Citations

Abstract The finding that most grades II and III gliomas harbor isocitrate dehydrogenase (IDH) mutations conveying a relatively favorable and fairly similar prognosis in both tumor grades highlights that these tumors represent a fundamentally different entity from IDH wild-type gliomas exemplified in most glioblastoma. Herein we review the most recent developments in molecular neuropathology leading to reclassification of these tumors based upon IDH and 1p/19q status, as well as the potential roles of methylation profiling and deletional analysis of cyclin-dependent kinase inhibitor 2A and 2B. We discuss the epidemiology, clinical manifestations, benefit of surgical resection, and neuroimaging features of lower-grade gliomas as they relate to molecular subtype, including advanced imaging techniques such as 2-hydroxyglutarate magnetic resonance spectroscopy and amino acid PET scanning. Recent, ongoing, and planned studies of radiation therapy and both cytotoxic and targeted chemotherapies are summarized, including both small molecule and immunotherapy approaches specifically targeting the mutant IDH protein.

AbstractPurposeThe aim of this review was to compare the clinical outcomes of anterior cruciate ligament reconstruction (ACLR) with either meniscal repair or meniscectomy for concomitant meniscal injury. The primary hypothesis was that short‐term clinical outcomes (≤ 2‐year follow‐up) for ACLR concomitant with either meniscal repair or resection would be similar. The secondary hypothesis was that ACLR with meniscal repair would result in better longer term outcomes compared with meniscal resection.MethodsThe authors searched two online databases (EMBASE and MEDLINE) from inception until March 2018 for the literature on ACLR and concurrent meniscal surgery. Two reviewers systematically screened studies in duplicate, independently, and based on a priori criteria. Quality assessment was also performed in duplicate. The Knee injury and Osteoarthritis Outcome Score (KOOS) sub‐scale scores at 2 years post‐operatively were combined in a meta‐analysis of proportions using a random‐effects model.ResultsOf 2566 initial studies, 25 studies satisfied full‐text inclusion criteria. Mean follow‐up was 2.09 years, with a total sample of 37,087 subjects including controls. The meta‐analysis demonstrated equivocal results at 2 years, except for KOOS symptom scores which favoured meniscal resection over repair. Mean KT‐1000 side‐to‐side difference (SSD) scores were 1.51 ± 0.60 mm for meniscal repair, 1.96 ± 0.36 mm for meniscal resection, and 1.58 ± 0.20 for control patients (isolated ACLR). Medial meniscal repair showed decreased anterior knee joint laxity compared to medial meniscal resection (P < 0.001). Patients with meniscal repair had higher rates of re‐operation (13.3% vs 0.8% for meniscal resection, P < 0.001).ConclusionPatients with ACLR combined with meniscal resection demonstrate better symptoms at 2‐year follow‐up compared to patients with ACLR combined with meniscal repair. ACLR combined with meniscal repair results in decreased anterior knee joint laxity with evidence of improved patient‐reported outcomes in the long term, but also higher re‐operation rates.Level of evidenceIII.

Manually delivered intermittent bolus (MIB) and programmable intermittent bolus (PIB), alternatives to continuous infusion (CI), involve administering a set volume of solution at a set interval of time. The benefits of intermittent bolus techniques in truncal and peripheral nerve blockade (TPNB) are unclear, and studies have largely demonstrated conflicting results. Using MEDLINE, Embase, Google Scholar, and the Cochrane Library, we conducted an evidenced-based review of published randomized controlled trials comparing intermittent bolus and CI methods in TPNB. In total, 13 randomized controlled trials were identified and evaluated. Outcomes data addressed in these studies included assessments of pain, opioid and local anesthetic consumption, patient satisfaction, adverse events, and physical therapy metrics. The overall quality of current evidence was found to be low given the small sample sizes, heterogeneity of data, and the variations in intermittent bolus techniques between studies. At this time, we found limited supportive data to endorse MIB or PIB over CI in TPNB. While unable to provide data-driven conclusions for local anesthetic delivery methods at this time, we propose that future studies and quantitative analysis between techniques should be on an anatomic, site-specific basis, with greater focus on evaluation of opioid use, adverse events, patient satisfaction, and rehabilitative metrics.

ABSTRACTObjectives:The aim of the present study was to investigate the natural history of chronic pancreatitis (CP); patients in the North American Pancreatitis Study2 (NAPS2, adults) and INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE, pediatric) were compared.Methods:Demographics, risk factors, disease duration, management and outcomes of 224 children and 1063 adults were compared using appropriate statistical tests for categorical and continuous variables.Results:Alcohol was a risk in 53% of adults and 1% of children (P < 0.0001); tobacco in 50% of adults and 7% of children (P < 0.0001). Obstructive factors were more common in children (29% vs 19% in adults, P = 0.001). Genetic risk factors were found more often in children. Exocrine pancreatic insufficiency was similar (children 26% vs adult 33%, P = 0.107). Diabetes was more common in adults than children (36% vs 4% respectively, P < 0.0001). Median emergency room visits, hospitalizations, and missed days of work/school were similar across the cohorts. As a secondary analysis, NAPS2 subjects with childhood onset (NAPS2‐CO) were compared with INSPPIRE subjects. These 2 cohorts were more similar than the total INSPPIRE and NAPS2 cohorts, including for genetic risk factors. The only risk factor significantly more common in the NAPS2‐CO cohort compared with the INSPPIRE cohort was alcohol (9% NAPS2‐CO vs 1% INSPPIRE cohorts, P = 0.011).Conclusions:Despite disparity in age of onset, children and adults with CP exhibit similarity in demographics, CP treatment, and pain. Differences between groups in radiographic findings and diabetes prevalence may be related to differences in risk factors associated with disease and length of time of CP.

Aim Angina pectoris in the absence of obstructive coronary artery disease (CAD) is common and is associated with poor quality of life (QOL). Coronary microvascular endothelial dysfunction is associated with myocardial ischaemia and is a common cause of angina. We hypothesise that evaluation of coronary endothelial function, its diagnosis and treatment will favourably impact QOL in patients with angina symptoms and non-obstructive CAD. Methods and results Follow-up was done on 457 patients with chest pain and non-obstructive coronary arteries who had undergone coronary vascular reactivity evaluation by administration of intracoronary acetylcholine at the time of diagnostic study. After a mean follow-up of 8.4±4.7 years, QOL was assessed by administration of the SF-36 QOL survey. Patients diagnosed and treated for microvascular endothelial dysfunction had a higher (better) overall mental composite score (44.8 vs 40.9, p=0.036) and mental health score (44.2 vs 40.7, p=0.047), and a trend towards higher vitality scores (39.1 vs 35.9, p=0.053) and role emotional scores (43.6 vs 40.4, p=0.073), compared with patients with normal endothelial function. Conclusion Among patients with chest pain and normal coronaries, diagnosis and treatment of coronary microvascular endothelial dysfunction in those with angina pectoris and non-obstructive CAD are associated with better QOL compared with patients with normal endothelial function.

The Ice Hockey Summit III provided updated scientific evidence on concussions in hockey to inform these five objectives: 1) describe sport-related concussion (SRC) epidemiology, 2) classify prevention strategies, 3) define objective, diagnostic tests, 4) identify treatment, and 5) integrate science and clinical care into prioritized action plans and policy. Our action plan evolved from 40 scientific presentations. The 155 attendees (physicians, athletic trainers, physical therapists, nurses, neuropsychologists, scientists, engineers, coaches, and officials) voted to prioritize these action items in the final Summit session. 1) Establish a national and international hockey data base for SRC at all levels, 2) eliminate body checking in Bantam youth hockey games, 3) expand a behavior modification program (Fair Play) to all youth hockey levels, 4) enforce game ejection penalties for fighting in Junior A and professional hockey leagues, 5) establish objective tests to diagnose concussion at point of care (POC), and 6) mandate baseline testing to improve concussion diagnosis for all age groups. Expedient implementation of the Summit III prioritized action items is necessary to reduce the risk, severity, and consequences of concussion in the sport of ice hockey.

Alpha‐1 antitrypsin deficiency (AATD) liver disease is characterized by marked heterogeneity in presentation and progression, despite a common underlying gene mutation, strongly suggesting the involvement of other genetic and/or epigenetic modifiers. Variation in clinical phenotype has added to the challenge of detection, diagnosis, and testing of new therapies in patients with AATD. We examined the contribution of DNA methylation (5‐methylcytosine [5mC]) to AATD liver disease heterogeneity because 5mC responds to environmental and genetic cues and its deregulation is a major driver of liver disease. Using liver biopsies from adults with early‐stage AATD and the ZZ genotype, genome‐wide 5mC patterns were interrogated. We compared DNA methylation among patients with early AATD, and among patients with normal liver, cirrhosis, and hepatocellular carcinoma derived from multiple etiologic exposures, and linked patient clinical/demographic features. Global analysis revealed significant genomic hypomethylation in AATD liver–impacting genes related to liver cancer, cell cycle, and fibrosis, as well as key regulatory molecules influencing growth, migration, and immune function. Further analysis indicated that 5mC changes are localized, with hypermethylation occurring within a background of genome‐wide 5mC loss and with patients with AATD manifesting distinct epigenetic landscapes despite their mutational homogeneity. By integrating clinical data with 5mC landscapes, we observed that CpGs differentially methylated among patients with AATD disease are linked to hallmark clinical features of AATD (e.g., hepatocyte degeneration and polymer accumulation) and further reveal links to well‐known sex‐specific effects of liver disease progression. Conclusion: Our data reveal molecular epigenetic signatures within this mutationally homogeneous group that point to ways to stratify patients for liver disease risk.