Citations

PURPOSE: Based on the success of hematopoietic stem-cell transplantation (HSCT) for multiple myeloma, HSCT is being used to treat patients with primary systemic amyloidosis (AL). This article addresses the extent to which eligibility to undergo HSCT is a favorable prognostic feature and explores prognostic factors within the subset of eligible patients. PATIENTS AND METHODS: The Mayo Clinic amyloid database was queried for all patients with AL seen at the Mayo Clinic from 1983 through 1997 who would have been eligible for peripheral-blood stem-cell transplantation. Inclusion criteria included biopsy-proven amyloid, symptomatic disease, absence of a clinical diagnosis of multiple myeloma, age ≤ 70 years, cardiac interventricular septal thickness ≤ 15 mm, cardiac ejection fraction more than 55%, serum creatinine ≤ 2 mg/dL, and direct bilirubin ≤ 2.0 mg/dL. RESULTS: Median age was 56 years (range, 25 to 70) with 79 (34%) older than 60 years. One hundred patients had early cardiac involvement; 41, hepatic involvement; 167, renal involvement; and 39, nerve involvement. The 229 patients have had a median follow-up of 52 months, and 151 have died. The median survival was 42 months with 5- and 10-year survival rates of 36% and 15%, respectively. Important predictors of survival were size of M-component in 24-hour urine, number of involved organs, alkaline phosphatase, performance score, and weight loss. CONCLUSION: The same patients who are eligible for HSCT are a good-risk population who do relatively well with chemotherapy (median survival, 42 months), substantially better than the expected median survival of 18 months for all patients with AL. A randomized trial is needed to assess the true effect of HSCT.

Nonselective beta‐blockers (NSBBs) have played an important role in the prevention of portal hypertensive bleeding in patients with cirrhosis. However, recent studies have suggested that NSBBs may be harmful in some patients with end‐stage liver disease. The purpose of this article is to evaluate the association between use of NSBB and the incidence of acute kidney injury (AKI). We conducted a nested case‐control study in a cohort of liver transplant wait‐list registrants. Each patient with AKI was matched to a control by the Model for End‐Stage Liver Disease–Na score, age, serum creatinine, and follow‐up duration. Out of a total of 2361 wait‐list registrants, 205 patients developed AKI after a median follow‐up duration of 18.2 months. When compared with matched controls, ascites (79.0% versus 51.7%) and non‐Caucasian race (16.6% versus 7.8%) were more common among the cases. The frequency of NSBB use was higher among the cases than controls, albeit insignificantly (45.9% versus 37.1%; P = 0.08). In multivariate analyses, the impact of nonselective beta blockade on the development of AKI was dependent on the presence of ascites: nonselective beta blockade in patients with ascites significantly increased the risk of AKI (hazard ratio [HR], 3.31; 95% confidence interval [CI], 1.57‐6.95), whereas in patients without ascites, NSBB use reduced it (HR, 0.19; 95% CI, 0.06‐0.60). Potential benefits and harms of a NSBB in terms of AKI depend on the presence of ascites in liver transplant candidates. NSBB therapy in patients with cirrhosis may need to be individualized. Liver Transplantation 23 733–740 2017 AASLD.

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 Objective: Several attributes of female reproductive history, including age at natural menopause (ANM), have been related to primary open-angle glaucoma (POAG). We assembled 18 previously reported common genetic variants that predict ANM to determine their association with ANM or POAG. Methods: Using data from the Nurses’ Health Study (7,143 women), we validated the ANM weighted genetic risk score in relation to self-reported ANM. Subsequently, to assess the relation with POAG, we used data from 2,160 female POAG cases and 29,110 controls in the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (NEIGHBORHOOD), which consists of 8 datasets with imputed genotypes to 5.6+ million markers. Associations with POAG were assessed in each dataset, and site-specific results were meta-analyzed using the inverse weighted variance method. Results: The genetic risk score was associated with self-reported ANM (P = 2.2 × 10–77) and predicted 4.8% of the variance in ANM. The ANM genetic risk score was not associated with POAG (Odds Ratio (OR) = 1.002; 95% Confidence Interval (CI): 0.998, 1.007; P = 0.28). No single genetic variant in the panel achieved nominal association with POAG (P ≥0.20). Compared to the middle 80 percent, there was also no association with the lowest 10th percentile or highest 90th percentile of genetic risk score with POAG (OR = 0.75; 95% CI: 0.47, 1.21; P = 0.23 and OR = 1.10; 95% CI: 0.72, 1.69; P = 0.65, respectively). Conclusions: A genetic risk score predicting 4.8% of ANM variation was not related to POAG; thus, genetic determinants of ANM are unlikely to explain the previously reported association between the two phenotypes.

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.