: 24.9 (17.8), p = 0.004 MME). Patients under regional anesthesia had a significantly higher incidence of urinary retention (G: 3.1%, R: 28.6%, p = 0.009) and increased time spent in PACU (G = 181.9 (86.3), R: 251.4 (80.4), p = 0.0001). Conclusions: The administration of regional anesthesia resulted in significantly lower pain scores and perioperative opioid consumption compared to general anesthesia in patients undergoing hip. This may be the optimal anesthetic technique for pain control;however, incidence of urinary retention and time to discharge are significantly increased. Prospective randomized control trials are needed to compare general anesthesia and regional anesthesia for hip arthroscopy.
基金Supported by The American Society of Preventive Oncology/Prevent Cancer Foundation/American Society for Clinical Oncology Cancer Prevention Research Fellowship to SVAthe Australasian Colorectal Cancer Family Registry, No. U01CA097735+5 种基金the Familial Colorectal Neoplasia Collaborative Group, No. U01 CA074799the Mayo Clinic Cooperative Family Registry for Colon Cancer Studies, No. U01 CA074800the Ontario Registry for Studies of Familial Colorectal Cancer, No.U01 CA074783the Seattle Colorectal Cancer Family Registry,No. U01 CA074794the University of Hawaii Colorectal Cancer Family Registry, No. U01 CA074806the University of California, Irvine Informatics Center, No. U01 CA078296
文摘AIM: To investigate the survival of individuals with colorectal cancer (CRC) with inflammatory bowel disease (IBD-associated CRC) compared to that of individuals without IBD diagnosed with CRC. METHODS: Epidemiologic, clinical, and follow-up data were obtained from the Colon Cancer Family Registry (Colon CFR). IBD-associated cases were identified from self-report of physician diagnosis. For a subset of participants, medical records were examined to confirm self-report of IBD. Cox proportional hazards regression was applied to estimate adjusted hazard ratios (aHR) and 95%CI of mortality, comparing IBD-associated to non-IBD-associated CRC, adjusted for age at CRC diagnosis, sex, Colon CFR phase, and number of prior endoscopies. Following imputation to complete CRC stage information, adjustment for CRC stage was examined. RESULTS: A total of 7202 CRC cases, including 250 cases of IBD-associated CRC, were analyzed. Over a twelve year follow-up period following CRC diagnosis, 2013 and 74 deaths occurred among non-IBD associated CRC and IBD-associated CRC patients, respectively. The difference in survival between IBD-associated and non-IBD CRC cases was not statistically significant (aHR = 1.08; 95%CI: 0.85-1.36). However, the assumption of proportional hazards necessary for valid inference from Cox regression was not met over the entire follow-up period, and we therefore limited analyses to within five years after CRC diagnosis when the assumption of proportional hazards was met. Over this period, there was evidence of worse prognosis for IBD-associated CRC (aHR = 1.36; 95%CI: 1.05-1.76). Results were similar when adjusted for CRC stage, or restricted to IBD confirmed in medical records. CONCLUSION: These results support the hypothesis that IBD-associated CRC has a worse prognosis than non-IBD-associated CRC.
文摘In the current biomedical data movement, numerous efforts have been made to convert and normalize a large number of traditional structured and unstructured data (e.g., EHRs, reports) to semi-structured data (e.g., RDF, OWL). With the increasing number of semi-structured data coming into the biomedical community, data integration and knowledge discovery from heterogeneous domains become important research problem. In the application level, detection of related concepts among medical ontologies is an important goal of life science research. It is more crucial to figure out how different concepts are related within a single ontology or across multiple ontologies by analysing predicates in different knowledge bases. However, the world today is one of information explosion, and it is extremely difficult for biomedical researchers to find existing or potential predicates to perform linking among cross domain concepts without any support from schema pattern analysis. Therefore, there is a need for a mechanism to do predicate oriented pattern analysis to partition heterogeneous ontologies into closer small topics and do query generation to discover cross domain knowledge from each topic. In this paper, we present such a model that predicates oriented pattern analysis based on their close relationship and generates a similarity matrix. Based on this similarity matrix, we apply an innovated unsupervised learning algorithm to partition large data sets into smaller and closer topics and generate meaningful queries to fully discover knowledge over a set of interlinked data sources. We have implemented a prototype system named BmQGen and evaluate the proposed model with colorectal surgical cohort from the Mayo Clinic.
文摘Introduction: Hepatic magnetic resonance elastography (MRE) allows for noninvasive assessment of liver fibrosis. The purpose of this study was to evaluate the usefulness of MRE in detecting and quantifying liver fibrosis in patients with rheumatoid arthritis (RA) who have received methotrexate (MTX). Methods: The association between mean liver stiffness value as determined by MRE and variables of interest was determined. The decision for a liver biopsy in participants with an abnormal liver stiffness was made based on clinical judgment. Results: Sixty-five RA patients were enrolled. Mean liver stiffness value by MRE was abnormal in 7 patients, suggestive of hepatic injury. As a result of findings from the MRE, biopsies were performed in 5 patients and all correlated with elevated liver stiffness values. Elevated mean liver stiffness values were associated with body mass index (BMI) (OR = 1.18 per 1 kg/m2;95% CI: 1.03, 1.36;p = 0.017). Neither the total MTX dose nor the duration of MTX treatment was associated with mean liver stiffness value (p = 0.51 and P = 0.20, respectively). Conclusion: MRE provides a reliable, non-invasive assessment of liver fibrosis in patients with RA receiving MTX. Patients with RA receiving MTX who have an elevated BMI may be at increased risk for chronic hepatic injury, regardless of MTX cumulative dose or duration of treatment.
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.
文摘Objective: To investigate the association of Parkinson disease (PD) with education and occupations using a case-control study design. Methods: The authors used the medical records-linkage system of the Rochester Epidemiology Project to identify all subjects who developed PD in Olmsted County, MN, from 1976 through 1995. Each incident case was matched by age (±1 year) and sex to a general population control. The authors collected information about education and occupations using two independent sources of data: a review of the complete medical records in the system and a telephone interview. Occupations were coded using the 1980 Standard Occupational Classification. Results: Subjects with 9 or more years of education were at increased risk of PD (OR = 2.0; 95%CI = 1.1 to 3.6; p = 0.02), and there was a trend of increasing risk with increasin g education (test for linear trend, p = 0.02; medical records data). Physicians were at significantly increased risk of PD using both sources of occupational data. By contrast, four occupational groups showed a significantly decreased risk of PD using one source of data: construction and extractive workers (e.g., miner s, oil well drillers), production workers (e.g., machine operators, fabricators), metal workers, and engineers. These associations with increased or decreased risk did not change noticeably after adjustment for education. Conclusion: Subjects with higher education and physicians have an increased risk of Parkinson disease (PD), while subjects with some occupations presumed to involve high physical activity have a decreased risk of PD.
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supported by the National Institute on Aging of the National Institutes of Health under Award Number R01AG034676.
文摘Objective To assess the relationship between ovarian hyperstimulation syndrome(OHSS)and adverse outcomes using population-based data in the United States.The hypothesis is that patients with OHSS were more likely to deliver preterm and more likely to have hypertensive disorders.Methods This retrospective cohort study identified 94 patients with OHSS and 183 matched referents in eight counties in Minnesota.Data were collected regarding pregnancy history,infertility treatment,and pregnancy outcomes.Using the Rochester Epidemiology Project,study subjects were identified from female patients,aged 18 to 49 years,who were diagnosed with infertility from January 2,1995 to December 1,2017,and had a pregnancy greater than 20 weeks'gestation.The primary outcome was preterm delivery or hypertensive disorder of pregnancy incidence in the OHSS group when compared with control patients.Chi-squared test,t test,and multivariate logistic models were used where appropriate.Results Patients with OHSS were more likely to deliver preterm(odds ratio,2.14;95%confidence interval,1.26–3.65;P<0.01),and their neonates were more likely to be small for gestational age(odds ratio,4.78;95%confidence interval,1.61–14.19;P<0.01).No significant differences between the groups were observed in any other outcome.Patients with OHSS are more likely to deliver preterm if they undergo fresh transfer compared with a freeze all and subsequent frozen transfer(odds ratio,3.03,95%confidence interval,1.20–7.66,P=0.02).Conclusion OHSS may lead to preterm birth and small-for-gestational-age neonates,which changes patient counseling and leads to arranging specialized obstetrical care for these patients with OHSS.
基金by the Barmore Fund for Parkinson’s Researchthe MUSC Department of Neurology and Neurosurgery,by the South Carolina Clinical&Translational Research(SCTR)Institute,with an academic home at the Medical University of South Carolina+1 种基金supported by NIH/NCATS Grant Number UL1TR000062by NIH NINDS Grant Number 1K23NS091391-01A1.
文摘Background:Freezing of gait(FoG)is a common and debilitating condition in Parkinson’s disease(PD)associated with executive dysfunction.A subtype of FoG does not respond to dopaminergic therapy and may be related to noradrenergic deficiency.This pilot study explores the effects of atomoxetine on gait in PD patients with dopaunresponsive FoG using a novel paradigm for objective gait assessment.Findings:Ten patients with PD and dopa-unresponsive FoG were enrolled in this eight-week open label pilot study.Assessments included an exploratory gait analysis protocol that quantified spatiotemporal parameters during straight-away walking and turning,while performing a dual task.Clinical,and subjective assessments of gait,quality of life,and safety were also administered.The primary outcome was a validated subjective assessment for FoG(FOG-Q).Atomoxetine was well tolerated,however,no significant change was observed in the primary outcome.The gait analysis protocol correlated well with clinical scales,but not with subjective assessments.DBS patients were more likely to increase gait velocity(p=0.033),and improved in other clinical assessments.Conclusions:Objective gait analysis protocols assessing gait while dual tasking are feasible and useful for this patient population,and may be superior correlates of FoG severity than subjective measures.These findings can inform future trials in this population.
基金Our work was supported by a Direct Grant for Research from The Chinese University of Hong Kong, Hong Kong SAR, China （No. 4053150） to JQ, research grants from Research Grants Council, Hong Kong SAR, China （No. 17121414M）, the National Natural Science Foundation of China （Nos. 81572786 and 91529303）, startup funds from Mayo Clinic （Mayo Clinic Arizona and Center for Individualized Medicine） to JW, and the National Natural Science Foundation of China （No. 11526144） and the Natural Science Foundation of Guangdong （No. 2016A030310038） to YH.
文摘Functional genomics employs dozens of OMICs technologies to explore the functions of DNA, RNA and protein regulators in gene regulation processes. Despite each of these technologies being powerful tools on their own, fike the parable of blind men and an elephant, any one single technology has a limited ability to depict the complex regulatory system. Integrative OMICS approaches have emerged and become an important area in biology and medicine. It provides a precise and effective way to study gene regulations. Results： This article reviews current popular OMICs technologies, OMICs data integration strategies, and bioinformatics tools used for multi-dimensional data integration. We highlight the advantages of these methods, particularly in elucidating molecular basis of biological regulatory mechanisms. Conclusions： To better understand the complexity of biological processes, we need powerful bioinformatics tools to integrate these OMICs data. Integrating multi-dimensional OMICs data will generate novel insights into system-level gene regulations and serves as a foundation for further hypothesis-driven research.
文摘Intrahepatic cholangiocarcinoma(iCCA)is an often-fatal malignancy,with an annual incidence rate that closely approximates the mortality rate(1,2).The poor prognosis of these cancers is due in part to their nonspecific clinical presentation and the often-late stage at diagnosis—which is not amenable to curative treatment.While understanding the underlying biology of iCCA is important for early detection and therapy development,there is also a need to ascertain the temporal trends of the disease incidence and mortality.A thorough appraisal of trends in iCCA incidence and mortality would inform strategies for the prevention and identification of high-risk populations for screening and surveillance.Many studies have shown that the incidence and mortality rates of iCCA have increased in the US over the last few decades(1-6),but while some of these studies suggest that the increase in iCCA incidence appears to have plateaued(2,5),others show continuous rise of both the incidence and mortality of iCCA in the US(3,4,6).
文摘Background.Patients increasingly use asynchronous communication platforms to converse with care teams.Natural language processing(NLP)to classify content and automate triage of these messages has great potential to enhance clinical efficiency.We characterize the contents of a corpus of portal messages generated by patients using NLP methods.We aim to demonstrate descriptive analyses of patient text that can contribute to the development of future sophisticated NLP applications.Methods.We collected approximately 3,000 portal messages from the cardiology,dermatology,and gastroenterology departments at Mayo Clinic.After labeling these messages as either Active Symptom,Logistical,Prescription,or Update,we used NER(named entity recognition)to identify medical concepts based on the UMLS library.We hierarchically analyzed the distribution of these messages in terms of departments,message types,medical concepts,and keywords therewithin.Results.Active Symptom and Logistical content types comprised approximately 67%of the message cohort.The“Findings”medical concept had the largest number of keywords across all groupings of content types and departments.“Anatomical Sites”and“Disorders”keywords were more prevalent in Active Symptom messages,while“Drugs”keywords were most prevalent in Prescription messages.Logistical messages tended to have the lower proportions of“Anatomical Sites,”,“Disorders,”,“Drugs,”,and“Findings”keywords when compared to other message content types.Conclusions.This descriptive corpus analysis sheds light on the content and foci of portal messages.The insight into the content and differences among message themes can inform the development of more robust NLP models.
