Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 17 de 17
Filter
Add more filters










Publication year range
1.
Int J Surg ; 110(6): 3617-3632, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38935828

ABSTRACT

BACKGROUND: The global burden of trauma disproportionately affects low-income countries and middle-income countries (LMIC), with variability in trauma systems between countries. Military and civilian healthcare systems have a shared interest in building trauma capacity for use during peace and war. However, in LMICs it is largely unknown if and how these entities work together. Understanding the successful integration of these systems can inform partnerships that can strengthen trauma care. This scoping review aims to identify examples of military-civilian trauma systems integration and describe the methods, domains, and indicators associated with integration including barriers and facilitators. METHODS: A scoping review of all appropriate databases was performed to identify papers with evidence of military and civilian trauma systems integration. After manuscripts were selected for inclusion, relevant data was extracted and coded into methods of integration, domains of integration, and collected information regarding indicators of integration, which were further categorized into facilitators or barriers. RESULTS: Seventy-four studies were included with authors from 18 countries describing experiences in 23 countries. There was a predominance of authorship and experiences from High-Income Countries (91.9 and 75.7%, respectively). Five key domains of integration were identified; Academic Integration was the most common (45.9%). Among indicators, the most common facilitator was administrative support and the lack of this was the most common barrier. The most common method of integration was Collaboration (50%). CONCLUSION: Current evidence demonstrates the existence of military and civilian trauma systems integration in several countries. High-income country data dominates the literature, and thus a more robust understanding of trauma systems integration, inclusive of all geographic locations and income statuses, is necessary prior to development of a framework to guide integration. Nonetheless, the facilitators identified in this study describe the factors and environment in which integration is feasible and highlight optimal indicators of entry.


Subject(s)
Wounds and Injuries , Humans , Wounds and Injuries/therapy , Developing Countries , Global Health , Military Health Services , Military Medicine/organization & administration
3.
J Pediatr ; 261: 113549, 2023 10.
Article in English | MEDLINE | ID: mdl-37301281

ABSTRACT

OBJECTIVE: To develop a complexity scoring system to characterize the diverse population served in pediatric aerodigestive clinics and help predict their treatment outcomes. STUDY DESIGN: A 7-point medical complexity score was developed through an iterative group consensus of relative stakeholders to capture the spectrum of comorbidities among the aerodigestive population. One point was assigned for each comorbid diagnosis in the following categories: airway anomaly, neurologic, cardiac, respiratory, gastrointestinal, genetic diagnoses, and prematurity. A retrospective chart review was conducted of patients seen in the aerodigestive clinic who had ≥2 visits between 2017 and 2021. The predictive value of the complexity score for the selected outcome of feeding progression among children with dysphagia was analyzed with univariate and multivariable logistic regression. RESULTS: We analyzed 234 patients with complexity scores assigned, showing a normal distribution (Shapiro Wilk P = .406) of the scores 1-7 (median, 4; mean, 3.50 ± 1.47). In children with dysphagia, there was waning success in the improvement of oral feeding with increasing complexity scores (OR, 0.66; 95% CI, 0.51-0.84; P = .001). Tube-fed children with higher complexity scores were incrementally less likely to achieve full oral diet (OR, 0.60; 95% CI, 0.40-0.89; P = .01). On multivariable analysis, neurologic comorbidity (OR, 0.26; P < .001) and airway malformation (OR, 0.35; P = .01) were associated with a decreased likelihood to improve in oral feeding. CONCLUSIONS: We propose a novel complexity score for the pediatric aerodigestive population that is easy to use, successfully stratifies diverse presentations, and shows promise as a predictive tool to assist in counseling and resource use.


Subject(s)
Deglutition Disorders , Child , Humans , Deglutition Disorders/epidemiology , Deglutition Disorders/diagnosis , Retrospective Studies , Enteral Nutrition , Comorbidity , Ambulatory Care Facilities
4.
Otolaryngol Head Neck Surg ; 169(2): 374-381, 2023 08.
Article in English | MEDLINE | ID: mdl-36939625

ABSTRACT

OBJECTIVE: The aim of this study was to develop an international expert consensus on priority pediatric otolaryngology-head and neck surgery (OHNS) conditions and procedures for which all national health systems globally should be capable of managing. STUDY DESIGN: The Delphi method is a multiround online questionnaire and was administered internationally to otolaryngologists with a focus on pediatric populations. This study was administered in parallel to a Delphi survey focusing on adult OHNS conditions amongst adult otolaryngology experts. SETTING: International online survey. METHODS: In round 1, participants listed the top 15 pediatric otolaryngological conditions and top 15 pediatric otolaryngology procedures for their World Bank region. In round 2, participants ranked round 1 responses in order of global importance on a 5-point Likert scale. In round 3, participants reranked conditions and procedures that did not achieve consensus, defined as at least 70% of the round 2 Likert responses being ranked as either "important" or "very important." Descriptive statistics were calculated for each round. RESULTS: The survey was distributed to 35 experts globally, with a 40% (n = 14) response rate. Fifty percent (n = 7) of participants were from low- and middle-income countries, with at least 1 participant from each World Bank region. A list of 28 consensus surgical procedures and 11 consensus conditions were identified. CONCLUSION: This Delphi survey method of world experts in pediatric otolaryngology identified a core list of medical conditions and surgical procedures that should be a part of every national health system's clinical goals of treatment, research, and capacity building.


Subject(s)
Otolaryngology , Adult , Child , Humans , Consensus , Otolaryngologists , Delphi Technique
5.
J Surg Res ; 283: 666-673, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36455420

ABSTRACT

INTRODUCTION: Traumatic injury is a leading cause of morbidity globally, particularly in low-income and middle-income countries (LMICs). In high-income countries (HICs), it is well documented that military and civilian integration can positively impact trauma care in both healthcare systems, but it is unknown if this synergy could benefit LMICs. This case series examines the variety of integration between the civilian and military systems of various countries and international partnerships to elucidate if there are commonalities in facilitators and barriers. METHODS: A convenience sampling method was utilized to identify subject matter experts on civilian and military trauma system integration. Data were collected and coded through an iterative process, focusing on the historical impetuses and subsequent outcomes of civilian and military trauma care collaboration. RESULTS: Eight total case studies were completed, five addressing specific countries and three addressing international partnerships. Themes which emerged as drivers for integration included history of conflict, geography, and skill maintenance for military physicians. High-level government support was a central theme for successful integration, and financial issues were often seen as the greatest barrier. CONCLUSIONS: Various approaches in civilian-military integration exist throughout the world, and the studied nations and international partnerships demonstrated similar motivators and barriers to integration. This study highlights the need for further investigation, particularly in LMICs, where less is known about integration strategies.


Subject(s)
Military Medicine , Military Personnel , Physicians , Humans
7.
Front Public Health ; 10: 995595, 2022.
Article in English | MEDLINE | ID: mdl-36388301

ABSTRACT

Introduction: On January 12, 2010, a 7.0 magnitude earthquake struck the Republic of Haiti. The human cost was enormous-an estimated 316,000 people were killed, and a further 300,000 were injured. The scope of the disaster was matched by the scope of the response, which remains the largest multinational humanitarian response to date. An extensive scoping review of the relevant literature was undertaken, to identify studies that discussed the civilian and military disaster relief efforts. The aim was to highlight the key-lessons learned, that can be applied to future disaster response practise. Methods: Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidance was followed. Seven scientific databases were searched, using consistent search terms-followed by an analysis of the existent Haitian literature. This process was supplemented by reviewing available grey literature. A total of 2,671 articles were reviewed, 106 of which were included in the study. In-depth analysis was structured, by aligning data to 12 key-domains, whilst also considering cross-sector interaction (Civilian-Civilian, Military-Military, and Civilian-Military). Dominant themes and lessons learned were identified and recorded in an online spreadsheet by an international research team. This study focuses on explicitly analysing the medical aspects of the humanitarian response. Results: An unpreceded collaborative effort between non-governmental organisations, international militaries, and local stakeholders, led to a substantial number of disaster victims receiving life and limb-saving care. However, the response was not faultless. Relief efforts were complicated by large influxes of inexperienced actors, inadequate preliminary needs assessments, a lack of pre-existing policy regarding conduct and inter-agency collaboration, and limited consideration of post-disaster redevelopment during initial planning. Furthermore, one critical theme that bridged all aspects of the disaster response, was the failure of the international community to ensure Haitian involvement. Conclusions: No modern disaster has yet been as devastating as the 2010 Haiti earthquake. Given the ongoing climate crisis, as well as the risks posed by armed conflict-this will not remain the case indefinitely. This systematic analysis of the combined civilian and military disaster response, offers vital evidence for informing future medical relief efforts-and provides considerable opportunity to advance knowledge pertaining to disaster response.


Subject(s)
Disasters , Earthquakes , Relief Work , Humans , Haiti , Needs Assessment
8.
JAMA Otolaryngol Head Neck Surg ; 148(10): 985-986, 2022 10 01.
Article in English | MEDLINE | ID: mdl-35925579

ABSTRACT

This cross-sectional study evaluates demographic characteristics, surgical characteristics, and audiometric data associated with closure of the air-bone gap to less than 10 dB or 15 dB.


Subject(s)
Otosclerosis , Stapes Surgery , Bone Conduction , Humans , Otosclerosis/surgery , Retrospective Studies , Treatment Outcome
9.
Int J Pediatr Otorhinolaryngol ; 159: 111193, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35724492

ABSTRACT

OBJECTIVE: Transcutaneous laryngeal ultrasonography has been utilized to document vocal cord mobility in the adult perioperative thyroidectomy setting with variable success. The aims of this study were to assess the feasibility of using transcutaneous ultrasound in vocal cord visualization in children, to determine the accuracy in detecting vocal cord immobility compare to flexible laryngoscopy, and to identify any barriers that may affect its utility. METHODS: This is a prospective blinded-assessor study. Transcutaneous laryngeal ultrasound and flexible laryngoscopy were performed in two pediatric settings: perioperative thyroid surgery and inpatient consultation for airway, voice, or swallowing concerns. The video recordings of ultrasound and laryngoscopy were assessed by two fellowship-trained pediatric otolaryngologists independently. RESULTS: A total of 83 paired laryngoscopy and ultrasound assessments were performed, 39 for perioperative thyroidectomy and 44 for inpatient consultation. The majority had normal vocal cord mobility (65/83, 78%), while 16 had unilateral cord palsy and 2 had bilateral palsy. The vocal cords were successfully visualized on ultrasound in 82/83 (99%) evaluations. Compared to gold standard laryngoscopy, the sensitivity for diagnosing vocal cord palsy on ultrasound was 53-83%, and the specificity was 97-98%. The sensitivity for detecting asymmetric vocal cord movement was 56-88%, and the specificity was 99%. The agreement between ultrasound and laryngoscopy diagnoses were 87-94% (κ = 0.58-0.83, moderate to near perfect agreement). The intra-rater agreement was 95-100% (κ = 0.64-1.0), and inter-rater agreement was 90% (κ = 0.66). Both subjects with bilateral vocal cord palsy had incorrect ultrasound diagnoses by both observers. CONCLUSION: We were able to utilize transcutaneous laryngeal ultrasound to successfully visualize vocal cord mobility in almost all pediatric patients with a high degree of specificity. The modality has limitations in the assessment of bilateral vocal cord palsy, and its sensitivity was observer-dependent.


Subject(s)
Vocal Cord Paralysis , Vocal Cords , Adult , Child , Feasibility Studies , Humans , Laryngoscopy , Prospective Studies , Thyroidectomy , Ultrasonography , Vocal Cord Paralysis/diagnostic imaging , Vocal Cords/diagnostic imaging
10.
OTO Open ; 6(1): 2473974X221089840, 2022.
Article in English | MEDLINE | ID: mdl-35356270

ABSTRACT

Objective: To better understand the impact of the otolaryngology-specific workforce on the burden of related diseases. Study Design: Retrospective analysis of existing workforce density data as compared with the incidence, mortality, and morbidity data for 4 otolaryngologic diseases. Setting: An overall 138 countries with known otolaryngology-head and neck surgery workforce and epidemiologic data. Methods: We obtained raw data on workforce estimates of ear, nose, and throat surgical specialists from the World Health Organization. Disease burdens for 4 conditions were estimated via 2 ratios, the mortality:incidence ratio (MIR) and YLD:incidence ratio (years lost to disability), as specified in the Global Burden of Disease database. These were correlated to country-specific otolaryngologist density data in univariate and multivariate analyses. Results: Increased density of the ear, nose, and throat workforce correlated with better outcomes for otolaryngologic-treated surgical diseases. A 10% increase in otolaryngology workforce density was associated with a 0.27% reduction in YLD:incidence ratio for chronic otitis media, a 0.94% reduction in MIR for lip and oral cavity cancer, a 1.46% reduction in MIR for laryngeal cancer, and a 1.34% reduction in MIR for pharyngeal cancer (all P < .001)-an effect that remained after adjustment for health systems factors for all conditions but chronic otitis media. Conclusion: The density of the surgical workforce is assumed to affect disease outcomes, but ours is the first analysis to show that increased workforce density for a specific surgical specialty correlates with improved disease outcomes. While there is a consensus to increase access to health care providers, quantifying the effect on disease outcomes is an important metric for those performing health economics modeling, particularly where resources are limited.

11.
Otolaryngol Head Neck Surg ; 167(4): 669-677, 2022 10.
Article in English | MEDLINE | ID: mdl-35077240

ABSTRACT

OBJECTIVE: The objective of this study was to develop an international expert consensus on priority otolaryngology-head and neck surgery conditions and procedures globally for which national health systems should be capable of caring. STUDY DESIGN: The Delphi method was employed via a multiround online survey administered to attending otolaryngologists in an international research collaborative of >180 otolaryngologists in >40 countries. SETTING: International online survey. METHODS: In round 1, participants listed the top 15 otolaryngologic conditions and top 15 otolaryngology procedures for their World Bank regions. In round 2, participants ranked round 1 responses in order of global importance on a 5-point Likert scale. In round 3, participants reranked conditions and procedures that did not achieve consensus, defined as 50% of the round 2 Likert responses being ranked as "important" or "very important." Descriptive statistics were calculated for each round. RESULTS: The survey was distributed to 53 experts globally, with a response rate of 38% (n = 20). Fifty percent (n = 10) of participants were from low- and middle-income countries, with at least 1 participant from each World Bank region. Ten consensus surgical procedures and 10 consensus conditions were identified. CONCLUSION: This study identified a list of priority otolaryngology-head and neck surgery conditions and surgical procedures for which all national health systems around the world should be capable of managing. Acute and infectious conditions with preventative and emergent procedures were highlighted. These findings can direct future research and guide international collaborations.


Subject(s)
Otolaryngology , Consensus , Delphi Technique , Humans , Otolaryngologists , Surveys and Questionnaires
12.
Clin Cancer Res ; 27(24): 6772-6786, 2021 12 15.
Article in English | MEDLINE | ID: mdl-34548317

ABSTRACT

PURPOSE: Human papillomavirus (HPV) plays a major role in oncogenesis and circular extrachromosomal DNA (ecDNA) is found in many cancers. However, the relationship between HPV and circular ecDNA in human cancer is not understood. EXPERIMENTAL DESIGN: Forty-four primary tumor tissue samples were obtained from a cohort of patients with HPV-positive oropharynx squamous cell carcinoma (OPSCC). Twenty-eight additional HPV oropharyngeal cancer (HPVOPC) tumors from The Cancer Genome Atlas (TCGA) project were analyzed as a separate validation cohort. Genomic, transcriptomic, proteomic, computational, and functional analyses of HPVOPC were applied to these datasets. RESULTS: Our analysis revealed circular, oncogenic DNA in nearly all HPVOPC, with circular human and human-viral hybrid ecDNA present in over a third of HPVOPC and viral circular DNA in remaining tumors. Hybrid ecDNA highly express fusion transcripts from HPV promoters and HPV oncogenes linked to downstream human transcripts that drive oncogenic transformation and immune evasion, and splice multiple, diverse human acceptors to a canonical SA880 viral donor site. HPVOPC have high E6*I expression with specific viral oncogene expression pattern related to viral or hybrid ecDNA composition. CONCLUSIONS: Nonchromosomal circular oncogenic DNA is a dominant feature of HPVOPC, revealing an unanticipated link between HPV and ecDNA that leverages the power of extrachromosomal inheritance to drive HPV and somatic oncogene expression.


Subject(s)
Alphapapillomavirus , Head and Neck Neoplasms , Oncogene Proteins, Viral , Oropharyngeal Neoplasms , Papillomavirus Infections , DNA, Circular , DNA, Viral/genetics , Head and Neck Neoplasms/genetics , Humans , Oncogene Proteins, Viral/genetics , Oncogenes/genetics , Oropharyngeal Neoplasms/genetics , Papillomaviridae/genetics , Papillomavirus Infections/complications , Papillomavirus Infections/genetics , Proteomics
13.
Ann Glob Health ; 87(1): 17, 2021 02 15.
Article in English | MEDLINE | ID: mdl-33633928

ABSTRACT

Member States at this year's World Health Assembly 73 (WHA73), held virtually for the first time due to the COVID-19 pandemic, passed multiple resolutions that must be considered when framing efforts to strengthen surgical systems. Surgery has been a relatively neglected field in the global health landscape due to its nature as a cross-cutting treatment rather than focusing on a specific disease or demographic. However, in recent years, access to essential and emergency surgical, obstetric, and anesthesia care has gained increasing recognition as a vital aspect of global health. The WHA73 Resolutions concern specific conditions, as has been characteristic of global health practice, yet proper care for each highlighted disease is inextricably linked to surgical care. Global surgery advocates must recognize how surgical system strengthening aligns with these strategic priorities in order to ensure that surgical care continues to be integrated into efforts to decrease global health disparities.


Subject(s)
Anesthesia/standards , COVID-19 , General Surgery , Global Health , Health Services Accessibility/organization & administration , Healthcare Disparities/organization & administration , Obstetrics/standards , COVID-19/epidemiology , COVID-19/therapy , General Surgery/organization & administration , General Surgery/standards , Global Health/standards , Global Health/trends , Humans , Quality Improvement , SARS-CoV-2
14.
J Craniofac Surg ; 31(1): 142-146, 2020.
Article in English | MEDLINE | ID: mdl-31652215

ABSTRACT

BACKGROUND: The impact of metopic craniosynostosis on intracranial volume (ICV) and ICV growth is unclear. In addition, the relationship between head circumference (HC) and ICV in these patients is not previously described. METHODS: A retrospective review of 72 patients with metopic craniosynostosis was performed. The ICVs were calculated from manually segmented preoperative computed tomography scans. Magnetic resonance imaging data for 270 healthy children were available. The ICVs were calculated in FreeSurfer.First, a growth curve for metopic patients was generated and a logarithmic best-fit curve was calculated. Second, the impact of metopic craniosynostosis on ICV relative to healthy controls was assessed using multivariate linear regression. Third, the growth curves for metopic patients and healthy children were compared.Pearson's correlation was used to measure the association between HC and ICV. RESULTS: Mean metopic ICV was significantly lower than normal ICV within the first 3 to 6 months (674.9 versus 813.2 cm; P = 0.002), 6 to 9 months (646.6 versus 903.9 cm; P = 0.005), and 9 to 12 months of life (848.0 versus 956.6 cm; P = 0.038). There was no difference in ICV after 12 months of age (P = 0.916).The ICV growth in patients with metopic craniosynostosis is defined by a significantly different growth curve than in normal children (P = 0.005).The ICV and HC were highly correlated across a broad range of ICVs and patient age (r = 0.98, P < 0.001). CONCLUSION: Patients with metopic craniosynostosis have significantly reduced ICVs compared to healthy children, yet greater than normal ICV growth, which allows them to achieve normal volumes by 1 year of age. The HC is a reliable metric for ICV in these patients.


Subject(s)
Craniosynostoses/diagnostic imaging , Algorithms , Cephalometry/methods , Child , Female , Humans , Magnetic Resonance Imaging , Male , Multimodal Imaging , Retrospective Studies , Tomography, X-Ray Computed/methods
15.
Ann Plast Surg ; 82(5S Suppl 4): S295-S300, 2019 05.
Article in English | MEDLINE | ID: mdl-30973835

ABSTRACT

BACKGROUND: Calculation of intracranial volume from neuroimaging can be complex and time consuming. In the adult population, there is evidence suggesting that owing to its strong correlation, head circumference (HC) may be used as a surrogate for intracranial volume (ICV). We were interested in studying the correlation between HC and ICV in patients with craniosynostosis. METHODS: After institutional review board approval, a retrospective review was performed on patients with craniosynostosis. GE Healthcare AdW 4.3 volume assessment software was used to calculate ICV and HC based on preoperative computed tomographic scans. Pearson correlation was used to estimate correlation coefficients between ICV and HC for this patient population, with 0 to 0.3 considered a weak correlation, 0.4 to 0.6 considered a moderate correlation, 0.7 to 1 considered a strong correlation, and P < 0.05 was considered statistically significant. RESULTS: A total of 196 craniosynostosis patients were included in this study. There were 121 male and 75 female patients. Seventy-nine patients had metopic, 45 had coronal, 64 had sagittal, and 8 had lambdoid synostosis. Mean age was 8.2 months. Mean HC and ICV were 42.9 cm and 829 cm, respectively. Overall, there was a strong correlation between HC and ICV (r = 0.81). Patients were further categorized by craniosynostosis type. Very strong correlation was obtained for patients with coronal (0.89), metopic (0.98), and lambdoid craniosynostosis (0.97). Strong correlation was obtained for patients with sagittal synostosis (0.73). When categorized by sex, a stronger correlation was obtained for female patients (0.84) compared with male patients (0.80). Statistical significance was reached for all reported correlations. CONCLUSION: Our preliminary data suggest that a very strong correlation exists between HC and ICV for male and female patients with all types of craniosynostosis, making HC a useful surrogate for ICV in this patient population.


Subject(s)
Brain/anatomy & histology , Cephalometry , Craniosynostoses/pathology , Correlation of Data , Dimensional Measurement Accuracy , Female , Humans , Infant , Male , Organ Size , Retrospective Studies
16.
Ann Plast Surg ; 82(5S Suppl 4): S301-S305, 2019 05.
Article in English | MEDLINE | ID: mdl-30973836

ABSTRACT

BACKGROUND: The aims of the current analysis were to study the change in ventricular volume (VV) obtained with cranial distraction in patients with craniosynostosis and compare it with the change in total intracranial volume (ICV) and brain volume. METHODS: After institutional review board approval, a retrospective review was performed on patients undergoing cranial distraction over a 5-year period. GE Healthcare AdW 4.3 volume assessment software was utilized to calculate preoperative and postdistraction ICV, VV, and whole-brain volume. Data were also collected on patient demographics, age at the time of distraction, time spent in distraction and consolidation, and length of stay. t Tests were used for comparison. RESULTS: Twenty-three patients met our inclusion criteria. Forty-eight percent of patients (n = 11) had right-sided cranial distraction, 30% (n = 7) had bilateral distraction, and 22% of patients (n = 5) had left-sided distraction. At the preoperative stage, mean head circumference was 42.5 ± 4.7 cm, mean ICV was 810.1 ± 27 cm, mean non-VV (NVV) was 796.2 ± 268 cm, and mean VV was 13.9 ± 9 cm. After a mean of 27.4 mm of distraction, occurring over a mean of 26 days and consolidation period of 149 days, a second computed tomography scan was obtained. Mean postdistraction head circumference was 49.1 ± 3.9 cm, mean ICV was 1074.1 ± 203 cm, mean NVV was 1053.5 ± 197 cm, and VV was 20.6 ± 14 cm. Mean % increase in ICV at this stage was 47.4%; mean % NVV increase was 48.5% as opposed to 60.3% increase in VV. CONCLUSIONS: Cranial distraction is known to effectively increase ICV. Our study suggests that the effect of this volumetric increase is much more pronounced on the VV compared with the brain volume. Further studies are underway to investigate whether this short-term marked increase in VV is sustained over a long-term period.


Subject(s)
Cerebral Ventricles/growth & development , Craniosynostoses/surgery , Osteogenesis, Distraction , Brain/growth & development , Female , Humans , Infant , Male , Organ Size , Retrospective Studies
17.
Cancer Cell ; 30(5): 683-693, 2016 Nov 14.
Article in English | MEDLINE | ID: mdl-27746144

ABSTRACT

Small-molecule inhibitors targeting growth factor receptors have failed to show efficacy for brain cancers, potentially due to their inability to achieve sufficient drug levels in the CNS. Targeting non-oncogene tumor co-dependencies provides an alternative approach, particularly if drugs with high brain penetration can be identified. Here we demonstrate that the highly lethal brain cancer glioblastoma (GBM) is remarkably dependent on cholesterol for survival, rendering these tumors sensitive to Liver X receptor (LXR) agonist-dependent cell death. We show that LXR-623, a clinically viable, highly brain-penetrant LXRα-partial/LXRß-full agonist selectively kills GBM cells in an LXRß- and cholesterol-dependent fashion, causing tumor regression and prolonged survival in mouse models. Thus, a metabolic co-dependency provides a pharmacological means to kill growth factor-activated cancers in the CNS.


Subject(s)
Brain Neoplasms/drug therapy , Cholesterol/metabolism , Glioblastoma/drug therapy , Indazoles/administration & dosage , Liver X Receptors/metabolism , Animals , Brain Neoplasms/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Female , Glioblastoma/metabolism , Humans , Indazoles/pharmacology , Mice , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL