Publications by authors named "Christopher Brooks"

110 Publications

Multiple non-contiguous anticoagulation-related spontaneous acute spinal intradural extramedullary hemorrhages.

Surg Neurol Int 2022 3;13:235. Epub 2022 Jun 3.

Department of Neurosurgery, Concord Repatriation General Hospital, Concord, Australia.

Background: Spinal intradural extramedullary hemorrhage is a rare and important pathology that may precipitate acute compressive myelopathy. It is most commonly associated with spinal trauma, neoplasia, vasculopathy, and iatrogenesis. In rare circumstances, it occurs spontaneously secondary to anticoagulant and antiplatelet medications without an underlying structural lesion. In these instances, it may be related to vasculopathy and/ or cardiovascular disease risk factors. We highlight the salient clinical and radiological features of this pathology, discuss putative mechanisms of its pathogenesis, and describe surgical considerations related to its management.

Case Description: This report describes an elderly gentleman who presented with two discrete spinal hemorrhages associated with separate foci of bleeding, in the context of therapeutic anticoagulation, on a background of significant structural and functional cardiovascular disease with risk factors.

Conclusion: Our report is novel in that there are no other cases, to the best of our knowledge, of multiple non-contiguous anticoagulation-related spontaneous acute spinal intradural extramedullary hemorrhages in the medical literature. This article is written with the purpose of assisting clinicians to recognize and expedite treatment of this rare pathology. Prompt diagnosis followed by urgent decompressive surgery provides the best functional outcomes.
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http://dx.doi.org/10.25259/SNI_178_2022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282782PMC
June 2022

Long-Term Benefits of Tagraxofusp for Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm.

J Clin Oncol 2022 Jul 12:JCO2200034. Epub 2022 Jul 12.

Dana-Farber Cancer Institute, Boston, MA.

JCO Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive myeloid malignancy. We report long-term results, including data from the continued access phase, of the largest prospective BPDCN trial evaluating the CD123-targeted therapy tagraxofusp (TAG) in adults with treatment-naive and relapsed/refractory BPDCN. The primary outcome was complete response (CR) + clinical CR (CRc: CR with residual skin abnormality not indicative of active disease). Eighty-four (65 treatment-naive and 19 relapsed/refractory) of 89 patients received TAG 12 μg/kg once daily; the median follow-up was 34.0 months. For treatment-naive patients, the overall response rate was 75%; 57% achieved CR + CRc. The median time to remission was 39 (range, 14-131) days, and the median CR + CRc duration was 24.9 (95% CI, 3.8 to not reached) months. Nineteen patients (51%) with CR + CRc were bridged to stem-cell transplant, with a median CR + CRc duration of 22.2 (range, 1.5-57.4) months. Most common adverse events were increased alanine (64%) or aspartate (60%) aminotransferase and hypoalbuminemia (51%); most occurred in cycle 1 and were transient. Capillary leak syndrome occurred in 21% of patients (grade ≥ 3: 7%). In first-line patients with BPDCN, TAG monotherapy resulted in high and durable responses, allowing many to bridge to stem-cell transplant. TAG was generally well-tolerated with a predictable and manageable safety profile.
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http://dx.doi.org/10.1200/JCO.22.00034DOI Listing
July 2022

Thoracic spondylodiscitis secondary to urosepsis-a case report.

J Spine Surg 2022 Mar;8(1):54-61

Department of Neurosurgery, Concord Repatriation General Hospital, Concord, Australia.

Spondylodiscitis is an insidious and infectious pathology of the spinal column attributable to pathogenic micro-organisms and occurs in a variety of contexts. These micro-organisms can be inoculated surgically or can metastasise from distant sites of infection. species are important community-acquired and nosocomial pathogens but are uncommonly implicated in spinal infection. is more obscure than its generic relative and has only five times previously been reported in spondylodiscitis. It possesses the ability to acquire inducible and recombinant antibiotic resistance, especially in the hospital setting. We describe the case of an elderly man with complex urology and this rare sequela due to incomplete treatment of a urinary infection. He developed sepsis that recurred after incomplete antibiosis and seeded to his thoracic spine causing overt spondylodiscitis. The infection fulminated and his spinal lesion deteriorated into acute spinal cord compression with neurological compromise, requiring surgical decompression, fixation and long-term antibiotics. This is a sixth documented instance of a rare spinal bacterial infection. We describe the relevant microbiology and pathology, neurosurgical considerations, and general practice points for clinicians. Our report is a novel illustration of the potentially catastrophic consequences of inadequately treated urosepsis and is a stark reminder of the importance of antimicrobial stewardship.
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http://dx.doi.org/10.21037/jss-21-124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990402PMC
March 2022

Clinical Remission in Severe Asthma: A Pooled Post Hoc Analysis of the Patient Journey with Benralizumab.

Adv Ther 2022 05 14;39(5):2065-2084. Epub 2022 Mar 14.

BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA.

Introduction: Consensus definitions for clinical remission and super-response were recently established for severe asthma. Benralizumab is an interleukin-5 (IL-5) receptor α-directed monoclonal antibody for severe, uncontrolled asthma; efficacy and safety were demonstrated in previous pivotal phase 3 trials (SIROCCO, CALIMA, ZONDA). This analysis applied a composite remission definition to characterize individual responses to benralizumab after 6 and 12 months.

Methods: In previous phase 3 studies, eligible patients were those with severe, uncontrolled asthma receiving medium- or high-dosage inhaled corticosteroids plus long-acting β-agonists. This post hoc analysis included patients randomized to the approved benralizumab dose and not receiving oral corticosteroids (OCS) at baseline (SIROCCO/CALIMA) or OCS ≤ 12.5 mg per day (ZONDA). Individual remission components were zero exacerbations; zero OCS use; Asthma Control Questionnaire-6 (ACQ-6) score < 1.5 or ≤ 0.75; and pre-bronchodilator forced expiratory volume in 1 s (FEV) increase ≥ 100 mL; clinical remission incorporated zero exacerbations, zero OCS use, ACQ-6 score ≤ 0.75, and pre-bronchodilator FEV increase ≥ 100 mL after 6 or 12 months.

Results: Overall, 609 patients (N = 301 and N = 308) and 586 patients (N = 293 and N = 293) receiving benralizumab in SIROCCO and CALIMA were included at 6 and 12 months, respectively; 40 ZONDA patients were included after 6 months. In SIROCCO/CALIMA, similar to 6-month findings,  approx. 83% and approx. 49% receiving benralizumab, and 77% and 37% on placebo achieved ≥ 2 and ≥ 3 remission components after 12 months; 14.5% (85/586) on benralizumab and 7.7% (48/620) on placebo achieved clinical remission at 12 months. Among ZONDA patients, 75% and approx. 48% on benralizumab and 35% and 20% on placebo achieved ≥ 2 and ≥ 3 remission components at 6 months, respectively; 22.5% (9/40) on benralizumab and 7.5% on placebo achieved clinical remission.

Conclusions: This analysis demonstrates clinical remission is achievable by targeting the underlying drivers of inflammation. Precision medicines can help shift treatment paradigms toward treat-to-target, with clinical remission as the ultimate therapeutic goal in severe asthma.

Clinical Trial Registration: SIROCCO (NCT01928771); CALIMA (NCT01914757); ZONDA (NCT02075255).
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http://dx.doi.org/10.1007/s12325-022-02098-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9056458PMC
May 2022

Pseudochoreoathetosis secondary to progressive spondylotic cervical myelopathy.

BMJ Case Rep 2021 Dec 31;14(12). Epub 2021 Dec 31.

Neurosurgery, Liverpool Hospital, Sydney, New South Wales, Australia.

Pseudochoreoathetosis is a rare movement disorder associated with loss of proprioception. Culprit lesions may occur at any point between the cerebral cortex and the peripheral nerve. Seldom is the underlying cause reversible or prone to improvement. An elderly man presented to our tertiary centre with choreoathetoid movements secondary to spondylotic subaxial cervical myelopathy. His myelopathy fulminated and he was emergently treated with posterior decompressive neurosurgery. Unexpectedly, his choreoathetoid movements improved significantly post-operatively. There are a multitude of reports of pseudochoreoathetosis secondary to lesions of various aetiologies; however, few have reported this disorder secondary to cervical spondylosis. To our knowledge, there is only one other report in the medical literature. Herein, we report a second case, for the purposes of raising awareness of this disorder, and to highlight relevant clinical pearls for clinicians who encounter this rare pathology.
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http://dx.doi.org/10.1136/bcr-2021-247471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720953PMC
December 2021

Survival from Canadian Seaplane Water Accidents: 1995 to 2019.

Aerosp Med Hum Perform 2021 Oct;92(10):798-805

Each year in Canada, there are a number of pilots and passengers who die in seaplane water accidents. A study examining the human factors and fatality rates associated with these accidents was conducted. Seaplane water accident investigations by the Transportation Safety Board of Canada (TSB) between 1995 and 2019 were reviewed. There were 487 accidents involving 1144 occupants (487 pilots, 657 passengers). There were less than 15 s warning in 86% of cases. There were 60 pilots and 88 passengers who dieda survival rate of 87%. Drowning, trapped within the cabin was the principal cause of death (54%). Loss of control on landing, wheels down landings, and other landing problems (49%) were the principal causes of the accidents and 77% of the fatalities occurred in this group. These arose because the pilot(s) misjudged wind, waves, and glassy water. Over 50% of seaplanes inverted and 10% floated briefly then sank, resulting in the highest percentage of fatalities. Wearing the seat harness incorrectly, injury, in-rushing water, and inability to locate and operate exit mechanisms (including rescuers inability to open the exits external to the fuselage) all contributed to the fatalities. Life jackets would have been of benefit in several cases. Of the accidents, 57% were private flights. Passengers require a thorough preflight briefing, life jackets should be worn by all pilots and passengers, and private and commercial pilots should receive Underwater Egress Training. .
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http://dx.doi.org/10.3357/AMHP.5784.2021DOI Listing
October 2021

Transformational Steam Infusion Processing for Resilient and Sustainable Food Manufacturing Businesses.

Foods 2021 Jul 30;10(8). Epub 2021 Jul 30.

National Centre for Food Manufacturing, University of Lincoln, Holbeach PE12 7PT, UK.

Here we show how food and beverage manufacturers report more incisive sustainability and product fulfilment outcomes for their business enterprises when innovative processing technologies are used. The reported steam infusion technology heats food materials within a Vaction Pump device so that steam is directed into the food material within a much reduced volume, reducing the use of steam and processing time. This study reports how such technological interventions will enable supply chain stakeholders to demonstrate responsible consumption by connecting assessments for the reduction of greenhouse gas emissions with consumer-focused outcomes such as product quality. The technology reported in this research not only improves operational agility by improving processing speed, but also improves the responsiveness of factory production to changes in demand. Heating procedures are systemic processes in the food industry that can be used to pasteurize, achieve commercially viable shelf-life, and provide cleaning in place. The reported research defines how these technologies can reduce the carbon footprint of products, improve quality attributes, and lower operating costs across supply chains. They provide an important step in developing distributed manufacturing in the food system because the technologies reported here are modular and can be installed into existing operations. The specific technology can reduce energy consumption by 17.3% compared to basic direct steam heating, with a reduction of 277.8 processing hours and 8.7 tonnes GHG emissions per kettle production line each year. Food and beverage manufacturers are increasingly required to report across the sustainability, nutrition, and product quality outcomes of their business enterprises more incisively so that supply chain stakeholders can demonstrate responsible production and consumption. The steam infusion technologies assessed in this research enable alignment to the UN Sustainable Development Goals, specifically SDG12, Responsible Production and Consumption, using in situ data logging in factory trials for novel heating procedures used to process foods.
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http://dx.doi.org/10.3390/foods10081763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393886PMC
July 2021

Computed tomography-occult discoligamentous instability following blunt cervical spine trauma.

BMJ Case Rep 2021 Aug 25;14(8). Epub 2021 Aug 25.

Neurosurgery, Liverpool Hospital, Liverpool, New South Wales, Australia.

Plain CT is routinely ordered following blunt trauma of the cervical spine, and performs well in the exclusion of significant bony injuries. MRI is reserved for cases of suspected neural or posterior ligamentous compromise, and when other imaging modalities are contraindicated. There are patients however, with unremarkable radiology, and without suggestive clinical features, who are later found to have significant discoligamentous instability. In this report, we present two such cases. In both instances, worsening neurological symptoms prompted follow-up imaging, that demonstrated interval development of sub-axial cervical spondylolisthesis, requiring surgery and instrumentation. We identify and discuss radiological features that may be associated with occult discoligamentous injury, and highlight them as avenues for future research. These may prove useful in stratifying at-risk patients for further imaging in the acute setting.
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http://dx.doi.org/10.1136/bcr-2021-244136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388292PMC
August 2021

Traumatic intracranial nail-gun injury of the right internal carotid artery causing pseudoaneurysm and caroticocavernous fistula.

BMJ Case Rep 2021 Aug 24;14(8). Epub 2021 Aug 24.

The School of Medicine, The University of Sydney, Sydney, New South Wales, Australia.

Penetrating trauma due to nail gun is an uncommon yet important clinical entity. There are numerous case reports describing these injuries, yet few describe those resulting in cerebrovascular injury. Laceration of cerebral blood vessels may result in significant intracranial haemorrhage and cerebral ischaemia, with catastrophic consequences. In the present study, we report a female patient who was shot in the face with a nail gun in a domestic assault. The nail entered her right cavernous sinus and lacerated her right internal carotid artery causing a pseudoaneurysm and a caroticocavernous fistula. This report details the approach to, and pitfalls of, managing a cerebrovascular injury due to penetrating intracranial nail. Catheter cerebral angiography is essential in the diagnosis and treatment of these injuries. Best treatment and outcomes require clinicians with expertise in endovascular and surgical repair strategies.
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http://dx.doi.org/10.1136/bcr-2021-243789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386238PMC
August 2021

Targeting CD123 in hematologic malignancies: identifying suitable patients for targeted therapy.

Leuk Lymphoma 2021 11 17;62(11):2568-2586. Epub 2021 May 17.

Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Following the observation of interleukin 3 receptor α chain (IL-3Rα; CD123) upregulation on leukemia stem cells (LSCs) almost two decades ago, targeted treatment CD123-diptheria toxin conjugates has now been tested in patients with diverse myeloid malignancies. Targeted eradication of LSCs could result in effective treatments for many challenging diseases initiated by these cells. Consequently, considerable effort has been directed toward targeting CD123 as a potential strategy for treating patients with hematologic malignancies in which CD123 is overexpressed. However, these therapies have had limited success so far, highlighting the need for suitable criteria to identify patients who could benefit from them. Given the diversity in CD123 expression across different hematologic malignancies, understanding CD123 expression patterns and the functional pathogenetic significance is crucial. Here, we review the methodologies available for CD123 assessment and discuss the biological and clinical characteristics of patients for whom CD123-targeting therapies may have a clinical impact.
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http://dx.doi.org/10.1080/10428194.2021.1927021DOI Listing
November 2021

Enhancing the undergraduate nursing education experience with clinical elective courses.

J Prof Nurs 2021 Mar-Apr;37(2):366-372. Epub 2020 Apr 26.

College of Health Professions, Pace University, 861 Bedford Road, Pleasantville, NY 10570, United States. Electronic address:

The nursing faculty, in concert with the University's vision of personalized learning for undergraduate students, sought creative opportunities for nursing students to explore distinctive career specialty paths. The development, implementation, and evaluation of three undergraduate clinical electives developed by a School of Nursing (SON) is described here, in collaboration with three clinical practice partners. These nursing elective courses were designed to meet student requests for additional content in specialty nursing practice areas, enhance new nurse career readiness, and meet practice partner staffing needs for nurses with additional knowledge and skills in specific identified specialties. These nursing specialties included perioperative nursing, neonatal intensive care nursing, and oncology nursing. The SON faculty and each practice partner co-developed unique specialty-nursing elective courses that provide foundational specialty knowledge and skills in each practice arena. Project outcomes include enhanced relationships between the SON and practice partners, high levels of satisfaction of students and employers, and subsequent recruitment and employment of these students as new graduate nurses by our practice partners.
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http://dx.doi.org/10.1016/j.profnurs.2020.04.014DOI Listing
June 2021

Assessing socio-economic profile of U-Reporters: Towards establishing a pool for equity analysis of future crowdsourced surveys.

J Glob Health 2021 Mar 1;11:09001. Epub 2021 Mar 1.

UNICEF Programme Division, New York, New York, USA.

Background: Crowdsourcing was recognized as having the potential to collect information rapidly, inexpensively and accurately. U-Report is a mobile empowerment platform that connects young people all over the world to information that will change their lives and influence decisions. Previous studies of U-Report's effectiveness highlight strengths in the timeliness, low cost and high credibility for collecting and sending information, however they also highlight areas to improve on concerning data representation. EquityTool has developed a simpler approach to assess the wealth quintiles of respondents based on fewer questions derived from large household surveys such as Multiple Indicators Cluster Surveys (MICS) and Demographic and Health Surveys (DHS).

Methods: The methodology of Equity Tool was adopted to assess the socio-economic profile of U-Reporters (ie, enrolled participants of U-Report) in Bangladesh. The RapidPro flow collected the survey responses and scored them against the DHS national wealth index using the EquityTool methodology. This helped placing each U-Reporter who completed all questions into the appropriate wealth quintile.

Results: With 19% of the respondents completing all questions, the respondents fell into all 5 wealth quintiles, with 79% in the top-two quintiles and only 21% in the lower-three resulting in an Equity Index of 53/100 where 100 is completely in line with Bangladesh equity distribution and 1 is the least in line. An equitable random sample of 1828 U-Reporters from among the regular and frequent respondents was subsequently created for future surveys and the sample has an Equity Index of 98/100.

Conclusions: U-Report in Bangladesh does reach the poorest quintiles while the initial recruitment skews to respondents towards better off families. It is possible to create an equitable random sub-sample of respondents from all five wealth quintiles and thus process information and data for future surveys. Moving forward, U-Reporters from the poorly represented quintiles may be incentivized to recruit peers to increase equity and representation. In times of COVID-19, U-Report in combination with the EquityTool has the potential to enhance the quality of crowdsourced data for statistical analysis.
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http://dx.doi.org/10.7189/jogh.11.09001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979256PMC
March 2021

Leveraging Academic-Clinical Partnerships to Create an Operating Room Nurse Pipeline.

J Nurs Adm 2021 Mar;51(3):168-172

Author Affiliations: Director (Mr Brooks), Nursing Professional Development and Education, Memorial Sloan Kettering Cancer Center, New York; Associate Dean for Academic Affairs & Strategic Partnerships (Dr Della Ratta), Stony Brook University; Chair (Dr LaSala), Department of Undergraduate Studies, Stony Brook University; and Perioperative Nurse Professional Development Specialist (Ms Gerberich) and Deputy Chief Nursing Officer (Dr Browne), Memorial Sloan Kettering Cancer Center, New York, New York.

This article describes an academic-clinical partnership program between a school of nursing and an American Nurse Credentialing Center Magnet®- and National Cancer Institute-designated Comprehensive Cancer Center based on a shared vision and multifaceted for optimal new graduate operating room (OR) recruitment and use of clinical partner resources. The program, now in its 3rd year, has a 100% retention rate among the cohorts. Implementing a multifaceted OR partnership program based on nursing theory is a strategy for workforce development to increase retention of new graduate OR nurses.
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http://dx.doi.org/10.1097/NNA.0000000000000989DOI Listing
March 2021

T2-hyperintense, non-gadolinium-enhancing, diffusion-restricted symmetrical curvilinear lesion of the anterior pons: a rare radiological pattern of leptomeningeal metastatic disease secondary to likely lung adenocarcinoma.

BMJ Case Rep 2021 Jan 18;14(1). Epub 2021 Jan 18.

Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia.

Leptomeningeal carcinomatosis is a devastating sequelae of metastatic cancer. It has protean manifestations on imaging. An elderly woman presented to our tertiary centre with symptoms suggestive of a cerebrovascular accident. Investigations revealed no evidence of this. There was clinical, contextual and radiological evidence of an underlying neoplasm.Magnetic resonance imaging (MRI) demonstrated evidence of a rare morphology (anterolateral pontine leptomeningeal enhancement) in the presence of a probable concomitant lung adenocarcinoma. Other reports have previously described this same neuroradiology, seemingly always in association with lung adenocarcinoma.The purpose of this report is to highlight an unusual case and discuss its peculiarity and pathophysiology. Our patient is the latest documented of a small cohort with this constellation of clinical and neuroradiological features.This study demonstrates the importance of differential diagnosis in stroke medicine, specifically the need to consider neoplastic phenomena in patients admitted following putative cerebrovascular events.
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http://dx.doi.org/10.1136/bcr-2020-236265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813415PMC
January 2021

Trainee surgeons and patient outcomes in carotid endarterectomy: a retrospective cohort study.

ANZ J Surg 2020 09 19;90(9):1710-1715. Epub 2020 Aug 19.

Department of Surgery, Alfred Health, Melbourne, Victoria, Australia.

Background: In Australia and New Zealand, more than 2000 carotid endarterectomies are performed annually. The major morbidities arising from this procedure are post-operative stroke, cranial nerve injury and death. Carotid endarterectomy surgery is a key component of the vascular surgical training programme. We assessed the impact of having a surgical trainee perform a major component of this procedure on the post-operative rates of stroke, cranial nerve injury and mortality.

Methods: We performed a retrospective cohort study of vascular surgical patients undergoing carotid endarterectomy, with data obtained from the Australasian Vascular Audit database between January 2010 and December 2014. The dataset comprised of 6528 carotid endarterectomies performed during this time. The collected data were stratified into two categories - consultant-led cases, and those in which trainee surgeons performed at least a major component of the surgery under consultant supervision. The results were analysed for differences in post-operative stroke, cranial nerve injury and inpatient mortality. Differences between groups were assessed using multivariate analysis, adjusting for potentially confounding covariables.

Results: On multivariate analysis, there was no statistically significant difference in the rates of post-operative stroke (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.57-1.36, P = 0.55), cranial nerve injury (OR 0.68, 95% CI 0.39-1.21, P = 0.19) or inpatient mortality (OR 0.78, 95% CI 0.29-2.13, P = 0.63) between the two cohorts.

Conclusion: Having surgical trainees perform components of carotid endarterectomies under supervision is not associated with an increased rate of post-operative stroke, cranial nerve injury or mortality.
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http://dx.doi.org/10.1111/ans.16209DOI Listing
September 2020

Prevalence and factors associated with advanced care directives in a motor neuron disease multidisciplinary clinic in Australia.

Postgrad Med J 2021 Sep 11;97(1151):566-570. Epub 2020 Aug 11.

Department of Neurology and Neurophysiology, Liverpool Hospital, Liverpool, Australia.

Objectives: Motor neuron disease (MND) is a neurodegenerative disorder leading to functional decline and death. Multidisciplinary MND clinics provide an integrated approach to management and facilitate discussion on advanced care directives (ACDs). The study objectives are to analyse (1) the prevalence of ACD in our MND clinic, (2) the relationship between ACD and patient demographics and (3) the relationship between ACD decision-making and variables such as NIV, PEG, hospital admissions and location of death.

Methods: Using clinic records, all patients who attended the MND clinic in Liverpool Hospital between November 2014 and November 2019 were analysed. Data include MND subtypes, symptom onset to time of diagnosis, time of diagnosis to death, location and reason of death. ACD prevalence, non-invasive ventilation (NIV) and percutaneous endoscopic gastrostomy (PEG) requirements were analysed.

Results: There were 78 patients; M:F=1:1. 44 (56%) patients were limb onset, 28 (36%) bulbar onset, 4 primary lateral sclerosis and 2 flail limb syndrome presentations. 27% patients completed ACDs, while 32% patients declined ACDs. Patients born in Australia or in a majority English-speaking country were more likely to complete ACDs compared to those born in a non-English-speaking country. There was no significant correlation between ACD completion and age, gender, MND subtype, symptom duration, NIV, PEG feeding, location of death.

Conclusion: One-quarter of patients completed ACDs. ACDs did not correlate with patient age, gender, MND subtype and symptom duration or decision-making regarding NIV, PEG feeding or location of death. Further studies are needed to address factors influencing patients' decisions regarding ACDs.
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http://dx.doi.org/10.1136/postgradmedj-2020-138184DOI Listing
September 2021

The oncogenic potential of a mutant TP53 gene explored in two spontaneous lung cancer mice models.

BMC Cancer 2020 Aug 8;20(1):738. Epub 2020 Aug 8.

Department of Human & Molecular Genetics, Herbert Wertheim College of Medicine, The Florida International University, Miami, Florida, 33199, USA.

Background: Lung cancer is the number one cancer killer worldwide. A major drawback in the lung cancer treatment field is the lack of realistic mouse models that replicate the complexity of human malignancy and immune contexture within the tumor microenvironment. Such models are urgently needed. Mutations of the tumor protein p53 are among the most common alterations in human lung cancers.

Methods: Previously, we developed a line of lung cancer mouse model where mutant human TP53-273H is expressed in a lung specific manner in FVB/N background. To investigate whether the human TP53 mutant has a similar oncogenic potential when it is expressed in another strain of mouse, we crossed the FVB/N-SPC-TP53-273H mice to A/J strain and created A/J-SPC-TP53-273H transgenic mice. We then compared lung tumor formation between A/J-SPC-TP53-273H and FVB/N-SPC-TP53-273H.

Results: We found the TP53-273H mutant gene has a similar oncogenic potential in lung tumor formation in both mice strains, although A/J strain mice have been found to be a highly susceptible strain in terms of carcinogen-induced lung cancer. Both transgenic lines survived more than 18 months and developed age related lung adenocarcinomas. With micro CT imaging, we found the FVB-SPC-TP53-273H mice survived more than 8 weeks after initial detection of lung cancer, providing a sufficient window for evaluating new anti-cancer agents.

Conclusions: Oncogenic potential of the most common genetic mutation, TP53-273H, in human lung cancer is unique when it is expressed in different strains of mice. Our mouse models are useful tools for testing novel immune checkpoint inhibitors or other therapeutic strategies in the treatment of lung cancer.
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http://dx.doi.org/10.1186/s12885-020-07212-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414707PMC
August 2020

Behavioral plasticity mitigates the effect of warming on white-tailed deer.

Ecol Evol 2020 Mar 11;10(5):2579-2587. Epub 2020 Feb 11.

Department of Biological Sciences Mississippi State University Mississippi State Mississippi.

Climate change is expected to create novel environments in which extant species cannot persist, therefore leading to the loss of them and their associated ecological functions within the ecosystem. However, animals may employ behavioral mechanisms in response to warming that could allow them to maintain their functional roles in an ecosystem despite changed temperatures. Specifically, animals may shift their activity in space or time to make use of thermal heterogeneity on the landscape. However, few studies consider the role of behavioral plasticity and spatial or temporal heterogeneity in mitigating the effects of climate change. We conducted experiments to evaluate the potential importance of behavior in mediating the net effects of warming on white-tailed deer (). We used shade structures to manipulate the thermal environment around feeding stations to monitor deer feeding activity and measure total consumption. In individual experiments where deer only had access to unshaded feeders, deer fed less during the day but compensated by increasing feeding during times when temperature was lower. In group experiments where deer had access to both shaded and unshaded feeders, deer often fed during the day but disproportionally preferred the cooler, shaded feeders. Our results suggest that deer can capitalize on temporal and spatial heterogeneity in the thermal environment to meet nutritional and thermal requirements, demonstrating the importance of behavioral plasticity when predicting the net effects of climate change.
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http://dx.doi.org/10.1002/ece3.6087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069326PMC
March 2020

Medical Cases Adjudicated by the Transportation Appeal Tribunal of Canada: 2000-2018.

Aerosp Med Hum Perform 2020 Feb;91(2):79-85

In Canada, aviators and seafarers are required to be medically fit by international and domestic standards to be issued a medical certificate by Transport Canada (TC). In the event of denial or restriction, individuals have the right to a review by an independent decision-maker with medical expertise/training in marine and/or aviation medicine. This paper presents the results of cases submitted to the Transportation Appeal Tribunal of Canada over 19 yr. The Tribunal's repository of medical records was searched and 112 adjudicated cases were reviewed. Since 2000, 55 (49%) cases were in the aviation sector and, since 2010, 57 (51%) cases were in the marine sector. The mean age of applicants was 49 and 54 yr for seafarers and pilots, respectively. Mental illness, cardiovascular disease, visual, and neurological disease were the most common reasons for a medical certificate restriction/denial. The Tribunal upheld the refusal to issue or renew a medical certificate in 89 (79%) cases and 23 (21%) cases were referred back to TC. Mental illness is the most frequent diagnosis that precipitates a request. The international literature is sparse on the number, causes, and results of the appeal process. Our findings and the application of the medical standards in Canada are generally comparable with those of the United Kingdom. It was not possible to make more than indirect comparisons to those of the United States.
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http://dx.doi.org/10.3357/AMHP.5489.2020DOI Listing
February 2020

Reintroduction of foods after a negative oral food challenge: A 2-year follow-up.

Ann Allergy Asthma Immunol 2020 04 16;124(4):398-399. Epub 2020 Jan 16.

University of Minnesota, Minneapolis, Minnesota; Allergy and Asthma Specialists, Minneapolis, Minnesota.

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http://dx.doi.org/10.1016/j.anai.2020.01.005DOI Listing
April 2020

A Collaborative Academic-Practice Approach to Meeting Educational and Workforce Needs.

J Nurs Adm 2019 Oct;49(10):463-465

Author Affiliations: Executive Associate Dean and Professor (Dr Maneval), Dean and Professor (Dr Feldman), Assistant Professor (Dr Henderson), and Associate Professor (Dr Epstein), College of Health Professions, Lienhard School of Nursing, Pace University, New York; Deputy Chief Nursing Officer (Dr Browne) and Director (Mr Brooks), Nursing Professional Development, Memorial Sloan Kettering Cancer Center, New York; Senior Director (Ms Scuderi), Nursing Education, Practice & Quality, Westchester Medical Center, Valhalla, New York.

This article describes an innovative academic-practice partnership designed to promote new nurse competency and meet employer needs for graduates with in-demand knowledge and competencies in specialty patient populations. Three practice partners identified areas of need and with the school of nursing developed specialty nursing elective courses with precepted clinical experiences.
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http://dx.doi.org/10.1097/NNA.0000000000000788DOI Listing
October 2019

DNA methyltransferase inhibition overcomes diphthamide pathway deficiencies underlying CD123-targeted treatment resistance.

J Clin Invest 2019 11;129(11):5005-5019

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.

The interleukin-3 receptor α subunit, CD123, is expressed in many hematologic malignancies including acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN). Tagraxofusp (SL-401) is a CD123-targeted therapy consisting of interleukin-3 fused to a truncated diphtheria toxin payload. Factors influencing response to tagraxofusp other than CD123 expression are largely unknown. We interrogated tagraxofusp resistance in patients and experimental models and found that it was not associated with CD123 loss. Rather, resistant AML and BPDCN cells frequently acquired deficiencies in the diphthamide synthesis pathway, impairing tagraxofusp's ability to ADP-ribosylate cellular targets. Expression of DPH1, encoding a diphthamide pathway enzyme, was reduced by DNA CpG methylation in resistant cells. Treatment with the DNA methyltransferase inhibitor azacitidine restored DPH1 expression and tagraxofusp sensitivity. We also developed a drug-dependent ADP-ribosylation assay in primary cells that correlated with tagraxofusp activity and may represent an additional novel biomarker. As predicted by these results and our observation that resistance also increased mitochondrial apoptotic priming, we found that the combination of tagraxofusp and azacitidine was effective in patient-derived xenografts treated in vivo. These data have important implications for clinical use of tagraxofusp and led to a phase 1 study combining tagraxofusp and azacitidine in myeloid malignancies.
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http://dx.doi.org/10.1172/JCI128571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819120PMC
November 2019

Genetic structure at three spatial scales is consistent with limited philopatry in Ricord's Rock Iguanas ().

Ecol Evol 2019 Jul 2;9(14):8331-8350. Epub 2019 Jul 2.

Mississippi State University Mississippi State Mississippi USA.

is an endemic iguana from Hispaniola Island and is threatened on the IUCN Red List. The main threats are predation by introduced mammals, habitat destruction, and hunting pressure. The present study focused on two nesting sites from Pedernales Province in the Dominican Republic. The hypothesis that natal philopatry influences dispersal and nest-site selection was tested. Monitoring and sampling took place in 2012 and 2013. Polymorphic markers were used to evaluate whether natal philopatry limits dispersal at multiple spatial scales. Ripley's revealed that nests were significantly clustered at multiple scales, when both nesting sites were considered and within each nesting site. This suggests a patchy, nonrandom distribution of nests within nest sites. Hierarchical AMOVA revealed that nest-site aggregations did not explain a significant portion of genetic variation within nesting sites. However, a small but positive correlation between geographic and genetic distance was detected using a Mantel's test. Hence, the relationship between geographic distance and genetic distance among hatchlings within nest sites, while detectable, was not strong enough to have a marked effect on fine-scale genetic structure. Spatial and genetic data combined determined that the nesting sites included nesting females from multiple locations, and the hypothesis of "natal philopatry" was not supported because females nesting in the same cluster were no more closely related to each other than to other females from the same nesting site. These findings imply that nesting aggregations are more likely associated with cryptic habitat variables contributing to optimal nesting conditions.
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http://dx.doi.org/10.1002/ece3.5414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662429PMC
July 2019

Tagraxofusp in Blastic Plasmacytoid Dendritic-Cell Neoplasm.

N Engl J Med 2019 04;380(17):1628-1637

From the University of Texas M.D. Anderson Cancer Center, Houston (N.P., M.D., H.M.K., M.K.); Dana-Farber Cancer Institute (A.A.L.) and Boston University School of Medicine (J.M.S.), Boston, and Veristat, Southborough (J.B.) - all in Massachusetts; H. Lee Moffitt Cancer Center, Tampa, FL (K.L.S., J.E.L.); City of Hope National Medical Center, Duarte, CA (A.S.S.); Ohio State University, Columbus (S.V.); Winship Cancer Institute of Emory University, Atlanta (W.B.); Duke University Medical Center, Durham, NC (D.A.R.); and Roswell Park Comprehensive Cancer Center, Buffalo (E.S.W.), and Stemline Therapeutics, New York (S. Spence, S. Shemesh, C.L.B., I.B.) - both in New York.

Background: Blastic plasmacytoid dendritic-cell neoplasm (BPDCN) is an aggressive hematologic cancer that is caused by transformed plasmacytoid dendritic cells that overexpress interleukin-3 receptor subunit alpha (IL3RA or CD123). Tagraxofusp (SL-401) is a CD123-directed cytotoxin consisting of human interleukin-3 fused to truncated diphtheria toxin.

Methods: In this open-label, multicohort study, we assigned 47 patients with untreated or relapsed BPDCN to receive an intravenous infusion of tagraxofusp at a dose of 7 μg or 12 μg per kilogram of body weight on days 1 to 5 of each 21-day cycle. Treatment continued until disease progression or unacceptable toxic effects. The primary outcome was the combined rate of complete response and clinical complete response among patients who had not received previous treatment for BPDCN. A secondary outcome was the duration of response.

Results: Of the 47 patients, 32 were receiving tagraxofusp as first-line treatment and 15 had received previous treatment. The median age of the patients was 70 years (range, 22 to 84). Among the 29 previously untreated patients who received tagraxofusp at a dose of 12 μg per kilogram, the primary outcome occurred in 21 (72%), and the overall response rate was 90%; of these patients, 45% went on to undergo stem-cell transplantation. Survival rates at 18 and 24 months were 59% and 52%, respectively. Among the 15 previously treated patients, the response rate was 67%, and the median overall survival was 8.5 months. The most common adverse events were increased levels of alanine aminotransferase (64%) and aspartate aminotransferase (60%), hypoalbuminemia (55%), peripheral edema (51%), and thrombocytopenia (49%). Capillary leak syndrome was reported in 19% of the patients and was associated with one death in each of the dose subgroups.

Conclusions: In adult patients with untreated or relapsed BPDCN, the use of tagraxofusp led to clinical responses. Serious adverse events included capillary leak syndrome; hepatic dysfunction and thrombocytopenia were common. (Funded by Stemline Therapeutics and the Leukemia and Lymphoma Society Therapy Acceleration Program; ClinicalTrials.gov number, NCT02113982.).
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http://dx.doi.org/10.1056/NEJMoa1815105DOI Listing
April 2019

Type of TP53 mutation influences oncogenic potential and spectrum of associated K-ras mutations in lung-specific transgenic mice.

Int J Cancer 2019 11 13;145(9):2418-2426. Epub 2019 Apr 13.

Department of Human & Molecular Genetics, Herbert Wertheim College of Medicine, The Florida International University, Miami, FL, USA.

TP53 and K-ras mutations are two of the major genetic alterations in human nonsmall cell lung cancers. The association between these two genes during lung tumorigenesis is unknown. We evaluated the potential of two common Type I (273H, contact) and Type II (175H, conformational) TP53 mutations to induce lung tumors in transgenic mice, as well as K-ras status, and other driver mutations in these tumors. Among 516 (138 nontransgenic, 207 SPC-TP53-273H, 171 SPC-TP53-175H) mice analyzed, 91 tumors, all adenocarcinomas, were observed. Type II mutants developed tumors more frequently (as compared to nontransgenics, p = 0.0003; and Type I, p = 0.010), and had an earlier tumor onset compared to Type I (p = 0.012). K-ras mutations occurred in 21 of 50 (42%) of murine lung tumors sequenced. For both the nontransgenic and the SPC-TP53-273H transgenics, tumor K-ras codon 12-13 mutations occurred after 13 months with a peak incidence at 16-18 months. However, for the SPC-TP53-175H transgenics, K-ras codon 12-13 mutations were observed as early as 6 months, with a peak incidence between the ages of 10-12 months. Codons 12-13 transversion mutations were the predominant changes in the SPC-TP53-175H transgenics, whereas codon 61 transition mutations were more common in the SPC-TP53-273H transgenics. The observation of accelerated tumor onset, early appearance and high frequency of K-ras codon 12-13 mutations in the Type II TP53-175H mice suggests an enhanced oncogenic function of conformational TP53 mutations, and gains in early genetic instability for tumors containing these mutations compared to contact mutations.
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http://dx.doi.org/10.1002/ijc.32279DOI Listing
November 2019

Detection of critical antibiotic resistance genes through routine microbiome surveillance.

PLoS One 2019 14;14(3):e0213280. Epub 2019 Mar 14.

Department of Biological Sciences, Mississippi State University, Starkville, MS, United States of America.

Population-based public health data on antibiotic resistance gene carriage is poorly surveyed. Research of the human microbiome as an antibiotic resistance reservoir has primarily focused on gut associated microbial communities, but data have shown more widespread microbial colonization across organs than originally believed, with organs previously considered as sterile being colonized. Our study demonstrates the utility of postmortem microbiome sampling during routine autopsy as a method to survey antibiotic resistance carriage in a general population. Postmortem microbial sampling detected pathogens of public health concern including genes for multidrug efflux pumps, carbapenem, methicillin, vancomycin, and polymixin resistances. Results suggest that postmortem assessments of host-associated microbial communities are useful in acquiring community specific data while reducing selective-participant biases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213280PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417727PMC
December 2019

Fractured Tooth Stabilized with Auto Body Repair Resin on a 1970 Royal Navy Polaris Submarine Patrol.

Aerosp Med Hum Perform 2019 Feb;90(2):135-138

In February 1970, halfway through a Polaris submarine war patrol in SSBN-02 HMS (port crew), a Petty Officer presented to the sick bay in excruciating pain with a broken upper left molar tooth. The zinc oxide/clove oil mixture would not stick on to the vertical face of the fracture. In preparation for such events, Royal Navy (RN) submarine medical officers are taught excellent fundamental dental skills. In this case, it seemed a very difficult job to extract the remains of the tooth. The author reports the first known use of glass fiber/resin in the RN to crown and treat a fractured molar, cover the root, and save the tooth, and to recommend that all military and civilian medical staff working anywhere in isolation with no dental facility locally be given similar training to that which RN submarine medical officers receive before being sent on extended dives.
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http://dx.doi.org/10.3357/AMHP.5208.2019DOI Listing
February 2019

Room-temperature cycling of metal fluoride electrodes: Liquid electrolytes for high-energy fluoride ion cells.

Science 2018 12;362(6419):1144-1148

Electrochemical Technologies Group, Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109, USA.

Fluoride ion batteries are potential "next-generation" electrochemical storage devices that offer high energy density. At present, such batteries are limited to operation at high temperatures because suitable fluoride ion-conducting electrolytes are known only in the solid state. We report a liquid fluoride ion-conducting electrolyte with high ionic conductivity, wide operating voltage, and robust chemical stability based on dry tetraalkylammonium fluoride salts in ether solvents. Pairing this liquid electrolyte with a copper-lanthanum trifluoride ([email protected]) core-shell cathode, we demonstrate reversible fluorination and defluorination reactions in a fluoride ion electrochemical cell cycled at room temperature. Fluoride ion-mediated electrochemistry offers a pathway toward developing capacities beyond that of lithium ion technology.
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http://dx.doi.org/10.1126/science.aat7070DOI Listing
December 2018

The interleukin-3 receptor CD123 targeted SL-401 mediates potent cytotoxic activity against CD34CD123 cells from acute myeloid leukemia/myelodysplastic syndrome patients and healthy donors.

Haematologica 2018 08 17;103(8):1288-1297. Epub 2018 May 17.

Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA

Diseases with clonal hematopoiesis such as myelodysplastic syndrome and acute myeloid leukemia have high rates of relapse. Only a small subset of acute myeloid leukemia patients are cured with chemotherapy alone. Relapse in these diseases occurs at least in part due to the failure to eradicate leukemic stem cells or hematopoietic stem cells in myelodysplastic syndrome. CD123, the alpha chain of the interleukin-3 receptor heterodimer, is expressed on the majority of leukemic stem cells and myelodysplastic syndrome hematopoietic stem cells and in 80% of acute myeloid leukemia. Here, we report indiscriminate killing of CD123 normal and acute myeloid leukemia / myelodysplastic syndrome cells by SL-401, a diphtheria toxin interleukin-3 fusion protein. SL-401 induced cytotoxicity of CD123 primary cells/blasts from acute myeloid leukemia and myelodysplastic syndrome patients but not CD123 lymphoid cells. Importantly, SL-401 was highly active even in cells expressing low levels of CD123, with minimal effect on modulation of the CD123 target in acute myeloid leukemia. SL-401 significantly prolonged survival of leukemic mice in acute myeloid leukemia patient-derived xenograft mouse models. In addition to primary samples, studies on normal cord blood and healthy marrow show that SL-401 has activity against normal hematopoietic progenitors. These findings indicate potential use of SL-401 as a "bridge-to-transplant" before allogeneic hematopoietic cell transplantation in acute myeloid leukemia / myelodysplastic syndrome patients.
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http://dx.doi.org/10.3324/haematol.2018.188193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068035PMC
August 2018
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