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Background Eosinophils have been implicated in the pathogenesis of ulcerative colitis and have been associated with disease course and therapeutic response. However, associations between eosinophil density, histologic activity, and clinical features have not been rigorously studied. Methods A deep learning algorithm was trained to identify eosinophils in colonic biopsies and validated against pathologists’ interpretations. The algorithm was applied to sigmoid colon biopsies from a cross-sectional cohort of 88 ulcerative colitis patients with histologically active disease as measured by the Geboes score and Robarts histopathology index (RHI). Associations between eosinophil density, histologic activity, and clinical features were determined. Results The eosinophil deep learning algorithm demonstrated almost perfect agreement with manual eosinophil counts determined by 4 pathologists (interclass correlation coefficients: 0.805–0.917). Eosinophil density varied widely across patients (median 113.5 cells per mm2, interquartile range 108.9). There was no association between eosinophil density and RHI (P = 0.5). Significant differences in eosinophil density were seen between patients with Montreal E3 vs E2 disease (146.2 cells per mm2 vs 88.2 cells per mm2, P = 0.005). Patients on corticosteroids had significantly lower eosinophil density (62.9 cells per mm2 vs 124.1 cells per mm2, P = 0.006). No association between eosinophil density and biologic use was observed (P = 0.5). Conclusions We developed a deep learning algorithm to quantify eosinophils in colonic biopsies. Eosinophil density did not correlate with histologic activity but did correlate with disease extent and corticosteroid use. Future studies applying this algorithm in larger cohorts with longitudinal follow-up are needed to further elucidate the role of eosinophils in ulcerative colitis.

Background: Sarcopenia, the age-related loss of skeletal muscle mass/function, has been identified as a marker of frailty. We examined the association between sarcopenia and adverse events following transcatheter aortic valve implantation (TAVI). Methods: A retrospective cohort study was conducted at Toronto General Hospital. All patients who underwent TAVI in the time period 2007-2017 with preoperative computed tomography were included. Skeletal muscle index (SMI) was calculated radiographically using psoas muscle area at the L3 vertebral level, divided by height. Various measures of sarcopenia, including mean SMI, SMI below the sex-specific median, and SMI in the lowest sex-specific quartile were calculated. The primary outcome was postoperative adverse events, defined as a composite of in-hospital mortality and morbidity including cardiovascular, pulmonary, neurologic, access-related, and gastrointestinal complications. Univariate and multivariate logistic regression were performed to determine the association between sarcopenia and adverse events. Results: A total of 468 patients (mean age: 80.7 years) were included. Baseline comorbidity burden was high, particularly congestive heart failure (93.4%). Postoperative adverse events occurred in 62 patients (13.2%). Univariate logistic regression demonstrated that postoperative adverse events were correlated with mean SMI (odds ratio [OR] 0.81, 95% confidence interal [CI] 0.66-0.97), events were less than the SMI (OR 2.16, 95% CI 1.24-3.84), and SMI in the sex-specific lowest quartile (OR 2.34, 95% CI 1.33-4.07). On multivariate analysis, SMI in the sex-specific lowest quartile was an independent predictor of adverse events (OR 2.53, 95% CI 1.41-4.50). Conclusions: Sarcopenia defined by radiologic psoas muscle measurements was independently associated with in-hospital mortality and morbidity following TAVI. Résumé: Contexte: La sarcopénie, soit la perte de masse et de fonction des muscles squelettiques liée à l’âge, a été identifiée comme un marqueur de fragilité. Nous avons examiné l’association entre la sarcopénie et les événements indésirables suivant l’implantation valvulaire aortique par cathéter (IVAC). Méthodologie: Une étude de cohorte rétrospective a été menée au Toronto General Hospital. Tous les patients ayant subi une IVAC avec tomodensitométrie préopératoire au cours de la période 2007-2017 ont été inclus. L’indice de masse musculaire squelettique (IMMS) a été calculé par radiographie en utilisant la surface du psoas au niveau de la vertèbre L3, divisée par la taille. Diverses mesures de la sarcopénie, y compris l’IMMS moyen, l’IMMS sous la médiane selon le sexe et l’IMMS dans le quartile inférieur selon le sexe, ont été calculées. Le critère d’évaluation principal était les événements indésirables postopératoires, définis comme un critère composite comprenant la mortalité et la morbidité à l’hôpital, notamment les complications cardiovasculaires, pulmonaires, neurologiques, gastro-intestinales et liées à l’accès vasculaire. Des régressions logistiques univariée et multivariée ont été effectuées pour déterminer l’association entre la sarcopénie et les événements indésirables. Résultats: Un total de 468 patients (âge moyen : 80,7 ans) ont été inclus. Le fardeau de comorbidité au départ était élevé, en particulier pour ce qui est de l’insuffisance cardiaque congestive (93,4 %). Des événements indésirables postopératoires sont survenus chez 62 patients (13,2 %). La régression logistique univariée a montré que les événements indésirables postopératoires étaient en corrélation avec un IMMS moyen (rapport des cotes [RC] : 0,81, intervalle de confiance [IC] à 95 % : 0,66 à 0,97), un IMMS sous la médiane selon le sexe (RC : 2,16; IC à 95 % : 1,24 à 3,84) et un IMMS dans le quartile inférieur selon le sexe (RC : 2,34; IC à 95 % : 1,33 à 4,07). Lors de l’analyse multivariée, un IMMS situé dans le quartile inférieur selon le sexe était un prédicteur indépendant d’événements indésirables (RC : 2,53; IC à 95 % : 1,41 à 4,50). Conclusions: La sarcopénie définie par les mesures radiologiques du psoas était indépendamment associée à la mortalité et à la morbidité à l’hôpital à la suite d’une IVAC.

OBJECTIVE Meningiomas can have significant impact on health-related quality of life (HRQOL). Patient-centered, disease-specific instruments for assessing HRQOL in these patients are lacking. To this end, the authors sought to develop and validate a meningioma-specific HRQOL questionnaire through a standardized, patient-centered questionnaire development methodology. METHODS The development of the questionnaire involved three main phases: item generation, item reduction, and validation. Item generation consisted of semistructured interviews with patients (n = 30), informal caregivers (n = 12), and healthcare providers (n = 8) to create a preliminary list of items. Item reduction with 60 patients was guided by the clinical impact method, multiple correspondence analysis, and hierarchical cluster analysis. The validation phase involved 162 patients and collected evidence on extreme-groups validity; concurrent validity with the SF-36, FACT-Br, and EQ-5D; and test-retest reliability. The questionnaire takes on average 11 minutes to complete. RESULTS The meningioma-specific quality-of-life questionnaire (MQOL) consists of 70 items representing 9 domains. Cronbach’s alpha for each domain ranged from 0.61 to 0.91. Concurrent validity testing demonstrated construct validity, while extreme-groups testing (p = 1.45E-11) confirmed the MQOL’s ability to distinguish between different groups of patients. CONCLUSIONS The MQOL is a validated, reliable, and feasible questionnaire designed specifically for evaluating QOL in meningioma patients. This disease-specific questionnaire will be fundamentally helpful in better understanding and capturing HRQOL in the meningioma patient population and can be used in both clinical and research settings.

Hepatocellular carcinoma (HCC) is a very peculiar cancer because it presents several molecular alterations linked to the activation of survival and antiapoptotic signal pathways that are protein in form and not easily targetable by even the newest targeted therapies. In addition, it is almost always a consequence of liver cirrhosis, a serious disease condition in which several drugs are often not tolerated. This is why the study of HCC was such a challenge for Professor Natale D'Alessandro, to whom this work is dedicated, during the latter years of his career. The aim of this review is to summarize studies on different molecules involved in the development, progression, and chemoresistance of HCC, topics on which we have focused our research over the last decade. In particular, we have analyzed the role of inflammatory mediators, such as the cyclooxygenase (COX) enzymes, nuclear factor ?B (NF-?B), interleukin 6 (IL-6), as well as other important factors, such as Yin Yang 1 (YY1), in HCC. Moreover, we have reviewed some more recent literature on research aimed at identifying druggable targets in HCC as well as candidate agents for its prevention and treatment.

The superior vena cava is a short ∼7-cm valveless vessel that brings blood from the upper half of the body to the heart but has connections to the infracardiac venous structures as well. It can become obstructed, mostly by advanced lung cancer but benign conditions account for one-fourth of cases. When possible, reconstruction can be by biological material or via ring reinforced grafts. When perfomed, replacement should be with small caliber grafts to allow for rapid flow of blood, which, with the addition of anticoagulants, reduces the risk of thrombosis. Even with advanced malignancy, treatment may confer reasonable survival.

OBJECTIVE Competency-based medical education (CBME), an outcomes-based approach to medical education, continues to be implemented across many postgraduate medical education programs worldwide, including a recent introduction into Canadian neurosurgical training programs (July 2019). The success of this educational paradigm shift requires frequent faculty observation and evaluation of residents performing defined tasks of the specialty. A main challenge involves providing residents with frequent performance evaluations and feedback that are feasible for faculty to complete. This study aims to define what is currently happening and what changes are needed to make CBME successful for the certification of neurosurgeons' competence. METHODS A 55-item questionnaire was emailed nationwide to survey Canadian neurosurgical faculty. RESULTS Fifty-two complete responses were received and achieved a distribution highly correlated with the number of faculty neurosurgeons practicing in each Canadian province (Pearson's r = 0.94). Two-thirds (35/52) of faculty reported currently taking a median of 10 minutes to complete evaluation forms at the end of a resident's rotation block. Regardless of the faculty's province of practice (p = 0.50) or years of experience (p = 0.06), they reported 3 minutes (minimum 1 minute, maximum 10 minutes, interquartile range [IQR] 3 minutes) as a feasible amount of time to spend completing an evaluation form following an observation of a resident's performance of an entrustable professional activity (EPA). If evaluation forms took 3 minutes to complete, 85% of respondents (44/52) would complete EPA evaluations weekly or daily. The faculty recommended 5 minutes as a feasible amount of time to provide oral feedback (minimum 1 minute, maximum 20 minutes, IQR 3.25 minutes), which was significantly higher (p = 0.00099) than their recommended amount of time for completing evaluation forms. The majority of faculty (71%) stated they would prefer to access resident evaluation forms through a mobile application compared to a paper form (12%), an evaluation website (8%), or through a URL link sent via email (10%; p = 0.0032). CONCLUSIONS To facilitate the successful implementation of CBME into a neurosurgical training curriculum, resident EPA assessment forms should take 3 minutes or less to complete and be accessible through a mobile application.

Hepatocellular carcinoma (HCC), is the sixth most frequent form of cancer and leads to the fourth highest number of deaths each year. HCC results from a combination of environmental factors and aging as there are driver mutations at oncogenes which occur during aging. Most of HCCs are diagnosed at advanced stage preventing curative therapies. Treatment in advanced stage is a challenging and pressing problem, and novel and well-tolerated therapies are urgently needed. We will discuss further advances beyond sorafenib that target additional signaling pathways and immune checkpoint proteins. The scenario of possible systemic therapies for patients with advanced HCC has changed dramatically in recent years. Personalized genomics and various other omics approaches may identify actionable biochemical targets, which are activated in individual patients, which may enhance therapeutic outcomes. Further studies are needed to identify predictive biomarkers and aberrantly activated signaling pathways capable of guiding the clinician in choosing the most appropriate therapy for the individual patient.

Effective detection of microbiological contaminations present in medicinal cellular products is a crucial step to ensure patients’ safety. In recent decades, several rapid microbiological methods have been developed and validated, but variabilities linked to the use of different resources have led to discordant validation of methods and performance results. Considering this, while developing an in-house BacT/Alert-based method, we evaluated all of the materials used in its validation. Of particular importance, we noticed that the syringe gauge used to inject the samples into the bottles was crucial to obtain robust results. We chose to conduct a comparative test between the BacT/Alert system and the compendial method described in the European Pharmacopoeia, using five dilutions of nine reference microorganism strains and 21G or 27G needles. Our results confirmed that the BacT/Alert system is a valid and faster alternative method to assess sterility of clinical cell therapy products, and that the use of 27G needles increases its sensitivity to detect reference anaerobe microorganisms., Graphical Abstract, The BacT/Alert system is used in GMP control activities to test the sterility of ATMPs. The use of 27G needles decreases the TTD of most of the tested microorganisms, when compared to the European Pharmacopeia method, and allows less air intrusion and improves the growth and sensitivity of the method for anaerobic microorganisms.

Although homeless persons experience traumatic brain injury (TBI) frequently, little is known about the structural and functional brain changes in this group. We aimed to describe brain volume changes and related cognitive/motor deficits in homeless persons with or without TBI versus controls. Participants underwent T1-weighted magnetic resonance imaging (MRI), neuropsychological (NP) tests (the Grooved Pegboard Test [GPT]/Finger Tapping Test [FTT]), alcohol/drug use screens (the Alcohol Use Disorders Identification Test [AUDIT]/Drug Abuse Screening Test [DAST]), and questionnaires (the Brain Injury Screening Questionnaire [BISQ]/General Information Questionnaire [GIQ]) to determine TBI. Normalized volumes of brain substructures from MRI were derived from FreeSurfer. Comparisons were tested by Mann-Whitney U and Kruskal-Wallis rank sum tests. Leave-one-out cross-validation using random forest classifier was applied to determine the ability of predicting TBI. Diagnostic ability of this classifier was assessed using area under the receiver operating characteristic curve (AUC). Fifty-one participants—25 homeless persons (9 with TBI) and 26 controls—were included. The homeless group had higher AUDIT scores and smaller thalamus and brainstem volumes (p < 0.001) than controls. Within homeless participants, the TBI group had reduced normalized volumes of nucleus accumbens, thalamus, ventral diencephalon, and brainstem compared with the non-TBI group (p < 0.001). Homeless participants took more time on the GPT compared with controls using both hands (p < 0.0001); but the observed effects were more pronounced in the homeless group with TBI in the non-dominant hand. Homeless persons with TBI had fewer dominant hand finger taps than controls (p = 0.0096), and homeless participants with (p = 0.0148) or without TBI (p = 0.0093) tapped less than controls with their non-dominant hand. In all participants, TBI was predicted with an AUC of 0.95 (95% confidence interval [CI]: 0.89-1.00) by the classifier modeled on MRI, NP tests, and screening data combined. The MRI-data-based classifier was the best predictor of TBI within the homeless group (AUC: 0.76, 95% CI: 0.53-0.99). Normalized volumes of specific brain substructures were important indicators of TBI in homeless participants and they are important indicators of TBI in the state of homelessness itself. They may improve predictive ability of NP and screening tests in determining these outcomes.

Competency-based medical education requires evaluations of residents' performances of tasks of the discipline (ie. entrustable professional activities (EPAs)). Using neurosurgical Faculty perspectives, this study investigated whether a sample of neurosurgical EPAs accurately reflected the expectations of general neurosurgical practice.A questionnaire was sent to all Canadian neurosurgery Faculty using a SurveyMonkey® platform.The proportion of respondents who believed the EPAs were representative of general neurosurgery competences varied significantly across all EPAs [47%-100%] (p 0.0001). For 9/15 proposed EPAs, ≥75% agreed they were appropriate for general neurosurgery training and expected residents to attain the highest standard of performance. However, a range of 27-53% of the respondents felt the other six EPAs would be more appropriate for fellowship training and thus, require a lower standard of performance from graduating residents.The shift towards subspecialization in neurosurgery has implications for curriculum design, delivery and certification of graduating residents.

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).

Foster children are exposed to high levels of abuse, violence, and other adverse events throughout their childhood and adolescent years. Forms of brain injury, notably traumatic brain injury (TBI), are understudied in the foster child population. This study aimed to explore different forms of brain injury and their cognitive, behavioral, and psychological/emotional effects on current and former foster children using a life course perspective. A thematic analysis with a life course perspective was used to examine semi-structured, open-ended interviews conducted with current and previous foster children between the ages of 16 and 29 years. The study included 47 participants: 25 males (53%) and 22 females (47%) with an average age of 21 years and an average of 11.2 years of education. Of 47 current and previous foster children between the ages of 16 and 29, two-thirds had sustained one or more TBIs. Through a thematic analysis, four overarching and inter-related themes emerged from the data: frequent TBI, normalization (of abuse, violence, injury, and neglect), emotional trauma, and dangerous coping methods such as alcohol use in 94% and recreational drug use in 81%. Normalization of adverse events, emotional trauma, and the use of dangerous coping methods occurred in 66%, 81%, and 49% of participants, respectively, and are the cumulative toxic long-term effects of early negative life experiences and repeated forms of brain injury. Early and continued exposure to TBI, abuse, violence, and/or neglect with continued maladaptive behaviors suggests that the participants may have experienced changes in brain structure and function over their lives that provided the milieu for continued vulnerability to personal and future injury to future generations. These behavioral and perceptual changes point to a toxic combination of injuries that result in continued vulnerability to repeated injury through contextual exposure to risks and maladaptive normalization, emotional trauma, and risky coping styles.

Chronic subdural hematomas (CSDHs) are a common neurological condition, whose incidence is expected to increase with an aging population. Although surgical evacuation is the mainstay of treatment, it results in a recurrence requiring reoperation (RrR) in 3–30% of cases. Recurrence is thought to be driven by a combination of inflammatory and angiogenic processes occurring within the CSDH outer membrane. Pathological specimens of 72 primary CSDHs were examined for eosinophilic infiltrate. For each case, the pre-operative computed tomography (CT) scan was graded according to the Nakaguchi grading scheme as homogeneous, laminar, separated, or trabecular. Rate of RrR was compared based on eosinophilic infiltrate and CT grade. A dense eosinophilic infiltrate was observed in 22% of specimens. The rate of RrR among specimens with a dense eosinophilic infiltrate was 0%, whereas it was 14.3% among specimens without a dense eosinophilic infiltrate. Incidence among homogeneous, laminar, separated, and trabecular CT subtypes was 4%, 27%, 58%, and 24%, respectively. A dense eosinophilic infiltrate found within the outer membrane of a CSDH may be a marker of hematoma maturation, signaling a transition toward healing and fibrosis, and a lower risk of RrR.

Nearly 50,000 Canadian children live in foster care. Compared with their peers, foster children experience greater independence and decreased guidance, predisposing them to harmful exposures such as traumatic brain injury (TBI), illicit drugs, and alcohol. Foster children also report a higher level of childhood abuse compared with the general population. This study aimed to: 1) investigate substance/alcohol use disorder, adverse childhood events (ACE), TBI, aggression levels, and the difference between normalized percentages of brain regions of interest (ROIs) in a sample of Canadian youths with and without foster care history; 2) determine the prevalence of substance/alcohol use disorder, ACE, and aggression levels within individuals with foster care history when stratified by likelihood of TBI; and 3) determine the significant correlates of elevated aggression levels within this population. Participants completed standardized questionnaires that measured the prevalence of TBI, substance and alcohol use disorder, ACE, and aggression. Magnetic resonance imaging (MRI) was used to measure differences in brain ROI. Regression and network analysis were used to study interactions between variables. Seventy-four participants (51 individuals with foster care history and 23 age-matched controls from the general population) completed standardized questionnaires. Fifty-five of these individuals (39 foster participants and 16 controls) underwent brain MRI. Foster participants had higher prevalence of substance use disorder (p

The multikinase inhibitor sorafenib was the first drug approved by the FDA for treating patients with advanced hepatocellular carcinoma (HCC). However, sorafenib resistance remains a major challenge for improving the effectiveness of HCC treatment. Previously, we identified several genes modulated after sorafenib treatment of human HCC cells, including the stress-inducible nuclear protein 1 (NUPR1) gene. Multiple studies have shown that NUPR1 regulates autophagy, apoptosis, and chemoresistance. Here, we demonstrate that treatment of HCC cells with sorafenib resulted in the activation of autophagic flux. NUPR1 knock-down (KD) in HCC cells was associated with increased p62 expression, suggesting an impairment of autophagic flux, and with a significant increase of cell sensitivity to sorafenib. In NUPR1 KD cells, reduced levels of NUPR1 were associated with the increased expression of p73 as well as its downstream transcription targets PUMA, NOXA, and p21. Simultaneous silencing of p73 and NUPR1 in HCC cells resulted in increased resistance to sorafenib, as compared to the single KD of either gene. Conversely, pharmacological activation of p73, via the novel p73 small molecule activator NSC59984, determined synergistic anti-tumor effects in sorafenib-treated HCC cells. The combination of NSC59984 and sorafenib, when compared to either treatment alone, synergistically suppressed tumor growth of HCC cells in vivo. Our data suggest that the activation of the p73 pathway achieved by NUPR1 KD potentiates sorafenib-induced anti-tumor effects in HCC cells. Moreover, combined pharmacological therapy with the p73 activator NSC59984 and sorafenib could represent a novel approach for HCC treatment.

Meningiomas are the most common primary intracranial neoplasm. The current World Health Organization (WHO) classification categorizes meningiomas based on histopathological features, but emerging molecular data demonstrate the importance of genomic and epigenomic factors in the clinical behavior of these tumors. Treatment options for symptomatic meningiomas are limited to surgical resection where possible and adjuvant radiation therapy for tumors with concerning histopathological features or recurrent disease. At present, alternative adjuvant treatment options are not available in part due to limited historical biological analysis and clinical trial investigation on meningiomas. With advances in molecular and genomic techniques in the last decade, we have witnessed a surge of interest in understanding the genomic and epigenomic landscape of meningiomas. The field is now at the stage to adopt this molecular knowledge to refine meningioma classification and introduce molecular algorithms that can guide prediction and therapeutics for this tumor type. Animal models that recapitulate meningiomas faithfully are in critical need to test new therapeutics to facilitate rapid-cycle translation to clinical trials. Here we review the most up-to-date knowledge of molecular alterations that provide insight into meningioma behavior and are ready for application to clinical trial investigation, and highlight the landscape of available preclinical models in meningiomas.

Background Few studies have evaluated the health-related quality of life (HRQoL) of patients with meningiomas. Here, we report the largest prospective, longitudinal cross-sectional cohort study of HRQoL in meningiomas to date, in order to identify possible actionable determinants of global HRQoL. Methods Adults who had undergone resection of a grade I intracranial meningioma and were in routine follow-up at a single large tertiary center underwent HRQoL assessment using the QLQ-C30 questionnaire administered opportunistically at follow-up visits. Averaged transformed QLQ-C30 scores at 12-month intervals were compared with scores from a normative reference population, with reference to known minimal clinically meaningful difference (CMD) in scores. To evaluate for possible determinants of changes in global HRQoL, global HRQoL scores were correlated (Spearman's Rho) with subdomain and symptom scores and with interval time from surgical resection. Results A total of 291 postoperative patients with histologically confirmed and surgically treated grade I meningiomas consented to participation and a total of 455 questionnaires were included for analysis. Patients with meningiomas reported reduced global HRQoL at nearly every 12-month interval with clinically and statistically significant impairments at 12, 48, 108, and 120 months postoperative compared with the normative population (P < 0.05). Meningioma patients at the 12-month interval also reported a reduction of each subdomain of HRQoL assessment (P < 0.05); however, a CMD was only seen in cognitive functioning. Physical, emotional, cognitive, and social subdomains, as well as fatigue and sleep/insomnia, were significantly associated with global HRQoL at the first 12-month interval. Overall, there was no significant correlation between time from surgery and global HRQoL or the subdomain functional or symptom sections of the QLQ-C30. Conclusions Meningioma patients report considerable limitations in HRQoL for more than 120 months after surgery, particularly in cognitive, emotional, and social function, as well as suffering significant fatigue and sleep impairment compared with a normative reference population. The majority of these reported functional impairments and symptoms are strongly associated with global HRQoL and thus can be considered determinants of global HRQoL that if treated, have the potential to improve HRQoL for our meningioma patients. This hypothesis requires future study of targeted interventions to determine their efficacy.

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.

Graphical abstract, Highlights • Cardiac masses are a rare but important finding requiring detailed investigation. • Echocardiography is a first-line imaging modality. • CT and MRI together allow precise structural and tissue characterization. • Surgical removal is a potentially curative treatment for cardiac hydatid cysts.

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.

Objective Women with advanced gynecologic cancer and malignant bowel obstruction (MBO) undergo repeated hospitalizations, experience feelings of isolation and abandonment, and often die in acute settings. Innovative outpatient models of care are needed to address the unmet needs of this population at the end-of-life. We implemented a novel supported self-management (SMS) program focused on increasing patients' skill and confidence in managing MBO proactively in the ambulatory setting. Methods We performed a qualitative descriptive study embedded in a prospective single-arm evaluative trial ( Clinicaltrials.gov ID: NCT03260647 ) to understand the impact of this program on patients' sense of support, degree of distress, quality of care, and capacity to self-manage. Semi-structured interviews were completed and analysed using the Chronic Care Model as a theoretical framework. Data saturation was confirmed after 15 interviews. Results Fifteen patients (age range: 47–82) with diagnoses of advanced ovarian, endometrial, and cervical cancer were interviewed; 10 had died by end of follow-up, with a median interval from interview to death of 5 months. Patients were able to self-manage the: (i) medical aspects; (ii) psychological consequences, and (iii) changes in life roles and expectations resulting from their condition. Patients felt greatly supported, less isolated, and secure in their knowledge and ability to access care due to SMS. While patients understood their disease was not curative they did not fully appreciate that MBO signalled a significantly poorer prognosis. Conclusion Outpatient SMS interventions can be successfully implemented even for rapidly fatal conditions at the end-of-life and offer significant benefit to gynecologic cancer patients with MBO. Counselling should focus on the specific trajectory of MBO, and early palliative care referrals should be standard practice.

Introduction Currently, biomechanics has not been able to effectively predict when a mild traumatic brain injury may occur as a result of head impact. To improve prediction of brain trauma and the development of protective innovations, it is important to create an understanding of the relationship between the biomechanics of the head impact event and the structural damage incurred by the brain as a result of that event. The purpose of this research was to examine the relationship between diffusion tensor imaging measures and biomechanical characteristics of a head impact. Methods Diffusion tensor imaging was conducted on concussed subjects to identify regions of white matter structural differences. The injury event was reconstructed using physical and finite element methods to identify the biomechanical parameters of the impact as well as strain to the regions of the brain. Results A significant relationship was found between shear strain, rotational acceleration, and impact velocity on increases in radial diffusivity and mean diffusivity in the fornix. Linear acceleration was also found to have a weaker but significant relationship with a decrease in radial diffusivity in the cingulum hippocampus. Conclusion These results demonstrate that impacts resulting in high shear strains may affect radial diffusivity and mean diffusivity measures, and that impact mechanics likely have an important role in what regions may present differences in diffusion tensor imaging measures.

To provide an overview of fundamental concepts in machine learning (ML), review the literature on ML applications in imaging analysis of pituitary tumors for the last 10 years, and highlight the future directions on potential applications of ML for pituitary tumor patients. We presented an overview of the fundamental concepts in ML, its various stages used in healthcare, and highlighted the key components typically present in an imaging-based tumor analysis pipeline. A search was conducted across four databases (PubMed, Ovid, Embase, and Google Scholar) to gather research articles from the past 10 years (2009-2019) involving imaging related to pituitary tumor and ML. We grouped the studies by imaging modalities and analyzed the ML tasks in terms of the data inputs, reference standards, methodologies, and limitations. Of the 16 studies included in our analysis, 10 appeared in 2018–2019. Most of the studies utilized retrospective data and followed a semi-automatic ML pipeline. The studies included use of magnetic resonance imaging (MRI), facial photographs, surgical microscopic video, spectrometry, and spectroscopy imaging. The objectives of the studies covered 14 distinct applications and majority of the studies addressed a binary classification problem. Only five of the 11 MRI-based studies had an external validation or a holdout set to test the performance of a final trained model. Through our concise evaluation and comparison of the studies using the concepts presented, we highlight future directions so that potential ML applications using different imaging modalities can be developed to benefit the clinical care of pituitary tumor patients.

BackgroundPotential concussive events (PCEs) are a major health concern in football. Though there are protocols set in place for assessments of PCEs, there has been no evidence of adherence in major football tournaments.MethodsOur research goal is to determine if PCEs in elite football are professionally assessed according to the International Conference on Concussion in Sport (ICCS) consensus statement recommendations. Identification and analysis of PCEs in the 2018 World Cup (WC) were accomplished through standardised observation of video footage by trained observers. Results were contrasted with data from the 2014 WC and 2016 Euro Cup. Our primary outcomes include frequency and professional assessment of PCEs, signs of concussions and time stopped for assessments.FindingsIn the 64 games of the 2018 WC, 87 PCEs (1.36 per game) were identified. Thirty-one (35.6%) PCEs were professionally assessed, resulting in the removal of three (3.5%) players from the match. Six (6.9%) PCEs showed one sign of concussion, 60 (69.0%) showed two signs, 20 (23.0%) showed three signs and 1 (1.2%) showed four or more signs. The mean time stopped for assessment was 63.3 s. No significant change in the percentage of professional assessments (mean=33.4%, 95% CI 20.7% to 46.1%) were identified across tournaments (p=0.42).InterpretationThese findings demonstrate a need for adherence to concussion protocols in order to improve the brain-health of athletes. Proper enforcement of the ICCS protocols during these tournaments and promoting player health and safety can influence the officiating, coaching and playing of football worldwide by promoting player safety.

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.

Background and AimsNon-alcoholic fatty liver disease and related hepatic syndromes affect up to one third of the adult population. The molecular mechanisms underlying NAFL etiology remain elusive. Nuclear Protein 1 (NUPR1) expression increases upon cell injury in all organs and recently we report its active participation in the activation of the Unfolded Protein Response (UPR). The UPR typically maintains protein homeostasis, but downstream mediators of the pathway regulate metabolic functions, including lipid metabolism. NUPR1 and UPR increase have been reported in obesity and liver pathologies and the goal of this study was to investigate the roles of NUPR1 in this context.MethodsWe used patient-derived liver biopsies and in vitro and in vivo NUPR1 loss of functions models. First, we analysed NUPR1 expression in a cohort of morbidly obese patients (MOPs), with either simple fatty liver (NAFL) or more severe steatohepatitis (NASH). Next, we explored the metabolic roles of NUPR1 in wild type (Nupr1+/+) or Nupr1 knockout mice (Nupr1-/-) fed ad libitum with a high fat diet (HFD) for up to 15 weeks.ResultsNUPR1 expression is inversely correlated to hepatic steatosis progression. We found that NUPR1 participates in the activation of PPAR-α signalling via UPR. PPAR-α signalling, is involved in the maintenance of fat metabolism and proper lipid homeostasis and energy balance. As PPAR-α signalling is controlled by UPR, collectively, these findings suggest a novel function for NUPR1 in protecting liver from metabolic distress by controlling lipid homeostasis, possibly through the UPR.ObjectiveNon-alcoholic fatty liver (NAFL) disease and related hepatic syndromes affect up to one third of the adult population in industrialised and developing countries. However, the molecular mechanisms underlying NAFL etiology remain elusive. Nuclear Protein 1 (NUPR1) expression increases upon cell injury in all organs including the liver. Recently, we report NUPR1 actively participates in activation of the Unfolded Protein Response (UPR). The UPR typically maintains protein homeostasis, but downstream mediators of the pathway regulate metabolic functions, including lipid metabolism. NUPR1 and UPR increase have been reported in obesity and liver pathologies and the goal of this study was to investigate the roles of NUPR1 in this context.DesignWe used patient-derived liver biopsies and in vitro and in vivo NUPR1 loss of functions models. First, we analysed NUPR1 expression in a cohort of morbidly obese patients (MOPs), with either simple fatty liver (NAFL) or more severe steatohepatitis (NASH). Next, we explored the metabolic roles of NUPR1 in wild type (Nupr1+/+) or Nupr1 knockout mice (Nupr1-/-) fed ad libitum with a high fat diet (HFD) for up to 15 weeks.ResultsNUPR1 expression is inversely correlated to hepatic steatosis progression. Mechanistically, we found NUPR1 participates in the activation of PPAR-α signalling via UPR. PPAR-α signalling, is involved in the maintenance of fat metabolism and proper lipid homeostasis and energy balance. As PPAR-α signalling is controlled by UPR, collectively, these findings suggest a novel function for NUPR1 in protecting liver from metabolic distress by controlling lipid homeostasis, possibly through the UPR.ConclusionsAs PPAR-α signalling is controlled by UPR, collectively, these findings suggest a novel function for NUPR1 in protecting liver from metabolic distress by controlling lipid homeostasis, possibly through the UPR.Lay summaryNUPR1 is activated during high caloric intake in both mice and patients. Decrease in expression or inhibition of NUPR1 worsens lipid deposition and hepatic damage.Graphical abstractHighlightsNUPR1 protects liver from high caloric intake hepatic damageThe function of NUPR1 in this context is to control the lipid homeostasis through the UPR and more specifically through PPAR-α signalling.NUPR1 could be used as a predictive marker for the gravity of NAFL progression. Moreover, as clinical interest is being raised around NUPR1 inhibitors to treat liver and pancreatic cancer, care should be taken in monitoring lipotoxic parameters.

The classification of adenohypophysial neoplasms as "pituitary neuroendocrine tumors" (PitNETs) was proposed in 2017 to reflect their characteristics as epithelial neuroendocrine neoplasms with a spectrum of clinical behaviors ranging from small indolent lesions to large, locally invasive, unresectable tumors. Tumor growth and hormone hypersecretion cause significant morbidity and mortality in a subset of patients. The proposal was endorsed by a WHO working group that sought to provide a unified approach to neuroendocrine neoplasia in all body sites. We review the features that are characteristic of neuroendocrine cells, the epidemiology and prognosis of these tumors, as well as further refinements in terms used for other pituitary tumors to ensure consistency with the WHO framework. The intense study of PitNETs has provided information about the importance of cellular differentiation in tumor prognosis as a model for neuroendocrine tumors in different locations.

A glucose-lowering medication that acts by a different mechanism than metformin, or other approved diabetes medications, can supplement monotherapies when patients fail to meet blood glucose goals. We examined the actions underlying the effects of an insulin sensitizer, tolimidone (MLR-1023) and investigated its effects on body weight. Diet-induced obesity (CD1/ICR) and type 2 diabetes (db/db) mouse models were used to study the effect of MLR-1023 on metabolic outcomes and to explore its synergy with menthol. We also examined the efficacy of MLR-1023 alone in a clinical trial (NCT02317796), as well as in combination with menthol in human adipocytes. MLR-1023 produced weight loss in humans in four weeks, and in mice fed a high-fat diet it reduced weight gain and fat mass without affecting food intake. In human adipocytes from obese donors, the upregulation of Uncoupling Protein 1, Glucose (UCP)1, adiponectin, Glucose Transporter Type 4 (GLUT4), Adipose Triglyceride Lipase (ATGL), Carnitine palmitoyltransferase 1 beta (CPT1β), and Transient Receptor Potential Melastin (TRPM8) mRNA expression suggested the induction of thermogenesis. The TRPM8 agonist, menthol, potentiated the effect of MLR-1023 on the upregulation of genes for energy expenditure and insulin sensitivity in human adipocytes, and reduced fasting blood glucose in mice. The amplification of the thermogenic program by MLR-1023 and menthol in the absence of adrenergic activation will likely be well-tolerated, and bears investigation in a clinical trial.

The authors report a 27-year-old woman with a remote left femoral osteosarcoma and amputation above the left knee who presented with a large right ventricular mass. Initial evaluation with thoracic CT was inconclusive regarding thrombus versus tumor, but metastatic osteosarcoma was suggested by findings at transthoracic echocardiography, cardiac CT, and cardiac MRI. The patient underwent tumor debulking, and osteosarcoma was confirmed with pathologic examination. She responded to chemotherapy, which resulted in reduction in size of the residual right ventricular tumor and of a few pulmonary metastases. Following induction chemotherapy, patient remains well undergoing maintenance therapy with an oral tyrosine kinase inhibitor. Keywords: CT, Echocardiography, MR Imaging, Intraoperative, Cardiac, Heart, Right Ventricle, Imaging Sequences, Metastases, Oncology Supplemental material is available for this article. © RSNA, 2021

KEY POINTS Balancing the competing demands of parenthood and a career in medicine is a challenge that many physicians and physicians-in-training experience. Delay of child-bearing to attain specific career milestones may result in increased rates of infertility and adverse pregnancy outcomes among

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

Objectives To estimate total direct health care costs associated to diagnosis and treatment of women with breast cancer in Italy, and to investigate their distribution by service type according to the disease pathway and patient characteristics. Methods Data on patients provided by population-based Cancer Registries are linked at individual level with data on health-care services and corresponding claims from administrative databases. A combination of cross-sectional approach and a threephase of care decomposition model with initial, continuing and final phases-of-care defined according to time occurred since diagnosis and disease outcome is adopted. Direct estimation of cancer-related costs is obtained. Results Study cohort included 49,272 patients, 15.2% were in the initial phase absorbing 42% of resources, 79.7% in the continuing phase absorbing 44% of resources and 5.1% in the final phase absorbing 14% of resources. Hospitalization was the most important cost driver, accounting for over 55% of the total costs. Conclusions This paper represents the first attempt in Italy to estimate the economic burden of cancer at population level taking into account the entire disease pathway and using multiple current health care databases. The evidence produced by the study can be used to better plan resources allocation. The model proposed is replicable to countries with individual health care information on services and claims.

The integration and synthesis of the data in different areas of science is drastically slowed and hindered by a lack of standards and networking programmes. Long-term studies of individually marked animals are not an exception. These studies are especially important as instrumental for understanding evolutionary and eco-logical processes in the wild. Furthermore, their number and global distribution provides a unique opportunity to assess the generality of patterns and to address broad-scale global issues (e.g. climate change)., To solve data integration issues and enable a new scale of ecological and evolution-ary research based on long-term studies of birds, we have created the SPI-Birds Network and Database (www.spibirds.org)—a large-scale initiative that connects data from, and researchers working on, studies of wild populations of individually recognizable (usually ringed) birds. Within year and a half since the establishment, SPI-Birds has recruited over 120 members, and currently hosts data on almost 1.5 million individual birds collected in 80 populations over 2,000 cumulative years, and counting., SPI-Birds acts as a data hub and a catalogue of studied populations. It prevents data loss, secures easy data finding, use and integration and thus facilitates collab-oration and synthesis. We provide community-derived data and meta-data stand-ards and improve data integrity guided by the principles of Findable, Accessible, Interoperable and Reusable (FAIR), and aligned with the existing metadata lan-guages (e.g. ecological meta-data language)., The encouraging community involvement stems from SPI-Bird's decentralized ap-proach: research groups retain full control over data use and their way of data management, while SPI-Birds creates tailored pipelines to convert each unique data format into a standard format. We outline the lessons learned, so that other communities (e.g. those working on other taxa) can adapt our successful model. Creating community-specific hubs (such as ours, COMADRE for animal demogra-phy, etc.) will aid much-needed large-scale ecological data integration., The SPI-Birds have been supported by an NWO personal grant (grant number 016.Veni.181.054) to A.C., and a Research Council of Norway grant: 223257 (SFF-III) and 267511 (EVOCLIM).

Pituitary neuroendocrine tumors (PitNETs) : nomenclature evolution, not clinical revolution

Transvenous lead extraction can have serious adverse events, such as cardiac or vascular perforation. Risk factors have not been well characterized.The purpose of this study was to identify factors associated with perforation and death, and to characterize lead extraction in a large contemporary population.We performed a retrospective multicenter study examining patients undergoing lead extraction at 8 Canadian institutions from 1996 through 2016. Demographic and clinical data were used to identify variables associated with perforation and mortality using logistic regression modeling.A total of 2325 consecutive patients (age 61.9 ±16.5 years) underwent extraction of 4527 leads. Perforation rate was 2.7% (63/2325) and 30-day mortality was 1.6% (38/2325), with mortality of 0.4% due to perforation (10/2325). Variables associated with perforation included no previous cardiac surgery (odds ratio [OR] 3.33; 95% confidence interval [CI] 1.54-7.19; P = .002), female sex (OR 3.27; 95% CI 1.91-5.60; P.001); left ventricular ejection fraction ≥40% (OR 2.81; 95% CI 1.28-6.14; P = .010); lead age8 years (OR 2.64; 95% CI 1.52-4.60; P.001); ≥2 leads extracted (OR 2.49; 95% CI 1.23-5.04; P = .011); and diabetes (OR 2.12; 95% CI 1.16-3.86; P = .014). Variables associated with death included infection as indication for extraction (OR 3.85; 95% CI 1.38-10.73; P = .010); anemia (OR 3.14; 95% CI 1.38-6.61; P = .003), and patient age (OR 1.04; 95% CI 1.01-1.07; P = .012).Risk factors associated with perforation in lead extraction include no history of cardiac surgery, female sex, preserved left ventricular ejection fraction, lead age8 years, ≥2 leads extracted, and diabetes.

Objective Spinal meningiomas are one of the frequently seen intradural extramedullary spinal tumors. They are almost always World Health Organization grade I, and a complete removal of the tumor can be curative. However, ventrally located spinal meningioma removal can be challenging due to the position in front of the spinal cord through a narrow corridor provided by routine dorsal approaches. Incomplete excision of the relatively inaccessible dural attachment can consequently lead to recurrence. We describe a safe and reproducible technique used to achieve Simpson grade I removal of ventrally located spinal meningioma. Methods Since the spinal dura can be easily divided into inner and outer layers and the tumor usually spares the outer layer, we developed a simple technique to achieve total resection of the tumor and involved dura while leaving the outer dural layer intact. Results An advantage of this procedure is that it exploits an interdural approach to allow early devascularization of the tumor without cord manipulation and provides access to the ventral dura to achieve Simpson grade I excision. Another advantage is complete dural closure to minimize postoperative cerebrospinal fluid leak or ventral cord herniation without the need for dural substitutes. Conclusion Its novel interdural approach can be used for all ages and all spinal meningiomas.

Annually, over three million people in North America suffer concussions. Every age group is susceptible to concussion, but youth involved in sporting activities are particularly vulnerable, with about 6% of all youth suffering a concussion annually. Youth who suffer concussion have also been shown to have higher rates of suicidal ideation, substance and alcohol use, and violent behaviors. A significant body of research over the last decade has led to changes in policies and laws intended to reduce the incidence and burden of concussions. However, it is also clear that youth engaging in high-risk activities like sport often underreport concussion, while others may embellish reports for specific purposes. For such policies and laws to work, they must operate effectively within a facilitative social context so understanding the culture around concussion becomes essential to reducing concussion and its consequences. We present an automated deep neural network approach to analyze tweets with sport-related concussion context to identify the general public’s sentiment towards concerns in sport-related concussion. A single-layer and multi-layer convolutional neural networks, Long Short-Term Memory (LSTM) networks, and Bidirectional LSTM were trained to classify the sentiments of the tweets. Afterwards, we train an ensemble model to aggregate the predictions of our networks to provide a final decision of the tweet’s sentiment. The system achieves an evaluation F1 score of 62.71% based on Precision and Recall. The trained system is then used to analyze the tweets in the FIFA World Cup 2018 to measure audience reaction to events involving concussion. The neural network system provides an understanding of the culture around concussion through sentiment analysis.

Intensive neurological assessments in neurocritical care settings for unduly prolonged period result in profound sleep deprivation in those patients that confounds the true neurological status of these patients, and the mounting apprehension in providers can beget a vicious cycle of even more intensive neurological assessments resulting in further sleep deprivation from being constantly woken up to be “assessed.” This iatrogenic state drives these patients into deep sleep stages that impact spontaneous breathing trials, weaken immunity, and lead to unwarranted investigations and interventions. There is dwindling value of prolonged frequent neurochecks beyond the initial 24–48 h of an intracranial event. We insist that sleep must be considered on at least an equal par to other functions that are routinely assessed. We reason that therapeutic sleep must be allowed to these patients in suitable amounts especially beyond the first 36–48 h to achieve ideal and swift recovery. This merits a paradigm shift.

Multi-disciplinary teams present the framework in the increasingly challenging care provided for patients. Wang et al. present a 37 year old female who is 35 weeks pregnant when a rare cardiac angiosarcoma is diagnosed.

Background and aim Lipomatous hypertrophy of the interatrial septum (LHIS), a fatty tumor, is usually diagnosed on both echo and CT/MRI imaging. Cases of LHIS located outside of the interatrial septum are extremely rare and rarer still are these cases large enough to cause symptoms. The clinical literature demonstrates a misunderstanding that fatty tumors outside the intra-atrial area represent lipomas. However, pathologic understanding of these fatty tumors is clear and is based on microscopic findings. Methods The tumor was removed by diving the base of attachment at the left ventricular apex via a median sternotomy on cardiopulmonary bypass. Results The patient made an uneventful recovery and remains well at 6 months postoperatively. Conclusions On rare occasions, LHIS can arise from outside the interatrial septum. An LHIS can be differentiated from a lipoma by the presence of entrapped cardiac myocytes in LHIS, making it a pathological, rather than an anatomic, diagnosis.

BackgroundDiffuse low-grade gliomas (DLGGs) are heterogeneous tumors that inevitably differentiate into malignant entities, leading to disability and death. Recently, a shift toward up-front maximal safe resection of DLGGs has been favored. However, this transition is not supported by randomized controlled trial (RCT) data. Here, we sought to survey the neuro-oncology community on considerations for a surgical RCT for DLGGs.MethodsA 21-question survey focusing on a surgical RCT for DLGGs was developed and validated by 2 neurosurgeons. A sample case of a patient for whom management might be debatable was presented to gather additional insight. The survey was disseminated to members of the Society for Neuro-Oncology (SNO) and responses were collected from March 16 to July 10, 2018.ResultsA total of 131 responses were collected. Sixty-three of 117 (54%) respondents thought an RCT would not be ethical, 39 of 117 (33%) would consider participating, and 56 of 117 (48%) believed an RCT would be valuable for determining the differing roles of biopsy, surgery, and observation. This was exemplified by an evenly distributed selection of the latter management options for our sample case. Eighty-three of 120 (69.2%) respondents did not believe in equipoise for DLGG patients. Quality of life and overall survival were deemed equally important end points for a putative RCT.ConclusionsBased on our survey, it is evident that management of certain DLGG patients is not well defined and an RCT may be justified. As with any surgical RCT, logistic challenges are anticipated. Robust patient-relevant end points and standardization of perioperative adjuncts are necessary if a surgical RCT is undertaken.

Cardiac tumors are rare. Most surgeons will encounter few primary cardiac tumors outside of myxomas. This article offers the authors' approach to simple and complex primary and secondary cardiac tumors. Symptoms of primary cardiac tumors are primarily determined by tumor size and anatomic location. Most simple primary tumors and some complex primary tumors are best managed by surgical resection. Secondary tumors are 30 times more frequent than primary cardiac tumors. Surgical resection of secondary tumors is rational in a few highly selected patients. For complex primary and secondary tumors, the authors recommend referral to an experienced multidisciplinary cardiac tumor team.

Background Concussion is an injury that occurs in non-sporting and sporting environments. To determine improved clinical methods for identifying this injury, it is important to develop and understand how the impact event results in quantifiable differences in brain functioning—functioning that has been quantified in the past using saccadic measures. The purpose of this research was to examine the relationships between oculomotor deficits, specifically antisaccade responses, and the biomechanics of impact for a concussion. Methods Participants underwent a diffusion tensor imaging protocol as well as saccadic testing to determine differences in brain functioning in comparison to controls. The injury event was then reconstructed in laboratory using physical and finite element models to determine the biomechanics of the impact and brain tissue strain. Relationships between the biomechanical variables and antisaccade responses were then examined. Results The diffusion tensor imaging analyses found that there was a decrease in radial diffusivity and axial diffusivity found in the cerebral peduncle (p Conclusion While the sample of this research was small, this research suggests that to improve the understanding of the relationship between impact biomechanics and concussion, methods that can quantify the damage to brain structures through imaging, such as diffusion tensor imaging, may be more appropriate.

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.

The purpose of this research was to conduct reconstructions of concussive and non-concussive impacts in ice hockey to determine the biomechanics and thresholds of concussive injury in ice hockey. Videos of concussive and non-concussive impacts in an elite professional ice hockey league in North America were reconstructed using physical and finite element model methods. Eighty concussive and 45 non-concussive events were studied. Logistic regressions indicate significant thresholds for concussion for linear/rotational acceleration and CSDM

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.