The scalable precision medicine open knowledge engine (SPOKE): a massive knowledge graph of biomedical information.

MOTIVATION: Knowledge graphs (KGs) are being adopted in industry, commerce and academia. Biomedical KG presents a challenge due to the complexity, size and heterogeneity of the underlying information. RESULTS: In this work, we present the Scalable Precision Medicine Open Knowledge Engine (SPOKE), a biomedical KG connecting millions of concepts via semantically meaningful relationships. SPOKE contains 27 million nodes of 21 different types and 53 million edges of 55 types downloaded from 41 databases. The graph is built on the framework of 11 ontologies that maintain its structure, enable mappings and facilitate navigation. SPOKE is built weekly by python scripts which download each resource, check for integrity and completeness, and then create a 'parent table' of nodes and edges. Graph queries are translated by a REST API and users can submit searches directly via an API or a graphical user interface. Conclusions/Significance: SPOKE enables the integration of seemingly disparate information to support precision medicine efforts. AVAILABILITY AND IMPLEMENTATION: The SPOKE neighborhood explorer is available at https://spoke.rbvi.ucsf.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Metabolic Enzyme Alterations and Astrocyte Dysfunction in a Murine Model of Alexander Disease With Severe Reactive Gliosis.

Alexander disease (AxD) is a rare and fatal neurodegenerative disorder caused by mutations in the gene encoding glial fibrillary acidic protein (GFAP). In this report, a mouse model of AxD (GFAPTg;Gfap+/R236H) was analyzed that contains a heterozygous R236H point mutation in murine Gfap as well as a transgene with a GFAP promoter to overexpress human GFAP. Using label-free quantitative proteomic comparisons of brain tissue from GFAPTg;Gfap+/R236H versus wild-type mice confirmed upregulation of the glutathione metabolism pathway and indicated proteins were elevated in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which had not been reported previously in AxD. Relative protein-level differences were confirmed by a targeted proteomics assay, including proteins related to astrocytes and oligodendrocytes. Of particular interest was the decreased level of the oligodendrocyte protein, 2-hydroxyacylsphingosine 1-beta-galactosyltransferase (Ugt8), since Ugt8-deficient mice exhibit a phenotype similar to GFAPTg;Gfap+/R236H mice (e.g., tremors, ataxia, hind-limb paralysis). In addition, decreased levels of myelin-associated proteins were found in the GFAPTg;Gfap+/R236H mice, consistent with the role of Ugt8 in myelin synthesis. Fabp7 upregulation in GFAPTg;Gfap+/R236H mice was also selected for further investigation due to its uncharacterized association to AxD, critical function in astrocyte proliferation, and functional ability to inhibit the anti-inflammatory PPAR signaling pathway in models of amyotrophic lateral sclerosis (ALS). Within Gfap+ astrocytes, Fabp7 was markedly increased in the hippocampus, a brain region subjected to extensive pathology and chronic reactive gliosis in GFAPTg;Gfap+/R236H mice. Last, to determine whether the findings in GFAPTg;Gfap+/R236H mice are present in the human condition, AxD patient and control samples were analyzed by Western blot, which indicated that Type I AxD patients have a significant fourfold upregulation of FABP7. However, immunohistochemistry analysis showed that UGT8 accumulates in AxD patient subpial brain regions where abundant amounts of Rosenthal fibers are located, which was not observed in the GFAPTg;Gfap+/R236H mice.

Communication Disparities and Trusted Sources of COVID-19 Information in Massachusetts School Districts.

CONTEXT: The COVID-19 pandemic led to the closure of prekindergarten to grade 12 schools and an inequitable return to full-time in-person learning. OBJECTIVE: To explore how ethnic and racial differences across school districts in Massachusetts correlate with parents' attitudes, beliefs, and trusted sources of information about COVID-19 and mitigation strategies. DESIGN: An electronic survey was distributed by school administrators to parents and guardians in November and December 2021 using existing school district contact lists and established methods of communication (email in 2 school districts; email and text message in 1 district). SETTING: Three school districts in Massachusetts (Chelsea, Medford, and Somerville). PARTICIPANTS: Parents of prekindergarten to grade 12 school students attending public schools. MAIN OUTCOME MEASURES: Parental attitudes and beliefs regarding mitigation strategies for COVID-19 (surveillance testing, masking, and vaccination); trusted information sources about COVID-19; preferred methods of communication from schools. RESULTS: A total of 1496 survey responses were analyzed. Chelsea respondents were predominantly Hispanic/LatinX (88%); Medford and Somerville were predominantly White/non-Hispanic (80% and 68%, respectively). Testing, masks, and vaccination were supported by >80% of parents/guardians across districts. However, there were statistically significant differences between school districts regarding participation in testing programs, implications of a child testing positive, vaccination of young children, communication preferences, and trusted sources of information. CONCLUSIONS: Although primarily focused on COVID-19, these results highlight opportunities for public health personnel and school administrators to work directly with parents and guardians in their school districts to improve communication strategies and be a trusted source of information for a variety of public health issues.

Murine bone marrow mesenchymal stromal cells have reduced hematopoietic maintenance ability in sickle cell disease.

Sickle cell disease (SCD) is characterized by hemolytic anemia, which can trigger oxidative stress, inflammation, and tissue injury that contribute to disease complications. Bone marrow mesenchymal stromal cells (MSCs) tightly regulate hematopoietic stem cell (HSC) homeostasis in health and disease, but their functionality in SCD remains unclear. We identified for the first time that murine SCD MSCs have altered gene signatures, reduced stem cell properties, and increased oxidative stress, due in part to hemolysis. Murine SCD MSCs had lower HSC maintenance ability in vitro and in vivo, as manifested by increased HSC mobilization and decreased HSC engraftment after transplant. Activation of Toll-like receptor-4 through p65 in MSCs further contributed to MSC dysfunction. Transfusions led to an improved MSC and HSC oxidative state in SCD mice. Improving the regulation between MSCs and HSCs has vital implications for enhancing clinical HSC transplantation and gene therapy outcomes and for identification of new molecular targets for alleviating SCD complications.

Nurturing diversity and inclusion in AI in Biomedicine through a virtual summer program for high school students.

Artificial Intelligence (AI) has the power to improve our lives through a wide variety of applications, many of which fall into the healthcare space; however, a lack of diversity is contributing to limitations in how broadly AI can help people. The UCSF AI4ALL program was established in 2019 to address this issue by targeting high school students from underrepresented backgrounds in AI, giving them a chance to learn about AI with a focus on biomedicine, and promoting diversity and inclusion. In 2020, the UCSF AI4ALL three-week program was held entirely online due to the COVID-19 pandemic. Thus, students participated virtually to gain experience with AI, interact with diverse role models in AI, and learn about advancing health through AI. Specifically, they attended lectures in coding and AI, received an in-depth research experience through hands-on projects exploring COVID-19, and engaged in mentoring and personal development sessions with faculty, researchers, industry professionals, and undergraduate and graduate students, many of whom were women and from underrepresented racial and ethnic backgrounds. At the conclusion of the program, the students presented the results of their research projects at the final symposium. Comparison of pre- and post-program survey responses from students demonstrated that after the program, significantly more students were familiar with how to work with data and to evaluate and apply machine learning algorithms. There were also nominally significant increases in the students' knowing people in AI from historically underrepresented groups, feeling confident in discussing AI, and being aware of careers in AI. We found that we were able to engage young students in AI via our online training program and nurture greater diversity in AI. This work can guide AI training programs aspiring to engage and educate students entirely online, and motivate people in AI to strive towards increasing diversity and inclusion in this field.

A robust and interpretable end-to-end deep learning model for cytometry data.

Cytometry technologies are essential tools for immunology research, providing high-throughput measurements of the immune cells at the single-cell level. Existing approaches in interpreting and using cytometry measurements include manual or automated gating to identify cell subsets from the cytometry data, providing highly intuitive results but may lead to significant information loss, in that additional details in measured or correlated cell signals might be missed. In this study, we propose and test a deep convolutional neural network for analyzing cytometry data in an end-to-end fashion, allowing a direct association between raw cytometry data and the clinical outcome of interest. Using nine large cytometry by time-of-flight mass spectrometry or mass cytometry (CyTOF) studies from the open-access ImmPort database, we demonstrated that the deep convolutional neural network model can accurately diagnose the latent cytomegalovirus (CMV) in healthy individuals, even when using highly heterogeneous data from different studies. In addition, we developed a permutation-based method for interpreting the deep convolutional neural network model. We were able to identify a CD27- CD94+ CD8+ T cell population significantly associated with latent CMV infection, confirming the findings in previous studies. Finally, we provide a tutorial for creating, training, and interpreting the tailored deep learning model for cytometry data using Keras and TensorFlow (https://github.com/hzc363/DeepLearningCyTOF).

Surgery Is Underutilized in the Management of Tertiary Hyperparathyroidism.

INTRODUCTION: Tertiary hyperparathyroidism (3HPT) is observed in up to 40% of renal transplant patients. Standard guidelines defining 3HPT and indications for operative intervention are not well described. METHODS: We conducted a retrospective, single-institution cohort study of patients who underwent renal transplant between January 1, 2012 and January 30, 2018, with a minimum of 13-month follow-up and at least 1 y of allograft function. We defined 3HPT as having elevated serum level parathyroid hormone (>88 pg/mL) after successful renal transplantation or multiple instances of elevated serum calcium starting at least 3 mo after transplant. We compared graft failure rates after stratifying the cohort based on management strategy: expectant, medical management with cinacalcet, and parathyroidectomy. RESULTS: Out of the 381 transplanted patients with functional grafts at 1 y, 178 patients (46.6%) were found to have 3HPT. One hundred twenty-nine patients (72.5%) were managed expectantly without medications, 35 patients (19.7%) were managed medically, and 14 patients (7.8%) were managed with parathyroidectomy. Twenty-two patients (17.1%) in the observation group had graft failure, 4 patients (11.4%) in the medically managed group had graft failure, and 0 patients in the surgery group had graft failure. Surgical intervention was associated with decreased renal allograft failure when compared to the combined cohort of nonoperative 3HPT patients (P = 0.03). All patients who underwent parathyroidectomy were cured and did not have graft failure as of December 30, 2019. Calcium elevation, but not PTH elevation, was associated with referral for parathyroidectomy on multivariable logistic regression analysis (P < 0.01). CONCLUSIONS: At our institution, the referral rate for parathyroidectomy among patients with 3HPT remains low. Parathyroidectomy was associated with high cure rates and reduced graft failure. Surgery may be underutilized in the management of 3HPT.

Comparison of cervical neck strain in common otolaryngology surgeries.

BACKGROUND: Cervical neck strain and surgical ergonomics is an increasingly important topic being addressed in this time and age. With new technologies, visualizations, and approaches to surgeries, there are now different strains and duration of strains to the cervical neck. Recently the effect of chronic cell phone use has been described as "text neck." In a similar fashion we understand that certain otolaryngology surgeries can also impart chronic strain to the cervical neck. We aim to quantitatively describe strain for different types of surgeries by looking at posture, duration of surgery, and anatomic ergonomics of specific surgeries. METHODS: Lateral photo documentation of posture during 6 common otolaryngology procedures, used to estimate cervical neck angle and calculate force and impulse to cervical neck. RESULTS: Six common otolaryngology procedures show various cervical neck angles ranging from around 0° to 60° of neck flexion, with subsequent forces ranging from 16 lb to 60 lb of force. When accounting for surgical time, bigger differences arose with impulses ranging from 270,000 N∗s to 3,300,000 N∗s. Noticeably, thyroidectomy and cleft palate showed much higher impulses than the other four types of surgeries. CONCLUSION: Both cervical neck flexion and duration of surgery play important roles in total neck theoretical strain. Variance exists between neck strains of common otolaryngology surgeries. There is a necessity for continued study and improvement in surgical ergonomics.

Recent lessons learned for ex-vivo platelet production.

PURPOSE OF REVIEW: Platelet transfusion can be life-saving but carries a risk of infection or alloimmunization and is limited by insufficient donor sources and restricted unit shelf life. Generating sufficient platelets in vitro to replace a unit of collected blood remains a challenge. Here, we examine the latest advances in the regulation of megakaryocyte maturation and expansion along with platelet formation and survival. We also discuss alternative therapies investigated to induce platelet production. RECENT FINDINGS: Recent studies examined candidate niche cells in the bone marrow microenvironment for promoting platelet formation and developed an explant-based bioreactor to enhance platelet production ex vivo. Chemical inhibitors were examined for their ability to promote megakaryocyte maturation and expansion. Microparticles from megakaryocytes or platelets were found to improve megakaryocyte maturation and platelet formation. Membrane budding was identified as a novel mode of platelet formation. Lastly, a chemical inhibitor to improve cold-stored platelets was identified. SUMMARY: Recent advances in the regulation of megakaryocyte expansion and platelet production provide exciting promise for the development of improved approaches to generate platelets in vitro. These findings bring the field one step closer to achieving the ultimate goal of creating a unit of platelets without the need for donation.

Long-term Impact of Bariatric Surgery on Venous Thromboembolic Risk: A Matched Cohort Study.

OBJECTIVE: The aim of this study is to evaluate the effect of bariatric surgery on long-term risk of VTEs in a large cohort of patients with obesity. BACKGROUND: Obesity is a well-established risk factor for VTEs, such as pulmonary embolism and deep vein thrombosis. The rising prevalence of obesity and its associated co-morbidities, including VTE, represent a growing public health issue. METHODS: A nested, retrospective matched cohort study was designed and conducted on prospectively collected national electronic healthcare records data from the Clinical Practice Research Datalink. Eight thousand, one hundred twelve patients were included in the study: the 4056 patients on the database who had undergone bariatric surgery, and equal numbers of age, sex, and body mass index matched controls. The primary endpoint was the occurrence of VTEs; secondary endpoints were the occurrence of deep vein thrombosis alone, pulmonary embolism alone. RESULTS: Patients were followed up for a median of 10.7 years. The bariatric surgery cohort had a significantly lower occurrence of the primary outcome [hazard ratio (HR) 0.601; 95% confidence interval (CI) 0.430-0.841, P = 0.003]; mainly driven by a reduction in deep vein thrombosis (HR 0.523; 95% CI 0.349-0.783, P = 0·002) and not in pulmonary embolism (HR 0.882; 95% CI 0.511-1.521, P = 0.651). CONCLUSIONS: The results of this nation-wide study set out to characterize the impact of bariatric surgery on long-term risk of thromboembolic events outline a significant reduction in thromboembolic events, driven by a reduction in deep vein thrombosis.

Pathologic Features Associated With Molecular Subtypes of Well-Differentiated Thyroid Cancer.

OBJECTIVE: To determine the association between pathologic features and molecular classes (BRAF-like, RAS-like, and non-BRAF-like non-RAS-like [NBNR]). METHODS: Retrospective review of a merged database containing 676 patients, 84% (571/676) were assigned to a molecular class from publicly accessible sequenced data of thyroid neoplasms. RESULTS: The merged cohort included 571 neoplasms: 353 (62%) BRAF-like, 172 (30%) RAS-like, and 46 (8.1%) NBNR. Lymph node metastasis (any N1 disease) was present in 166/337 (49%) of BRAF-like, 23/164 (14%) of RAS-like, and 0/46 (0%) of NBNR and are significantly different (P < .001). Gross extra-thyroidal extension was observed in 27 patients, including 24/331 (7%) of BRAF-like, 2/160 (1%) of RAS-like, and 1/46 (2%) of NBNR (P = .01). N1B lymph node metastases or T4 disease was present in 74/333 (22%) of BRAF-like, 10/160 (6%) of RAS-like, and 1/46 (2%) of NBNR (P < .0001). Distant metastasis was present in 4/151 (2.6%) of BRAF-like, 2/50 (4%) of RAS-like and 0/46 for NBNR (P = .627). Angioinvasion was present in 0/81 (0%) of BRAF-like, 3/53 (6%) of RAS-like, and 3/46 (7%) of NBNR (P = .08); and multifocality was present in 27/81 (33%) of BRAF-like, 9/53 (17%) of RAS-like, and 1/46 (2%) for NBNR (P = .0001). CONCLUSION: Pathological features of metastasis, gross extra-thyroidal extension, and multifocality were more prevalent in BRAF-like samples compared to RAS-like and NBNR. A trend towards increased frequency of angioinvasion in RAS-like and NBNR cancers compared to BRAF-like samples was observed. Further studies are needed to evaluate if preoperative knowledge of molecular mutations in thyroid tumors aids in decision-making regarding extent of surgery.

Long-term incidence and outcomes of obesity-related peripheral vascular disease after bariatric surgery.

BACKGROUND AND AIMS: Patients with obesity are at high risk of suffering from arterial and venous peripheral vascular disease (PVD). Bariatric surgery is an effective strategy to achieve weight reduction for patients with obesity. The long-term impact of bariatric surgery on obesity-related morbidity is subject to increasing research interest. This study aimed to ascertain the impact of bariatric surgery on the long-term occurrence of PVD in patients with obesity. METHODS: The study population was extracted from the Clinical Practice Research Datalink, a nation-wide database containing primary and secondary care records of consenting patients. The intervention cohort was 2959 patients who had undergone bariatric surgery during follow-up; their controls were 2959 propensity-score-matched counterparts. The primary endpoint was development of any PVD: arterial or venous. Secondary endpoints were incident peripheral arterial disease alone, incident peripheral venous disease alone. RESULTS: Three hundred forty-six patients suffered a primary endpoint during follow-up. Bariatric surgery did not improve peripheral vascular disease rates as a whole, but it was associated with significantly lower event rates of arterial disease (HR = 0.560, 95%CI 0.327-0.959, p = 0.035) but higher event rates of venous disease (HR = 1.685, 95%CI 1.256-2.262, p < 0.001). CONCLUSIONS: Bariatric surgery was associated with significantly reduced long-term occurrence of arterial disease but increased occurrence of venous disease in patients with obesity.

Effect of bariatric surgery on long-term cardiovascular outcomes: a nationwide nested cohort study.

AIMS: This study aims to evaluate the long-term effect of bariatric surgery on cardiovascular outcomes of patients with obesity. METHODS AND RESULTS: A nested cohort study was carried out within the Clinical Practice Research Datalink. The study cohort included the 3701 patients on the database who had undergone bariatric surgery and 3701 age, gender, and body mass index-matched controls. The primary endpoint was the composite of fatal or non-fatal myocardial infarction and fatal or non-fatal ischaemic stroke. Secondary endpoints included fatal or non-fatal myocardial infarction alone, fatal or non-fatal ischaemic stroke alone, incident heart failure, and mortality. The median follow-up achieved was 11.2 years. Patients who had undergone bariatric surgery had a significantly lower occurrence of major adverse cardiovascular events [hazard ratio (HR) 0.410, 95% confidence interval (CI) 0.274-0.615; P < 0.001]. This was mainly driven by a reduction in myocardial infarction (HR 0.412, 95% CI 0.280-0.606; P < 0.001) and not in acute ischaemic stroke (HR 0.536, 95% CI 0.164-1.748; P = 0.301). A reduction was also observed in new diagnoses of heart failure (HR 0.403, 95% CI 0.181-0.897; P = 0.026) and mortality (HR 0.254, 95% CI 0.183-0.353; P < 0.001). CONCLUSION: The results of this large, nationwide cohort study support the association of bariatric surgery with lower long-term risk of major cardiovascular events and incident heart failure in patients with obesity.

Global mid-upper arm circumference cut-offs for adults: a call to action.

Since 2009, mid-upper arm circumference (MUAC) has become an accepted measure for screening children for acute malnutrition and determining eligibility for services to manage acute malnutrition. Use of MUAC has increased the reach and enhanced the quality of community-based management of acute malnutrition services. Increasingly, MUAC is also used to assess nutritional status and eligibility for nutrition support among adolescents and adults, including pregnant and lactating women and HIV and TB clients. However, globally recognised cut-offs have not been established to classify malnutrition among adults using MUAC. Therefore, different countries and programmes use different MUAC cut-offs to determine eligibility for programme services. Patient monitoring guidelines provided by WHO for country adaptation to support the integrated management of adult illness do not include MUAC, in part because guidance does not exist about what MUAC cut-off should trigger further action.

Determining a global mid-upper arm circumference cut-off to assess underweight in adults (men and non-pregnant women).

OBJECTIVE: To determine if a global mid-upper arm circumference (MUAC) cut-off can be established to classify underweight in adults (men and non-pregnant women). DESIGN: We conducted an individual participant data meta-analysis (IPDMA) to explore the sensitivity (SENS) and specificity (SPEC) of various MUAC cut-offs for identifying underweight among adults (defined as BMI < 18·5 kg/m2). Measures of diagnostic accuracy were determined every 0·5 cm across MUAC values from 19·0 to 26·5 cm. A bivariate random effects model was used to jointly estimate SENS and SPEC while accounting for heterogeneity between studies. Various subgroup analyses were performed. SETTING: Twenty datasets from Africa, South Asia, Southeast Asia, North America and South America were included. PARTICIPANTS: All eligible participants from the original datasets were included. RESULTS: The total sample size was 13 835. Mean age was 32·6 years and 65 % of participants were female. Mean MUAC was 25·7 cm, and 28 % of all participants had low BMI (<18·5 kg/m2). The area under the receiver operating characteristic curve for the pooled dataset was 0·91 (range across studies 0·61-0·98). Results showed that MUAC cut-offs in the range of ≤23·5 to ≤25·0 cm could serve as an appropriate screening indicator for underweight. CONCLUSIONS: MUAC is highly discriminatory in its ability to distinguish adults with BMI above and below 18·5 kg/m2. This IPDMA is the first step towards determining a global MUAC cut-off for adults. Validation studies are needed to determine whether the proposed MUAC cut-off of 24 cm is associated with poor functional outcomes.

Surgical Techniques for Head and Neck Reconstruction in the Vessel-Depleted Neck.

The vessel-depleted neck presents a unique and challenging scenario for reconstructive surgery of the head and neck. Prior surgery and radiation often result in significant scarring and damage to the neck vasculature, making identification of suitable recipient vessels for microvascular free tissue transfer exceedingly difficult. Therefore, alternative reconstructive techniques and/or vessel options must be considered to obtain a successful reconstructive outcome for a patient. In this article, we discuss our experience and approach to the management of the vessel-depleted neck, emphasizing the importance of preoperative planning and having multiple backup options prior to surgery. The various preoperative imaging modalities and available options for recipient arteries and veins are presented in detail. Additionally, we discuss modifications of select free flaps to maximize their utility in successful reconstruction. Together with thoughtful preoperative planning, these techniques can help aid the reconstructive surgeon in addressing the complex decisions associated with the vessel-depleted neck.

Self-Flagellation as Possible Route of Human T-Cell Lymphotropic Virus Type-1 Transmission.

We report human T-cell lymphotropic virus type 1 infection associated with self-flagellation in 10 UK residents. These persons were heterosexual men from Pakistan, India, and Iraq. One person showed seroconversion in adulthood; 1 was co-infected with hepatitis C virus. No other risk factors for bloodborne virus acquisition were identified. Onward sexual transmission has occurred.

Content guidance for mobile phones short message service (SMS)-based antiretroviral therapy adherence and appointment reminders: a review of the literature.

Mobile phones are increasingly being used to support health activities, including the care and management of people living with HIV/AIDS. Short message service (SMS) has been explored as a means to optimize and support behaviour change. However, there is minimal guidance on messaging content development. The purpose of this review was to inform the content of SMS messages for mobile health (mHealth) initiatives designed to support anti-retroviral therapy adherence and clinic appointment keeping in resource-limited settings. PubMed, OvidMedline, Google Scholar, K4Health's mHealth Evidence database, the mHealth Working Group project resource, and Health COMpass were searched. A request to online communities for recommendations on message content was also made. 1010 unique sources were identified, of which 51 were included. The information was organized into three categories: pre-message development, message development, and security and privacy. Fifteen of the publications explicitly provided their message content. Important lessons when developing the content of SMS were: (1) conducting formative research; (2) grounding content in behaviour change theory; and (3) reviewing proposed content with experts. Best practices exist for developing message content for behaviour change. Efforts should be continued to apply lessons learned from the existing literature to inform mHealth initiatives supporting HIV/AIDS care and treatment.

Decompressive craniectomy in paediatric traumatic brain injury: a systematic review of current evidence.

INTRODUCTION: Paediatric traumatic brain injury (pTBI) is one of the most frequent neurological presentations encountered in emergency departments worldwide. Every year, more than 200,000 American children suffer pTBIs, many of which lead to long-term damage. OBJECTIVES: We aim to review the existing evidence on the efficacy of the decompressive craniectomy (DC) in controlling intracranial pressure (ICP) and improving long-term outcomes in children with pTBI. METHODS: A comprehensive search of the MEDLINE and EMBASE databases led to the screening of 212 studies, 12 of which satisfied inclusion criteria. Data extracted included the number and ages of patients, Glasgow Coma Scale scores at presentation, treatment protocols and short- and long-term outcomes. RESULTS: Each of the nine studies including ICP as an outcome reported that it was successfully controlled by DC. The 6-12 month outcome scores of patients undergoing DC were positive, or superior to those of medically treated groups in nine of 11 studies. Mortality was compared in only two studies, and was lower in the DC group in both.Very few studies are currently available investigating short- and long-term outcomes in children with TBI undergoing DC. CONCLUSION: The currently available evidence may support a beneficial role of DC in controlling ICP and improving long-term outcomes.

Idiopathic intracranial hypertension in the British population with obesity.

PURPOSE: Idiopathic intracranial hypertension (IIH) is a syndrome that is characterized by persistently high intracranial pressure and associated with high rates of morbidity and visual loss. Its exact etiology and clinical picture is poorly understood, but it is known to be associated with obesity. The aim of this study was to investigate the prevalence and clinical manifestations of IIH using a large nationwide database of British subjects. MATERIALS AND METHODS: The anonymized healthcare records of patients with a BMI of ≥ 30 kg/m2 were extracted from the Clinical Practice Research Datalink (CPRD), and analyzed. RESULTS: The patients with IIH were older and more likely to have peripheral vascular disease, ischemic heart disease, and anemia; to have had a previous myocardial infarction; and have used non-steroidal anti-inflammatory drugs (NSAIDs) and steroids. Multivariate analysis with adjustment for confounders showed that anemia (p = 0.033) and the use of NSAIDs (p = 0.011) were the only factors independently associated with IIH. Increases in BMI beyond the threshold of obesity did not independently increase risk of IIH. CONCLUSIONS: IIH is a multifactorial disease; the risk of which is increased in patients with a background of anemia, and those who use NSAIDs. Across BMI categories beyond the threshold for obesity (BMI ≥ 30 kg/m2), there is no continuation of the previously described "dose-response" relationship between BMI and IIH. ETHICAL APPROVAL: Scientific approval for the study was granted from the Regulatory Agency's Independent Scientific Advisory Committee and ethical approval by the Health Research Authority IRAS Project ID: 203143. ISAC approval registration number 16_140R2.