Publications by authors named "Daniel Johnson"

683 Publications

Histopathologic and clinical outcomes of Milan System categories "non-diagnostic" and "non-neoplastic" of salivary gland fine needle aspirations.

J Am Soc Cytopathol 2021 Mar 19. Epub 2021 Mar 19.

Department of Pathology, The University of Chicago, Chicago, Illinois.

Introduction: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) specifies six categories with estimated risks of malignancy (ROM) and suggested management. The estimated ROM is 25% for Non-Diagnostic (ND) category, and 10% for Non-Neoplastic (NN). This study aimed to investigate histopathologic and clinical outcomes of MSRSGC categories ND and NN at the authors' institution.

Materials And Methods: Cytopathology fine needle aspiration reports from 2008-2020 were searched for the word "salivary", "parotid", and "submandibular". Cases fitting Non-Diagnostic (ND) and Non-Neoplastic (NN) categories were identified. Follow-up cyto-/histopathologic and clinical data were extracted.

Results: There were 43 ND and 46 NN cases. The average age was 58.3 years. Neoplastic lesions were found in 13 of 43 (30%) ND and 3 of 46 (6.5%) NN. The rate of malignancy in ND category was 14.0% (6/43) and 0% (0/46) in NN category. Four cases in ND (9.3%) and 6 (13.0%) in NN had no neoplasm and instead had an underlying reactive condition (e.g., chronic sialadenitis) or inflammatory lesion (e.g., lymphoepithelial cyst) on histologic follow-up. There was no follow-up pathology in 46.5% NDs (20/43) and 82.6% NNs (38/46); however, no lesions were apparent clinically with a mean follow-up of 3 years and 1.5 years, respectively.

Conclusions: MSRSGC categories ND and NN are helpful for reporting salivary gland FNA results. With proper clinical and radiologic correlation, ROM of NN is low; however, ROM of ND remains significant. Repeat FNA after correlation for ND cases seems prudent as neoplasms and malignancies may have gone undetected.
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http://dx.doi.org/10.1016/j.jasc.2021.03.001DOI Listing
March 2021

A Review of Filamentary Keratitis.

Surv Ophthalmol 2021 Apr 13. Epub 2021 Apr 13.

Department of Ophthalmology, Long School of Medicine, University of Texas Health San Antonio, San Antonio, Texas. Electronic address:

Filamentary keratitis (FK) is characterized by presence of filaments on the corneal surface that are often associated with symptoms of foreign body sensation, irritation, and eye pain. FK is associated with a variety of ocular and systemic conditions, most notably dry eye disease. These filaments are composed primarily of epithelium, mucus, and cellular debris; however, their pathogenesis remains an area of debate. Aggravating factors for FK include desiccation, inflammatory mediators, as well as eyelid mechanical forces. Management consists of addressing associated conditions, especially dry eye disease, and providing medical and procedural treatments to alleviate symptoms and restore the ocular surface. Mainstay treatments include filament removal, increased lubrication with artificial tears and punctal occlusion, hypertonic saline, antiinflammatory and mucolytic medications, and autologous serum eye drops, as well as bandage contact lenses. A stepwise approach is required to manage patients with acute or chronic FK. Prolonged therapy is often necessary to prevent recurrence of this bothersome condition.
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http://dx.doi.org/10.1016/j.survophthal.2021.04.002DOI Listing
April 2021

Synovial sarcoma with overwhelming glandular (adenocarcinoma-like) component: A case report and review of the literature.

Pathol Res Pract 2021 Mar 27;222:153418. Epub 2021 Mar 27.

Department of Pathology, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, 251 East Huron St, Feinberg 7-342A, Chicago, IL 60611, United States.

Synovial sarcoma is an uncommon tumor of soft tissue, characterized by a specific SS18-SSX1/2/4 fusion gene. It is generally a lesion composed of monomorphic spindle cells, and can sometimes show variable epithelial differentiation. Here, we present the case of a young woman with a synovial sarcoma of the abdominal wall that showed an overwhelming (>90 %) epithelial glandular component mimicking adenocarcinoma, and only rare spindled areas. The diagnosis was confirmed by detection of targeted fusion transcripts associated with synovial sarcoma. We review the literature pertaining to synovial sarcoma, and we show that this case is only the sixth molecularly proven epithelial predominant synovial sarcoma in the literature. This report emphasizes the importance of molecular approaches in modern soft tissue pathology. Recognition of synovial sarcoma with predominant glandular component is imperative in order to avoid misdiagnosis of the tumor as metastatic adenocarcinoma, another type of sarcoma with epithelial differentiation, or a carcinoma with a sarcomatous component (sarcomatoid carcinoma), all of which have markedly different clinical management.
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http://dx.doi.org/10.1016/j.prp.2021.153418DOI Listing
March 2021

Neurological complications during veno-venous extracorporeal membrane oxygenation: Does the configuration matter? A retrospective analysis of the ELSO database.

Crit Care 2021 03 17;25(1):107. Epub 2021 Mar 17.

Departments of Surgery, University of Maryland School of Medicine, Program in Trauma, R Adams Cowley Shock Trauma Center, Baltimore, USA.

Background: Single- (SL) and double-lumen (DL) catheters are used in clinical practice for veno-venous extracorporeal membrane oxygenation (V-V ECMO) therapy. However, information is lacking regarding the effects of the cannulation on neurological complications.

Methods: A retrospective observational study based on data from the Extracorporeal Life Support Organization (ELSO) registry. All adult patients included in the ELSO registry from 2011 to 2018 submitted to a single run of V-V ECMO were analyzed. Propensity score (PS) inverse probability of treatment weighting estimation for multiple treatments was used. The average treatment effect (ATE) was chosen as the causal effect estimate of outcome. The aim of the study was to evaluate differences in the occurrence and the type of neurological complications in adult patients undergoing V-V ECMO when treated with SL or DL cannulas.

Results: From a population of 6834 patients, the weighted propensity score matching included 6245 patients (i.e., 91% of the total cohort; 4175 with SL and 20,270 with DL cannulation). The proportion of patients with at least one neurological complication was similar in the SL (306, 7.2%) and DL (189, 7.7%; odds ratio 1.10 [95% confidence intervals 0.91-1.32]; p = 0.33). After weighted propensity score, the ATE for the occurrence of least one neurological complication was 0.005 (95% CI - 0.009 to 0.018; p = 0.50). Also, the occurrence of specific neurological complications, including intracerebral hemorrhage, acute ischemic stroke, seizures or brain death, was similar between groups. Overall mortality was similar between patients with neurological complications in the two groups.

Conclusions: In this large registry, the occurrence of neurological complications was not related to the type of cannulation in patients undergoing V-V ECMO.
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http://dx.doi.org/10.1186/s13054-021-03533-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968168PMC
March 2021

Patient-Reported Outcomes Measurement Information System Validation in Hip Arthroscopy: A Shift Towards Reducing Survey Burden.

Cureus 2021 Feb 10;13(2):e13265. Epub 2021 Feb 10.

Department of Orthopaedics, Northwestern University Feinberg School of Medicine, Chicago, USA.

Background The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed to provide measures of patient-reported symptoms and healthcare outcomes across a variety of conditions in an easily accessible manner. The purpose of this study was to validate PROMIS against traditional legacy measures in patients undergoing hip arthroscopy for femoral acetabular impingement (FAI). Methodology Outcome measures collected pre- and post-operatively included PROMIS Pain Interference (PI) and Physical Function (PF), modified Harris Hip Score (mHHS), Hip Outcome Score-Activities of Daily Living and Sport (HOS-ADL and HOS-Sport), Nonarthritic Hip Score (NAHS), and Visual Analog Scale (VAS). Pearson's correlation coefficients were calculated between each outcome measure. Results Strong correlations were observed between the PROMIS PF T-Score and the mHHS (r = 0.64-0.83, p < 0.0001), HOS-ADL (r = 0.54-0.81, p < 0.0001), HOS-Sport (r = 0.55-0.74, p < 0.0001), and NAHS (r = 0.61-0.78, p < 0.0001) measurement tools. PROMIS Computer Adaptive Testing PI T-Score and VAS also demonstrated a strong correlation (r = 0.64-0.80, p < 0.0001). Conclusions PROMIS PF scores correlate strongly with mHHS, HOS-ADL, HOS-Sport, and NAHS scores at all time points. Likewise, PROMIS PI scores correlate strongly with VAS pain scores. On average, patients completing PROMIS need to fill out only four or five questions. This study supports the use of PROMIS as an efficient, valid outcome tool for patients with FAI undergoing hip arthroscopy.
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http://dx.doi.org/10.7759/cureus.13265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948318PMC
February 2021

Corrigendum to 'The Potential Value of Performing Preoperative Urinalysis Prior to Total Knee Arthroplasty' [The Journal of Arthroplasty 36 (2021) 118-121].

J Arthroplasty 2021 Mar 10. Epub 2021 Mar 10.

Department of Orthopaedic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL.

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http://dx.doi.org/10.1016/j.arth.2021.02.021DOI Listing
March 2021

Tilsotolimod with ipilimumab drives tumor responses in anti-PD-1 refractory melanoma.

Cancer Discov 2021 Mar 11. Epub 2021 Mar 11.

Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center

Many patients with advanced melanoma are resistant to immune checkpoint inhibition. In the ILLUMINATE-204 phase 1/2 trial, we assessed intratumoral tilsotolimod, an investigational Toll-like receptor 9 agonist, with systemic ipilimumab in patients with anti-PD-1-resistant advanced melanoma. In all patients, 48.4% experienced grade 3/4 treatment-emergent adverse events. The overall response rate at the recommended phase 2 dose of 8 mg was 22.4%, and an additional 49% of patients had stable disease. Responses in non-injected lesions and in patients expected to be resistant to ipilimumab monotherapy were observed. Rapid induction of a local interferon-alpha gene signature, dendritic cell maturation and enhanced markers of antigen presentation, and T-cell clonal expansion correlated with clinical response. A phase 3 clinical trial with this combination (NCT03445533) is ongoing.
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http://dx.doi.org/10.1158/2159-8290.CD-20-1546DOI Listing
March 2021

Root water gates and not changes in root structure provide new insights into plant physiological responses to drought, flooding and salinity.

J Exp Bot 2021 Mar 2. Epub 2021 Mar 2.

Warnell School of Forestry and Natural Resources, University of Georgia, Athens, USA.

The influence of aquaporin (AQP) activity on plant water movement remains unclear, especially in plants subject to unfavorable conditions. We applied a multitiered approach at a range of plant scales to (i) characterize the resistances controlling water transport under drought, flooding and flooding plus salinity conditions; (ii) quantify the respective effects of AQP activity and xylem structure on root (Kroot), stem (Kstem) and leaf (Kleaf) conductances, and (iii) evaluate the impact of AQP-regulated transport capacity on gas exchange. We found that drought, flooding and flooding-salinity reduced Kroot and root AQP activity in Pinus taeda, whereas Kroot of the flood-tolerant Taxodium distichum did not decline under flooding. The extent of the AQP-control of transport efficiency varied among organs and species, ranging from 35%-55% in Kroot to 10%-30% in Kstem and Kleaf. In response to treatments, AQP-mediated inhibition of Kroot rather than changes in xylem acclimation controlled the fluctuations in Kroot. The reduction in stomatal conductance and its sensitivity to vapor pressure deficit were direct responses to decreased whole-plant conductance triggered by lower Kroot and larger resistance belowground. Our results provide new mechanistic and functional insights on plant hydraulics that are essential to quantifying the influences of future stress on ecosystem function.
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http://dx.doi.org/10.1093/jxb/erab100DOI Listing
March 2021

Evaluating the Early Impact of the COVID-19 Pandemic on Sports Surgery Fellowship Education.

Cureus 2021 Jan 27;13(1):e12943. Epub 2021 Jan 27.

Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, USA.

Purpose The COVID-19 pandemic forced many hospitals to cancel elective surgeries to minimize the risk of viral transmission and ensure the availability of vital health resources. The unintended consequences of this action on the education and training of orthopaedic sports surgeons are unknown. The purpose of this study is to measure the impact of COVID-19 on orthopaedic sports surgery fellows, their education and training, and their readiness for practice. Methods A comprehensive survey was created and distributed to all U.S. fellows and fellowship directors registered with the American Orthopaedic Society for Sports Medicine. Responses were collected between April 22, 2020, and May 5, 2020. Results Fifty-one sports fellows and twenty-nine sports fellowship directors completed the survey. Over 80.4% of fellows reported a greater than 50% decrease in the case volume since the cessation of elective cases. Average hours worked per week decreased by 58.2% during the pandemic. Fellows reported completing an average of 324.6 ± 97.4 cases prior to the COVID-19 crisis and 86.0% expected to complete at least 11% to 25% fewer cases by graduation compared to previous fellows. 87.5% of fellows were not concerned about their ability to complete their fellowship training but more than one-third of fellows voiced concerns to their fellowship directors regarding their readiness for independent practice. Fellowship directors were generally not concerned that COVID-19 would prevent their fellows from completing the fellowship. At least 54.2% are somewhat concerned about the impact of COVID-19 on their future job opportunities. Conclusions The COVID-19 pandemic has universally affected work hours and case volume of sports fellows. Nevertheless, most sports fellows feel prepared to enter practice and are generally supported by the confidence of their fellowship directors. The results of this survey emphasize the importance of the fellowship year in sports training and highlight the future of online education and simulation as useful adjuncts.
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http://dx.doi.org/10.7759/cureus.12943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910193PMC
January 2021

Wildlife disturbances as a source of conspecific negative density-dependent mortality in tropical trees.

Proc Biol Sci 2021 Mar 3;288(1946):20210001. Epub 2021 Mar 3.

Forest Global Earth Observatory, Smithsonian Tropical Research Institute, Washington, DC, USA.

Large vertebrates are rarely considered important drivers of conspecific negative density-dependent mortality (CNDD) in plants because they are generalist consumers. However, disturbances like trampling and nesting also cause plant mortality, and their impact on plant diversity depends on the spatial overlap between wildlife habitat preferences and plant species composition. We studied the impact of native wildlife on a hyperdiverse tree community in Malaysia. Pigs () are abnormally abundant at the site due to food subsidies in nearby farmland and they construct birthing nests using hundreds of tree saplings. We tagged 34 950 tree saplings in a 25 ha plot during an initial census and assessed the source mortality by recovering tree tags from pig nests ( = 1672 pig-induced deaths). At the stand scale, pigs nested in flat dry habitats, and at the local neighbourhood scale, they nested within clumps of saplings, both of which are intuitive for safe and efficient nest building. At the stand scale, flat dry habitats contained higher sapling densities and higher proportions of common species, so pig nesting increased the weighted average species evenness across habitats. At the neighbourhood scale, pig-induced sapling mortality was associated with higher heterospecific and especially conspecific sapling densities. Tree species have clumped distributions due to dispersal limitation and habitat filtering, so pig disturbances in sapling clumps indirectly caused CNDD. As a result, Pielou species evenness in 400 m quadrats increased 105% more in areas with pig-induced deaths than areas without disturbances. Wildlife induced CNDD and this supported tree species evenness, but they also drove a 62% decline in sapling densities from 1996 to 2010, which is unsustainable. We suspect pig nesting is an important feature shaping tree composition throughout the region.
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http://dx.doi.org/10.1098/rspb.2021.0001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935013PMC
March 2021

Time to Cannulation after ICU Admission Increases Mortality for Patients Requiring Veno-Venous ECMO for COVID-19 Associated Acute Respiratory Distress Syndrome.

Ann Surg 2020 Dec 22. Epub 2020 Dec 22.

*University of North Carolina at Chapel Hill, Division of Acute Care Surgery, Department of Surgery, Chapel Hill, NC †University of North Carolina at Chapel Hill School of Medicine ‡University of North Carolina at Chapel Hill, Division of Hospital Medicine, Department of Medicine, Chapel Hill, NC §University of North Carolina at Chapel Hill, Division of Acute Care Surgery, Department of General Surgery, Chapel Hill, NC.

Objective: COVID-19 can cause acute respiratory distress syndrome (ARDS) that is rapidly progressive, severe, and refractory to conventional therapies. Extracorporeal membrane oxygenation (ECMO) can be used as a supportive therapy to improve outcomes but evidence-based guidelines have not been defined.

Summary Background Data: Initial mortality rates associated with ECMO for ARDS in COVID-19 were high, leading some to believe that there was no role for ECMO in this viral illness. With more experience, outcomes have improved. The ideal candidate, timing of cannulation, and best post-cannulation management strategy, however, has not yet been defined.

Methods: We conducted a retrospective review from April 1 to July 31 2020 of the first 25 patients with COVID-19 associated ARDS placed on V-V ECMO at our institution. We analyzed the differences between survivors to hospital discharge and those who died. Modified Poisson regression was used to model adjusted risk factors for mortality.

Results: 44% of patients (11/25) survived to hospital discharge. Survivors were significantly younger (40.5 years vs. 53.1 years; p < 0.001) with no differences between cohorts in mean body mass index, diabetes, or PaO2:FiO2 at cannulation. Survivors had shorter duration from symptom onset to cannulation (12.5 days vs. 19.9 days, p = 0.028) and shorter duration of intensive care unit (ICU) length of stay (LOS) prior to cannulation (5.6 days vs. 11.7 days, p = 0.045). Each day from ICU admission to cannulation increased the adjusted risk of death by 4% and each year increase in age increased the adjusted risk 6%.

Conclusions: ECMO has a role in severe, refractory ARDS associated with COVID-19. Increasing age and time from ICU admission were risk factors for mortality and should be considered in patient selection. Further studies are needed to define best practices for V-V ECMO use in COVID-19.
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http://dx.doi.org/10.1097/SLA.0000000000004683DOI Listing
December 2020

Evaluation of In-cage Filter Paper as a Replacement for Sentinel Mice in the Detection of Murine Pathogens.

J Am Assoc Lab Anim Sci 2021 Mar 24;60(2):160-167. Epub 2021 Feb 24.

Departments of Comparative Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.

Recent studies have evaluated alternatives to the use of live animals in colony health monitoring. Currently, an alternative method that is suitable for all rack types and that has been verified to detect the infectious agents most commonly excluded from mouse colonies is unavailable. We compared the use of filter paper placed on the inside floor of mouse cages to the traditional use of sentinel mice in the detection of several prevalent murine pathogens including mouse hepatitis virus (MHV), murine norovirus (MNV), minute virus of mice (MVM), mouse parvovirus (MPV), Theiler murine encephalomyelitis virus (TMEV), spp., and Experimental groups comprised 7 cages containing either 2 pieces of filter paper on the cage floor or 2 ICR sentinel mice. Soiled bedding from pet-store mice was transferred to the experimental cages weekly for 8 wk. At 1 and 2 mo after bedding transfer, the filter papers were evaluated by PCR and sentinel mice were tested by serology and fecal PCR. Filter papers detected all pathogens as effectively (MHV, MNV, MPV, MVM, TMEV and ) or more effectively ( spp.) than sentinel mice at both time points. Filter papers more readily detected pathogens with a high copy number per RT-PCR analysis than a low copy number. spp. were not detected by sentinel mice at either time point. These results indicate that the use of filter paper placed on the interior floor of empty mouse cages and exposed to soiled bedding is efficient in detecting bacteria, endoparasites, and most of the common mouse viruses included in an animal health monitoring program.
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http://dx.doi.org/10.30802/AALAS-JAALAS-20-000086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974814PMC
March 2021

Clinical trials optimizing investigator and self-collection of buccal cells for RNA yield.

Laryngoscope Investig Otolaryngol 2021 Feb 18;6(1):116-121. Epub 2021 Jan 18.

Department of Medicine, Division of Hematology/Oncology University of Arizona College of Medicine Tucson Arizona USA.

Objective: Buccal cells are an ideal surrogate tissue for studying biologic effects of carcinogens or drugs, however inherent fragility and salivary RNAses limit RNA yield. We conducted healthy volunteer trials to optimize collection conditions.

Methods: We conducted: (a) a single-arm crossover study evaluating four test conditions on RNA yield by buccal cytobrush; (b) a single-arm prospective study evaluating RNA yield by investigator vs self-collection.

Results: Antecedent toothbrushing, time of day, and number of cytobrush strokes did not significantly impact RNA yield. RNA yield was doubled by using 2 vs 1 cytobrush per buccal surface ( = .0054). Self-collection of buccal cells for RNA was feasible; 36 of 50 (72%) samples passed quality control.

Conclusion: RNA yield was doubled by using two cytobrushes per buccal surface. Healthy volunteers can self-collect sufficient buccal RNA for gene expression studies. Techniques from these pragmatic trials could enhance availability of a limited tissue for serial biomarker measurements.

Level Of Evidence: 1b-Prognosis Study (Individual prospective cohort study).
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http://dx.doi.org/10.1002/lio2.516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883625PMC
February 2021

Differences in leaf anatomy determines temperature response of leaf hydraulic and mesophyll CO conductance in phylogenetically related C and C grass species.

New Phytol 2021 Feb 19. Epub 2021 Feb 19.

School of Biological Sciences, Washington State University, Pullman, WA, 99164, USA.

Leaf hydraulic and mesophyll CO conductance are both influenced by leaf anatomical traits, however it is poorly understood how the temperature response of these conductances differs between C and C species with distinct leaf anatomy. This study investigated the temperature response of leaf hydraulic conductance (K ), stomatal (g ) and mesophyll (g ) conductance to CO , and leaf anatomical traits in phylogenetically related Panicum antidotale (C ) and P. bisulcatum (C ) grasses. The C species had lower hydraulic conductance outside xylem (K ) and K compared with the C species. However, the C species had higher g compared with the C species. Traits associated with leaf water movement, K and K , increased with temperature more in the C than in the C species, whereas traits related to carbon uptake, A and g , increased more with temperature in the C than the C species. Our findings demonstrate that, in addition to a CO concentrating mechanism, outside-xylem leaf anatomy in the C species P. antidotale favours lower water movement through the leaf and stomata that provides an additional advantage for greater leaf carbon uptake relative to water loss with increasing leaf temperature than in the C species P. bisulcatum.
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http://dx.doi.org/10.1111/nph.17287DOI Listing
February 2021

A thin line between life and death: Radial sap flux failure signals trajectory to tree mortality.

Plant Cell Environ 2021 May 3;44(5):1311-1314. Epub 2021 Mar 3.

USDA Forest Service, PNW Research Station, Corvallis, Oregon, USA.

This article comments on: Seeking the "point of no return" in the sequence of events leading to mortality of mature trees.
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http://dx.doi.org/10.1111/pce.14033DOI Listing
May 2021

USPHS Corps Care : Force Health Protection for Public Health Officers During the Ebola and COVID-19 Responses.

Public Health Rep 2021 Mar-Apr;136(2):148-153. Epub 2021 Feb 4.

Commissioned Corps (permanent), Rockville, MD, USA.

Force health protection (FHP) is defined as "the prevention of disease and injury in order to protect the strength and capabilities" of any service population. FHP was the foundational principal of the US Public Health Service (USPHS). President John Adams' signing of An Act for Sick and Disabled Seamen on July 16, 1798, marked the first dedication of US federal resources to ensuring the well-being of US civilian sailors and Naval service members. On January 4, 1889, President Cleveland enacted the USPHS Commissioned Corps, creating the world's first (and still only) uniformed service dedicated to promoting, protecting, and advancing the health and safety of the United States and the world. Building on the lessons of the 2014-2015 response to the Ebola virus pandemic, the Corps Care program was formalized in 2017 to establish and implement a uniform and comprehensive strategy to meet the behavioral health, medical, and spiritual needs of all Commissioned Corps officers. Its role was expanded in response to the coronavirus disease 2019 (COVID-19) pandemic, which has placed unprecedented demands on health care workers and spotlighted the need for FHP strategies. We describe the FHP roles of the Corps Care program for the resiliency of Commission Corps officers in general and the Corps' impact during the response to the COVID-19 pandemic. Qualitative analysis of FHP discussions with deployed officers highlights the unique challenges to FHP presented by the pandemic response.
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http://dx.doi.org/10.1177/0033354920984775DOI Listing
February 2021

MicroRNA let-7b downregulates AML1-ETO oncogene expression in t(8;21) AML by targeting its 3'UTR.

Exp Hematol Oncol 2021 Feb 2;10(1). Epub 2021 Feb 2.

Moores Cancer Center, University of California, La Jolla, San Diego, CA, USA.

Background: Acute myeloid leukemia (AML) with the t(8;21)(q22;q22) chromosomal translocation is among the most common subtypes of AML and produces the AML1-ETO (RUNX1-ETO, RUNX1-RUNX1T1) oncogenic fusion gene. AML1-ETO functions as an aberrant transcription factor which plays a key role in blocking normal hematopoiesis. Thus, the expression of AML1-ETO is critical to t(8;21) AML leukemogenesis and maintenance. Post-transcriptional regulation of gene expression is often mediated through interactions between trans-factors and cis-elements within transcript 3'-untranslated regions (UTR). AML1-ETO uses the 3'UTR of the ETO gene, which is not normally expressed in hematopoietic cells. Therefore, the mechanisms regulating AML1-ETO expression via the 3'UTR are attractive therapeutic targets.

Methods: We used RNA-sequencing of t(8;21) patients and cell lines to examine the 3'UTR isoforms used by AML1-ETO transcripts. Using luciferase assay approaches, we test the relative contribution of 3'UTR cis elements to AML1-ETO expression. We further use let-7b microRNA mimics and anti-let-7b sponges for functional studies of t(8;21) AML cell lines.

Results: In this study, we examine the regulation of AML1-ETO via the 3'UTR. We demonstrate that AML1-ETO transcripts primarily use a 3.7 kb isoform of the ETO 3'UTR in both t(8;21) patients and cell lines. We identify a negative regulatory element within the AML1-ETO 3'UTR. We further demonstrate that the let-7b microRNA directly represses AML1-ETO through this site. Finally, we find that let-7b inhibits the proliferation of t(8;21) AML cell lines, rescues expression of AML1-ETO target genes, and promotes differentiation.

Conclusions: AML1-ETO is post-transcriptionally regulated by let-7b, which contributes to the leukemic phenotype of t(8;21) AML and may be important for t(8;21) leukemogenesis and maintenance.
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http://dx.doi.org/10.1186/s40164-021-00204-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856722PMC
February 2021

Targeting the JAK/STAT pathway in solid tumors.

J Cancer Metastasis Treat 2020 21;6. Epub 2020 Aug 21.

Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco 94158, USA.

Aberrant activation of signal transducer and activator of transcription (STAT) proteins is associated with the development and progression of solid tumors. However, as transcription factors, these proteins are difficult to target directly. In this review, we summarize the role of targeting Janus kinases (JAKs), upstream activators of STATs, as a strategy for decreasing STAT activation in solid tumors. Preclinical studies in solid tumor cell line models show that JAK inhibitors decrease STAT activation, cell proliferation, and cell survival; in models, they also inhibit tumor growth. JAK inhibitors, particularly the JAK1/2 inhibitor ruxolitinib, sensitize cell lines and murine models to chemotherapy, immunotherapy, and oncolytic viral therapy. Ten JAK inhibitors have been or are actively being tested in clinical trials as monotherapy or in combination with other agents in patients with solid tumors; two of these inhibitors are already Food and Drug Administration (FDA) approved for the treatment of myeloproliferative disorders and rheumatoid arthritis, making them attractive agents for use in patients with solid tumors as they are known to be well-tolerated. Four JAK inhibitors (two of which are FDA approved for other indications) have exhibited promising anti-cancer effects in preclinical studies; however, clinical studies specifically assessing their activity against the JAK/STAT pathway in solid tumors have not yet been conducted. In summary, JAK inhibition is a viable option for targeting the JAK/STAT pathway in solid tumors and merits further testing in clinical trials.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845926PMC
August 2020

COVID-19 and the rise of virtual medicine in spine surgery: a worldwide study.

Eur Spine J 2021 Jan 16. Epub 2021 Jan 16.

Department of Orthopaedic Surgery, Rush University Medical Center, Orthopaedic Building, Suite 204-G, 1611 W Harrison Street, Chicago, IL, 60612, USA.

Purpose: The COVID-19 pandemic forced many surgeons to adopt "virtual medicine" practices, defined as telehealth services for patient care and online platforms for continuing medical education. The purpose of this study was to assess spine surgeon reliance on virtual medicine during the pandemic and to discuss the future of virtual medicine in spine surgery.

Methods: A comprehensive survey addressing demographic data and virtual medicine practices was distributed to spine surgeons worldwide between March 27, 2020, and April 4, 2020.

Results: 902 spine surgeons representing seven global regions responded. 35.6% of surgeons were identified as "high telehealth users," conducting more than half of clinic visits virtually. Predictors of high telehealth utilization included working in an academic practice (OR = 1.68, p = 0.0015) and practicing in Europe/North America (OR 3.42, p < 0.0001). 80.1% of all surgeons were interested in online education. Dedicating more than 25% of one's practice to teaching (OR = 1.89, p = 0.037) predicted increased interest in online education. 26.2% of respondents were identified as "virtual medicine surgeons," defined as surgeons with both high telehealth usage and increased interest in online education. Living in Europe/North America and practicing in an academic practice increased odds of being a virtual medicine surgeon by 2.28 (p = 0.002) and 1.15 (p = 0.0082), respectively. 93.8% of surgeons reported interest in a centralized platform facilitating surgeon-to-surgeon communication.

Conclusion: COVID-19 has changed spine surgery by triggering rapid adoption of virtual medicine practices. The demonstrated global interest in virtual medicine suggests that it may become part of the "new normal" for surgeons in the post-pandemic era.
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http://dx.doi.org/10.1007/s00586-020-06714-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811348PMC
January 2021

Sociodemographic differences in utilization and outcomes for temporary cardiovascular mechanical support in the setting of cardiogenic shock.

Am Heart J 2021 Feb 25. Epub 2021 Feb 25.

Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO; Center for Health Economics and Policy, Institute for Public Health at Washington University, St. Louis, MO. Electronic address:

Background: Temporary mechanical circulatory support (MCS) devices are increasingly used in cardiogenic shock, but whether sociodemographic differences by sex, race and/or ethnicity, insurance status, and neighborhood poverty exist in the utilization of these devices is unknown.

Methods: Retrospective cross-sectional study using the National Inpatient Sample for 2012-2017. Logistic regression models were used to examine predictors of use of temporary MCS devices and for in-hospital mortality, clustering by hospital-year.

Results: Our study population included 109,327 admissions for cardiogenic shock. Overall, 14.3% of admissions received an intra-aortic balloon pump, 4.2% a percutaneous ventricular assist device, and 1.8% extracorporeal membranous oxygenation (ECMO). After adjusting for age, comorbidities, and hospital characteristics, use of temporary MCS was lower in women compared to men (adjusted odds ratio [aOR] = 0.76, P < .001), Black patients compared to white ones (aOR = 0.73, P < .001), those insured by Medicare (aOR = 0.75, P < .001), Medicaid (aOR = 0.74, P < .001), or uninsured (aOR = 0.90, P = .015) compared to privately insured, and those in the lowest income neighborhoods (aOR = 0.94, P = .003) versus other neighborhoods. Women, admissions covered by Medicare, Medicaid, or uninsured, and those from low-income neighborhoods also had higher mortality rates even after adjustment for MCS implantation.

Conclusions: There are differences in the use of temporary MCS in the setting of cardiogenic shock among specific populations within the United States. The growing use of MCS for treating cardiogenic shock highlights the need to better understand its impact on outcomes.
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http://dx.doi.org/10.1016/j.ahj.2020.12.014DOI Listing
February 2021

Colorado Palliative Care and Hospice Crisis Standards: Moving Beyond Critical Care Planning.

J Pain Symptom Manage 2020 Dec 19. Epub 2020 Dec 19.

Emergency Medicine, Denver Health Medical Center, Denver, Colorado, USA.

Palliative care (PC) and hospice services have experienced shortages before 2020, and during the initial phases of the current pandemic, more critical gaps are expected with future surges, much as scarcity in intensive care unit services may recur during the COVID-19 pandemic. Although ethical allocation of ventilators and intensive care unit care is the subject of important discussions during this pandemic, caring for those at the end of life and those not desiring or qualifying for critical interventions must not be neglected, as critical care and comfort-focused care are intertwined. We review state and regional gaps already recognized in planning for scarcity in PC and hospice services during this pandemic and describe the planning initiatives Colorado has developed to address potential scarcities for this vulnerable and diverse group of people. We hope to encourage other state and regional groups to anticipate needs in the coming surges of this pandemic or in public health crises to come. Such planning is key to avoid the degradation of care that may result if it is necessary to invoke crisis standards of care and ration these essential services to our communities.
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http://dx.doi.org/10.1016/j.jpainsymman.2020.12.009DOI Listing
December 2020

Conformation of the nuclear pore in living cells is modulated by transport state.

Elife 2020 12 21;9. Epub 2020 Dec 21.

Laboratory of Cellular Biophysics, Rockefeller University, New York, United States.

While the static structure of the nuclear pore complex (NPC) continues to be refined with cryo-EM and x-ray crystallography, conformational changes of the NPC remain under-explored. We developed sensors that report on the orientation of NPC components by rigidly conjugating mEGFP to different NPC proteins. Our studies show conformational changes to select domains of nucleoporins (Nups) within the inner ring (Nup54, Nup58, Nup62) when transport through the NPC is perturbed and no conformational changes to Nups elsewhere in the NPC. Our results suggest that select components of the NPC are flexible and undergo conformational changes upon engaging with cargo.
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http://dx.doi.org/10.7554/eLife.60654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752133PMC
December 2020

A prospective single-institution study of intraoperative radiotherapy (IORT) for early-stage breast cancer.

Breast J 2021 Mar 3;27(3):231-236. Epub 2020 Dec 3.

Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

Intraoperative radiation therapy (IORT) is an option for breast-conserving therapy in early-stage breast cancer. IORT is given in one fraction at the time of surgery and eliminates the need for adjuvant external beam radiation therapy. However, previous trials indicate increased local failure rates compared with whole-breast irradiation, which engenders controversy around the appropriate use of IORT. We conducted a prospective study of patients diagnosed with early-stage breast cancer (T1-T2, N0-N1) at the University of Oklahoma Health Sciences Center (OUHSC) between 2013 and 2017 and treated with lumpectomy followed by intraoperative radiation therapy (IORT). Data collected included stage of disease, tumor location, histology, tumor markers, lymph node status, surgical margin size, recurrence, cosmetic outcomes, and length of follow-up. In-breast tumor recurrence rate (IBTR) in the 77 evaluable patients was 3.9% (3 patients). Margins were close (1 mm or less) in all three recurrent patients, and two were initially diagnosed with DCIS. Recurrence rates in our patients were comparable to prior reports. All recurrences were in patients with close margins indicating that this may represent a predictive feature for exclusion from IORT; additional studies are essential to determine the recurrence rates among patients treated with IORT and to identify potential predictors of IORT eligibility.
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http://dx.doi.org/10.1111/tbj.14128DOI Listing
March 2021

Trial of a novel experimental design to test depuration of PFASs from the edible tissues of Giant Mud Crab following exposure under natural conditions in the wild.

Sci Total Environ 2021 Mar 20;758:143650. Epub 2020 Nov 20.

RPS AAP Consulting Pty Ltd, 255 Pitt St, Sydney, NSW 2000, Australia.

Poly and perfluorinated alkyl substances (PFASs) are persistent organic pollutants (POPs) that are highly resistant to environmental degradation, and have been detected in a broad range of terrestrial and aquatic species. Portunid crabs have been shown to accumulate comparatively high concentrations of PFASs, but previous work examining depuration in crabs was inconclusive. Here, we trialled a novel experimental design to study depuration of PFASs from edible tissues of portunid crabs, using paired claw samples, and trial this design with Giant Mud Crab Scylla serrata exposed to the contaminant under natural conditions. We found evidence for depuration of perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS) and perfluorooctanoic acid (PFOA), but with depuration half-lives as high as 40 days (for PFOS). We also observed substantial variability in the data, including differences in PFAS concentrations between claws from the same individuals, potentially resulting from claw loss and re-growth prior to capture. These results have broad implications for assessing and minimising exposure risk in seafood species.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143650DOI Listing
March 2021

Head and neck squamous cell carcinoma.

Nat Rev Dis Primers 2020 11 26;6(1):92. Epub 2020 Nov 26.

Department of Otolaryngology-Head and Neck Surgery, University of California at San Francisco, San Francisco, CA, USA.

Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma (HNSCC). Oral cavity and larynx cancers are generally associated with tobacco consumption, alcohol abuse or both, whereas pharynx cancers are increasingly attributed to infection with human papillomavirus (HPV), primarily HPV-16. Thus, HNSCC can be separated into HPV-negative and HPV-positive HNSCC. Despite evidence of histological progression from cellular atypia through various degrees of dysplasia, ultimately leading to invasive HNSCC, most patients are diagnosed with late-stage HNSCC without a clinically evident antecedent pre-malignant lesion. Traditional staging of HNSCC using the tumour-node-metastasis system has been supplemented by the 2017 AJCC/UICC staging system, which incorporates additional information relevant to HPV-positive disease. Treatment is generally multimodal, consisting of surgery followed by chemoradiotherapy (CRT) for oral cavity cancers and primary CRT for pharynx and larynx cancers. The EGFR monoclonal antibody cetuximab is generally used in combination with radiation in HPV-negative HNSCC where comorbidities prevent the use of cytotoxic chemotherapy. The FDA approved the immune checkpoint inhibitors pembrolizumab and nivolumab for treatment of recurrent or metastatic HNSCC and pembrolizumab as primary treatment for unresectable disease. Elucidation of the molecular genetic landscape of HNSCC over the past decade has revealed new opportunities for therapeutic intervention. Ongoing efforts aim to integrate our understanding of HNSCC biology and immunobiology to identify predictive biomarkers that will enable delivery of the most effective, least-toxic therapies.
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http://dx.doi.org/10.1038/s41572-020-00224-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944998PMC
November 2020

STAT3 decoy oligonucleotide-carrying microbubbles with pulsed ultrasound for enhanced therapeutic effect in head and neck tumors.

PLoS One 2020 18;15(11):e0242264. Epub 2020 Nov 18.

Center for Ultrasound Molecular Imaging and Therapeutics, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, United States of America.

Signal transducer and activator of transcription-3 (STAT3) is an oncogenic transcription factor implicated in carcinogenesis, tumor progression, and drug resistance in head and neck squamous cell carcinoma (HNSCC). A decoy oligonucleotide targeting STAT3 offers a promising anti-tumor strategy, but achieving targeted tumor delivery of the decoy with systemic administration poses a significant challenge. We previously showed the potential for STAT3 decoy-loaded microbubbles, in conjunction with ultrasound targeted microbubble cavitation (UTMC), to decrease tumor growth in murine squamous cell carcinoma. As a next step towards clinical translation, we sought to determine the anti-tumor efficacy of our STAT3 decoy delivery platform against human HNSCC and the effect of higher STAT3 decoy microbubble loading on tumor cell inhibition. STAT3 decoy was loaded on cationic lipid microbubbles (STAT3-MB) or loaded on liposome-conjugated lipid microbubbles to form STAT3-loaded liposome-microbubble complexes (STAT3-LPX). UTMC treatment efficacy with these two formulations was evaluated in vitro using viability and apoptosis assays in CAL33 (human HNSCC) cells. Anti-cancer efficacy in vivo was performed in a CAL33 tumor murine xenograft model. UTMC with STAT3-MB caused significantly lower CAL33 cell viability compared to UTMC with STAT3-LPX (56.8±8.4% vs 84.5±8.8%, respectively, p<0.05). In vivo, UTMC with STAT3-MB had strong anti-tumor effects, with significantly less tumor burden and greater survival compared to that of UTMC with microbubbles loaded with a mutant control decoy and untreated control groups (p<0.05). UTMC with STAT3 decoy-loaded microbubbles significantly decreases human HNSSC tumor progression. These data set the stage for clinical translation of our microbubble platform as an imaged-guided, targeted delivery strategy for STAT3 decoy, or other nucleotide-based therapeutics, in human cancer treatment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242264PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673576PMC
December 2020

Targeting STAT3 with Proteolysis Targeting Chimeras and Next-Generation Antisense Oligonucleotides.

Mol Cancer Ther 2021 02 17;20(2):219-228. Epub 2020 Nov 17.

Department of Otolaryngology - Head and Neck Surgery, University of California at San Francisco, San Francisco, California.

STAT3 has been recognized for its key role in the progression of cancer, where it is frequently upregulated or constitutively hyperactivated, contributing to tumor cell proliferation, survival, and migration, as well as angiogenesis and suppression of antitumor immunity. Given the ubiquity of dysregulated STAT3 activity in cancer, it has long been considered a highly attractive target for the development of anticancer therapies. Efforts to target STAT3, however, have proven to be especially challenging, perhaps owing to the fact that transcription factors lack targetable enzymatic activity and have historically been considered "undruggable." Small-molecule inhibitors targeting STAT3 have been limited by insufficient selectivity and potency. More recently, therapeutic approaches that selectively target STAT3 protein for degradation have been developed, offering novel strategies that do not rely on inhibition of upstream pathways or direct competitive inhibition of the STAT3 protein. Here, we review these emerging approaches, including the development of STAT3 proteolysis targeting chimera agents, as well as preclinical and clinical studies of chemically stabilized antisense molecules, such as the clinical agent AZD9150. These therapeutic strategies may robustly reduce the cellular activity of oncogenic STAT3 and overcome the historical limitations of less selective small molecules.
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http://dx.doi.org/10.1158/1535-7163.MCT-20-0599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888537PMC
February 2021

Oropharyngeal carcinoma: A single institution study of 338 primaries with special reference to high-risk human papillomavirus-mediated carcinoma with aggressive behavior.

Pathol Res Pract 2020 Dec 9;216(12):153243. Epub 2020 Oct 9.

Department of Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, 675 N St Clair St, Galter 15-200, Chicago, IL, 60611, United States.

In a retrospective review, we identified 332 patients with 338 pathologically diagnosed primary oropharyngeal carcinomas (OPC) between January 2013 and March 2020 with known p16/HPV status from a tumor registry at Northwestern Memorial Hospital. The tumors predominantly involved the palatine tonsil (51 %) and the base of the tongue/lingual tonsil (38 %). The most common type of cancer was non-keratinizing squamous cell carcinoma (60 %), and the majority of primaries were p16 positive/HPV-mediated (86 %). A cohort of p16 positive/HPV mediated OPC (27/283, 9.5 %) presented with aggressive clinical behavior, including multiple distant metastases at unusual sites. Tumor size >2 cm and the presence of tumor anaplasia/multinucleation were significantly associated with an increased rate of distant metastases in p16 positive/HPV mediated cases, both in unadjusted and adjusted analyses (all P < 0.05). Of the 332 individuals in the overall cohort, 38 individuals died due to their disease within the observed follow-up time. Among the 283 patients with p16 positive/HPV mediated tumors, survival was estimated at 97 % (95 % CI 95 %, 100 %) at 1 year, 95 % (95 % CI 92 %, 98 %) at 2 years, and 80 % (95 % CI 72 %, 89 %) at 5 years. The presence of tumor anaplasia/multinucleation and distant metastasis were both significantly associated with poorer disease-specific survival in p16 positive/HPV mediated cases (both P < 0.05), with the survival effect of tumor anaplasia/multinucleation likely mediated in part through its association with distant metastasis. For p16 positive/HPV-mediated OPC, age, smoking status, tumor status, and lymph node status were not significantly associated with disease-specific survival in our study.
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http://dx.doi.org/10.1016/j.prp.2020.153243DOI Listing
December 2020

Multivariate mortality analyses in COVID-19: Comparing patients with cancer and patients without cancer in Louisiana.

Cancer 2021 01 28;127(2):266-274. Epub 2020 Oct 28.

Ochsner Cancer Institute, New Orleans, Louisiana.

Background: This is the largest and only multivariate study evaluating the difference in mortality from coronavirus disease 2019 (COVID-19) between patients with cancer and patients without cancer in the United States. The objective was to assess COVID-19 mortality rates in patients with cancer versus patients without cancer and uncover possible statistically significant characteristics contributing to mortality.

Methods: This retrospective study analyzed patients with cancer and patients without cancer who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 1 through April 30, 2020. This was a multicenter study in the state of Louisiana throughout the Ochsner Health System in both tertiary and nontertiary centers. Patients older than 18 years were eligible. Three hundred twelve patients with cancer were compared with 4833 patients without cancer.

Results: Mortality was found to be higher in the cancer group. Patients of advanced age with cancer had a significant increase in mortality (odds ratio [OR], 5.96; P < .001). Other significant risk factors for increased mortality were male sex (OR, 2.15), a history of chronic kidney disease (OR, 3.84), and obesity (OR, 1.30). In hospitalized patients with cancer, adverse vital signs on admission, decreased absolute lymphocyte counts, thrombocytopenia, elevated creatinine, lactic acidosis, and elevated procalcitonin all seemed to increase the risk of death. Among patients with cancer, active or progressive disease (P < .001) and recent therapy (OR, 2.34; 95% confidence interval, 1.08-5.08) were shown to increase mortality.

Conclusions: Patients with cancer have increased mortality in the setting of infection with SARS-CoV-2 in comparison with patients without cancer. Patients with cancer who are 65 years of age or older and those with certain comorbidities have the greatest risk of death. Recent cancer-directed therapy and disease status also seem to play roles in mortality.

Lay Summary: This is the largest study of patients with cancer versus patients without cancer to date and is the first multivariate analysis study comparing these 2 patient populations. This study confirms the hypothesis that patients with cancer are at increased risk for mortality and that there are multiple characteristics posing the potential to risk-stratify these patients in the setting of a future outbreak.
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http://dx.doi.org/10.1002/cncr.33243DOI Listing
January 2021

Radiographic Reference Intervals of the Cardiac Silhouette Width in the Bald Eagle ().

J Avian Med Surg 2020 Oct;34(3):260-267

Avian and Exotic Animal Care, Raleigh, NC 27617, USA.

Radiograph imaging is an important diagnostic tool for assessing cardiac size in avian patients. The bald eagle (), once on the United States Federal List of Endangered and Threatened Wildlife and Plants, is now a thriving species in the United States. However, there is surprisingly little information regarding bald eagle cardiac reference values obtained through radiographic imaging for use in assessment of cardiac disease in this species. This study was performed to establish reference values of cardiac size in the bald eagle. Ventrodorsal radiographic images were taken from 9 healthy birds obtained from a raptor rehabilitation facility. Cardiac silhouette width to thorax width, cardiac silhouette width to sternum width, cardiac silhouette width to hepatic silhouette width, and cardiac silhouette width to coracoid width were obtained. Ratios were calculated between the respective areas measured. The results showed that the cardiac silhouette averages 44%-52% of the thoracic width, 71%-86% of the sternal width, 94%-117% of the width of the hepatic silhouette, and 500%-920% of the coracoid width. In the individuals studied there was a strong correlation between cardiac silhouette width to thoracic and sternal width whereas cardiac width with hepatic and coracoid widths had a moderate to weak correlation respectively. The values obtained in this study can be used to radiographically assess the cardiac size of bald eagles, thus aiding in the diagnosis of cardiomegaly in this species.
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http://dx.doi.org/10.1647/1082-6742-34.3.260DOI Listing
October 2020