This study explores free convective heat transfer in an electrically conducting nanofluid flow over a moving semi-infinite flat plate under the influence of an induced magnetic field and viscous dissipation.The veloci...This study explores free convective heat transfer in an electrically conducting nanofluid flow over a moving semi-infinite flat plate under the influence of an induced magnetic field and viscous dissipation.The velocity and magnetic field vectors are aligned at a distance from the plate.The Spectral Relaxation Method(SRM)is used to numerically solve the coupled nonlinear partial differential equations,analyzing the effects of the Eckert number on heat and mass transfer.Various nanofluids containing Cu,Ag,Al_(2)O_(3),and TiO_(2) nanoparticles are examined to assess how external magnetic fields influence fluid behavior.Key parameters,including the nanoparticle volume fraction ϕ,magnetic parameter M,magnetic Prandtl number Prm,and Eckert number Ec,are evaluated for their impact on velocity,induced magnetic field,and heat transfer.Results indicate that increasing the magnetic parameter reduces velocity and magnetic field components in alumina-water nanofluids,while a higher nanoparticle volume fraction enhances the thermal boundary layer.Greater viscous dissipation(Ec)increases temperature,and Al_(2)O_(3) nanofluids exhibit higher speeds than Cu,Ag,and TiO_(2) due to density differences.Silver-water nanofluids,with their higher density,move more slowly.The SRM results closely align with those from Maple,confirming the method’s accuracy.展开更多
BACKGROUND Due to development of an immune-dysregulated phenotype,advanced liver disease in all forms predisposes patients to sepsis acquisition,including by opportunistic pathogens such as fungi.Little data exists on...BACKGROUND Due to development of an immune-dysregulated phenotype,advanced liver disease in all forms predisposes patients to sepsis acquisition,including by opportunistic pathogens such as fungi.Little data exists on fungal infection within a medical intensive liver unit(MILU),particularly in relation to acute on chronic liver failure.AIM To investigate the impact of fungal infections among critically ill patients with advanced liver disease,and compare outcomes to those of patients with bacterial infections.METHODS From our prospective registry of MILU patients from 2018-2022,we included 27 patients with culture-positive fungal infections and 183 with bacterial infections.We compared outcomes between patients admitted to the MILU with fungal infections to bacterial counterparts.Data was extracted through chart review.RESULTS All fungal infections were due to Candida species,and were most frequently blood isolates.Mortality among patients with fungal infections was significantly worse relative to the bacterial cohort(93%vs 52%,P<0.001).The majority of the fungal cohort developed grade 2 or 3 acute on chronic liver failure(ACLF)(90%vs 64%,P=0.02).Patients in the fungal cohort had increased use of vasopressors(96%vs 70%,P=0.04),mechanical ventilation(96%vs 65%,P<0.001),and dialysis due to acute kidney injury(78%vs 52%,P=0.014).On MILU admission,the fungal cohort had significantly higher Acute Physiology and Chronic Health Evaluation(108 vs 91,P=0.003),Acute Physiology Score(86 vs 65,P=0.003),and Model for End-Stage Liver Disease-Sodium scores(86 vs 65,P=0.041).There was no significant difference in the rate of central line use preceding culture(52%vs 40%,P=0.2).Patients with fungal infection had higher rate of transplant hold placement,and lower rates of transplant;however,differences did not achieve statistical significance.CONCLUSION Mortality was worse among patients with fungal infections,likely attributable to severe ACLF development.Prospective studies examining empiric antifungals in severe ACLF and associations between fungal infections and transplant outcomes are critical.展开更多
The steady flow behavior in terminal bronchus of human lung for cylindrical channel of porous medium has been studied. The governing equations have been solved analytically and numerically for cylindrical channel. Fin...The steady flow behavior in terminal bronchus of human lung for cylindrical channel of porous medium has been studied. The governing equations have been solved analytically and numerically for cylindrical channel. Finite difference method is incorporated to simulate the problem. The numerical results are compared with square duct channel for different parametric effect. It is observed that the flow rate is increased in cylindrical channel compared to square duct channel for the increasing value of pressure gradient, porosity and permeability. On the contrary, the flow rate is decreased in square duct channel compared to cylindrical channel for increasing value of viscosity. Flow rate in both channels is analyzed and compared for non-porous medium also. It is observed that flow rate is increased very high in cylindrical channel compared to square duct channel for both medium.展开更多
AIM: To study the small bowel (SB) mucosa on biopsy in cirrhotic patients with portal hypertension and in non-cirrhotic controls and grade fi ndings according to the Marsh criteria. METHODS: We prospectively enrolled ...AIM: To study the small bowel (SB) mucosa on biopsy in cirrhotic patients with portal hypertension and in non-cirrhotic controls and grade fi ndings according to the Marsh criteria. METHODS: We prospectively enrolled 51 consecutive patients undergoing an upper endoscopy for their routine medical care. Twenty f ive patients with cirrhosis and portal hypertension were compared to 26 controls. We obtained coeliac serology and multiple upper small bowel biopsies on all 51 patients. A GI pathologist interpreted biopsies and graded fi ndings according to the Marsh criteria. We assessed equivalence in Marsh grade between cirrhotic and non-cirrhotic controls using the Mann-Whitney test for equivalence. RESULTS: Gender, ethnicity and age were similar between both groups. Marsh grades were equivalent between the groups. Grade of 0 was present in 96% and grade of 1 was present in 4% of both groups and there was no villus atrophy or decrease in villus/crypt ratio in patients with portal hypertension. CONCLUSION: This study provides evidence for the lack of villus atrophy in patients with cirrhosis and portal hypertension, and supports the continuous reliance on the Marsh criteria when the diagnosis of coeliac disease is to be made in the presence of cirrhosis.展开更多
Greater understanding of the biology and epidemiology of prostate cancer in the last several decades have led to significant advances in its management. Prostate cancer is now detected in greater numbers at lower stag...Greater understanding of the biology and epidemiology of prostate cancer in the last several decades have led to significant advances in its management. Prostate cancer is now detected in greater numbers at lower stages of disease and is amenable to multiple forms of efficacious treatment. However, there is a lack of conclusive data demonstrating a definitive mortality benefit from this earlier diagnosis and treatment of prostate cancer. It is likely due to the treatment of a large proportion of indolent cancers that would have had little adverse impact on health or lifespan if left alone. Due to this overtreatment phenomenon, active surveillance with delayed intervention is gaining traction as a viable management approach in contemporary practice. The ability to distinguish clinically insignificant cancers from those with a high risk of progression and/or lethality is critical to the appropriate selection of patients for surveillance protocols versus immediate intervention. This chapter will review the ability of various prediction models, including risk groupings and nomograms, to predict indolent disease and determine their role in the contemporary management of clinically localized prostate cancer.展开更多
AIM:To evaluate the association between alpha-1 antitrypsin deficiency(A1ATD) and hepatocellular carcinoma(HCC) in patients with end-stage liver disease(ESLD).METHODS:Patients with cirrhosis and ESLD referred to the C...AIM:To evaluate the association between alpha-1 antitrypsin deficiency(A1ATD) and hepatocellular carcinoma(HCC) in patients with end-stage liver disease(ESLD).METHODS:Patients with cirrhosis and ESLD referred to the Cleveland Clinic Foundation for liver transplantation between 2003 and 2014 were included in the study(N = 675). ESLD was defined as having histological features of cirrhosis and/or radiological evidence of cirrhosis in the context of portal hypertension(ascites,variceal bleeding,thrombocytopenia,or hepatic encephalopathy). A1 ATD was diagnosed using phenotype characterization(MZ or ZZ),liver biopsy detection of PAS-positive diastaseresistant(PAS+) globules,or both. Patients with other causes of liver diseases such as hepatitis C virus(HCV),alcoholic liver disease and non-alcoholic steatohepatitis(NASH) or NASH were also included in the study. HCC was diagnosed by using imaging modalities,biopsy findings,or explanted liver inspection. Follow-up time was defined as the number of years from the diagnosis of cirrhosis to the diagnosis of hepatocellular carcinoma,or from the diagnosis of cirrhosis to the last follow up visit. The rate of HCC was assessed using time-tointerval analysis for interval censored data.RESULTS:This study included 675 patients. 7% of subjects had A1ATD(n = 47). Out of all subjects who did not have A1 ATD,46% had HCV,17% had alcoholic liver disease,19% had NASH and 18% had another primary diagnosis. Of the 47 subjects with A1 ATD,15 had a primary diagnosis of A1ATD(PI*ZZ phenotype and PAS+ globules),8 had a PI*MZ phenotype alone,14 had PAS+ alone,and 10 had both the PI*MZ phenotype and PAS+. Median follow-up time was 3.4(25th,75 th percentiles:1,5.2) years. The overall rate of hepatocellular carcinoma in all subjects was 29%(n = 199). In the A1 ATD group,the incidence rate of HCC was 8.5% compared to 31% in the group of patients with other causes of cirrhosis(P = 0.001). Patients with ESLD due to A1 ATD had the lowest yearly cumulative rate of hepatocellular carcinoma at 0.88% per year compared to 2.7% for those with HCV cirrhosis,1.5% in patients with NASH and 0.9% in alcohol-induced liver disease(P < 0.001).CONCLUSION:Within this group of patients with ESLD,there was no significant association between A1 ATD and increased risk of HCC.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is the hepatic manifestation of the metabolic syndrome(MetS)and is characterized by steatosis in the absence of significant alcohol consumption.However,MetS and signif...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is the hepatic manifestation of the metabolic syndrome(MetS)and is characterized by steatosis in the absence of significant alcohol consumption.However,MetS and significant alcohol intake coexist in certain individuals which may lead to the development of BAFLD.AIM To assess the clinical characteristics of patients with both alcoholic and NAFLD(BAFLD)in a large cohort in the United States.METHODS Adults from the National Health and Nutrition Examination Survey between 2003-2014 were included.NAFLD was diagnosed based on elevated alanine aminotransferase(ALT)and being overweight or obese in the absence of other liver diseases.BAFLD patients met the criteria for NAFLD but also had either MetS or type 2 diabetes and consumed excessive amounts of alcohol.Univariable and multivariable analysis were performed to assess differences between NAFLD and BAFLD and to compare severity based on a validated fibrosis score(FIB4 index).RESULTS The prevalence of NAFLD was at 25.9%(95%CI;25.1-26.8)and that of BAFLD was 0.84%(0.67,1.02)which corresponds to an estimated 1.24 million Americans affected by BAFLD.Compared to NAFLD,patients with BAFLD were more likely to be male,smokers,have higher ALT,aspartate aminotransferase,triglycerides,and lower platelets;P<0.01 for all.More importantly,after adjusting for MetS components,BAFLD patients were significantly more likely to have advanced fibrosis[adjusted OR(95%CI)based on FIB4 index>2.67 was 3.2(1.4,7.0),P=0.004].CONCLUSION A significant percentage of the American general population is afflicted by BAFLD and these patients tend to have more advanced liver fibrosis.展开更多
BACKGROUND Chronic hepatitis B virus(HBV)and hepatitis C virus(HCV)infections are known risk factors for liver disease,cirrhosis and hepatocellular carcinoma(HCC).There is substantial global variation in HBV and HCV p...BACKGROUND Chronic hepatitis B virus(HBV)and hepatitis C virus(HCV)infections are known risk factors for liver disease,cirrhosis and hepatocellular carcinoma(HCC).There is substantial global variation in HBV and HCV prevalence resulting in variations in cirrhosis and HCC.We previously reported high prevalence of HBV and HCV infections in Somali immigrants seen at an academic medical center in Minnesota.AIM To determine the prevalence of chronic viral hepatitis in Somali immigrants in Minnesota through a community-based screening program.METHODS We conducted a prospective community-based participatory research study in the Somali community in Minnesota in partnership with community advisory boards,community clinics and local mosques between November 2010 and December 2015(data was analyzed in 2020).Serum was tested for hepatitis B surface antigen,hepatitis B core antibody,hepatitis B surface antibody and anti-HCV antibody.RESULTS Of 779 participants,15.4%tested positive for chronic HBV infection,50.2%for prior exposure to HBV and 7.6%for chronic HCV infection.Calculated age-adjusted frequencies in males and females for chronic HBV were 12.5%and 11.6%;for prior exposure to HBV were 44.8%and 41.3%;and for chronic HCV were 6.7%and 5.7%,respectively.Seven participants developed incident HCC during follow up.CONCLUSION Chronic HBV and HCV are major risk factors for liver disease and HCC among Somali immigrants,with prevalence of both infections substantially higher than in the general United States population.Community-based screening is essential for identifying and providing health education and linkage to care for diagnosed patients.展开更多
BACKGROUND The Karnofsky Performance Status(KPS)scale has been widely validated for clinical practice for over 60 years.AIM To examine the extent to which poor pre-transplant functional status,assessed using the KPS s...BACKGROUND The Karnofsky Performance Status(KPS)scale has been widely validated for clinical practice for over 60 years.AIM To examine the extent to which poor pre-transplant functional status,assessed using the KPS scale,is associated with increased risk of mortality and/or graft failure at 1-year post-transplantation.METHODS This study included 38278 United States adults who underwent first,non-urgent,liver-only transplantation from 2005 to 2014(Scientific Registry of Transplant Recipients).Functional impairment/disability was categorized as severe,moderate,or none/normal.Analyses were conducted using multivariableadjusted Cox survival regression models.RESULTS The median age was 56 years,31%were women,median pre-transplant Model for End-Stage for Liver Disease score was 18.Functional impairment was present in 70%;one-quarter of the sample was severely disabled.After controlling for key recipient and donor factors,moderately and severely disabled patients had a 1-year mortality rate of 1.32[confidence interval(CI):1.21-1.44]and 1.73(95%CI:1.56-1.91)compared to patients with no impairment,respectively.Subjects with moderate and severe disability also had a multivariable-adjusted 1-year graft failure rate of 1.13(CI:1.02-1.24)and 1.16(CI:1.02-1.31),respectively.CONCLUSION Pre-transplant functional status is a useful prognostic indicator for 1-year posttransplant patient and graft survival.展开更多
To evaluate the risk of immediate and delayed bleeding following sphincterotomy procedure. METHODSThis retrospective cohort study was conducted with all patients who underwent endoscopic sphincterotomy during January ...To evaluate the risk of immediate and delayed bleeding following sphincterotomy procedure. METHODSThis retrospective cohort study was conducted with all patients who underwent endoscopic sphincterotomy during January 2006 to September 2015 at a tertiary academic center. Patients were grouped according to pre procedural usage of serotonin reuptake inhibitors (SRIs). Both groups were matched for demographic and clinical characteristics. Patients with thrombocytopenia, increased international normalized ratio, or a history of bleeding or coagulation disorders, concurrent use of other antiplatelet/anticoagulants were excluded from the study. RESULTSA total of 447 patients were included, of which 219 (45.9%) used SRIs and 228 (54.1%) cases did not. There was no significant difference in acute or delayed bleeding during endoscopic sphincterotomy between the two groups. (8.2% vs 12.3%, P = 0.16). CONCLUSIONThe use of SRIs was not associated with an increased risk of post-sphincterotomy bleeding. To our best knowledge, this is the first study to explore this association.展开更多
AIM: To fi nd risk factors of cancer in patients who had a repeat biopsy and to develop the nomogram using our cohort. METHODS: Among 3500 patients who had a prostate biopsy over 11 years between 2000 and 2010 at our ...AIM: To fi nd risk factors of cancer in patients who had a repeat biopsy and to develop the nomogram using our cohort. METHODS: Among 3500 patients who had a prostate biopsy over 11 years between 2000 and 2010 at our hospital, we studied a total of 807 repeat biopsy sessions in 459 patients who had at least 1 initial negative biopsy. At each biopsy session, we recorded patient age, number of previous biopsy sessions, number of biopsy cores, number of previously negative biopsy cores, months from the initial biopsy, months from the previous biopsy, serum PSA, PSA slope, digital rectal examination fi ndings, hypoechoic lesions suspicious for a cancer on transrectal ultrasonography, total prostate volume, transitional zone(TZ) volume, PSA density, PSA TZ density and history of high grade prostatic intraepithelial neoplasia(HGPIN) or atypical small acinar proliferation(ASAP). Clinical and pathological variables were correlated with the outcome of repeat biopsies. A nomogram was developed based on logistic regression analyses and calibration was performed.RESULTS: Overall, 17% of repeat biopsies had a cancer. With receiver operating characteristics analyses, the highest area under the curve(AUC) was obtained based on all available 13 variables, which were age, PSA, digital rectal examination, PSA density, prostate volume, TZ volume, PSA TZ density, cumulative number of biopsy cores, HGPIN, ASAP, months from previous negative biopsy, initial negative biopsy and number of biopsy cores. Based on multivariable logistic regression analysis, a nomogram was constructed with an AUC of 0.74, which was greater than that of any single risk factor. The calibration plot seemed to be good.CONCLUSION: Our nomogram for predicting a positive repeat biopsy can provide probabilities for cancer and may help clinical judgment on whether to do a repeat prostate biopsy.展开更多
BACKGROUND The coronavirus disease 2019(COVID-19)course may be affected by environmental factors.Ecological studies previously suggested a link between climatological factors and COVID-19 fatality rates.However,indivi...BACKGROUND The coronavirus disease 2019(COVID-19)course may be affected by environmental factors.Ecological studies previously suggested a link between climatological factors and COVID-19 fatality rates.However,individual-level impact of these factors has not been thoroughly evaluated yet.AIM To study the association of climatological factors related to patient location with unfavorable outcomes in patients.METHODS In this observational analysis of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study:COVID-19 Registry cohort,the latitudes and altitudes of hospitals were examined as a covariate for mortality within 28 d of admission and the length of hospital stay.Adjusting for baseline parameters and admission date,multivariable regression modeling was utilized.Generalized estimating equations were used to fit the models.RESULTS Twenty-two thousand one hundred eight patients from over 20 countries were evaluated.The median age was 62(interquartile range:49-74)years,and 54%of the included patients were males.The median age increased with increasing latitude as well as the frequency of comorbidities.Contrarily,the percentage of comorbidities was lower in elevated altitudes.Mortality within 28 d of hospital admission was found to be 25%.The median hospital-free days among all included patients was 20 d.Despite the significant linear relationship between mortality and hospital-free days(adjusted odds ratio(aOR)=1.39(1.04,1.86),P=0.025 for mortality within 28 d of admission;aOR=-1.47(-2.60,-0.33),P=0.011 for hospital-free days),suggesting that adverse patient outcomes were more common in locations further away from the Equator;the results were no longer significant when adjusted for baseline differences(aOR=1.32(1.00,1.74),P=0.051 for 28-day mortality;aOR=-1.07(-2.13,-0.01),P=0.050 for hospital-free days).When we looked at the altitude’s effect,we discovered that it demonstrated a non-linear association with mortality within 28 d of hospital admission(aOR=0.96(0.62,1.47),1.04(0.92,1.19),0.49(0.22,0.90),and 0.51(0.27,0.98),for the altitude points of 75 MASL,125 MASL,400 MASL,and 600 MASL,in comparison to the reference altitude of 148 m.a.s.l,respectively.P=0.001).We detected an association between latitude and 28-day mortality as well as hospital-free days in this worldwide study.When the baseline features were taken into account,however,this did not stay significant.CONCLUSION Our findings suggest that differences observed in previous epidemiological studies may be due to ecological fallacy rather than implying a causal relationship at the patient level.展开更多
BACKGROUND There is concern regarding potential long-term cardiotoxicity with systemic distribution of metals in total joint arthroplasty(TJA)patients.AIM To determine the association of commonly used implant metals w...BACKGROUND There is concern regarding potential long-term cardiotoxicity with systemic distribution of metals in total joint arthroplasty(TJA)patients.AIM To determine the association of commonly used implant metals with echocardiographic measures in TJA patients.METHODS The study comprised 110 TJA patients who had a recent history of high chromium,cobalt or titanium concentrations.Patients underwent two-dimensional,three-dimensional,Doppler and speckle-strain transthoracic echocardiography and a blood draw to measure metal concentrations.Age and sex-adjusted linear and logistic regression models were used to examine the association of metal concentrations(exposure)with echocardiographic measures(outcome).RESULTS Higher cobalt concentrations were associated with increased left ventricular end-diastolic volume(estimate 5.09;95%CI:0.02-10.17)as well as left atrial and right ventricular dilation,particularly in men but no changes in cardiac function.Higher titanium concentrations were associated with a reduction in left ventricle global longitudinal strain(estimate 0.38;95%CI:0.70 to 0.06)and cardiac index(estimate 0.08;95%CI,-0.15 to-0.01).CONCLUSION Elevated cobalt and titanium concentrations may be associated with structural and functional cardiac changes in some patients.Longitudinal studies are warranted to better understand the systemic effects of metals in TJA patients.展开更多
Clonal hematopoiesis(CH)of indeterminate potential(CHIP),driven by somatic mutations in leukemia-associated genes,confers increased risk of hematologic malignancies,cardiovascular disease,and all-cause mortality.In bl...Clonal hematopoiesis(CH)of indeterminate potential(CHIP),driven by somatic mutations in leukemia-associated genes,confers increased risk of hematologic malignancies,cardiovascular disease,and all-cause mortality.In blood of healthy individuals,small CH clones can expand over time to reach 2% variant allele frequency(VAF),the current threshold for CHIP.Nevertheless,reliable detection of low-VAF CHIP mutations is challenging,often relying on deep targeted sequencing.Here,we present UNISOM,a streamlined workflow for enhancing CHIP detection from whole-genome and whole-exome sequencing data that are underpowered,especially for low VAFs.UNISOM utilizes a meta-caller for variant detection,in couple with machine learning models which classify variants into CHIP,germline,and artifact.In whole-exome sequencing data,UNISOM recovered nearly 80% of the CHIP mutations identified via deep targeted sequencing in the same cohort.Applied to whole-genome sequencing data from Mayo Clinic Biobank,it recapitulated the patterns previously established in much larger cohorts,including the most frequently mutated CHIP genes and predominant mutation types and signatures,as well as strong associations of CHIP with age and smoking status.Notably,30% of the identified CHIP mutations had<5%VAFs,demonstrating its high sensitivity toward small mutant clones.This workflow is applicable to CHIP screening in population genomic studies.The UNISOM pipeline is freely available at https://github.com/shulanmayo/UNISOM and https://ngdc.cncb.ac.cn/biocode/tool/7816.展开更多
BACKGROUND The prevalence of nonalcoholic fatty liver disease(NAFLD) is significantly rising worldwide. Type-2 diabetes(T2D) is a major risk factor for NAFLD progression.AIM To assess the association of commonly used ...BACKGROUND The prevalence of nonalcoholic fatty liver disease(NAFLD) is significantly rising worldwide. Type-2 diabetes(T2D) is a major risk factor for NAFLD progression.AIM To assess the association of commonly used medications to advanced fibrosis(AF) in patients with biopsy-proven NAFLD and T2D.METHODS We used the International Classification of Disease 9 th Revision Clinical Modification coding system to identify patients with T2D and included patients who underwent liver biopsy for suspected NAFLD between January 1, 2000 to December 31, 2015. We compared demographics, clinical characteristics, and differences in pattern of medication use in patients who had biopsy-proven AF to those without it. A univariate and multivariate analysis was performed to assess the association of different classes of medication with the presence of AF.RESULTS A total of 1183 patients were included in the final analysis, out of which 32%(n =381) had AF on liver biopsy. Mean age of entire cohort was 52 years and majority were females(65%) and Caucasians(85%). Among patients with AF, 51% were on oral hypoglycemics, 30% were on insulin, 66% were on antihypertensives and 27% were on lipid lowering agents for the median duration of 19 mo, 10 mo, 26 mo, and 24 mo respectively. Medications associated with decreased risk of AF included metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin while the use of furosemide and spironolactone were associated with higher prevalence of AF.CONCLUSION In our cohort of T2D with biopsy proven NAFLD, the patients who were receiving metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin were less likely to have AF on biopsy, while patients who were receiving furosemide and spironolactone had a higher likelihood of having AF when they underwent liver biopsy. Future studies are needed to confirm these findings and to establish measures for prevention of NAFLD progression in patients with T2D.展开更多
AIM: To identify plasma analytes using metabolomics that correlate with the diagnosis and severity of liver disease in patients with alcoholic hepatitis(AH).METHODS: We prospectively recruited patients with cirrhosis ...AIM: To identify plasma analytes using metabolomics that correlate with the diagnosis and severity of liver disease in patients with alcoholic hepatitis(AH).METHODS: We prospectively recruited patients with cirrhosis from AH(n = 23) and those with cirrhosis with acute decompensation(AD) from etiologies other than alcohol(n = 25). We used mass spectrometry to identify 29 metabolic compounds in plasma samples from fasted subjects. A receiver operating characteristics analysis was performed to assess the utility of biomarkers in distinguishing acute AH from alcoholic cirrhosis. Logistic regression analysis was performed to build a predictive model for AH based on clinical characteristics. A survival analysis was used to construct Kaplan Meier curves evaluating transplant-free survival.RESULTS: A comparison of model for end-stage liver disease(MELD)-adjusted metabolomics levels between cirrhosis patients who had AD or AH showed that patients with AH had significantly higher levels of betaine, and lower creatinine, phenylalanine, homocitrulline, citrulline, tyrosine, octenoyl-carnitine, and symmetric dimethylarginine. When considering combined levels, betaine and citrulline were highly accurate predictors for differentiation between AH and AD(area under receiver operating characteristics curve = 0.84). The plasma levels of carnitine [0.54(0.18, 0.91); P = 0.005], homocitrulline [0.66(0.34, 0.99); P < 0.001] and pentanoyl-carnitine [0.53(0.16, 0.90); P = 0.007] correlated with MELD scores in patients diagnosed with AH. Increased levels of many biomarkers(carnitine P = 0.005, butyrobetaine P = 0.32, homocitrulline P = 0.002, leucine P = 0.027, valine P = 0.024, phenylalanine P = 0.037, tyrosine P = 0.012, acetyl-carnitine P = 0.006, propionyl-carnitine P = 0.03, butyryl-carnitine P = 0.03, trimethyl-lisine P = 0.034, pentanoyl-carnitine P = 0.03, hexanoyl-carnitine P = 0.026) were associated with increased mortality in patients with AH. CONCLUSION: Metabolomics plasma analyte levels might be used to diagnose of AH or help predict patient prognoses.展开更多
BACKGROUND Monitoring ventilation accurately is an indispensable aspect of patient care in procedural settings.The current gold standard method of monitoring ventilation is by measuring exhaled carbon dioxide concentr...BACKGROUND Monitoring ventilation accurately is an indispensable aspect of patient care in procedural settings.The current gold standard method of monitoring ventilation is by measuring exhaled carbon dioxide concentration,known as capnography.A new device utilizing thermodynamic measurement,the Linshom Respiratory Monitoring Device(LRMD),has been designed to measure respiratory rate(RR)by using the temperature of exhaled breath.We hypothesized that the temperature sensor is at least equivalent in accuracy to capnography in monitoring ventilation.AIM To determine if the temperature sensor is equivalent to capnography in monitoring procedural ventilation.METHODS In this prospective study,participants were individually fitted with a face mask monitored by both LRMD and capnography.The following data were collected:gender,age,body mass index,type of procedure,and doses of medication.For each patient,we report the mean RR for each device as well as the mean difference.All analyses were performed using SAS,and a P<0.05 was considered statistically significant.RESULTS Twelve consecutive patients undergoing endoscopic procedures at our institution were enrolled.Four patients were excluded due to incomplete data,inadequate data,patient cooperation,and capnography failure.Overall,we found that LRMD RR highly correlated to capnography RR(P<0.001);the average capnography RR increases by 0.66 breaths for every one additional breath measured by the LRMD.In addition,apnea rates were 7.4%for the capnography and 6.4%for the LRMD(95%confidence interval:0.92-1.10).CONCLUSION The LRMD correlated with the gold standard capnography with respect to respiratory rate detection and apnea events.The LRMD could be used as an alternative to capnography for measuring respiration in endoscopy.展开更多
Background:Ablation is an alternative treatment modality for selected patients with colorectal liver metastases(CRLMs).Although initially widely performed via radiofrequency ablation(RFA),more recently,microwave ablat...Background:Ablation is an alternative treatment modality for selected patients with colorectal liver metastases(CRLMs).Although initially widely performed via radiofrequency ablation(RFA),more recently,microwave ablation(MWA)is being preferred due to its perceived superiority in creating the ablation zones.The aim of this study is to compare the long-term efficacy of these two modalities performed surgically.Methods:Patients undergoing surgical liver ablation from 2005-2023 at a tertiary center by a single surgeon for CRLM were included in a retrospective institutional review board-approved study.Outcomes were compared using Wilcoxon,Chi-square,Kaplan-Meier,and Cox multivariate regression analyses.Continuous data are presented as median(interquartile range).Results:There were a total of 242 patients.Laparoscopic RFA was done in 121 patients with 303 lesions and laparoscopic MWA in 121 patients with 300 lesions.There was no difference between the groups regarding operative time(161 vs.147 minutes,respectively,P=0.4),perioperative morbidity(3%vs.8%,respectively,P=0.2)or hospital stay(1 vs.1 day,P=0.05).Local recurrence(LR)per lesion with at least 1 year of imaging follow-up was 29%in the RFA and 13%in the MWA group(P<0.001).Based on univariate survival analysis,tumor size,blood vessel proximity,ablation margin,and ablation modality were independent predictors of LR.To control these variables,direct matching was performed.Each cohort included 189 lesions.Kaplan-Meier analysis of these cohorts showed increased LR-free survival in the MWA group vs.the RFA group(P=0.005).Conclusions:This large study confirms our initial observation that local tumor control rate is better after MWA vs.RFA.展开更多
BACKGROUND Critically ill patients with cirrhosis,particularly those with acute decompensation,have higher mortality rates in the intensive care unit(ICU)than patients without chronic liver disease.Prognostication of ...BACKGROUND Critically ill patients with cirrhosis,particularly those with acute decompensation,have higher mortality rates in the intensive care unit(ICU)than patients without chronic liver disease.Prognostication of short-term mortality is important in order to identify patients at highest risk of death.None of the currently available prognostic models have been widely accepted for use in cirrhotic patients in the ICU,perhaps due to complexity of calculation,or lack of universal variables readily available for these patients.We believe a survival model meeting these requirements can be developed,to guide therapeutic decision-making and contribute to cost-effective healthcare resource utilization.AIM To identify markers that best identify likelihood of survival and to determine the performance of existing survival models.METHODS Consecutive cirrhotic patients admitted to a United States quaternary care center ICU between 2008-2014 were included and comprised the training cohort.Demographic data and clinical laboratory test collected on admission to ICU were analyzed.Area under the curve receiver operator characteristics(AUROC)analysis was performed to assess the value of various scores in predicting inhospital mortality.A new predictive model,the LIV-4 score,was developed using logistic regression analysis and validated in a cohort of patients admitted to the same institution between 2015-2017.RESULTS Of 436 patients,119(27.3%)died in the hospital.In multivariate analysis,a combination of the natural logarithm of the bilirubin,prothrombin time,white blood cell count,and mean arterial pressure was found to most accurately predict in-hospital mortality.Derived from the regression coefficients of the independent variables,a novel model to predict inpatient mortality was developed(the LIV-4 score)and performed with an AUROC of 0.86,compared to the Model for End-Stage Liver Disease,Chronic Liver Failure-Sequential Organ Failure Assessment,and Royal Free Hospital Score,which performed with AUROCs of 0.81,0.80,and 0.77,respectively.Patients in the internal validation cohort were substantially sicker,as evidenced by higher Model for End-Stage Liver Disease,Model for End-Stage Liver Disease-Sodium,Acute Physiology and Chronic Health Evaluation III,SOFA and LIV-4 scores.Despite these differences,the LIV-4 score remained significantly higher in subjects who expired during the hospital stay and exhibited good prognostic values in the validation cohort with an AUROC of 0.80.CONCLUSION LIV-4,a validated model for predicting mortality in cirrhotic patients on admission to the ICU,performs better than alternative liver and ICU-specific survival scores.展开更多
文摘This study explores free convective heat transfer in an electrically conducting nanofluid flow over a moving semi-infinite flat plate under the influence of an induced magnetic field and viscous dissipation.The velocity and magnetic field vectors are aligned at a distance from the plate.The Spectral Relaxation Method(SRM)is used to numerically solve the coupled nonlinear partial differential equations,analyzing the effects of the Eckert number on heat and mass transfer.Various nanofluids containing Cu,Ag,Al_(2)O_(3),and TiO_(2) nanoparticles are examined to assess how external magnetic fields influence fluid behavior.Key parameters,including the nanoparticle volume fraction ϕ,magnetic parameter M,magnetic Prandtl number Prm,and Eckert number Ec,are evaluated for their impact on velocity,induced magnetic field,and heat transfer.Results indicate that increasing the magnetic parameter reduces velocity and magnetic field components in alumina-water nanofluids,while a higher nanoparticle volume fraction enhances the thermal boundary layer.Greater viscous dissipation(Ec)increases temperature,and Al_(2)O_(3) nanofluids exhibit higher speeds than Cu,Ag,and TiO_(2) due to density differences.Silver-water nanofluids,with their higher density,move more slowly.The SRM results closely align with those from Maple,confirming the method’s accuracy.
文摘BACKGROUND Due to development of an immune-dysregulated phenotype,advanced liver disease in all forms predisposes patients to sepsis acquisition,including by opportunistic pathogens such as fungi.Little data exists on fungal infection within a medical intensive liver unit(MILU),particularly in relation to acute on chronic liver failure.AIM To investigate the impact of fungal infections among critically ill patients with advanced liver disease,and compare outcomes to those of patients with bacterial infections.METHODS From our prospective registry of MILU patients from 2018-2022,we included 27 patients with culture-positive fungal infections and 183 with bacterial infections.We compared outcomes between patients admitted to the MILU with fungal infections to bacterial counterparts.Data was extracted through chart review.RESULTS All fungal infections were due to Candida species,and were most frequently blood isolates.Mortality among patients with fungal infections was significantly worse relative to the bacterial cohort(93%vs 52%,P<0.001).The majority of the fungal cohort developed grade 2 or 3 acute on chronic liver failure(ACLF)(90%vs 64%,P=0.02).Patients in the fungal cohort had increased use of vasopressors(96%vs 70%,P=0.04),mechanical ventilation(96%vs 65%,P<0.001),and dialysis due to acute kidney injury(78%vs 52%,P=0.014).On MILU admission,the fungal cohort had significantly higher Acute Physiology and Chronic Health Evaluation(108 vs 91,P=0.003),Acute Physiology Score(86 vs 65,P=0.003),and Model for End-Stage Liver Disease-Sodium scores(86 vs 65,P=0.041).There was no significant difference in the rate of central line use preceding culture(52%vs 40%,P=0.2).Patients with fungal infection had higher rate of transplant hold placement,and lower rates of transplant;however,differences did not achieve statistical significance.CONCLUSION Mortality was worse among patients with fungal infections,likely attributable to severe ACLF development.Prospective studies examining empiric antifungals in severe ACLF and associations between fungal infections and transplant outcomes are critical.
文摘The steady flow behavior in terminal bronchus of human lung for cylindrical channel of porous medium has been studied. The governing equations have been solved analytically and numerically for cylindrical channel. Finite difference method is incorporated to simulate the problem. The numerical results are compared with square duct channel for different parametric effect. It is observed that the flow rate is increased in cylindrical channel compared to square duct channel for the increasing value of pressure gradient, porosity and permeability. On the contrary, the flow rate is decreased in square duct channel compared to cylindrical channel for increasing value of viscosity. Flow rate in both channels is analyzed and compared for non-porous medium also. It is observed that flow rate is increased very high in cylindrical channel compared to square duct channel for both medium.
文摘AIM: To study the small bowel (SB) mucosa on biopsy in cirrhotic patients with portal hypertension and in non-cirrhotic controls and grade fi ndings according to the Marsh criteria. METHODS: We prospectively enrolled 51 consecutive patients undergoing an upper endoscopy for their routine medical care. Twenty f ive patients with cirrhosis and portal hypertension were compared to 26 controls. We obtained coeliac serology and multiple upper small bowel biopsies on all 51 patients. A GI pathologist interpreted biopsies and graded fi ndings according to the Marsh criteria. We assessed equivalence in Marsh grade between cirrhotic and non-cirrhotic controls using the Mann-Whitney test for equivalence. RESULTS: Gender, ethnicity and age were similar between both groups. Marsh grades were equivalent between the groups. Grade of 0 was present in 96% and grade of 1 was present in 4% of both groups and there was no villus atrophy or decrease in villus/crypt ratio in patients with portal hypertension. CONCLUSION: This study provides evidence for the lack of villus atrophy in patients with cirrhosis and portal hypertension, and supports the continuous reliance on the Marsh criteria when the diagnosis of coeliac disease is to be made in the presence of cirrhosis.
文摘Greater understanding of the biology and epidemiology of prostate cancer in the last several decades have led to significant advances in its management. Prostate cancer is now detected in greater numbers at lower stages of disease and is amenable to multiple forms of efficacious treatment. However, there is a lack of conclusive data demonstrating a definitive mortality benefit from this earlier diagnosis and treatment of prostate cancer. It is likely due to the treatment of a large proportion of indolent cancers that would have had little adverse impact on health or lifespan if left alone. Due to this overtreatment phenomenon, active surveillance with delayed intervention is gaining traction as a viable management approach in contemporary practice. The ability to distinguish clinically insignificant cancers from those with a high risk of progression and/or lethality is critical to the appropriate selection of patients for surveillance protocols versus immediate intervention. This chapter will review the ability of various prediction models, including risk groupings and nomograms, to predict indolent disease and determine their role in the contemporary management of clinically localized prostate cancer.
文摘AIM:To evaluate the association between alpha-1 antitrypsin deficiency(A1ATD) and hepatocellular carcinoma(HCC) in patients with end-stage liver disease(ESLD).METHODS:Patients with cirrhosis and ESLD referred to the Cleveland Clinic Foundation for liver transplantation between 2003 and 2014 were included in the study(N = 675). ESLD was defined as having histological features of cirrhosis and/or radiological evidence of cirrhosis in the context of portal hypertension(ascites,variceal bleeding,thrombocytopenia,or hepatic encephalopathy). A1 ATD was diagnosed using phenotype characterization(MZ or ZZ),liver biopsy detection of PAS-positive diastaseresistant(PAS+) globules,or both. Patients with other causes of liver diseases such as hepatitis C virus(HCV),alcoholic liver disease and non-alcoholic steatohepatitis(NASH) or NASH were also included in the study. HCC was diagnosed by using imaging modalities,biopsy findings,or explanted liver inspection. Follow-up time was defined as the number of years from the diagnosis of cirrhosis to the diagnosis of hepatocellular carcinoma,or from the diagnosis of cirrhosis to the last follow up visit. The rate of HCC was assessed using time-tointerval analysis for interval censored data.RESULTS:This study included 675 patients. 7% of subjects had A1ATD(n = 47). Out of all subjects who did not have A1 ATD,46% had HCV,17% had alcoholic liver disease,19% had NASH and 18% had another primary diagnosis. Of the 47 subjects with A1 ATD,15 had a primary diagnosis of A1ATD(PI*ZZ phenotype and PAS+ globules),8 had a PI*MZ phenotype alone,14 had PAS+ alone,and 10 had both the PI*MZ phenotype and PAS+. Median follow-up time was 3.4(25th,75 th percentiles:1,5.2) years. The overall rate of hepatocellular carcinoma in all subjects was 29%(n = 199). In the A1 ATD group,the incidence rate of HCC was 8.5% compared to 31% in the group of patients with other causes of cirrhosis(P = 0.001). Patients with ESLD due to A1 ATD had the lowest yearly cumulative rate of hepatocellular carcinoma at 0.88% per year compared to 2.7% for those with HCV cirrhosis,1.5% in patients with NASH and 0.9% in alcohol-induced liver disease(P < 0.001).CONCLUSION:Within this group of patients with ESLD,there was no significant association between A1 ATD and increased risk of HCC.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is the hepatic manifestation of the metabolic syndrome(MetS)and is characterized by steatosis in the absence of significant alcohol consumption.However,MetS and significant alcohol intake coexist in certain individuals which may lead to the development of BAFLD.AIM To assess the clinical characteristics of patients with both alcoholic and NAFLD(BAFLD)in a large cohort in the United States.METHODS Adults from the National Health and Nutrition Examination Survey between 2003-2014 were included.NAFLD was diagnosed based on elevated alanine aminotransferase(ALT)and being overweight or obese in the absence of other liver diseases.BAFLD patients met the criteria for NAFLD but also had either MetS or type 2 diabetes and consumed excessive amounts of alcohol.Univariable and multivariable analysis were performed to assess differences between NAFLD and BAFLD and to compare severity based on a validated fibrosis score(FIB4 index).RESULTS The prevalence of NAFLD was at 25.9%(95%CI;25.1-26.8)and that of BAFLD was 0.84%(0.67,1.02)which corresponds to an estimated 1.24 million Americans affected by BAFLD.Compared to NAFLD,patients with BAFLD were more likely to be male,smokers,have higher ALT,aspartate aminotransferase,triglycerides,and lower platelets;P<0.01 for all.More importantly,after adjusting for MetS components,BAFLD patients were significantly more likely to have advanced fibrosis[adjusted OR(95%CI)based on FIB4 index>2.67 was 3.2(1.4,7.0),P=0.004].CONCLUSION A significant percentage of the American general population is afflicted by BAFLD and these patients tend to have more advanced liver fibrosis.
基金Supported by the Mayo Clinic Center for Clinical and Translational Science from the National Center for Advancing Translational Sciences (5UL1TR000135-10)the Mayo Clinic Hepatobiliary SPORE from the National Cancer Institute (5P50CA210964-04)+1 种基金the Mayo Clinic Center for Cell Signaling in Gastroenterology (5P30DK084567-14)Gilead Sciences,Inc.(IN-US-174-0230)
文摘BACKGROUND Chronic hepatitis B virus(HBV)and hepatitis C virus(HCV)infections are known risk factors for liver disease,cirrhosis and hepatocellular carcinoma(HCC).There is substantial global variation in HBV and HCV prevalence resulting in variations in cirrhosis and HCC.We previously reported high prevalence of HBV and HCV infections in Somali immigrants seen at an academic medical center in Minnesota.AIM To determine the prevalence of chronic viral hepatitis in Somali immigrants in Minnesota through a community-based screening program.METHODS We conducted a prospective community-based participatory research study in the Somali community in Minnesota in partnership with community advisory boards,community clinics and local mosques between November 2010 and December 2015(data was analyzed in 2020).Serum was tested for hepatitis B surface antigen,hepatitis B core antibody,hepatitis B surface antibody and anti-HCV antibody.RESULTS Of 779 participants,15.4%tested positive for chronic HBV infection,50.2%for prior exposure to HBV and 7.6%for chronic HCV infection.Calculated age-adjusted frequencies in males and females for chronic HBV were 12.5%and 11.6%;for prior exposure to HBV were 44.8%and 41.3%;and for chronic HCV were 6.7%and 5.7%,respectively.Seven participants developed incident HCC during follow up.CONCLUSION Chronic HBV and HCV are major risk factors for liver disease and HCC among Somali immigrants,with prevalence of both infections substantially higher than in the general United States population.Community-based screening is essential for identifying and providing health education and linkage to care for diagnosed patients.
文摘BACKGROUND The Karnofsky Performance Status(KPS)scale has been widely validated for clinical practice for over 60 years.AIM To examine the extent to which poor pre-transplant functional status,assessed using the KPS scale,is associated with increased risk of mortality and/or graft failure at 1-year post-transplantation.METHODS This study included 38278 United States adults who underwent first,non-urgent,liver-only transplantation from 2005 to 2014(Scientific Registry of Transplant Recipients).Functional impairment/disability was categorized as severe,moderate,or none/normal.Analyses were conducted using multivariableadjusted Cox survival regression models.RESULTS The median age was 56 years,31%were women,median pre-transplant Model for End-Stage for Liver Disease score was 18.Functional impairment was present in 70%;one-quarter of the sample was severely disabled.After controlling for key recipient and donor factors,moderately and severely disabled patients had a 1-year mortality rate of 1.32[confidence interval(CI):1.21-1.44]and 1.73(95%CI:1.56-1.91)compared to patients with no impairment,respectively.Subjects with moderate and severe disability also had a multivariable-adjusted 1-year graft failure rate of 1.13(CI:1.02-1.24)and 1.16(CI:1.02-1.31),respectively.CONCLUSION Pre-transplant functional status is a useful prognostic indicator for 1-year posttransplant patient and graft survival.
文摘To evaluate the risk of immediate and delayed bleeding following sphincterotomy procedure. METHODSThis retrospective cohort study was conducted with all patients who underwent endoscopic sphincterotomy during January 2006 to September 2015 at a tertiary academic center. Patients were grouped according to pre procedural usage of serotonin reuptake inhibitors (SRIs). Both groups were matched for demographic and clinical characteristics. Patients with thrombocytopenia, increased international normalized ratio, or a history of bleeding or coagulation disorders, concurrent use of other antiplatelet/anticoagulants were excluded from the study. RESULTSA total of 447 patients were included, of which 219 (45.9%) used SRIs and 228 (54.1%) cases did not. There was no significant difference in acute or delayed bleeding during endoscopic sphincterotomy between the two groups. (8.2% vs 12.3%, P = 0.16). CONCLUSIONThe use of SRIs was not associated with an increased risk of post-sphincterotomy bleeding. To our best knowledge, this is the first study to explore this association.
文摘AIM: To fi nd risk factors of cancer in patients who had a repeat biopsy and to develop the nomogram using our cohort. METHODS: Among 3500 patients who had a prostate biopsy over 11 years between 2000 and 2010 at our hospital, we studied a total of 807 repeat biopsy sessions in 459 patients who had at least 1 initial negative biopsy. At each biopsy session, we recorded patient age, number of previous biopsy sessions, number of biopsy cores, number of previously negative biopsy cores, months from the initial biopsy, months from the previous biopsy, serum PSA, PSA slope, digital rectal examination fi ndings, hypoechoic lesions suspicious for a cancer on transrectal ultrasonography, total prostate volume, transitional zone(TZ) volume, PSA density, PSA TZ density and history of high grade prostatic intraepithelial neoplasia(HGPIN) or atypical small acinar proliferation(ASAP). Clinical and pathological variables were correlated with the outcome of repeat biopsies. A nomogram was developed based on logistic regression analyses and calibration was performed.RESULTS: Overall, 17% of repeat biopsies had a cancer. With receiver operating characteristics analyses, the highest area under the curve(AUC) was obtained based on all available 13 variables, which were age, PSA, digital rectal examination, PSA density, prostate volume, TZ volume, PSA TZ density, cumulative number of biopsy cores, HGPIN, ASAP, months from previous negative biopsy, initial negative biopsy and number of biopsy cores. Based on multivariable logistic regression analysis, a nomogram was constructed with an AUC of 0.74, which was greater than that of any single risk factor. The calibration plot seemed to be good.CONCLUSION: Our nomogram for predicting a positive repeat biopsy can provide probabilities for cancer and may help clinical judgment on whether to do a repeat prostate biopsy.
文摘BACKGROUND The coronavirus disease 2019(COVID-19)course may be affected by environmental factors.Ecological studies previously suggested a link between climatological factors and COVID-19 fatality rates.However,individual-level impact of these factors has not been thoroughly evaluated yet.AIM To study the association of climatological factors related to patient location with unfavorable outcomes in patients.METHODS In this observational analysis of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study:COVID-19 Registry cohort,the latitudes and altitudes of hospitals were examined as a covariate for mortality within 28 d of admission and the length of hospital stay.Adjusting for baseline parameters and admission date,multivariable regression modeling was utilized.Generalized estimating equations were used to fit the models.RESULTS Twenty-two thousand one hundred eight patients from over 20 countries were evaluated.The median age was 62(interquartile range:49-74)years,and 54%of the included patients were males.The median age increased with increasing latitude as well as the frequency of comorbidities.Contrarily,the percentage of comorbidities was lower in elevated altitudes.Mortality within 28 d of hospital admission was found to be 25%.The median hospital-free days among all included patients was 20 d.Despite the significant linear relationship between mortality and hospital-free days(adjusted odds ratio(aOR)=1.39(1.04,1.86),P=0.025 for mortality within 28 d of admission;aOR=-1.47(-2.60,-0.33),P=0.011 for hospital-free days),suggesting that adverse patient outcomes were more common in locations further away from the Equator;the results were no longer significant when adjusted for baseline differences(aOR=1.32(1.00,1.74),P=0.051 for 28-day mortality;aOR=-1.07(-2.13,-0.01),P=0.050 for hospital-free days).When we looked at the altitude’s effect,we discovered that it demonstrated a non-linear association with mortality within 28 d of hospital admission(aOR=0.96(0.62,1.47),1.04(0.92,1.19),0.49(0.22,0.90),and 0.51(0.27,0.98),for the altitude points of 75 MASL,125 MASL,400 MASL,and 600 MASL,in comparison to the reference altitude of 148 m.a.s.l,respectively.P=0.001).We detected an association between latitude and 28-day mortality as well as hospital-free days in this worldwide study.When the baseline features were taken into account,however,this did not stay significant.CONCLUSION Our findings suggest that differences observed in previous epidemiological studies may be due to ecological fallacy rather than implying a causal relationship at the patient level.
基金Supported by The National Institutes of Health,No.R01HL147155 and No.R01AG060920.
文摘BACKGROUND There is concern regarding potential long-term cardiotoxicity with systemic distribution of metals in total joint arthroplasty(TJA)patients.AIM To determine the association of commonly used implant metals with echocardiographic measures in TJA patients.METHODS The study comprised 110 TJA patients who had a recent history of high chromium,cobalt or titanium concentrations.Patients underwent two-dimensional,three-dimensional,Doppler and speckle-strain transthoracic echocardiography and a blood draw to measure metal concentrations.Age and sex-adjusted linear and logistic regression models were used to examine the association of metal concentrations(exposure)with echocardiographic measures(outcome).RESULTS Higher cobalt concentrations were associated with increased left ventricular end-diastolic volume(estimate 5.09;95%CI:0.02-10.17)as well as left atrial and right ventricular dilation,particularly in men but no changes in cardiac function.Higher titanium concentrations were associated with a reduction in left ventricle global longitudinal strain(estimate 0.38;95%CI:0.70 to 0.06)and cardiac index(estimate 0.08;95%CI,-0.15 to-0.01).CONCLUSION Elevated cobalt and titanium concentrations may be associated with structural and functional cardiac changes in some patients.Longitudinal studies are warranted to better understand the systemic effects of metals in TJA patients.
基金supported by the Mayo Clinic Center for Individualized Medicine,USA.
文摘Clonal hematopoiesis(CH)of indeterminate potential(CHIP),driven by somatic mutations in leukemia-associated genes,confers increased risk of hematologic malignancies,cardiovascular disease,and all-cause mortality.In blood of healthy individuals,small CH clones can expand over time to reach 2% variant allele frequency(VAF),the current threshold for CHIP.Nevertheless,reliable detection of low-VAF CHIP mutations is challenging,often relying on deep targeted sequencing.Here,we present UNISOM,a streamlined workflow for enhancing CHIP detection from whole-genome and whole-exome sequencing data that are underpowered,especially for low VAFs.UNISOM utilizes a meta-caller for variant detection,in couple with machine learning models which classify variants into CHIP,germline,and artifact.In whole-exome sequencing data,UNISOM recovered nearly 80% of the CHIP mutations identified via deep targeted sequencing in the same cohort.Applied to whole-genome sequencing data from Mayo Clinic Biobank,it recapitulated the patterns previously established in much larger cohorts,including the most frequently mutated CHIP genes and predominant mutation types and signatures,as well as strong associations of CHIP with age and smoking status.Notably,30% of the identified CHIP mutations had<5%VAFs,demonstrating its high sensitivity toward small mutant clones.This workflow is applicable to CHIP screening in population genomic studies.The UNISOM pipeline is freely available at https://github.com/shulanmayo/UNISOM and https://ngdc.cncb.ac.cn/biocode/tool/7816.
文摘BACKGROUND The prevalence of nonalcoholic fatty liver disease(NAFLD) is significantly rising worldwide. Type-2 diabetes(T2D) is a major risk factor for NAFLD progression.AIM To assess the association of commonly used medications to advanced fibrosis(AF) in patients with biopsy-proven NAFLD and T2D.METHODS We used the International Classification of Disease 9 th Revision Clinical Modification coding system to identify patients with T2D and included patients who underwent liver biopsy for suspected NAFLD between January 1, 2000 to December 31, 2015. We compared demographics, clinical characteristics, and differences in pattern of medication use in patients who had biopsy-proven AF to those without it. A univariate and multivariate analysis was performed to assess the association of different classes of medication with the presence of AF.RESULTS A total of 1183 patients were included in the final analysis, out of which 32%(n =381) had AF on liver biopsy. Mean age of entire cohort was 52 years and majority were females(65%) and Caucasians(85%). Among patients with AF, 51% were on oral hypoglycemics, 30% were on insulin, 66% were on antihypertensives and 27% were on lipid lowering agents for the median duration of 19 mo, 10 mo, 26 mo, and 24 mo respectively. Medications associated with decreased risk of AF included metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin while the use of furosemide and spironolactone were associated with higher prevalence of AF.CONCLUSION In our cohort of T2D with biopsy proven NAFLD, the patients who were receiving metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin were less likely to have AF on biopsy, while patients who were receiving furosemide and spironolactone had a higher likelihood of having AF when they underwent liver biopsy. Future studies are needed to confirm these findings and to establish measures for prevention of NAFLD progression in patients with T2D.
基金Supported by In part by NIH grant R01 HL122283(Brown JM)
文摘AIM: To identify plasma analytes using metabolomics that correlate with the diagnosis and severity of liver disease in patients with alcoholic hepatitis(AH).METHODS: We prospectively recruited patients with cirrhosis from AH(n = 23) and those with cirrhosis with acute decompensation(AD) from etiologies other than alcohol(n = 25). We used mass spectrometry to identify 29 metabolic compounds in plasma samples from fasted subjects. A receiver operating characteristics analysis was performed to assess the utility of biomarkers in distinguishing acute AH from alcoholic cirrhosis. Logistic regression analysis was performed to build a predictive model for AH based on clinical characteristics. A survival analysis was used to construct Kaplan Meier curves evaluating transplant-free survival.RESULTS: A comparison of model for end-stage liver disease(MELD)-adjusted metabolomics levels between cirrhosis patients who had AD or AH showed that patients with AH had significantly higher levels of betaine, and lower creatinine, phenylalanine, homocitrulline, citrulline, tyrosine, octenoyl-carnitine, and symmetric dimethylarginine. When considering combined levels, betaine and citrulline were highly accurate predictors for differentiation between AH and AD(area under receiver operating characteristics curve = 0.84). The plasma levels of carnitine [0.54(0.18, 0.91); P = 0.005], homocitrulline [0.66(0.34, 0.99); P < 0.001] and pentanoyl-carnitine [0.53(0.16, 0.90); P = 0.007] correlated with MELD scores in patients diagnosed with AH. Increased levels of many biomarkers(carnitine P = 0.005, butyrobetaine P = 0.32, homocitrulline P = 0.002, leucine P = 0.027, valine P = 0.024, phenylalanine P = 0.037, tyrosine P = 0.012, acetyl-carnitine P = 0.006, propionyl-carnitine P = 0.03, butyryl-carnitine P = 0.03, trimethyl-lisine P = 0.034, pentanoyl-carnitine P = 0.03, hexanoyl-carnitine P = 0.026) were associated with increased mortality in patients with AH. CONCLUSION: Metabolomics plasma analyte levels might be used to diagnose of AH or help predict patient prognoses.
文摘BACKGROUND Monitoring ventilation accurately is an indispensable aspect of patient care in procedural settings.The current gold standard method of monitoring ventilation is by measuring exhaled carbon dioxide concentration,known as capnography.A new device utilizing thermodynamic measurement,the Linshom Respiratory Monitoring Device(LRMD),has been designed to measure respiratory rate(RR)by using the temperature of exhaled breath.We hypothesized that the temperature sensor is at least equivalent in accuracy to capnography in monitoring ventilation.AIM To determine if the temperature sensor is equivalent to capnography in monitoring procedural ventilation.METHODS In this prospective study,participants were individually fitted with a face mask monitored by both LRMD and capnography.The following data were collected:gender,age,body mass index,type of procedure,and doses of medication.For each patient,we report the mean RR for each device as well as the mean difference.All analyses were performed using SAS,and a P<0.05 was considered statistically significant.RESULTS Twelve consecutive patients undergoing endoscopic procedures at our institution were enrolled.Four patients were excluded due to incomplete data,inadequate data,patient cooperation,and capnography failure.Overall,we found that LRMD RR highly correlated to capnography RR(P<0.001);the average capnography RR increases by 0.66 breaths for every one additional breath measured by the LRMD.In addition,apnea rates were 7.4%for the capnography and 6.4%for the LRMD(95%confidence interval:0.92-1.10).CONCLUSION The LRMD correlated with the gold standard capnography with respect to respiratory rate detection and apnea events.The LRMD could be used as an alternative to capnography for measuring respiration in endoscopy.
文摘Background:Ablation is an alternative treatment modality for selected patients with colorectal liver metastases(CRLMs).Although initially widely performed via radiofrequency ablation(RFA),more recently,microwave ablation(MWA)is being preferred due to its perceived superiority in creating the ablation zones.The aim of this study is to compare the long-term efficacy of these two modalities performed surgically.Methods:Patients undergoing surgical liver ablation from 2005-2023 at a tertiary center by a single surgeon for CRLM were included in a retrospective institutional review board-approved study.Outcomes were compared using Wilcoxon,Chi-square,Kaplan-Meier,and Cox multivariate regression analyses.Continuous data are presented as median(interquartile range).Results:There were a total of 242 patients.Laparoscopic RFA was done in 121 patients with 303 lesions and laparoscopic MWA in 121 patients with 300 lesions.There was no difference between the groups regarding operative time(161 vs.147 minutes,respectively,P=0.4),perioperative morbidity(3%vs.8%,respectively,P=0.2)or hospital stay(1 vs.1 day,P=0.05).Local recurrence(LR)per lesion with at least 1 year of imaging follow-up was 29%in the RFA and 13%in the MWA group(P<0.001).Based on univariate survival analysis,tumor size,blood vessel proximity,ablation margin,and ablation modality were independent predictors of LR.To control these variables,direct matching was performed.Each cohort included 189 lesions.Kaplan-Meier analysis of these cohorts showed increased LR-free survival in the MWA group vs.the RFA group(P=0.005).Conclusions:This large study confirms our initial observation that local tumor control rate is better after MWA vs.RFA.
文摘BACKGROUND Critically ill patients with cirrhosis,particularly those with acute decompensation,have higher mortality rates in the intensive care unit(ICU)than patients without chronic liver disease.Prognostication of short-term mortality is important in order to identify patients at highest risk of death.None of the currently available prognostic models have been widely accepted for use in cirrhotic patients in the ICU,perhaps due to complexity of calculation,or lack of universal variables readily available for these patients.We believe a survival model meeting these requirements can be developed,to guide therapeutic decision-making and contribute to cost-effective healthcare resource utilization.AIM To identify markers that best identify likelihood of survival and to determine the performance of existing survival models.METHODS Consecutive cirrhotic patients admitted to a United States quaternary care center ICU between 2008-2014 were included and comprised the training cohort.Demographic data and clinical laboratory test collected on admission to ICU were analyzed.Area under the curve receiver operator characteristics(AUROC)analysis was performed to assess the value of various scores in predicting inhospital mortality.A new predictive model,the LIV-4 score,was developed using logistic regression analysis and validated in a cohort of patients admitted to the same institution between 2015-2017.RESULTS Of 436 patients,119(27.3%)died in the hospital.In multivariate analysis,a combination of the natural logarithm of the bilirubin,prothrombin time,white blood cell count,and mean arterial pressure was found to most accurately predict in-hospital mortality.Derived from the regression coefficients of the independent variables,a novel model to predict inpatient mortality was developed(the LIV-4 score)and performed with an AUROC of 0.86,compared to the Model for End-Stage Liver Disease,Chronic Liver Failure-Sequential Organ Failure Assessment,and Royal Free Hospital Score,which performed with AUROCs of 0.81,0.80,and 0.77,respectively.Patients in the internal validation cohort were substantially sicker,as evidenced by higher Model for End-Stage Liver Disease,Model for End-Stage Liver Disease-Sodium,Acute Physiology and Chronic Health Evaluation III,SOFA and LIV-4 scores.Despite these differences,the LIV-4 score remained significantly higher in subjects who expired during the hospital stay and exhibited good prognostic values in the validation cohort with an AUROC of 0.80.CONCLUSION LIV-4,a validated model for predicting mortality in cirrhotic patients on admission to the ICU,performs better than alternative liver and ICU-specific survival scores.
