A molecularly integrated grade for meningioma

BackgroundMeningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a 3-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade. Additional prognostic information is needed to optimize patient management.MethodsWe evaluated whether chromosomal copy-number data improved prediction of time-to-recurrence for patients with meningioma who were treated with surgery, relative to the WHO schema. The models were developed using Cox proportional hazards, random survival forest, and gradient boosting in a discovery cohort of 527 meningioma patients and validated in 2 independent cohorts of 172 meningioma patients characterized by orthogonal genomic platforms.ResultsWe developed a 3-tiered grading scheme (Integrated Grades 1-3), which incorporated mitotic count and loss of chromosome 1p, 3p, 4, 6, 10, 14q, 18, 19, or CDKN2A. 32% of meningiomas reclassified to either a lower-risk or higher-risk Integrated Grade compared to their assigned WHO grade. The Integrated Grade more accurately identified meningioma patients at risk for recurrence, relative to the WHO grade, as determined by time-dependent area under the curve, average precision, and the Brier score.ConclusionWe propose a molecularly integrated grading scheme for meningiomas that significantly improves upon the current WHO grading system in prediction of progression-free survival. This framework can be broadly adopted by clinicians with relative ease using widely available genomic technologies and presents an advance in the care of meningioma patients.     

Health care utilization related to the introduction of designated GPs at care homes in Denmark: a register-based study

ObjectiveTo investigate the correlation between having designated general practitioners (GPs) in residential care homes and the residents’ number of contacts with primary care, number of hospital admissions and mortality.DesignA retrospective register-based longitudinal study.SettingForty-two care homes in Aarhus Municipality, Denmark.SubjectsA total of 2376 care home residents in the period from 1 September 2016 to 31 December 2018.Main outcome measuresWe used two models to calculate the incidence risk ratio (IRR) for primary care contacts, hospital admission or dying. Model 1 compared the residents’ risk time before with their risk time after implementation of the designated GP model. Model 2 included only risk time after implementation and was based on calculations of successful (rate ≥60%) implementation.ResultsWeighted by time at risk, the proportion of females across the two models ranged from 64% to 68%. The largest group was aged ‘85-94’ years. In Model 1, the mere implementation of the model did not correlate with changes in primary care contacts, hospital admissions, or mortality. Contrarily, in Model 2, residents living in care homes with successful implementation had fewer email contacts (IRR = 0.81, 95%CI: 0.68;0.96), fewer telephone contacts (IRR = 0.78, 95%CI: 0.68;0.90) and fewer hospital admissions (IRR = 0.85, 95%CI: 0.73;0.99), but more home visits (IRR = 1.70, 95%CI: 1.29;2.25) than residents living in care homes with lower implementation rates.ConclusionThe designated GP model seems promising, as a high implementation degree of the model correlated with a reduced the number of acute admissions, short-term admissions and readmissions. Future studies should focus on gaining deeper insight into the mechanisms of the designated GP model to further optimize the model.

Key points

• A new care model was introduced in Denmark in 2017, designating dedicated GPs to residential care homes for the elderly.
• Successful implementation correlated with significantly fewer hospital admissions, specifically for acute admissions, but also with fewer short-term admissions and readmissions.
• The implementation of the model correlated significantly with fewer e-mail and telephone contacts and with more home visits.
• Future studies should gain more insight into the mechanisms of the designated GP model to further optimize the model.

     

CT urography: definition,indications and techniques. A guideline for clinical practice

The aim was to develop clinical guidelines for multidetector computed tomography urography (CTU) by a group of experts from the European Society of Urogenital Radiology (ESUR). Peer-reviewed papers and reviews were systematically scrutinized. A summary document was produced and discussed at the ESUR 2006 and ECR 2007 meetings with the goal to reach consensus. True evidence-based guidelines could not be formulated, but expert guidelines on indications and CTU examination technique were produced. CTU is justified as a first-line test for patients with macroscopic haematuria, at high-risk for urothelial cancer. Otherwise, CTU may be used as a problem-solving examination. A differential approach using a one-, two- or three-phase protocol is proposed, whereby the clinical indication and the patient population will determine which CTU protocol is employed. Either a combined nephrographic-excretory phase following a split-bolus intravenous injection of contrast medium, or separate nephrographic and excretory phases following a single-bolus injection can be used. Lower dose (CTDIvol 5–6 mGy) is used for benign conditions and normal dose (CTDIvol 9–12 mGy) for potential malignant disease. A low-dose (CTDIvol 2–3 mGy) unenhanced series can be added on indication. The expert-based CTU guidelines provide recommendations to optimize techniques and to unify the radiologist’s approach to CTU. Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users. ESUR:     

Storage (irritative) and voiding (obstructive) symptoms as predictors of benign prostatic hyperplasia progression and related outcomes

OBJECTIVES: To assess the utility of voiding and filling symptom subscores in predicting features of benign prostatic hyperplasia (BPH) progression, including acute urinary retention (AUR) and prostate surgery. METHODS: The Proscar Long-term Efficacy and Safety Study (PLESS) was a 4-year study designed to evaluate the effects of finasteride versus placebo in men with lower urinary tract symptoms (LUTS), clinical evidence of BPH, and no evidence of prostate cancer. A self-administered questionnaire was employed to quantify LUTS at baseline. Receiver operating characteristics (ROC) curves were used to assess baseline characteristics from patients treated with placebo as predictors of outcomes. The characteristics assessed included the overall symptom score (Quasi-AUA SI), separate voiding and filling subscores, prostate volume (PV) and serum prostate-specific antigen (PSA) levels. RESULTS: PV and PSA were superior to the symptom scores at predicting episodes of spontaneous AUR and all types of AUR. The Quasi-AUA SI and the filling and voiding subscores were effective at predicting progression to surgery; however, PSA was more effective at predicting this outcome. To better evaluate symptoms as predictors of surgery, patients who experienced a preceding episode of AUR were excluded from the surgery analysis. In the absence of preceding AUR, the best predictors of future surgery were the Quasi-AUA SI and the filling subscore. CONCLUSIONS: Among men with LUTS, clinical BPH and no history of AUR, the overall symptom score and storage subscore are useful parameters to aid clinicians in identifying patients at risk for future prostate surgery. PV and PSA were the best predictors of AUR, while PSA was the best predictor of prostate surgery (for all indications).     

An educational approach based on a non-injury model compared with individual symptom-based physical training in chronic LBP. A pragmatic, randomised trial with a one-year follow-up

Background  

In the treatment of chronic back pain, cognitive methods are attracting increased attention due to evidence of effectiveness similar to that of traditional therapies. The purpose of this study was to compare the effectiveness of performing a cognitive intervention based on a non-injury model with that of a symptom-based physical training method on the outcomes of low back pain (LBP), activity limitation, LBP attitudes (fear-avoidance beliefs and back beliefs), physical activity levels, sick leave, and quality of life, in chronic LBP patients.     

Glycemia Determines the Effect of Type 2 Diabetes Risk Genes on Insulin Secretion

OBJECTIVE

Several single nucleotide polymorphisms (SNPs) in diabetes risk genes reduce glucose- and/or incretin-induced insulin secretion. Here, we investigated interactions between glycemia and such diabetes risk polymorphisms.

RESEARCH DESIGN AND METHODS

Insulin secretion was assessed by insulinogenic index and areas under the curve of C-peptide/glucose in 1,576 subjects using an oral glucose tolerance test (OGTT). Participants were genotyped for 10 diabetes risk SNPs associated with β-cell dysfunction: rs5215 (KCNJ11), rs13266634 (SLC30A8), rs7754840 (CDKAL1), rs10811661 (CDKN2A/2B), rs10830963 (MTNR1B), rs7903146 (TCF7L2), rs10010131 (WFS1), rs7923837 (HHEX), rs151290 (KCNQ1), and rs4402960 (IGF2BP2).Furthermore, the impact of the interaction between genetic variation in TCF7L2 and glycemia on changes in insulin secretion was tested in 315 individuals taking part in a lifestyle intervention study.

RESULTS

For the SNPs in TCF7L2 and WFS1, we found a significant interaction between glucose control and insulin secretion (all P ≤ 0.0018 for glucose × genotype). When plotting insulin secretion against glucose at 120 min OGTT, the compromising SNP effects on insulin secretion are most apparent under high glucose. In the longitudinal study, rs7903146 in TCF7L2 showed a significant interaction with baseline glucose tolerance upon change in insulin secretion (P = 0.0027). Increased glucose levels at baseline predicted an increase in insulin secretion upon improvement of glycemia by lifestyle intervention only in carriers of the risk alleles.

CONCLUSIONS

For the diabetes risk genes TCF7L2 and WFS1, which are associated with impaired incretin signaling, the level of glycemia determines SNP effects on insulin secretion. This indicates the increasing relevance of these SNPs during the progression of prediabetes stages toward clinically overt type 2 diabetes.Type 2 diabetes is a disorder characterized by chronically elevated blood glucose levels due to insulin resistance and a relative lack of compensatory pancreatic insulin secretion. Environmental triggers such as a sedentary lifestyle, physical inactivity, and increased body weight play an important role in the development of the disease. In this regard, genetics and especially gene-environment interactions play an important role. Recent research revealed more than 25 gene variants leading to a higher risk for the development of type 2 diabetes (1). Interestingly, most of the diabetes risk genes alter β-cell function (1). This supports the hypothesis that the main genetic effect in the development of type 2 diabetes could be impaired insulin secretion. Neither environmental triggers nor genetics alone can explain the multifactorial disease type 2 diabetes, thus a close interaction between both is presumed (2–4). Hence, environmental influences may determine an individual''s susceptibility for single nucleotide polymorphism (SNP) effects, or vice versa genotype may designate a person''s susceptibility toward environmental factors.One “environmental” factor that plays a role early in the pathogenesis of type 2 diabetes is elevated glucose. It is well known that years before type 2 diabetes occurs, glucose control is altered, as reflected by higher fasting glucose and/or higher postprandial glucose (5). High glucose exerts unfavorable effects on insulin sensitivity and secretion, known as glucotoxicity (6,7). On the other hand, elevated glucose levels are needed for the incretin effect. Glucagon-like peptide 1–induced insulin secretion becomes fully active only in the hyperglycemic range (8,9). Incretin-dependent insulin secretion might therefore be of particular importance when compensatory insulin hypersecretion is required.The aim of this study was to investigate whether glycemia influences the effects of genetic variation associated with type 2 diabetes on insulin secretion. We therefore studied 10 genome-wide association study–derived variants that were furthermore found to influence β-cell function in subsequent studies (rev. in 1,10). Of these, 2 (in the TCF7L2 and WFS1 loci) are associated with incretin-stimulated insulin secretion (1). As the magnitude of incretin-stimulated insulin secretion is dependent on elevated glucose levels (8,9), we hypothesized that glucose levels specifically interact with the effect of those SNPs on insulin secretion both in cross-sectional and longitudinal intervention studies.     

Modic changes following lumbar disc herniation

Only a small proportion (20%) of patients with LBP can be diagnosed based on a patho-anatomical entity. Therefore, the identification of relevant subgroups, preferably on a patoanatomical basis, is strongly needed. Modic changes have been described by several authors as being closely linked with LBP. The aims of this study were to describe the prevalence of Modic changes, their development as well as their association to LBP, previous disc contour, and surgery in patients with previous severe sciatica. This is a longitudinal cohort study where the patients were recruited from an RCT comparing two active conservative treatments, the 181 patients, who at baseline had radicular pain in or below the knee; all underwent a physical examination and MRI. MRI’s, pain history and physical examination of 166 patients were obtained at follow-up 14 months later. The prevalence of Modic changes type 1 increased from 9% at baseline to 29% at follow-up. At that time, a strong association between Modic changes and non-specific LBP was noted. Apparently, Modic changes type 1 was more strongly associated with non-specific lumbar pain than Modic changes type 2. The development of new Modic changes was closely related to the level of a previous disc herniation. A lumbar disc herniation is a strong risk factor for developing Modic changes (especially type 1) during the following year. Furthermore, Modic changes are strongly associated with LBP.     

Evaluation of the postoperative meniscus of the knee: a study comparing conventional arthrography, conventional MR imaging, MR arthrography with iodinated contrast material, and MR arthrography with gadolinium-based contrast material

Objective. To compare four imaging methods in the evaluation of the postoperative meniscus: conventional arthrography, conventional MR imaging, MR arthrography with iodinated contrast material, and MR arthrography with gadolinium-based contrast material. Design and patients. Thirty-three patients referred for knee MR examinations with a history of meniscal surgery were studied prospectively. At the first patient visit, conventional MR examination was followed by an MR arthrogram with gadolinium-based contrast material. At the second visit, a conventional arthrogram with iodinated contrast material was followed immediately by an MR examination. Imaging examinations were interpreted by a masked reader, and then compared with the results of repeat arthroscopic surgery in 12 patients. Results. The correct evaluation of the status of postoperative menisci was allowed in 12 of 13 patients (92%) by MR arthrography using gadolinium-based contrast agent, 10 of 13 patients (77%) by conventional MR examination, 9 of 12 patients (75%) by MR arthrography, and 7 of 12 patients (58%) by conventional arthrography. Conclusion. Intra-articular fluid is advantageous in the evaluation of patients with a suspected meniscal retear. MR arthrography with gadolinium-based contrast material is the most accurate imaging method for the diagnosis of meniscal retears. Received: 7 April 1999 Revision requested: 26 May 1999 Revision received: 17 June 1999 Accepted: 18 June 1999