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Introduction Primary tumors of the spine requiring enbloc resection are rare. Most published reports are small and focus on disease free survival and recurrence rates. Very few studies focus on the various anterior and posterior reconstructive options and subsequent outcomes with respect to fusion rates and need for revision due to hardware failure. The objective of this review was to (1) summarize the published literature and (2) report the failure rates of various anterior and posterior reconstructive techniques after enbloc resection of spinal tumors and (3) supplement the deficiencies in the available published literature with expert opinion for reconstructive options from a group of experienced international spine tumor surgeons. Material and Methods An electronic search of the literature was undertaken from January 1990 – December 2013 evaluating specific reconstructive techniques of the spine after primary tumor enbloc resection. Prospective/retrospective trials and case series were included in the final analysis when fusion rates or failure rates were reported. The data available for each reconstructive technique was then combined and construct survivorship was summarized. In addition, a questionnaire was administered to a group of 20 international spine tumor surgeons evaluating specific reconstructive preferences at different regions of the spine based on the number of vertebrae resected and whether post-operative radiation was planned. Results The initial search yielded 381 articles with 31 subsequently included for full text review. Fourteen articles were included in the final analysis. There were 146 patients included for final review. There were 2/9 (22%) patients revised from short to long segment constructs and 3 reports of broken pedicle screws with only one requiring revision in longer constructs. Rates of revision for anterior reconstruction were similar for autogenous strut grafts (10%), cages (7.7%) and allograft strut grafts (8.3%). No surgeons responding to the questionnaire recommended short segment posterior constructs. For anterior reconstruction, cages packed with morcellized allograft and autograft were preferred (75%, p < 0.05) while strut bone grafting was choosen more often at the cervicothoracic junction (65%, p < 0.05) and when more than one vertebrae was resected in the mid thoracic spine (75%, p < 0.05). Few surgeons changed their anterior reconstructive technique (15%) or posterior reconstructive technique (10%) when post-operative radiation was planned. Conclusion The literature and consensus opinion supports posterior reconstruction with at least two vertebral levels of support above and below. For anterior vertebral column reconstruction, structural allograft, autograft and cages packed with morcelized bone have shown similar rates of fusion and failure. Expert opinion, however, suggests that structural autograft or potentially vascularized strut grafts should be used when spanning a defect greater than 2 vertebral bodies especially at the cervicothoracic junction.

Abstract To move beyond a select few genes/drugs, the successful adoption of pharmacogenomics into routine clinical care requires a curated and machine-readable database of pharmacogenomic knowledge suitable for use in an electronic health record (EHR) with clinical decision support (CDS). Recognizing that EHR vendors do not yet provide a standard set of CDS functions for pharmacogenetics, the Clinical Pharmacogenetics Implementation Consortium (CPIC) Informatics Working Group is developing and systematically incorporating a set of EHR-agnostic implementation resources into all CPIC guidelines. These resources illustrate how to integrate pharmacogenomic test results in clinical information systems with CDS to facilitate the use of patient genomic data at the point of care. Based on our collective experience creating existing CPIC resources and implementing pharmacogenomics at our practice sites, we outline principles to define the key features of future knowledge bases and discuss the importance of these knowledge resources for pharmacogenomics and ultimately precision medicine.

SummaryNon‐Hodgkin lymphoma (NHL) is the third most common malignancy in children, adolescents and young adults (CAYA). NHL is a diverse set of diseases that arise at key regulatory checkpoints during B or T cell development in the bone marrow, germinal centre or thymus. While advances in the use of conventional cytotoxic agents have led to dramatic improvements in survival, these cures are associated with significant acute and long‐term toxicities. Moreover, the prognosis for CAYA patients with relapsed or refractory NHL remains dismal, with the vast majority dying of their disease. Thanks to a large number of candidate‐based biological studies, together with large‐scale sequencing efforts, there has been an explosion of knowledge regarding the molecular pathophysiology of B‐ and T‐NHL. This has ushered development of a flurry of novel therapeutic approaches that may simultaneously provide new hope for relapsed patients and an opportunity to reduce the therapeutic burden in newly diagnosed CAYA. Here we review a selection of the most promising new therapeutic approaches to these diseases. While the vast majority of these agents are untested in children, on‐going work from many cooperative groups will soon explore their use in paediatric disease, in hope of further improving outcomes while maximizing quality of life.

Abstract Background and Aims Depression and anxiety are often comorbid with alcoholism and contribute to craving and relapse. We aimed to estimate the prevalence of life‐time diagnoses of major depressive disorder (MDD), substance‐induced depression (SID), anxiety disorder (AnxD) and substance‐induced anxiety (SIA), the effects of these comorbidities on the propensity to drink in negative emotional states (negative craving), and test whether these effects differ by sex. Design Secondary analyses of baseline data collected in a single‐arm study of pharmacogenetic predictors of acamprosate response. Setting Academic medical center and affiliated community‐based treatment programs in the American upper mid‐west. Participants A total of 287 males and 156 females aged 18–80 years, meeting DSM‐IV criteria for alcohol dependence. Measurements The primary outcome measure was ‘propensity to drink in negative emotional situations’ (determined by the Inventory of Drug Taking Situations) and the key predictors/covariates were sex and psychiatric comorbidities, including MDD, SID, AnxD and SIA (determined by Psychiatric Research Interview of Substance and Mood Disorders). Findings The prevalence of the MDD, SID and AnxD was higher in females compared with males (33.1 versus 18.4%, 44.8 versus 26.4% and 42.2 versus 27.4%, respectively; P < 0.01, each), while SIA was rare (3.3%) and did not differ by sex. Increased propensity to drink in negative emotional situations was associated with comorbid MDD (β = 6.6, P = 0.013) and AnxD (β = 4.8, P = 0.042) as well as a SID × sex interaction effect ( P = 0.003), indicating that the association of SID with propensity to drink in negative emotional situations differs by sex and is stronger in males (β = 7.9, P = 0.009) compared with females (β = −6.6, P = 0.091). Conclusions There appears to be a higher prevalence of comorbid depression and anxiety disorders as well as propensity to drink in negative emotional situations in female compared with male alcoholics. Substance‐induced depression appears to have a sex‐specific effect on the increased risk for drinking in negative emotional situations in males.

Osteosarcoma is an aggressive primary bone tumor. It is currently treated with multimodality therapy including en bloc resection, which has been demonstrated to confer a survival benefit over intralesional resection. The authors present the case of an 8-year-old girl with a C-1 lateral mass osteosarcoma, which was treated with a 4-stage en bloc resection and spinal reconstruction. While technically complex, the feasibility of en bloc resection for spinal osteosarcoma should be explored in the pediatric population.

OBJECTIVE Primary spinal osteosarcomas are rare and aggressive neoplasms. Poor outcomes can occur, as obtaining marginal margins is technically demanding; further Enneking-appropriate en bloc resection can have significant morbidity. The goal of this study is to identify prognostic variables for local recurrence and mortality in surgically treated patients diagnosed with a primary osteosarcoma of the spine. METHODS A multicenter ambispective database of surgically treated patients with primary spine osteosarcomas was developed by AOSpine Knowledge Forum Tumor. Patient demographic, diagnosis, treatment, perioperative morbidity, local recurrence, and cross-sectional survival data were collected. Tumors were classified in 2 cohorts: Enneking appropriate (EA) and Enneking inappropriate (EI), as defined by pathology margin matching Enneking-recommended surgical margins. Prognostic variables were analyzed in reference to local recurrence and survival. RESULTS Between 1987 and 2012, 58 patients (32 female patients) underwent surgical treatment for primary spinal osteosarcoma. Patients were followed for a mean period of 3.5 ± 3.5 years (range 0.5 days to 14.3 years). The median survival for the entire cohort was 6.7 years postoperative. Twenty-four (41%) patients died, and 17 (30%) patients suffered a local recurrence, 10 (59%) of whom died. Twenty-nine (53%) patients underwent EA resection while 26 (47%) patients underwent EI resection with a postoperative median survival of 6.8 and 3.7 years, respectively (p = 0.048). EI patients had a higher rate of local recurrence than EA patients (p = 0.001). Patient age, previous surgery, biopsy type, tumor size, spine level, and chemotherapy timing did not significantly influence recurrence and survival. CONCLUSIONS Osteosarcoma of the spine presents a significant challenge, and most patients die in spite of aggressive surgery. There is a significant decrease in recurrence and an increase in survival with en bloc resection (EA) when compared with intralesional resection (EI). The effect of adjuvant and neoadjuvant chemotherapeutics, as well as method of biopsy, requires further exploration.

Abstract Rationale Respiratory failure represents a major risk for morbidity and mortality. Although generally managed in the intensive care unit (ICU), respiratory failure often begins elsewhere. Checklists of care processes to minimize the duration of mechanical ventilation and adverse events are routinely used in the ICU, but are uncommonly used outside the ICU. Objectives To develop consensus among a multidisciplinary expert panel on care practices to include in a checklist of best practices for critically ill patients with respiratory failure before and after ICU admission. Methods A multidisciplinary expert panel was assembled. The panel was tasked with creating a checklist of care processes aimed at decreasing progression to respiratory failure, duration of mechanical ventilation, mortality in mechanical ventilation, and adverse events. Over the course of multiple teleconferences and e-mail communications, the Prevention of Organ Failure Checklist list was reviewed, refined, and voted upon. Items that received greater than 75% of the vote were included in the final checklist. Measurements and Main Results: Using a modified Delphi process, the expert panel was able to compile Prevention of Organ Failure Checklist into 20 items that aimed to decrease mechanical ventilation by assessing the causes of acute respiratory failure, ventilation strategies, sedation, and general critical care processes, as well as to avoid unwanted or nonbeneficial interventions. Conclusions The modified Delphi process identified readily available preventative interventions suitable for checklist implementation in patients with or progressing to respiratory failure even before ICU admission.

AbstractIntroductionThe clinical and pathological phenotypes of Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) often overlap. We examined whether plasma lipids differed among individuals with autopsy‐confirmed Lewy Body pathology or AD pathology.MethodsWe identified four groups with available plasma 2 years before death: high (n = 12) and intermediate‐likelihood DLB (n = 14) based on the third report of the DLB consortium; dementia with Alzheimer's pathology (AD; n = 18); and cognitively normal with normal aging pathology (n = 21). Lipids were measured using ESI/MS/MS.ResultsThere were overall group differences in plasma ceramides C16:0, C18:1, C20:0, and C24:1 and monohexosylceramides C18:1 and C24:1. These lipids did not differ between the high‐likelihood DLB and AD groups, but both groups had higher levels than normals. Plasma fatty acid levels did not differ by group.DiscussionPlasma ceramides and monohexosylceramides are elevated in people with dementia with either high‐likelihood DLB or AD pathology.

There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly ( P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype.