BRAF V600E mutant oligodendroglioma‐like tumors with chromosomal instability in adolescents and young adults

We performed genome‐wide methylation analysis on 136 pediatric low‐grade gliomas, identifying a unique cluster consisting of three tumors with oligodendroglioma‐like histology, BRAF p.V600E mutations and recurrent whole chromosome gains of 7 and loss of 10. Morphologically, all showed similar features, including a diffusely infiltrative glioma composed of round nuclei with perinuclear halos, a chicken‐wire pattern of branching capillaries and microcalcification. None showed astrocytic features or characteristics suggestive of high‐grade tumors including necrosis or mitotic figures. All tumors harbored multiple chromosomal copy number abnormalities (>10 chromosomes altered), but none showed 1p/19q co‐deletion or IDH1 p.R132H mutation. Hierarchical clustering and t‐stochastic neighbor embedding analyses from DNA methylation data cluster them more closely to previously described pediatric‐type low‐grade gliomas and separate from adult gliomas. These tumors exhibit distinct clinical features; they are temporal lobe lesions occurring in adolescents and young adults with a prolonged history of seizures and all are alive with no recurrence (follow‐up 3.2 to 13.2 years). We encountered another young adult case with quite similar pathological appearance and molecular status except for TERT promoter mutation. Although the series is small, these may represent a new category of IDH wild‐type low‐grade gliomas which may be confused with “molecular GBM.” Further, they highlight the heterogeneity of IDH wild‐type gliomas and the relatively indolent behavior of “pediatric‐type” gliomas.     

Personal theories of substance use among middle-aged and older adults with bipolar disorder

Objectives: Most persons with bipolar disorder (BD) misuse alcohol and/or illicit drugs at some point, yet research specific to older adults with BD is nascent. The current study sought an in-depth understanding of the experiences and meanings of substance use in a sample of adults who self-reported substance misuse.

Methods: Semi-structured interviews were conducted and thematically analyzed to understand the personal theories of substance use by 12 adults (9 women and 3 men; M = 49 years old) who self-reported diagnoses of BD and regular alcohol or illicit drug use.

Results: Findings provide an in-depth picture of the theories middle-aged and older adults with BD have developed to explain their substance use. Participants’ theories suggest multiple reasons for substance use, including self-medication; increased confidence with substance use; rejection of prescribed medications; easy access to alcohol; early social exposure/use as facilitator; and living in a culture of substance use.

Conclusion: Findings suggest multiple theories for the comorbid link between BD and substance use, primarily that persons with BD use drugs and/or alcohol to relieve stress or manage symptoms. It is clinically relevant to incorporate personal reasons for actively and regularly using substances as part of personalized substance treatment and BD symptom management.     

Perioperative and long-term outcomes after radical cystectomy in hemodialysis patients

Purpose

Patients on hemodialysis have an increased risk of developing advanced stage bladder cancer. They also have a significant risk of noncancer–related mortality. Radical cystectomy (RC) is the standard of care for nonmetastatic muscle–invasive bladder cancer, however little is known regarding outcomes in this population.

The association of salvage intravesical therapy following BCG with pathologic outcomes and survival after radical cystectomy for patients with high-grade non-muscle invasive bladder cancer: A multi-institution analysis

IntroductionWhile numerous current clinical trials are testing novel salvage therapies (ST) for patients with recurrent nonmuscle invasive bladder cancer (NMIBC) after bacillus Calmette-Guérin (BCG), the natural history of this disease state has been poorly defined to date. Herein, we evaluated oncologic outcomes in patients previously treated with BCG and ST who subsequently underwent radical cystectomy (RC).MethodsWe identified 378 patients with high-grade NMIBC who received at least one complete induction course of BCG (n = 378) with (n = 62) or without (n = 316) additional ST and who then underwent RC between 2000 and 2018. Oncologic outcomes were compared using the Kaplan-Meier method and Cox proportional hazards models. Sensitivity analyses were conducted stratifying by presenting tumor stage, matched 1:3 for receipt vs. no receipt of ST.ResultsPatients receiving ST were more likely to initially present with CIS (26% vs. 17%) and less likely with T1 disease (34% vs. 50%, P = 0.06) compared to patients not treated with ST. Receipt of ST was not associated with increased risk of adverse pathology (≥pT2 or pN+) at RC (31% vs. 41%, P = 0.14). Likewise, 5-year cancer-specific survival did not significantly differ between groups on univariable Kaplan-Meier analysis (73% for ST and 74% for no ST, P = 0.7). Moreover, on multivariable analysis, receipt of ST was not significantly associated the risk of death from bladder cancer (HR 1.12; 95% CI 0.60–2.09, P = 0.7). Results were unchanged on sensitivity analysis.ConclusionsThese data suggest that, in carefully selected patients, ST following BCG for high grade NMIBC does not compromise oncologic outcomes for patients who ultimately undergo RC.     

The Composition and Structure of Depressive Symptomatology among Young and Older Caregivers of Persons with Dementia

Informal caregivers of persons with dementia (PWD) experience higher rates of clinical depression relative to general populations of older adults. Because caregivers range considerably in age (e.g., older spouses as compared to adult children or grandchildren), the need exists to evaluate the psychometric properties of depression screening measures to ascertain if cohort differences exist. The current study was conducted to determine whether responses to the Center for Epidemiological Studies–Depression (CES-D) Scale are equivalent between older (range 66 to 93 years; n?=?542) and younger PWD caregivers (range 21 to 65; n?=?884). Only responses to the interpersonal affect factor differ between the two. We contend that this pattern of consistency is due to similarity of role demands which may cause depressive symptoms to present more uniformly among PWD caregivers in contrast to heterogeneous groups of young and older adults. Overall, our findings support the higher-order factor structure of CES-D responses within a population at elevated risk for depression.     

Personality traits and existential concerns as predictors of the functions of reminiscence in older adults

This study examines to what extent personality and existential constructs predict the frequency of reminiscence, in general, and its various functions, in particular. Eighty-nine older adults completed the NEO-Five Factor Inventory, the Life Attitude Profile--Revised, and the Reminiscence Functions Scale. Neuroticism predicted total reminiscence frequency, as well as reminiscence for self-understanding and ruminating about a negative past. Extraversion predicted total reminiscence frequency, as well as reminiscence for generating stimulation, conversation, and maintaining memories of departed loved ones. Openness to experience predicted total reminiscence frequency and reminiscence for addressing life meaning and death. Existential concerns, and in particular low desire to seek new challenges, added significant additional predictive power for total reminiscence frequency and for such uses as generating stimulation, preparing for death, and ruminating about the past. The discussion draws the implications of the finding that the combination of personality traits and existential concerns predicted the overall reminiscence frequency together with the intrapersonal functions of reminiscence.     

Small-bowel absorption of D-tagatose and related effects on carbohydrate digestibility: an ileostomy study

BACKGROUND: The ketohexose D-tagatose is a new sweetener with a low energy content. This low energy content may be due to either low absorption of the D-tagatose or decreased absorption of other nutrients. OBJECTIVE: The aims of this study were to measure the excretion of D-tagatose from the human small bowel, to calculate the apparent absorption of D-tagatose, and to study the effects of D-tagatose on the small-bowel excretion of other carbohydrates. DESIGN: A controlled diet was served for 2 periods of 2 d during 3 consecutive weeks to 6 ileostomy subjects. In one of the periods, 15 g D-tagatose was added to the diet daily. Duplicate portions of the diet and ileostomy effluents were freeze-dried and analyzed to calculate the apparent net absorption of D-tagatose and carbohydrates. RESULTS: Median D-tagatose excretion was 19% (range: 12-31%), which corresponded to a calculated apparent absorption of 81% (69-88%). Of the total amount of D-tagatose excreted [2.8 g (1.7-4.4 g)], 60% (8-88%) was excreted within 3 h. Between 3 and 5 h, 32% (11-82%) was excreted. Excretion of wet matter increased by 41% (24-52%) with D-tagatose ingestion. Sucrose and D-glucose excretion increased to a small extent, whereas no significant changes were found in the excretion of dry matter, energy, starch, or D-fructose. CONCLUSIONS: The apparent absorption of 15 g D-tagatose/d was 81%. D-Tagatose had only a minor influence on the apparent absorption of other nutrients.     

Extended-Release Trospium Chloride Improves Quality of Life in Overactive Bladder

ObjectivesOveractive bladder syndrome (OAB) is a urinary condition that often exerts detrimental effects on an individual's quality of life (QoL). A once-daily, extended-release (ER) formulation of the quaternary amine trospium chloride has recently been developed for the treatment of OAB. The pooled health-related QoL (HRQoL) data from two multicenter, parallel-group, double-blind Phase III studies with trospium chloride ER 60 mg were analyzed.MethodsSubjects aged ≥18 years with urinary urgency, frequency, and an average of ≥1 urge urinary incontinence episode per day on a 3-day bladder diary were randomized (1:1) to receive once-daily trospium 60 mg ER or placebo for 12 weeks. HRQoL was assessed at baseline and at Week 12 using the King's Health Questionnaire (KHQ) and the OAB questionnaire (OAB-q).ResultsOverall, 1165 subjects were randomized (trospium ER, n = 578; placebo, n = 587). Trospium ER produced significantly greater improvements from baseline than placebo in seven of the nine KHQ domains. At Week 12, the improvement in mean OAB-q HRQoL total score (from approximately 52 at baseline) was significantly greater with trospium ER than with placebo (+25.8 vs. +20.7; P = 0.0003). Improvements from baseline were seen with trospium ER on all eight of the OAB-q symptom bother scales.ConclusionsOnce-daily trospium 60 mg ER improved the QoL of subjects with OAB, as assessed using the KHQ and the OAB-q, in two large Phase III clinical trials.     

Plant sterols in vegetables and fruits commonly consumed in Sweden

Summary Plant sterols are known to have serum cholesterol lowering effects. A high dietary intake might therefore have a positive impact on health. All food items of vegetable origin contain some amount of plant sterols. The aim of this study was to analyse the plant sterol content of vegetables and fruits commonly consumed in Sweden, and to compare fresh and cooked samples of the same items. Altogether 20 different vegetables and 14 fruits were analysed. All vegetables and fruits were purchased in two shops in the city of Gothenburg, Sweden. Lyophilization was performed within one month of the items being purchased. The samples were frozen at −20 (C and analysed within six months, with a GLC method after acid hydrolysis, alkaline hydrolysis and silylation with tri-methylsilylether. The acid hydrolysis was done in order to detect the fraction of glycosylated plant sterols, which are split during boiling with HCl. The median plant sterol content of vegetables was 14 (3.8–50) mg/100 g edible portion. The highest concentrations were found in broccoli, Brussels sprouts, cauliflower and olives. The median plant sterol content of fruits was 16 (3–44) mg/100 g edible portion. The highest concentrations were found in oranges and passion fruits. The plant sterol concentrations were thus low in vegetables and fruits commonly consumed in Sweden. A serum cholesterol lowering effect attributed to the plant sterols in vegetables and fruits would therefore be of limited significance. Received: 25 September 1998, Accepted: 10 February 1999