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Whether to repair nonsevere tricuspid regurgitation (TR) during surgery for ischemic mitral valve regurgitation (IMR) remains uncertain.The goal of this study was to investigate the incidence, predictors, and clinical significance of TR progression and presence of ≥moderate TR after IMR surgery.Patients (n = 492) with untreated nonsevere TR within 2 prospectively randomized IMR trials were included. Key outcomes were TR progression (either progression by ≥2 grades, surgery for TR, or severe TR at 2 years) and presence of ≥moderate TR at 2 years.Patients' mean age was 66 ± 10 years (67% male), and TR distribution was 60% ≤trace, 31% mild, and 9% moderate. Among 2-year survivors, TR progression occurred in 20 (6%) of 325 patients. Baseline tricuspid annular diameter (TAD) was not predictive of TR progression. At 2 years, 37 (11%) of 323 patients had ≥moderate TR. Baseline TR grade, indexed TAD, and surgical ablation for atrial fibrillation were independent predictors of ≥moderate TR. However, TAD alone had poor discrimination (area under the curve, ≤0.65). Presence of ≥moderate TR at 2 years was higher in patients with MR recurrence (20% vs. 9%; p = 0.02) and a permanent pacemaker/defibrillator (19% vs. 9%; p = 0.01). Clinical event rates (composite of ≥1 New York Heart Association functional class increase, heart failure hospitalization, mitral valve surgery, and stroke) were higher in patients with TR progression (55% vs. 23%; p = 0.003) and ≥moderate TR at 2 years (38% vs. 22%; p = 0.04).After IMR surgery, progression of unrepaired nonsevere TR is uncommon. Baseline TAD is not predictive of TR progression and is poorly discriminative of ≥moderate TR at 2 years. TR progression and presence of ≥moderate TR are associated with clinical events. (Comparing the Effectiveness of a Mitral Valve Repair Procedure in Combination With Coronary Artery Bypass Grafting [CABG] Versus CABG Alone in People With Moderate Ischemic Mitral Regurgitation, NCT00806988; Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation, NCT00807040).

BackgroundBetter understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management.MethodsImmunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed.FindingsThe median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63- 4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC.InterpretationIntegration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19.FundingNIH.

Hepatocellular carcinoma (HCC) is a highly malignant tumor that responds very poorly to existing therapies, most probably due to its extraordinary inter- and intra-tumor molecular heterogeneity. The modest therapeutic response to molecular targeted agents underlines the need for new therapeutic approaches for HCC. In our study, we took advantage of well-characterized human HCC cell lines, differing in transcriptomic subtypes, DNA mutation and amplification alterations, reflecting the heterogeneity of primary HCCs, to provide a preclinical evaluation of the specific heat shock protein 90 (HSP90) inhibitor AUY922 (luminespib). Indeed, HSP90 is highly expressed in different tumor types, but its role in hepatocarcinogenesis remains unclear. Here, we analyzed HSP90 expression in primary human HCC tissues and evaluated the antitumor effects of AUY922 in vitro as well as in vivo. HSP90 expression was significantly higher in HCC tissues than in cirrhotic peritumoral liver tissues. AUY922 treatment reduced the cell proliferation and viability of HCC cells in a dose-dependent manner, but did not do so for normal human primary hepatocytes. AUY922 treatment led to the upregulation of HSP70 and the simultaneous depletion of HSP90 client proteins. In addition, in a cell type-dependent manner, treatment induced either both caspase-dependent beta-catenin cleavage and the upregulation of p53, or Mcl-1 expression, or NUPR1 expression, which contributed to the increased efficacy of, or resistance to, treatment. Finally, in vivo AUY922 inhibited tumor growth in a xenograft model. In conclusion, HSP90 is a promising therapeutic target in HCC, and AUY922 could be a drug candidate for its treatment.

Modulation of tumor microenvironment is an emerging frontier for new therapeutics. However in meningiomas, the most frequent adult brain tumor, the correlation of microenvironment with tumor phenotype is scarcely studied. We applied a variety of systems biology approaches to bulk tumor transcriptomics to explore the immune environments of both skull base and convexity (hemispheric) meningiomas. We hypothesized that the more benign biology of skull base meningiomas parallels the relative composition and activity of immune cells that oppose tumor growth and/or survival. We firstly applied gene co-expression networks to tumor bulk transcriptomics from 107 meningiomas (derived from 3 independent studies) and found immune processes to be the sole biological mechanism correlated with anatomical location while correcting for tumour grade. We then derived tumor immune cell fractions from bulk transcriptomics data and examined the immune cell-cytokine interactions using a network-based approach. We demonstrate that oncolytic Gamma-Delta T cells dominate skull base meningiomas while mast cells and neutrophils, known to play a role in oncogenesis, show greater activity in convexity tumors. Our results are the first to suggest the importance of tumor microenvironment in meningioma biology in the context of anatomic location and immune landscape. These findings may help better inform surgical decision making and yield location-specific therapies through modulation of immune microenvironment.

Background Insomnia is a major predictor of adverse outcomes in mild traumatic brain injury (mTBI), including concussion; although insomnia symptoms may be due to various sleep disorders, those related to circadian rhythm sleep-wake disorders (CRSWDs) require specific assessment and treatment. The objective of the current study was to determine the prevalence of CRSWD in a sample of treatment-seeking people with chronic insomnia symptoms after an mTBI. Methods Participants aged 17-65 years who had experienced an mTBI and reported chronic insomnia were recruited from diverse community clinics in Ontario 3-24 months after their injury to participate in this cross-sectional observational study. Potential participants were screened by both telephone and intake interview. Exclusion criteria were alcohol or substance use disorders, preexisting brain disorder or previous neurosurgery, recent travel across more than 2 time zones or shift work. Assessments included a clinical interview, questionnaires, 2 weeks of actigraphy and a sleep diary, and a dim-light melatonin onset test. The main outcome measure was the proportion of patients with CRSWDs. Results Of the 50 participants (32 [64%] female; median age 39.5 yr), 13 (26% [standard deviation 12%]) had an CRSWD. The most common circadian diagnosis was delayed sleep-wake phase disorder (10 participants [20%]). Interpretation The prevalence of CRSWDs may be exceptionally high among people with chronic insomnia symptoms following mTBI. Proper detection and treatment of CRSWDs in this population is essential to facilitate recovery. The findings emphasize the relevance of a diagnostic circadian assessment in patients with mTBI presenting with chronic insomnia symptoms.

Background Hepatocellular carcinoma (HCC) is the most frequent primary invasive cancer of the liver. During the last decade, the epidemiology of HCC has been continuously changing in developed countries, due to more effective primary prevention and to successful treatment of virus-related liver diseases. The study aims to examine survival by level of access to care in patients with HCC, for all patients combined and by age. Methods We included 2018 adult patients (15–99 years) diagnosed with a primary liver tumour, registered in the Palermo Province Cancer Registry during 2006–2015, and followed-up to 30 October 2019. We obtained a proxy measure of access to care by linking each record to the Hospital Discharge Records and the Ambulatory Discharge Records. We estimated net survival up to 5 years after diagnosis by access to care (“easy access to care” versus “poor access to care”), using the Pohar-Perme estimator. Estimates were age-standardised using International Cancer Survival Standard (ICSS) weights. We also examined survival by access to care and age (15–64, 65–74 and ≥ 75 years). Results Among the 2018 patients, 62.4% were morphologically verified and 37.6% clinically diagnosed. Morphologically verified tumours were more frequent in patients aged 65–74 years (41.6%), while tumours diagnosed clinically were more frequent in patients aged 75 years or over (50.2%). During 2006–2015, age-standardised net survival was higher among HCC patients with “easy access to care” than in those with “poor access to care” (68% vs. 48% at 1 year, 29% vs. 11% at 5 years; p p Conclusions During 2006–2015, 5-year survival was higher for HCC patients with easier access to care, probably reflecting progressive improvement in the effectiveness of health care services offered to these patients. Our linkage algorithm could provide valuable evidence to support healthcare decision-making in the context of the evolving epidemiology of hepatocellular carcinoma.

Genetically modified foods (GMFs) have met with strong opposition for most of their existence. According to one account—the consequence-based perspective (CP)—lay people oppose GMFs because they deem them unsafe as well as of dubious value. The CP is backed by the data and offers a clear solution for easing GMF opposition. However, several scholars have claimed that the CP is faulty, that lay opposition derives from largely nonrational factors and is consequence blind. One recent statement of this, the moral-absolutism perspective (MAP), contends that GMFs’ opponents are principled “moral absolutists” who think that GMFs should be banned no matter their value or risk. Herein we critically weigh key arguments for this proposal. We also present five new studies that probed the clearest data that seem to favor the MAP—opponents affirming the statement that GMFs should be “prohibited,” no matter their value or risk. These studies jointly show that (a) most presumed absolutists do not understand the key question and/or (b) cannot validly answer it. We show that taking due steps in clarifying the question and screening for those participants who cannot validly answer it cuts down absolutism to near zero. Finally, we demonstrate that helping GMFs’ opponents imagine a world wherein GMFs are safe and constructive makes the majority willing to welcome GMFs in this context.

Background Falls are the leading cause of injuries in older adults. However, most falls in older adults do not cause serious injury, suggesting that older adults may fall in a manner that reduces the likelihood of impact to body sites that are most vulnerable to injury. In this observational study of falls in long-term care (LTC), we tested whether body parts differed in their probability of impact and injury. Methods We recorded and analyzed videos of 2388 falls by 658 LTC residents (mean age 84.0 (SD = 8.1); 56.4% female). We used Linear Mixed Models to test for differences between body parts in the probability of impact and injury, and injury when impacts occurred. Results Injuries were reported in 38.2% of falls, and 85.9% of injuries involved direct impact to the injured body part. Impact occurred most often to the hip/pelvis (probability (standard error) = 0.95 (0.01); p p Conclusion Our results help to explain why most falls by older adults in LTC do not cause serious injury: residents land on body parts that are the most resilient to injury. The high susceptibility of the head to injury reinforces the need to enhance upper limb protective responses for fall arrest. The dominant role of direct impact as the mechanism of injury supports approaches to attenuate impact forces through strategies like protective clothing and compliant flooring.

Ventricular remodeling following myocardial infarction (MI) is a major cause of heart failure, a condition prevalent in older individuals. Following MI, immune cells are mobilized to the myocardium from peripheral lymphoid organs and play an active role in orchestrating repair. While the effect of aging on mouse bone marrow (BM) has been studied, less is known about how aging affects human BM cells and their ability to regulate repair processes. In this study, we investigate the effect aging has on human BM cell responses post‐MI using a humanized chimeric mouse model. BM samples were collected from middle aged (mean age 56.4 ± 0.97) and old (mean age 72.7 ± 0.59) patients undergoing cardiac surgery, CD34+/− cells were isolated, and NOD‐scid‐IL2rγnull (NSG) mice were reconstituted. Three months following reconstitution, the animals were examined at baseline or subjected to coronary artery ligation (MI). Younger patient cells exhibited greater repopulation capacity in the BM, blood, and spleen as well as greater lymphoid cell production. Following MI, CD34+ cell age impacted donor and host cellular responses. Mice reconstituted with younger CD34+ cells exhibited greater human CD45+ recruitment to the heart compared to mice reconstituted with old cells. Increased cellular responses were primarily driven by T‐cell recruitment, and these changes corresponded with greater human IFNy levels and reduced mouse IL‐1β in the heart. Age‐dependent changes in BM function led to significantly lower survival, increased infarct expansion, impaired host cell responses, and reduced function by 4w post‐MI. In contrast, younger CD34+ cells helped to limit remodeling and preserve function post‐MI., To study the effect aging has on human cell responses post‐MI, we utilized a xenograft mouse (NSG) model using BM from middle aged (Y‐CD34+) and old patients (O‐CD34+). Our results demonstrate that O‐CD34+ reconstituted mice exhibit impaired donor and host cell responses while Y‐CD34+ reconstituted mice exhibit a greater donor lymphocyte and host myeloid cell responses post‐MI. Differences in cellular responses are associated with improved cardiac function in Y‐CD34+ reconstituted mice post‐MI.

Background: Scant real-world data exist on the clinical outcomes associated with the use of bevacizumab-containing chemotherapy (B+CT) in patients with metastatic colorectal cancer (mCRC). The primary objective of the GRETA cohort study was to compare the overall survival (OS) of patients with mCRC treated with first-line B+CT versus chemotherapy (CT) alone, in an Italian clinical practice setting. Materials and Methods: Incident patients with mCRC were identified during the period 2010–2012 from five population-based cancer registries in Italy. Cases were linked to regional health care utilization databases to obtain the entire spectrum of health services provided to each patient. Patients starting a first-line treatment with B+CT or CT alone within 90 days from the diagnosis were included in the study cohort. A propensity score (PS) method was applied to account for residual confounding. Results: Of 480 patients with mCRC included in the study cohort, 21.0 received first-line B+CT, and 79.0% received CT. Patients receiving B+CT were younger (p

This study identified the social determinants of health (SDoH) associated with psychological distress in adults with and without a self-reported history of traumatic brain injury (TBI), stratified by sex. Data from the 2014–2017 cycles of the Centre for Addiction and Mental Health Monitor Survey, a representative survey of adults ≥18 years in Ontario, Canada, were analyzed (N = 7,214). The six-item version of the Kessler Psychological Distress Scale was used to determine moderate to severe psychological distress. Self-reported lifetime TBI was defined as a head injury resulting in a loss of consciousness for ≥5 minutes or at least one-night stay in the hospital (16.4%). Among individuals reporting a history of TBI, 30.2% of males and 40.1% of females reported psychological distress (p = 0.0109). Among individuals who did not report a history of TBI, 17.9% of males and 23.5% of females reported psychological distress (p

Objective(s) This study was designed to compare 2 different perioperative analgesia strategies with respect to the incidence of postoperative delirium after a transapical approach for transcatheter aortic valve replacement (TAVR). The authors hypothesized that perioperative thoracic paravertebral analgesia with a local anesthetic would decrease opioid consumption and in turn reduce the incidence of postoperative delirium when compared with systemic opioid-based analgesia after a transapical TAVR procedure. Design Prospective, randomized controlled clinical trial. Setting Tertiary referral center, university hospital. Participants The study comprised 44 patients undergoing a transapical TAVR procedure. Patients with a history of serious mental illness, delirium, and severe dementia and/or patients with contraindications to regional anesthesia were excluded. Interventions Patients were randomly assigned to either the paravertebral group (perioperative continuous thoracic paravertebral block with local anesthetic) or the patient-controlled analgesia group (systemically administered opioids) using a computer-generated randomization code in blocks of four patients. Measurements and Main Results Assessment of postoperative delirium was performed by trained research staff using the confusion assessment method for intensive care unit preoperatively and postoperatively every 12 hours or more often if needed according to the patient's condition during the first 7 postoperative days or until discharge. Pain was assessed with a 10 cm Visual Analog Scale pain score system during the 48 hours postoperatively. The sedation level was assessed using the Sedation Agitation Scale during the same period. Overall postoperative delirium was detected in 12/44 (27%) patients, with 7/22 (32%) in the patient-controlled analgesia and 5/22 (23%) in the paravertebral groups, respectively (p = 0.73). Both groups were similar with respect to demographic data, preoperative medications, and comorbidities. Paravertebral analgesia was associated with an opioid-sparing effect during surgery and during the 48-hour postoperative period. Sedation and pain scores were similar between the 2 groups. In addition, paravertebral analgesia was associated with earlier extubation times; however, the overall morbidity and mortality were similar between the 2 groups. Conclusions Paravertebral analgesia in patients undergoing transapical TAVR procedures appears to have an opioid-sparing effect. However, it did not translate into a statistically significant decrease in the rate of postoperative delirium.

Many brain-injured patients are unable to self-report their pain during their hospitalization in the intensive care unit (ICU), and existing behavioral pain scales may not be well suited.The objectives of this study were to describe and compare behaviors in brain-injured patients with different levels of consciousness during nociceptive and nonnociceptive care procedures in the ICU and to examine interrater agreement of individual behaviors as well as discriminative and criterion validation of putative pain behaviors.Brain-injured ICU patients were observed using a 40-item behavioral checklist before and during soft touch (i.e., nonnociceptive procedure), turning, and other care procedures (nociceptive) by pairs of trained raters. When possible, patients self-reported their pain on a 0-10 visual thermometer. Patients were classified into unconscious (Glasgow Coma Scale, 3GCS≤8), altered consciousness (9≤GCS≤12), or conscious (13≤GCS≤15).A sample of 147 patients participated (65 conscious, 56 altered consciousness, and 26 unconscious). Active behaviors (e.g., face expressions and body movements) were more frequent in conscious patients. High-percentage interrater agreement (80%-98%) was obtained for most behaviors. The total number of active behaviors was significantly higher during turning and other nociceptive procedures compared with rest (Wilcoxon = 9.873, P 0.001) and soft touch (Wilcoxon = 9.486, P 0.001) regardless of levels of consciousness. The strongest predictors of pain intensity (n = 33) were grimace, mouth opening, orbit tightening, eye weeping, and eyes tightly closed; these behaviors were moderately correlated with self-reported pain intensity (Spearman rho = 0.47).These findings may guide the revision of existing pain scales to make their content more suited for this population.

Concussion can occur from a variety of events (falls to ice, collisions etc) in ice hockey, and as a result it is important to identify how these different impact sources affect the relationship between impact kinematics and strain that has been found to be associated to this injury. The purpose of this research was to examine the relationship between kinematic variables and strain in the brain for impact sources that led to concussion in ice hockey. Video of professional ice hockey games was analyzed for impacts that resulted in reported clinically diagnosed concussions. The impacts were reconstructed using physical models/ATDs to determine the impact kinematics and then simulated using finite element modelling to determine maximum principal strain and cumulative strain damage measure. A stepwise linear regression was conducted between linear acceleration, change in linear velocity, rotational acceleration, rotational velocity, and strain response in the brain. The results for the entire dataset was that rotational acceleration had the highest r2 value for MPS (r2 = 0.581) and change in rotational velocity for cumulative strain damage measure (r2 = 450). When the impact source (shoulder, elbow, boards, or ice impacts) was isolated the rotational velocity and acceleration r2 value increased, indicating that when evaluating the relationships between kinematics and strain based metrics the characteristics of the impact is an important factor. These results suggest that rotational measures should be included in future standard methods and helmet innovation and design in ice hockey as they have the highest association with strain in the brain tissues.

Background Facet dislocations of the lumbar spine, particularly without neurologic injury, are rare occurrences after major trauma. Although there are documented cases of lumbosacral dislocation in the published literature, strictly lumbar unilateral facet dislocation is rare. Case Description We report a case of a unilateral facet dislocation at L4-L5 after a single vehicle motorcycle accident. This injury was treated with posterior open reduction and instrumented stabilization with good results. Conclusions Given the rarity of this injury pattern, the management of this type of injury is not established. Careful imaging to make the diagnosis is crucial, and we recommend a surgical treatment in the form of an open reduction and instrumented stabilization. In our case, we achieved good outcomes with a posterior approach.

Traumatic brain injury (TBI) is a common injury characterized by a change in brain function after an external blow to the head and is associated with substance abuse, psychological distress, risk-taking, and impulsivity. Convenience and clinical samples have also linked TBI to problem gambling, but have not ruled out confounding variables such as hazardous drinking and psychological distress. This study examines the relationship between TBI and moderate to severe problem gambling in a general population probability sample controlling for hazardous drinking and psychological distress. The data were obtained from a 2015–2016 cross-sectional general population telephone survey of adults ages 18+from Ontario, Canada (N = 3809). Logistic regression was used to estimate the association as adjusted odds ratios (AOR). Moderate to severe problem gambling was independently associated with a history of TBI after adjusting for potential confounders (AOR: 2.80), and had a statistically significant relationship with psychological distress (AOR = 2.74), hazardous drinking (AOR = 2.69), and lower educational levels (AOR = 0.37). This study provides further data to suggest a link between TBI and moderate to severe problem gambling; however, more research is needed to determine if there is a causal relationship or the potential implications for prevention and treatment.

This study describes the association among lifetime traumatic brain injury (TBI) and past year hazardous/harmful drinking, as well as their unique and synergistic effects, on mental health problems and roadway aggression among Canadian adults. A cross-sectional sample of 6074 Ontario adults aged 18 years or older were surveyed between 2011 and 2013. TBI was defined as trauma to the head resulting in loss of consciousness or overnight hospitalization. Past year hazardous/harmful drinking was assessed using the Alcohol Use Disorders Identification Test. An estimated 13.1% (95%CI:12.0,14.2) adults reported a prior TBI (no hazardous/harmful drinking), 2.7% (95%CI:2.2,3.3) reported a prior TBI while concurrently screening positive for past year hazardous/harmful drinking and 9.8% (95%CI:8.9,10.9) screened positive for hazardous/harmful drinking (no TBI). Men had significantly higher odds of exhibiting all three conditions compared to women, especially for the concurrent class. Younger adults had significantly greater odds of hazardous/harmful drinking, or the concurrent class compared to adults 55 years and older. Adults in any of the three conditions had greater odds for mental health problems and roadway aggression. Concordance of both conditions corresponded to a greater than additive effect and greater odds of mild roadway aggression, than either condition alone. Results show that singly and jointly, these conditions are associated with adverse health and behavioral impediments.

Background Surface electromyographic (EMG) recordings collected during the performance of functional evaluations allow clinicians to assess aberrant patterns of muscle activity associated with musculoskeletal disorders. This assessment is typically achieved via visual inspection of the surface EMG data. This approach is time-consuming and leads to accurate results only when the assessment is carried out by an EMG expert. Methods A set of algorithms was developed to automatically evaluate aberrant patterns of muscle activity. EMG recordings collected during the performance of functional evaluations in 62 subjects (22 to 61 years old) were used to develop and characterize the algorithms. Clinical scores were generated via visual inspection by an EMG expert using an ordinal scale capturing the severity of aberrant patterns of muscle activity. The algorithms were used in a case study (i.e. the evaluation of a subject with persistent back pain following instrumented lumbar fusion who underwent lumbar hardware removal) to assess the clinical suitability of the proposed technique. Results The EMG-based algorithms produced accurate estimates of the clinical scores. Results were primarily obtained using a linear regression approach. However, when the results were not satisfactory, a regression implementation of a Random Forest was utilized, and the results compared with those obtained using a linear regression approach. The root-mean-square error of the clinical score estimates produced by the algorithms was a small fraction of the ordinal scale used to rate the severity of the aberrant patterns of muscle activity. Regression coefficients and associated 95% confidence intervals showed that the EMG-based estimates fit well the clinical scores generated by the EMG expert. When applied to the clinical case study, the algorithms appeared to capture the characteristics of the muscle activity patterns associated with persistent back pain following instrumented lumbar fusion. Conclusions The proposed approach relies on EMG-based measures to generate accurate estimates of the severity of aberrant patterns of muscle activity. The results obtained in the case study suggest that the proposed technique is suitable to derive clinically-relevant information from EMG data collected during functional evaluations.

Patient-derived xenografts retain the genotype of the parent tumors more readily than tumor cells maintained in culture. The two previously reported clival chordoma xenografts were derived from recurrent tumors after radiation. To study the genetics of clival chordoma in the absence of prior radiation exposure we established a patient-derived xenograft at primary resection of a clival chordoma. Epicranial grafting of clival chordoma collected during surgery was performed. Tumor growth was established in a nonobese diabetic/severe combined immunodeficiency mouse and tumors have been passaged serially for seven generations. Physaliferous cell architecture was shown in the regenerated tumors, which stained positive for Brachyury, cytokeratin, and S100 protein. The tumors showed bone invasion. Single-nucleotide polymorphism analysis of the tumor xenograft was compared with the parental tumor. Copy number gain of the T gene (brachyury) and heterozygous loss of cyclin dependent kinase inhibitor 2A (CDKN2A) was observed. Heterozygous loss of the tumor-suppressor fragile histidine triad (FHIT) gene also was observed, although protein expression was preserved. Accumulation of copy number losses and gains as well as increased growth rate was observed over three generations. The patient-derived xenograft reproduces the phenotype of clival chordoma. This model can be used in the future to study chordoma biology and to assess novel treatments.

Background Hurling is a fast-paced contact sport that places players at risk of concussion. Given the consequences of repeated concussive impacts, it is imperative that concussion management guidelines are followed. Hypothesis/Purpose. The aim of this study is to determine if potential concussive events (PCEs) in elite Hurling are assessed in accordance with league management guidelines. The secondary objective is to investigate the effectiveness of current concussion training programs. Methods Investigators used a video analysis approach to identify PCEs throughout the 2018 and 2019 inter-county Hurling seasons and championships. Subsequent assessment, return to play (RTP) decision, and signs of concussion were evaluated based on previously validated methods. The results were then compared year-over-year with previous research in Gaelic Football (GF). Results A total of 183 PCEs were identified over 82 matches. PCEs were frequently assessed (86.3%, n = 158) by medical personnel. The majority of assessments were less than 1 min in duration (81.0%, n = 128). Thirteen (7.1%) players were removed following a PCE. There were 43 (23.5%) PCEs that resulted in one or more signs of concussion, of which 10 (23.3%) were removed from play. There was no difference in rate of assessment, duration of assessment, or rate of RTP between 2018 and 2019 in both Hurling and GF, suggesting that current concussion training programs have had limited success. Conclusion In Hurling, players suspected of having sustained a concussion are frequently subject to a brief assessment, and are rarely removed from play. Affirmative action is needed to ensure the consistent application of standardized concussion assessment across the Gaelic Games.

To evaluate the relationships between calibration dose rate, calculated biologically effective dose (BED), and clinical factors and tumor control after stereotactic radiosurgery (SRS) for acoustic neuroma.We performed a retrospective study of all patients with acoustic neuromas treated with frame-based cobalt-60 SRS at a single institution between 2005 and 2019. The calibration dose rate and cobalt-60 half-life were used to calculate the nominal dose rate during treatment. An SRS-specific monoexponential model accounting for treatment time per lesion was used to estimate BED.The study included 607 patients with 612 acoustic neuromas. Median follow-up was 5.0 years. There was no association between dose rate or BED with local failure (LF), radiologic edema, or symptomatic edema. Cystic tumors (adjusted hazard ratio 0.26, P = 0.028) were associated with lower LF, while use of SRS as salvage treatment for growing tumors (adjusted hazard ratio 4.9, P0.0001) was associated with higher LF. LF occurred more frequently in larger-diameter tumors, while radiologic or symptomatic edema occurred more frequently in larger-volume tumors.Radiosurgery dose rate and BED were not associated with tumor control or radiologic or symptomatic edema. Salvage SRS and larger tumors were associated with a higher LF rate, while cystic tumors were associated with a lower LF rate. Patients with larger tumors should be counseled appropriately about potential side effects and when to seek follow-up care.

Gaelic football (GF) is a high-impact sport and Sport-Related Concussion (SRC) is an issue within the game. Our aim was to evaluate the characteristics of Potential Concussive Events (PCEs) that occur in the Gaelic Athletic Association National Football League and extrapolate this data to reduce the incidence and severity of SRC. PCEs may or may not lead to a clinical diagnosis of SRC, but represent high-risk events and therefore may be a useful indicator. A video-analysis approach was undertaken to identify PCEs throughout two seasons of play using broadcast footage, and characteristics of each PCE were measured based on previously validated methods. A total of 242 PCEs were identified over 111 matches (2.18 per match, 58.14 per 1000 hours of exposure). PCEs were frequently not anticipated by the player (40.5%, n = 98). The most common impact locations were the mandibular region (33.1%, n = 80) and the temporal region (21.1%, n = 51), and the most frequently observed mechanism was hand/fist to head (27.3%, n = 66). A second-hit was observed in 34 PCEs (14.0%). The findings provide initial guidance for the development of player protection strategies to reduce the incidence and severity of SRC in Gaelic Football.

No previous large population-based studies of traumatic spinal injury (TSI) rates, trends, and patterns exist. We aimed to fill this knowledge gap on TSI epidemiology using a population-based study of 13 million people.This is a descriptive cross-sectional cohort study that analyzes a national, mandatory reporting database for all emergency departments and ambulatory care centers in Ontario over 15 years. Demographics of TSI, trends in the TSI rate, etiology, transfer, disposition, comorbidities, and associated traumatic brain injury or spinal cord injury were analyzed.There were 167,357 TSI-related emergency department visits resulting in 70,684 hospitalizations and 376 deaths. The overall rate of TSI significantly increased from 66.94 to 118.61 per 100,000. Female patients had greater rates of TSI. Older patients had greater rates of TSI, especially related to falls. Fall was found to be the commonest mechanism of TSI, whereas motor vehicle collisions scaled down to the third commonest mechanism of TSI. Sport-related TSI had the greatest percentage of increase in the rate over all mechanisms (221%, P0.001). TSI with associated traumatic brain injury comprised 6% of the cohort but had the greatest percentage increase (91%) in the rate compared to all other TSI forms.The rate of TSI continues to rise in Ontario as the population ages. The rise is primarily attributed to a shift in the epidemiology and etiology of TSI from a younger male population toward an older female population, with falls as the primary injury mechanism. Establishing preventive measures to address this shift is essential.

The purpose of this investigation is to evaluate 2 different methods for reducing cortical wall thickness in sinus floor augmentation surgery. A manual bone scraper was compared in terms of efficacy, speed, and safety to an ultrasonic insert for osteoplasty, in a randomized controlled clinical trial with a split-mouth design. Twenty-five patients with severe posterior maxillary atrophy were treated with bilateral sinus floor elevation with lateral approach. Antrostomies were randomly performed by eroding the cortical wall with a manual bone scraper (test site) or with an ultrasonic insert (control site) until the membrane was visible under a thin layer of bone, before outlining the window with a piezoelectric device. Occurrence of membrane perforation, laceration of vascular branches, and surgical time were recorded. Mean surgical time of the antrostomy in the test sites was 9'18", while in the control sites was 9'47". No significant differences were found in terms of surgical time, incidence of membrane perforation during antrostomy (4.3% in both groups), or other intraoperative complications between the 2 techniques. Both surgical approaches represent effective options for performing lateral antrostomies during sinus floor elevation procedures in a safe and predictable way.

Objective: To evaluate short-term (2003–2014) cancer incidence and mortality trends in Italy. Methods: Italian Cancer Registries data, available in the AIRTUM database, from 17 out of 20 regions were used. The number of incident cases and deaths were estimated for those registries and those years with incomplete information. Age-standardized rates, overall and stratified by geographic area, region, sex, cancer site, and major age group, were computed. Time trends were expressed as annual percent change of rates. Results: In Italy, among males, incidence rates for all cancers showed during 2003–2014, a significant decrease (−0.9%/year), with stronger reductions in the northwest (−1.3%/year) and northeast (−2.0%/year since 2006) than in central (−0.7%/year) and southern (−0.4%/year) areas. Among females, a weak but significant overall reduction was detected (−0.1%/year), with a stronger decrease in the northwest (−0.5%/year). Incidence increased among women in the south (0.3%/year) of Italy. Mortality decreased in both sexes (−1.0%/year among males and −0.5%/year among females), but not in the south, where rates had a stable tendency. Conclusions: Incidence among males decreased, supported by trends for prostate, lung, colorectal, and urinary bladder cancers; among females the. The overall cancer incidence trend was stable, or even decreasing, in the northern and central areas and increasing in the southern areas, due to lung, thyroid, and melanoma rising trends. Study results provided information on the outcomes, in terms of cancer incidence and mortality, of primary and secondary prevention measures employed by regional health systems.

Objective: To evaluate the trends of colorectal cancer (CRC) incidence and mortality rates from 2003 to 2014 in Italy by age groups and regions. Methods: We used the data of 48 cancer registries from 17 Italian regions to estimate standardized incidence and mortality rates overall and by sex, age groups (Results: Incidence rates decreased from 104.3 (2003) to 89.9 × 100,000 (2014) in men and from 64.3 to 58.4 × 100,000 in women. Among men, incidence decreased during 2007–2010 (APC −4.0, 95% CI −6.0 to −1.9) and 2010–2014 (APC −0.7, 95% CI −1.4 to 0.0), while in women it linearly decreased during the whole period (APC −1.1, 95% CI −1.4 to −0.8). Mortality rates showed a linear reduction both in men (APC −0.7, 95% CI −1.0 to −0.3) and women (APC −0.9, 95% CI −1.2 to −0.6) and decreased respectively from 41.1 to 39.2 × 100,000 and from 24.6 to 23.1 × 100,000. In the 50- to 69-year-old range (screening target age), incidence showed a prescreening increase, followed by a peak after screening started, and a decline thereafter. Incidence and mortality rates significantly decreased in all areas but in the south and islands, where incidence increased and mortality remained stable. Conclusions: A renewed commitment by all regional health systems to invest in primary (i.e., lifestyle) and secondary (i.e., screening programs) prevention is of utmost importance.

To evaluate the impact of faecal immunochemical test (FIT) screening on stage distribution at diagnosis, and to estimate relative incidence rates by stage in screened at first and subsequent rounds vs. unscreened. We included all incident cases occurring in 2000-2008 in 50- to 71-year-olds residing in areas with an FIT-screening programme. Multinomial logistic models were computed to estimate the relative risk ratio (RRR) of stages I and IV, compared to stage II + III, adjusting for age, sex, geographical area, and incidence year. Proportions were then used to estimate incidence rate ratios (IRR) by stage for screened subjects at the first and at subsequent rounds vs. unscreened subjects, applying the expected changes in overall incidence during screening phases. 11,663 cancers were included: 5965 in not-invited and 5,698 in invited subjects, 3,425 of whom attendees. Compared to not-invited, invited subjects had RRR 2.04 (95% CI: 1.84; 2.46) of stage I and RRR 0.77 (95% CI: 0.69; 0.87) of stage IV. Differences were stronger comparing attendees vs. nonattendees. Interval cancers were more frequently stage I compared to non-invited (RRR 1.54; 95% CI: 1.15; 2.04), but there was no difference for stage IV. IRRs in screened at first round vs. unscreened were 4.6 (95% CI: 4.2; 5.1), 1.4 (95% CI: 1.3; 1.5) and 0.7 (95% CI: 0.6; 0.9) for stages I, II + III and IV, respectively; in the following rounds the IRRs of screened vs. unscreened were 1.4 (95% CI: 1.2; 1.6), 0.8 (95% CI: 0.7; 0.9) and 0.3 (95% CI: 0.1; 0.4) for stages I, II + III and IV, respectively. FIT screening reduces the incidence of metastatic cancers by about 70% after the first round.

A 24-year-old man presented with a 2-month history of progressive, painless vision loss in the right eye, with no history of headache, nasal congestion, rhinorrhea, or epistaxis. His visual acuity was counting fingers at 1 ft in the right eye and 20 of 20 in the left eye with a right relative afferent pupillary defect and mild temporal optic disc pallor. MRI of the brain and orbits showed a mass involving bilateral ethmoid and sphenoid sinuses and right nasal cavity. He underwent urgent extended endoscopic endonasal transsphenoidal approach for resection of the sinonasal skull base tumor and photon radiation therapy. Pathology revealed a well-differentiated cartilaginous neoplasm with focal areas of entrapped native bone, consistent with a chondrosarcoma WHO grade I/III. At 6-month follow-up after surgery, he had a visual acuity of 20/40 in the right eye and 20/20 in the left eye. Malignant tumors from the sinonasal area should be kept in the differential diagnosis for compressive optic neuropathies and may present with vision loss even in the absence of nasal or sinus symptoms.

Sport-related concussion (SRC) is a potential issue within Gaelic Football. Therefore, it is essential that concussion management guidelines are adhered to.The aim of this study is to determine if potential concussive events (PCEs) in the Gaelic Athletic Association (GAA) National Football League (NFL) are assessed in accordance with GAA concussion guidelines and compare this to other sports.A descriptive video analysis approach was undertaken to identify PCEs throughout two seasons of play. Subsequent assessment, return to play (RTP) decisions, and signs of concussion were evaluated.A total of 242 PCEs were identified over 111 matches. Most PCEs (87.2%, n = 211) were assessed by medical personnel. However, 187 (88.6%) of assessments were under 2 min in duration. Of the 242 PCEs, 189 (78.1%) returned to play after on-pitch assessment, and 12 (5.0%) were removed following a PCE. Sixty-one (25.2%) players sustaining a PCE demonstrated one or more signs of concussion, of which 9 (14.8%) were removed from play.In the GAA NFL, PCEs are often briefly assessed but rarely result in player removal. Introduction of video incident analysis and concussion substitutions, as in other sports, may reduce the long-term burden of SRC on Gaelic Football players.

OBJECTIVES There is an increasing proportion of patients with a previous sternotomy (PS) or durable left ventricular assist device (LVAD) undergoing heart transplantation (HT). We hypothesized that patients with LVAD support at the time of HT have a lower risk than patients with PS and may have a comparable risk to patients with a virgin chest (VC). METHODS This is a single-centre retrospective cohort study of all adults who underwent primary single-organ HT between 2002 and 2017. Multivariable Cox regression analyses were performed to compare 30-day and 1-year mortality between transplanted patients with a VC (VC-HT), a PS (PS-HT) or an LVAD explant (LVAD-HT). RESULTS Three hundred seventy-nine patients were analysed (VC-HT: 196, PS-HT: 94, LVAD-HT: 89). A larger proportion of patients in the LVAD-HT group were males (83%), had blood group O (52%), non-ischaemic aetiology (70%) and sensitization (67%). The PS-HT group had a higher frequency of patients with congenital heart disease (30%) and PSs compared to LVAD-HT patients (P CONCLUSIONS Transplants in recipients with PS-HT demonstrated increased early mortality compared to VC-HT patients. Although LVAD explant is often technically challenging, this population demonstrated similar mortality compared to those VC-HT patients. The chronic and perioperative support provided by the LVAD may play a favourable role in early patient outcomes compared to other redo sternotomy patients.

BackgroundMeningiomas, the most common adult brain tumors, recur in up to half of cases[1–3]. This requires timely intervention and therefore accurate risk assessment of recurrence is essential. Our current practice relies heavily on histological grade and extent of surgical excision to predict meningioma recurrence. However, prediction accuracy can be as poor as 50% for low or intermediate grade tumors, which constitute more than 90% of all cases. Moreover, attempts to find molecular markers, particularly for predicting recurrence of intermediate tumors have been impeded by low[4] or heterogenous[5–8] genetic signal. We therefore sought to apply systems-biology approaches to transcriptomic data to better predict meningioma recurrence.MethodsWe apply gene co-expression networks to a cohort of 252 adult patients from the publicly-available genetic repository Gene Expression Omnibus. Resultant gene clusters (“modules”) were represented by the first principle component of their expression levels, and their ability to predict recurrence assessed with a logistic regression model. External validation was done using an independent merged cohort of 108 patients using the same modules. We used the bioinformatics database DAVID[9] to examine the gene ontology associations of each module.ResultsUsing gene co-expression analysis, we were able predict tumor recurrence with high accuracy using a single module which mapped to cell cycle-related functions (AUC of 0.81 ± 0.09 in external validation). Further, the module maintained its accuracy with removal of up to 20 of it’s most individually predictive genes, suggesting robustness against noise at the single gene level.ConclusionsWith the easy accessibility of gene panels in healthcare diagnostics, our results offer a basis for routine molecular testing in meningioma management.

Background Patient engagement is the establishment of active partnerships between patients, families, and health professionals to improve healthcare delivery. The objective of this project was to conduct a series of patient engagement workshops to identify areas to improve the surgical experience and develop strategies to address areas identified as high priority. Methods Faculty surgeons and patients were invited to participate in three in-person meetings. Evaluation included identifying and developing strategies for three priority areas to improve the surgical experience and level of engagement achieved at each meeting. Results Sixteen faculty surgeons and 32 patients participated. Some 63 themes to improve the surgical experience were identified; the three highest-priority themes were physician communication, discharge process, and expectations at home after discharge. Individual improvement strategies for these three prioritized themes (12, 36 and 6 respectively) were used to develop a formal strategic plan, and included a physician communication survey, discharge process worksheet and video, and guideline regarding what to expect at home after discharge. Overall, the level of engagement achieved was considered high by over 85 per cent of the participants. Conclusion A high level of patient engagement was achieved. Priorities were identified with patients and surgeons to improve surgical experience, and strategies were developed to address these areas.

Stereotactic radiosurgery is an established treatment option for sporadic meningiomas, though limited data exists for radiation-induced lesions.Patients treated with cobalt-60 radiosurgery between October 2005 and December 2018 in an institutional registry were reviewed. Single fraction treatments were prescribed to the 50% isodose line. Lesions were deemed to be radiation-induced according to standard criteria previously established by Cahan et al. RESULTS: A total of 37 patients with 72 lesions were analysed. Median follow up per patient was 44 months (range, 1.4-150.7 months). Median age at initial radiotherapy was 5 years (4 months-48 years), and at radiosurgery was 38 years. Of the 72 lesions, 62 were grade 1 (n = 4) or radiologically-diagnosed (n = 58), six were grade 2 and four were grade 3. Median lesion volume was 2.13 cc (0.04-13.8 cc), while the median radiosurgery margin dose was 13 Gy. Local control, on a per lesion basis, was 88.6% at 5 years (95% confidence interval [CI] 72.3-95.6). For grade 1 or radiologically-diagnosed lesions, local control was 96.6% at 5 years (95% CI 77.9-99.5), whereas those with grade 2 or higher lesions had a local control of 40% at 5 years (95% CI 5.2-75.3, p = 0.005). Radiologic oedema developed in 17 lesions (23.6%) and was symptomatic in 12 patients (16.7%). Doses above 12 Gy were not associated with local control probability (p = 0.292).Radiosurgery is an effective treatment option for grade 1 or radiologically-diagnosed radiation-induced meningiomas, with 12 Gy appearing to be a sufficient dose.

BACKGROUND: As artificial intelligence (AI) approaches in research increase and AI becomes more integrated into medicine, there is a need to understand perspectives from members of the Canadian public and medical community. The aim of this project was to investigate current perspectives on ethical issues surrounding AI in health care. METHODS: In this qualitative study, adult patients with meningioma and their caregivers were recruited consecutively (August 2018–February 2019) from a neurosurgical clinic in Toronto. Health care providers caring for these patients were recruited through snowball sampling. Based on a nonsystematic literature search, we constructed 3 vignettes that sought participants’ views on hypothetical issues surrounding potential AI applications in health care. The vignettes were presented to participants in interviews, which lasted 15–45 minutes. Responses were transcribed and coded for concepts, frequency of response types and larger concepts emerging from the interview. RESULTS: We interviewed 30 participants: 18 patients, 7 caregivers and 5 health care providers. For each question, a variable number of responses were recorded. The majority of participants endorsed nonconsented use of health data but advocated for disclosure and transparency. Few patients and caregivers felt that allocation of health resources should be done via computerized output, and a majority stated that it was inappropriate to delegate such decisions to a computer. Almost all participants felt that selling health data should be prohibited, and a minority stated that less privacy is acceptable for the goal of improving health. Certain caveats were identified, including the desire for deidentification of data and use within trusted institutions. INTERPRETATION: In this preliminary study, patients and caregivers reported a mixture of hopefulness and concern around the use of AI in health care research, whereas providers were generally more skeptical. These findings provide a point of departure for institutions adopting health AI solutions to consider the ethical implications of this work by understanding stakeholders’ perspectives.

OBJECTIVECushing’s disease (CD) patients experience a range of debilitating symptoms that impair quality of life (QOL) as assessed using generic measures. These generic measures are inadequate to capture the disease-specific burden of illness. The development of the CD-specific QOL-CD measure of QOL using items generated by CD patients and healthcare professionals will provide a holistic assessment of patient outcomes and efficacy of novel therapies.METHODSA total of 96 CD patients participated. A list of 177 items (version 1.0) was generated by treated CD patients (n = 9), caregivers (n = 2), healthcare providers (n = 7), and results of a MEDLINE search. Item reduction was performed through content analysis and dual scaling. Patients’ rating of importance was incorporated to reduce to a final version of 56 items (version 3.0). Evidence for test-retest reliability was sought through administering the QOL-CD 1 week apart and Cronbach’s α of each subscale. Construct validity was assessed through extreme group analysis and comparison with the normal Canadian population. Concurrent validity was sought through comparison with the SF-36, Functional Assessment of Cancer Therapy–Brain (FACT-Br), and Karnofsky Performance Status (KPS). Perioperative testing was conducted on CD patients (n = 25) against nonfunctioning pituitary adenoma controls (n = 25) through pre- and postoperative testing.RESULTSA total of 96 CD patients (86 females and 10 males; mean age 45.23 ± 14.16 years) participated. The QOL-CD was feasible (mean completion time 15 minutes, with 70% believing accurate capture of QOL), reliable (CD 1 week apart: r = 0.86; control 1 week apart: r = 0.83; Cronbach’s α: general health = 0.73, emotional health = 0.85, physical health = 0.78, mental status = 0.82, social well-being = 0.63, medical treatment = 0.54), and valid (extreme group testing p < 0.001; SF-36 and QOL-CD general health: r = 0.56, social well-being: r = 0.21, emotional health: r = 0.61, total score: r = 0.58; FACT-Br and QOL-CD physical health: r = 0.47, social well-being: r = 0.21, emotional health: r = 0.34, total score: r = 0.68; KPS and QOL-CD general health: r = 0.32, total score: r = 0.14). Perioperative testing of CD patients (n = 25) demonstrated improvement in all subscales postoperatively, with a significant difference in emotional health (p < 0.001) and physical health (p < 0.001).CONCLUSIONSThe QOL-CD questionnaire has been developed for patients with CD and has demonstrated evidence for validity and reliability.

Anesthetic and surgical considerations for awake craniotomy (AC) include airway patency, patient comfort, and optimization of real-time brain mapping. The purpose of this study is to report our experience of using dexmedetomidine and scalp blocks, without airway intervention, as a means to facilitate and optimize intraoperative brain mapping and brain tumour resection during AC. We conducted a retrospective cohort study of 55 patients who underwent AC from March 2012 to September 2016. The incidence of critical airway outcomes, perioperative complications, and successful intraoperative mapping was determined. The primary outcome was the incidence of a failed AC anesthetic technique as defined by the need to convert to general anesthesia with a secured airway prior to (or during) brain mapping and brain tumour resection. Secondary outcomes were the intraoperative incidence of: 1) altered surgical management due to information acquired through real-time brain mapping, 2) interventions to restore airway patency or rescue the airway, 3) hemodynamic instability (> 20% from baseline), 4) nausea and vomiting, 5) new onset neurologic deficits, and 6) seizure activity. There were no anesthesia-related critical events and no patients required airway manipulation or conversion to a general anesthetic. Multimodal language, motor, and sensory assessment with direct cortical electrical stimulation was successfully performed in 100% of cases. In 24% (13/55) of patients, data acquired during intraoperative brain mapping influenced surgical decision-making regarding the extent of tumour resection. Nine (16%) patients had intraoperative seizures. Dexmedetomidine-based anesthesia and scalp block facilitated AC surgery without any requirement for urgent airway intervention or unplanned conversion to a full general anesthetic. This approach can enable physiologic testing before and during tumour resection facilitating real-time surgical decision-making based on intraoperative brain mapping with patients awake thereby minimizing the risk of neurologic deficit and increasing the opportunity for optimal surgical resection.

We examined the effect of age on listeners' ability to orient attention to an item in auditory short-term memory (ASTM) using high-density electroencephalography, while participants completed a delayed match-to-sample task. During the retention interval, an uninformative or an informative visual retro-cue guided attention to an item in ASTM. Informative cues speeded response times, but only for young adults. In young adults, informative retro-cues generated greater event-related potential amplitude between 450 and 650 ms at parietal sites, and an increased sustained potential over the left central scalp region, thought to index the deployment of attention and maintenance of the cued item in ASTM, respectively. Both modulations were reduced in older adults. Alpha and low beta oscillatory power suppression was greater when the retro-cue was informative than uninformative, especially in young adults. Our results point toward an age-related decline in orienting attention to the cued item in ASTM. Older adults may be dividing their attention between all items in working memory rather than selectively focusing attention on a single cued item.

Background The long-term cognitive and quality-of-life (QoL) outcomes after treatment of ruptured anterior communicating artery (ACoA) aneurysms are unknown. Methods Potential participants were all consecutive patients with ruptured ACoA aneurysms who were treated at one institution from July 1992 to December 2008. All potential participants were asked to complete the Cognitive Failures Questionnaire (CFQ), Center for Epidemiology Studies-Depression (CES-D) questionnaire, Short Form 36 (SF-36) questionnaire, and Telephone Interview for Cognitive Status-Modified (TICS-M). Patient charts were retrospectively reviewed for baseline demographics and clinical status, intra-operative details, and post-operative course. Reporting of cognitive and QoL assessment results was stratified by treatment method (endovascular coil embolization and surgical clipping by pterional craniotomy or orbitocranial craniotomy). Results In total, 82 patients (18 treated with coiling, 27 by orbitocranial craniotomy, and 37 by pterional craniotomy) were included in this study. In total, 32 patients (9 treated by coiling, 11 by orbitocranial craniotomy, and 16 by pterional craniotomy) completed follow-up cognitive and QoL questionnaires. The mean follow-up for patients who completed the questionnaires was 8.64±3.81 years. The three groups did not differ in questionnaires assessing cognitive status (TICS-M p=0.114, CFQ p=0.111). Moreover, there were no observed differences in QoL or depression scores between the three groups. Conclusions At long-term follow-up, QoL, cognitive, and depression test scores of patients with ruptured ACoA aneurysms are similar across open surgery and coiling modalities. Our results emphasize the importance of considering long-term outcomes with validated daily measures of functioning when reporting on outcomes after treatment for ruptured intracranial aneurysms. Larger prospective studies are required to further explore the results.

OBJECTIVEQuantitative assessment of tumor microvascularity has the potential to improve prognostication, advance understanding of tumor biology, and help narrow potential molecular therapies. While the role of tumor microvascularity has been widely studied in meningiomas, this study examines both the role of automated measurements and the impact on surgical outcome.METHODSTwo hundred seven patients with Grade I meningiomas underwent surgery between 1996 and 2011. Tissue samples from each patient were retrospectively evaluated for histopathological measures of microvascularity, including staining for von Willebrand factor (vWF), CD31, CD105, hypoxia-inducible factor 1 (HIF-1), vascular endothelial growth factor, glucose transporter 1, and carbonic anhydrase IX. Manual methods of assessing microvascularity were supplemented by a computational analysis of the microvascular patterns by means of fractal analysis. MIB-1 proliferation staining was also performed on the same tumors. These measures were compared with various patient characteristics, tumor volume, estimated blood loss (EBL) during surgery, progression-free survival (PFS), and overall survival (OS).RESULTSThe mean patient age was 55.4 ± 14.8 years, and 63 (30.4%) patients were male. Patients harboring tumors ≥ 3 cm were significantly older (56.9 ± 15.2 years vs 53.1 ± 13.6 years; p = 0.07), more frequently male (40.8% vs 14.6%; p = 0.0001), and had greater EBL (446.5 ± 532.2 ml vs 185.4 ± 197.2 ml; p = 0.0001), greater tumor volume (33.9 ± 38.1 ml vs 29.4 ± 23.5 ml; p = 0.0001), higher MIB-1 index values (3.0% ± 5.4% vs 1.7% ± 1.7%; p = 0.03), higher vWF levels (85.6% ± 76.9% vs 54.1% ± 52.4%; p = 0.001), lower HIF-1 expression (1.4 ± 1.3 vs 2.2 ± 1.4; p = 0.004), and worse OS (199.9 ± 7.6 months vs 180.8 ± 8.1 months; p = 0.05) than patients with tumors < 3 cm. In the multivariate logistic regression, MIB-1 (OR 1.14; p = 0.05), vWF (OR 1.01; p = 0.01), and HIF-1 (OR 1.54; p = 0.0001) significantly predicted tumor size. Although multiple factors were predictive of EBL in the univariate linear regression, only vWF remained significant in the multivariate analysis (β = 0.39; p = 0.004). Lastly, MIB-1 was useful via Kaplan-Meier survival analysis for predicting patients with disease progression, whereby an MIB-1 cutoff value of ≥ 3% conferred a 36% sensitivity and 82.5% specificity in predicting disease progression; an MIB-1 value ≥ 3% showed significantly shorter mean PFS (140.1 ± 11.7 months vs 179.5 ± 7.0 months; log-rank test, p = 0.05). The Cox proportional hazards model showed a trend for MIB-1 in predicting disease progression in a hazards model (OR 1.08; 95% CI 0.99–1.19; p = 0.08).CONCLUSIONSThese results support the importance of various microvascularity measures in predicting preoperative (e.g., tumor size), intraoperative (e.g., EBL), and postoperative (e.g., PFS and OS) outcomes in patients with Grade I meningiomas. An MIB-1 cutoff value of 3% showed good specificity for predicting tumor progression. The predictive ability of various measures to detect aberrant tumor microvasculature differed, possibly reflecting the heterogeneous underlying biology of meningiomas. It may be necessary to combine assays to understand angiogenesis in meningiomas.

Background Endoscopic transsphenoidal skull base surgery (ETSS) is now considered the criterion standard approach for resection of pituitary adenomas and other midline anterior skull base lesions. Normal sinonasal structures are resected during ETSS, which raises concerns for nasal morbidity and patient-based outcome. Objective To perform a surgical outcome assessment by examining whether the extent of ETSS approaches affected patient-specific sinonasal quality of life as measured by the 22-item Sino-Nasal Outcome Test (SNOT-22). Methods A single-center prospective cohort study of patients operated on by the same skull base team between 2012 and 2016. Patients with completed pre- and postoperative SNOT-22 were included. The primary outcome was SNOT-22 scores at preoperative, 0–1 month, 2–4 months, >5 months follow-up. Age, sex, tumor pathology, surgical procedure, and intraoperative cerebral spinal fluid leak repair were also obtained. Results Of the 249 ETSS performed, 148 patients (59%) had at least one completed SNOT-22; 45 (18%) met the inclusion criteria. Sinonasal quality of life based on SNOT-22 at the 0–1-month follow-up was significantly worse than the presurgical levels (p < 0.05). However, there was a return of SNOT-22 scores to preoperative levels at 2–4 months (p > 0.05), which was sustained at >5 months (p > 0.05). Factors such as the extent of ETSS, a previous nasal surgery, repair of an intraoperative cerebral spinal fluid leak, and the tumor pathology did not affect SNOT-22 scores at any follow-up intervals (p > 0.05). Conclusion Sinonasal quality of life worsened after ETSS at 0–1 month follow-up but returned to preoperative levels at 2–4 months and remained at postoperative levels >5 months. Analysis of these data will allow us to educate our patients that the anticipated nasal morbidity after ETSS is usually only transient and should be expected to recover to preoperative levels.

To determine the frequency and risk factors for non-home discharge (NHD) and its association with clinical outcomes and quality of life (QOL) at 1 year following cardiac surgery in patients with ischemic mitral regurgitation (IMR).Discharge disposition was evaluated in 552 patients enrolled in trials of severe or moderate IMR. Patient and in-hospital factors associated with NHD were identified using logistic regression. Subsequently, association of NHD with 1-year mortality, serious adverse events (SAEs), and QOL was assessed.NHD was observed in 30% (154/522) with 25% (n = 71/289) in moderate and 36% (n = 83/233) in patients with severe IMR (unadjusted P = .006), a difference not significant after including age (5-year change: adjusted odds ratio [adjOR], 1.52; 95% confidence interval [CI], 1.35-1.72; P .001), diabetes (adjOR, 1.94; 95% CI, 1.27-2.94; P = .002), and previous heart failure (adjOR, 1.64; 95% CI, 1.06-2.52; P = .03). Odds of NHD were increased for patients with postoperative SAEs (adjOR, 1.85; 95% CI, 1.19-2.86; P = .01) but not based on type of cardiac surgery. Greater rates of death and SAEs were observed in NHD patients at 1 year: adjusted hazard ratio, 4.29 (95% CI, 2.14-8.59; P .001) and adjusted rate ratio, 1.45 (95% CI, 1.03-2.02; P = .03), respectively. QOL did not differ significantly between groups.NHD is common following surgery for IMR, influenced by older age, diabetes, previous heart failure, and postoperative SAEs. These patients may be at greater risk of death and subsequent SAEs after discharge. Discussion of NHD with patients may have important implications for decision-making and guiding expectations following cardiac surgery.

This study describes the association between history of traumatic brain injury (TBI) and childhood symptoms of conduct disorder (CD). Data were based on telephone interviews with 6048 respondents derived from the 2011-2013 cycles of a representative cross-sectional survey of adults aged 18+ years in Ontario, Canada. TBI was defined as loss of consciousness for at least 5min or overnight hospitalization due to injury symptoms. Symptoms of CD before 15 years of age were assessed using five items based on the DSM-IV. Adults who reported a history of TBI reported odds 3 times higher for possible CD before 15 years of age. Odds remained significant even when age, sex, marital status, income, and education were statistically controlled. The nature of this data precludes determining if TBI occurred before or following CD symptoms. Nonetheless, the co-occurrence of a history of TBI with symptoms of CD supports the recommendation that practitioners be vigilant in assessing the history of both CD and TBI when diagnosing and treating one of these conditions. These findings do not exclude the possibility that TBI during childhood or youth may be interfering with brain development and could co-occur with conduct behaviors in both the short and long term.

Italy has one of the highest paediatric cancer incidence rates in Europe. We compared cancer incidence and survival rates in children (0&ndash, 14 years) and adolescents (15&ndash, 19 years) residing in Palermo Province (PP) with statistics derived from Italian and European surveillance systems. We included all incident cancer cases, malignant tumours and non-malignant neoplasm of central nervous system (benign and uncertain whether malignant or benign), detected in children and adolescents by the Palermo Province Cancer Registry (PPCR) between 2003 and 2012. A jointpoint regression model was applied. Annual Average Percentage Changes were calculated. The Besag&ndash, York-Mollie model was used to detect any cluster. The 5-year survival analysis was computed using Kaplan-Meier and actuarial methods. We identified 555 paediatric cancer incident cases (90% &ldquo, malignant tumours&rdquo, ). No difference in incidence rates was highlighted between PPCR and Italy 26 registries and between PPCR and Southern Europe. No jointpoint or significant trend was identified and no cluster was detected. The 5-year overall survival didn&rsquo, t differ between PP and the Italian AIRTUM pool. A borderline higher statistically significant survival was observed in age-group 1&ndash, 4 when comparing PPCR to EUROCARE-5. The epidemiological surveillance documented in the PP was a paediatric cancer burden in line with Italy and southern Europe. The study supports the supplementary role of general population-based cancer registries to provide paediatric cancer surveillance of local communities.

Background Left atrial (LA) size is a marker of prognosis in severe aortic stenosis (AS). The aims of this retrospective study were to assess the impact of transcatheter aortic valve implantation (TAVI) on the recovery of LA phasic function and to assess the relationship between LA function and new-onset atrial fibrillation (NAF) after TAVI. Methods In this retrospective cohort study, LA function was measured using biplane volumes and 2-dimensional (2D) speckle tracking echocardiography (STE) in 52 patients (median age, 81 years) with severe AS before TAVI and at midterm follow-up. Twenty healthy individuals ≥ 75 years were used as controls. Results Before TAVI, the 3 phasic volumetric emptying fractions and all STE-derived parameters of LA function were significantly reduced. At 5 ± 3 months after TAVI, there was an improvement in LA reservoir and contractile function. However, LA phasic volumes and emptying fractions showed minimal changes. Fourteen patients had NAF in the early postprocedural period after TAVI. These patients experienced longer hospitalization (11 days vs 6 days; P = 0.002). By bivariable logistic regression analysis, the use of a transapical approach and the LA early diastolic strain rate (SR) before TAVI were significantly associated with NAF immediately after TAVI. Conclusions Severe AS is associated with LA dysfunction. Intrinsic LA compliance and LA contractile properties by STE improved at midterm follow-up after TAVI. Preprocedural LA early diastolic SR may predict the development of NAF after TAVI pending confirmation by larger prospective evaluations.

We report two different cases of IgG4-related hypophysitis. In the first case, a pituitary lesion was accompanied by lymphocytic meningitis possibly mimicking tuberculous meningitis. The second case was unassociated with involvement of other organs. No histologic differences were noted between the two cases indicating that the morphologic features of the hypophysial lesion do not depend on the presence of other lesions. The pathogenesis of IgG4 hypophysitis is not known, and further study is necessary to explore the cause, progression, and influencing factors of this disease.

Background Intracranial dural arteriovenous fistulae (DAVF) may present a treatment challenge. Endovascular embolization is in most cases the first line of treatment but does not always achieve cure. Gamma Knife (GK) radiosurgery represents an alternative treatment option, and the purpose of this study was to further evaluate its utility. Methods We reviewed all cases of DAVF treated between 2009 and 2016 at our institution with GK radiosurgery independently, or following failed/refused endovascular or surgical management. Patients’ clinical files, radiological images, catheter angiograms, and surgical DAVF disconnection reports were retrospectively reviewed. Results Sixteen DAVF (14 patients) treated by GK radiosurgery were identified. Eleven fistulae were aggressive and five were benign. Marginal doses ranged from 15 to 25 Gy. Target volumes ranged from 0.04 to 4.47 cm3. In all symptomatic patients, GK treatment resulted in symptom palliation. In 13/15 lesions, cure of symptoms (86.0%) was reported. One lesion was asymptomatic. Angiographic cure was achieved in eight cases (50%), small residual DAVF occurred in four, and four were unchanged. One patient developed headache that resolved at one year. No hemorrhage occurred during the follow-up period. There was no significant association between Borden type and cure rate. Prior failed endovascular treatment and small target volume were associated with lower rates of cure. Conclusions Stereotactic radiosurgery is viable treatment for DAVF. It is very effective in palliating symptoms as a de novo approach or adjunctive to endovascular therapy. In our experience it is only somewhat effective in achieving complete angiographic cure.

Background Sepsis remains a complex medical problem and a major challenge in healthcare. Diagnostics and outcome predictions are focused on physiological parameters with less consideration given to patients’ medical background. Given the aging population, not only are diseases becoming increasingly prevalent but occur more frequently in combinations (“multimorbidity”). We hypothesized the existence of patient subgroups in critical care with distinct multimorbidity states. We further hypothesize that certain multimorbidity states associate with higher rates of organ failure, sepsis, and mortality co-occurring with these clinical problems. Methods We analyzed 36,390 patients from the open source Medical Information Mart for Intensive Care III (MIMIC III) dataset. Morbidities were defined based on Elixhauser categories, a well-established scheme distinguishing 30 classes of chronic diseases. We used latent class analysis to identify distinct patient subgroups based on demographics, admission type, and morbidity compositions and compared the prevalence of organ dysfunction, sepsis, and inpatient mortality for each subgroup. Results We identified six clinically distinct multimorbidity subgroups labeled based on their dominant Elixhauser disease classes. The “cardiopulmonary” and “cardiac” subgroups consisted of older patients with a high prevalence of cardiopulmonary conditions and constituted 6.1% and 26.4% of study cohort respectively. The “young” subgroup included 23.5% of the cohort composed of young and healthy patients. The “hepatic/addiction” subgroup, constituting 9.8% of the cohort, consisted of middle-aged patients (mean age of 52.25, 95% CI 51.85–52.65) with the high rates of depression (20.1%), alcohol abuse (47.75%), drug abuse (18.2%), and liver failure (67%). The “complicated diabetics” and “uncomplicated diabetics” subgroups constituted 9.4% and 24.8% of the study cohort respectively. The complicated diabetics subgroup demonstrated higher rates of end-organ complications (88.3% prevalence of renal failure). Rates of organ dysfunction and sepsis ranged 19.6–69% and 12.5–46.7% respectively in the six subgroups. Mortality co-occurring with organ dysfunction and sepsis ranges was 8.4–23.8% and 11.7–27.4% respectively. These adverse outcomes were most prevalent in the hepatic/addiction subgroup. Conclusion We identify distinct multimorbidity states that associate with relatively higher prevalence of organ dysfunction, sepsis, and co-occurring mortality. The findings promote the incorporation of multimorbidity in healthcare models and the shift away from the current single-disease paradigm in clinical practice, training, and trial design. Electronic supplementary material The online version of this article (10.1186/s13054-019-2486-6) contains supplementary material, which is available to authorized users.

Objective The Cardiothoracic Surgical Trials Network reported that left ventricular reverse remodeling at 2 years did not differ between patients with moderate ischemic mitral regurgitation randomized to coronary artery bypass grafting plus mitral valve repair (n = 150) or coronary artery bypass grafting alone (n = 151). To address health resource use implications, we compared costs and quality-adjusted survival. Methods We used individual patient data from the Cardiothoracic Surgical Trials Network trial on survival, hospitalizations, quality of life, and US hospitalization costs to estimate cumulative costs and quality-adjusted life years. A microsimulation model was developed to extrapolate to 10 years. Bootstrap and deterministic sensitivity analyses were performed to address uncertainty. Results In-hospital costs were $59,745 for coronary artery bypass grafting plus mitral valve repair versus $51,326 for coronary artery bypass grafting alone (difference $8419; 95% uncertainty interval, 2259-18,757). Two-year costs were $81,263 versus $67,341 (difference 13,922 [2370 to 28,888]), and quality-adjusted life years were 1.35 versus 1.30 (difference 0.05; −0.04 to 0.14), resulting in an incremental cost-effectiveness ratio of $308,343/quality-adjusted life year for coronary artery bypass grafting plus mitral valve repair. At 10 years, its costs remained higher ($107,733 vs $88,583, difference 19,150 [−3866 to 56,826]) and quality-adjusted life years showed no difference (−0.92 to 0.87), with 5.08 versus 5.08. The likelihood that coronary artery bypass grafting plus mitral valve repair would be considered cost-effective at 10 years based on a cost-effectiveness threshold of $100K/quality-adjusted life year did not exceed 37%. Only when this procedure reduces the death rate by a relative 5% will the incremental cost-effectiveness ratio fall below $100K/quality-adjusted life year. Conclusions: The addition of mitral valve repair to coronary artery bypass grafting for patients with moderate ischemic mitral regurgitation is unlikely to be cost-effective. Only if late mortality benefits can be demonstrated will it meet commonly used cost-effectiveness criteria.

Digital, Background: Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people with type 2 diabetes at risk for cardiovascular disease. We assessed the long-term effect of the GLP-1 receptor agonist dulaglutide on renal outcomes in an exploratory analysis of the REWIND trial of the effect of dulaglutide on cardiovascular disease. Methods: REWIND was a multicentre, randomised, double-blind, placebo-controlled trial at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo and followed up at least every 6 months for outcomes. Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) were estimated from urine and serum values measured in local laboratories every 12 months. The primary outcome (first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes), secondary outcomes (including a composite microvascular outcome), and safety outcomes of this trial have been reported elsewhere. In this exploratory analysis, we investigate the renal component of the composite microvascular outcome, defined as the first occurrence of new macroalbuminuria (UACR >33·9 mg/mmol), a sustained decline in eGFR of 30% or more from baseline, or chronic renal replacement therapy. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01394952. Findings: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). At baseline, 791 (7·9%) had macroalbuminuria and mean eGFR was 76·9 mL/min per 1·73 m2 (SD 22·7). During a median follow-up of 5·4 years (IQR 5·1-5·9) comprising 51 820 person-years, the renal outcome developed in 848 (17·1%) participants at an incidence rate of 3·5 per 100 person-years in the dulaglutide group and in 970 (19·6%) participants at an incidence rate of 4·1 per 100 person-years in the placebo group (hazard ratio [HR] 0·85, 95% CI 0·77-0·93; p=0·0004). The clearest effect was for new macroalbuminuria (HR 0·77, 95% CI 0·68-0·87; p, Ciencias Médicas y de la Salud