Therneau, Terry M.

AbstractBackground and Purpose. The causes of lumbopelvic imbalances in standing have been widely accepted by physical therapists, but there is a lack of scientific evidence available to support them. We examined the association between 9 variables and pelvic inclination and lumbar lordosis during relaxed standing. Subjects. Thirty men and 30 women with chronic low back pain (CLBP) for at least 4 months were examined (mean age=54.9 years, SD=9, range=40.4–69.8). Methods. Multiple linear regression modeling was used to assess the association of pelvic inclination and the magnitude of lumbar lordosis in standing with age, sex, body mass index (BMI), Oswestry Back Pain Disability Questionnaire (ODQ) scores, physical activity level, hip flexor muscle length, abdominal muscle force, and range of motion (ROM) for lumbar flexion and extension. Results. In women, age, BMI, and ODQ scores were associated univariately and multivariately with pelvic inclination. In men, lumbar extension ROM was related univariately to pelvic inclination; age, lumbar extension ROM, and ODQ scores were associated multivariately. Lumbar lordosis was associated univariately with only lumbar extension ROM for women and men. A weak correlation was found between angle of pelvic inclination and magnitude of lumbar lordosis in standing (r=.31 for women, r=.37 for men). Conclusion and Discussion. The odds ratio of having CLBP is increased if the score on the double-leg lowering test for abdominal muscles exceeds 50 degrees for men and 60 degrees for women. In patients with CLBP, the magnitude of the lumbar lordosis and pelvic inclination in standing is not associated with the force production of the abdominal muscles.

Abstract Introduction Our goal was to develop cut points for amyloid positron emission tomography (PET), tau PET, flouro‐deoxyglucose (FDG) PET, and MRI cortical thickness. Methods We examined five methods for determining cut points. Results The reliable worsening method produced a cut point only for amyloid PET. The specificity, sensitivity, and accuracy of cognitively impaired versus young clinically normal (CN) methods labeled the most people abnormal and all gave similar cut points for tau PET, FDG PET, and cortical thickness. Cut points defined using the accuracy of cognitively impaired versus age‐matched CN method labeled fewer people abnormal. Discussion In the future, we will use a single cut point for amyloid PET (standardized uptake value ratio, 1.42; centiloid, 19) based on the reliable worsening cut point method. We will base lenient cut points for tau PET, FDG PET, and cortical thickness on the accuracy of cognitively impaired versus young CN method and base conservative cut points on the accuracy of cognitively impaired versus age‐matched CN method.

Whether aspirin use is protective against cholangiocarcinoma (CCA) remains unclear. We determined the association between aspirin use and other risk factors for each CCA subtype individually. In a hospital‐based case‐control study, 2395 CCA cases (1169 intrahepatic, 995 perihilar, and 231 distal) seen at the Mayo Clinic, Rochester, MN, from 2000 through 2014 were enrolled. Controls selected from the Mayo Clinic Biobank were matched two to one with cases by age, sex, race, and residence (n = 4769). Associations between aspirin use, other risk factors, and CCA risk were determined. Aspirin was used by 591 (24.7%) CCA cases and 2129 (44.6%) controls. There was a significant inverse association of aspirin use with all CCA subtypes, with adjusted odds ratios (AORs) of 0.35 (95% confidence interval [CI], 0.29‐0.42), 0.34 (95% CI 0.27‐0.42), and 0.29 (95% CI 0.19‐0.44) for intrahepatic, perihilar, and distal CCA, respectively (P < 0.001 for all). Primary sclerosing cholangitis was more strongly associated with perihilar (AOR = 453, 95% CI 104‐999) than intrahepatic (AOR = 93.4, 95% CI 27.1‐322) or distal (AOR = 34.0, 95% CI 3.6‐323) CCA, whereas diabetes was more associated with distal (AOR = 4.2, 95% CI 2.5‐7.0) than perihilar (AOR = 2.9, 95% CI 2.2‐3.8) or intrahepatic (AOR = 2.5, 95% CI 2.0‐3.2) CCA. Cirrhosis not related to primary sclerosing cholangitis was associated with both intrahepatic and perihilar CCA, with similar AORs of 14. Isolated inflammatory bowel disease without primary sclerosing cholangitis was not associated with any CCA subtype. Conclusions: Aspirin use was significantly associated with a 2.7‐fold to 3.6‐fold decreased risk for the three CCA subtypes; our study demonstrates that individual risk factors confer risk of different CCA subtypes to different extents. (Hepatology 2016;64:785‐796)

AbstractGenetic risk factors for cholangiocarcinoma (CCA) remain poorly understood. We assessed the effect of single‐nucleotide polymorphisms (SNPs) of genes modulating inflammation or carcinogenesis on CCA risk and survival. We conducted a case‐control, candidate gene association study of 370 CCA patients and 740 age‐, sex‐, and residential area‐matched healthy controls. Eighteen functional or putatively functional SNPs in nine genes were genotyped. The log‐additive genotype effects of SNPs on CCA risk and survival were determined using logistic regression and the log‐rank test, respectively. Initial analysis identified significant associations between SNP rs2143417 and rs689466 in cyclooxygenase 2 (COX‐2) and CCA risk, after adjusting for multiple comparisons (cutoff of P = 0.0028). However, these findings were not replicated in another independent cohort of 212 CCA cases and 424 matched controls. No significant association was found between any SNP and survival of CCA patients. Although COX‐2 has been shown to contribute to cholangiocarcinogenesis, the COX‐2 SNPs tested were not associated with risk of CCA. This study shows a lack of association between variants of genes related to inflammation and carcinogenesis and CCA risk and survival. Other factors than these genetic variants may play more important roles in CCA risk and survival.

BACKGROUNDEfficacy trials have shown that antiviral therapy improves the outcomes of patients with chronic hepatitis B virus (HBV) infection. However, prospective data regarding the effect of antiviral therapy on the incidence of hepatocellular carcinoma (HCC), especially among patients without cirrhosis, are limited. The authors examined the impact of tenofovir disoproxil fumarate (TDF) on the incidence of HCC using a validated prediction model.METHODSThe incidence of HCC in patients treated with TDF was obtained in the pivotal TDF registration studies after 384 weeks of follow‐up. The predicted risk of HCC in individual patients was calculated using the Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH‐B) model, which estimates HCC incidence for up to 10 years based on age, sex, alanine aminotransferase level, hepatitis B e antigen status, and HBV‐DNA. Standardized incidence ratios (SIRs) were calculated comparing the observed and predicted numbers of HCC cases in the study cohort.RESULTSAmong 634 patients with evaluable baseline biopsies, 152 had cirrhosis (Ishak fibrosis score of 5 or 6) and 482 did not. During the 384 weeks of study, 14 cases of HCC were reported, with 4 occurring within the first year. The incidence of HCC was 0.37% per year in the study as a whole (0.28% among patients without cirrhosis and 0.65% among patients with cirrhosis). Among patients without cirrhosis, the observed incidence of HCC was significantly lower than predicted (SIR, 0.40; 95% confidence interval, 0.199‐0.795). The last HCC case in a patient with cirrhosis occurred around week 192 with an SIR of 0.51 (95% confidence interval, 0.231‐1.144) reported at week 384.CONCLUSIONSBased on the REACH‐B risk calculator, long‐term therapy with TDF was associated with a reduced incidence of HCC among patients without cirrhosis who met treatment criteria. Cancer 2015;121:3631–3638. © 2015 American Cancer Society.

Growing evidence suggests that pretransplant alpha‐fetoprotein (AFP) predicts outcomes of hepatocellular carcinoma (HCC) patients treated with liver transplantation. We aimed to determine whether pretransplant AFP, Lens culinaris agglutinin‐reactive alpha‐fetoprotein (AFP‐L3), and des‐gamma‐carboxyprothrombin (DCP) predicted HCC recurrence after transplantation. A retrospective cohort study of 313 HCC patients undergoing transplantation between 2000 and 2008 was conducted, and 48 (15.3%) developed recurrence during a median follow‐up of 90.8 months. The 127 patients with available serum drawn before transplantation were included; they included 86 without recurrence and 41 with recurrence. Serum was tested for AFP, AFP‐L3%, and DCP in a blinded fashion with the μTASWako i30 immunoanalyzer. All biomarkers were significantly associated with HCC recurrence. The hazard ratios (HRs) were 3.5 [95% confidence interval (CI), 1.9‐6.7; P < 0.0001] for DCP ≥ 7.5 ng/mL and 2.8 (95% CI, 1.4‐5.4; P = 0.002) for AFP ≥ 250 ng/mL. The HR increased to 5.2 (95% CI, 2.3‐12.0; P < 0.0001) when AFP ≥ 250 ng/mL and DCP ≥7.5 ng/mL were considered together. When they were combined with the Milan criteria, the HR increased from 2.6 (95% CI, 1.4‐4.7; P = 0.003) for outside the Milan criteria to 8.6 (95% CI, 3.0‐24.6; P < 0.0001) for outside the Milan criteria and AFP ≥ 250 ng/mL and to 7.2 (95% CI, 2.8‐18.1; P < 0.0001) for outside the Milan criteria and DCP ≥7.5 ng/mL. Our findings suggest that biomarkers are useful for predicting the risk of HCC recurrence after transplantation. Using both biomarkers and the Milan criteria may be better than using the Milan criteria alone in optimizing the decision of liver transplantation eligibility. Liver Transpl 21:599–606, 2015. © 2015 AASLD.

Background and Purpose— Identifying clinical data acquired at inpatient rehabilitation admission for stroke that accurately predict key outcomes at discharge could inform the development of customized plans of care to achieve favorable outcomes. The purpose of this analysis was to use a large comprehensive national data set to consider a wide range of clinical elements known at admission to identify those that predict key outcomes at rehabilitation discharge. Methods— Sample data were obtained from the Uniform Data System for Medical Rehabilitation data set with the diagnosis of stroke for the years 2005 through 2007. This data set includes demographic, administrative, and medical variables collected at admission and discharge and uses the FIM (functional independence measure) instrument to assess functional independence. Primary outcomes of interest were functional independence measure gain, length of stay, and discharge to home. Results— The sample included 148 367 people (75% white; mean age, 70.6±13.1 years; 97% with ischemic stroke) admitted to inpatient rehabilitation a mean of 8.2±12 days after symptom onset. The total functional independence measure score, the functional independence measure motor subscore, and the case-mix group were equally the strongest predictors for any of the primary outcomes. The most clinically relevant 3-variable model used the functional independence measure motor subscore, age, and walking distance at admission ( r 2 =0.107). No important additional effect for any other variable was detected when added to this model. Conclusions— This analysis shows that a measure of functional independence in motor performance and age at rehabilitation hospital admission for stroke are predominant predictors of outcome at discharge in a uniquely large US national data set.

Background and Purpose— Clinical equipoise of carotid revascularization therapies remains controversial. We sought to determine whether adverse outcomes after carotid endarterectomy (CEA) or carotid angioplasty and stenting (CAS) were similar using propensity score–matched analysis of retrospective data from a large hospital discharge database. Methods— All CEA and CAS cases were identified from the 2006 to 2011 Premier Perspective Database and subjected to 1:1 propensity score matching using 33 clinical covariates associated with carotid revascularization. A primary composite end point of peri- or postoperative mortality, stroke, or acute myocardial infarction and a modified composite end point excluding acute myocardial infarction were used to compare our findings with recent prospective controlled trials. Multivariate regression and Cox-proportional hazard ratio survival analysis were performed to compare revascularization therapy outcomes. Results— After 1:1 propensity score matching, 24 004 (12 002 CEA and CAS) asymptomatic and 3506 (1753 CEA and CAS) symptomatic procedures were included. The risk of the primary composite end point was significantly higher after CAS than CEA in both asymptomatic (odds ratio, 1.40 [1.19–1.65]; P <0.0001) and symptomatic (odds ratio=2.31 [1.78–3.00]; P <0.0001) presentations, irrespective of age ( P =0.28) or sex ( P =0.35). Similar findings were observed using the modified composite end point for both asymptomatic (odds ratio, 1.49 [1.25–1.78]; P <0.0001) and symptomatic (odds ratio, 3.02 [2.25–4.07]; P <0.0001) presentations. Acute myocardial infarction risk was not significantly different between revascularization therapies, regardless of clinical presentation ( P =0.71 and 0.24). Conclusions— Among individuals undergoing carotid artery revascularization from a large sample of US hospitals, CAS was associated with higher risk of perioperative mortality, stroke, and unfavorable discharges compared with CEA for all ages and clinical presentations.