Publications by authors named "Zachary Thompson"

72 Publications

Implementation of a Pharmacist-Led Antimicrobial Time-Out for Medical-Surgery Services in an Academic Pediatric Hospital.

J Pediatr Pharmacol Ther 2021 31;26(3):284-290. Epub 2021 Mar 31.

Objective: This report describes a quality improvement initiative to implement a pharmacist-led antimicrobial time-out (ATO) in a large, freestanding pediatric hospital. Our goal was to reach 90% ATO completion and documentation for eligible patients hospitalized on general pediatric medicine or surgery services.

Methods: A multidisciplinary quality improvement team developed an ATO process and electronic documentation tool. Clinical pharmacists were responsible to initiate and document an ATO for pediatric medicine or surgery patients on or before the fifth calendar day of therapy. The quality improvement team educated pharmacists and physicians and provided ATO audit and feedback to the pharmacists. We used statistical process control methods to track monthly rates of ATO completion retrospectively from October 2017 through March 2018 and prospectively from April 2018 through April 2019. Additionally, we retrospectively evaluated the completion of 6 data elements in the ATO note over the final 12-month period of the study.

Results: Among 647 eligible antimicrobial courses over the 19-month study period, the mean monthly documentation rate increased from 54.6% to 83.5% (p < 0.001). The mean ATO documentation rate increased from 32.8% to 74.2% (p < 0.001) for the pediatric medicine service and from 65.0% to 88.1% for the pediatric surgery service (p = 0.006). Among 302 notes assessed for completeness, 35.8% had all the required data fields completed. A tentative antimicrobial stop date was the data element completed least often (49.3%).

Conclusions: We implemented a pharmacist-led ATO, highlighting the role pharmacists play in antimicrobial stewardship. Additional efforts are needed to further increase ATO completion rates and to define treatment duration.
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http://dx.doi.org/10.5863/1551-6776-26.3.284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021243PMC
March 2021

ELN 2017 Genetic Risk Stratification Predicts Survival of Acute Myeloid Leukemia Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation.

Transplant Cell Ther 2021 Mar 2;27(3):256.e1-256.e7. Epub 2021 Feb 2.

Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. Electronic address:

European LeukemiaNet (ELN) 2017 risk stratification by genetics is prognostic of outcomes in patients with acute myeloid leukemia (AML). However, the prognostic impact of the 2017 ELN genetic risk stratification after allogeneic hematopoietic cell transplantation (alloHCT) is not well established. We examined the effect of 2017 ELN genetic risk stratification on alloHCT outcomes of AML. We included 500 adult (≥18 years) AML patients in first (n = 370) or second (n = 130) complete remission receiving alloHCT from 2005 to 2016. Patients were classified into favorable (12%), intermediate (57%), and adverse (32%) 2017 ELN risk groups. The Cox proportional hazard model was used to conduct the multivariable analyses of leukemia-free survival (LFS) and overall survival (OS). Relapse and nonrelapse mortality were analyzed by the Fine-Gray regression model. OS at 2 years was 72% in the favorable versus 60% in the intermediate versus 45% in the adverse risk groups (P < .001). In multivariable analyses, the 2017 ELN classifier was an independent predictor of OS after alloHCT with significantly higher overall mortality in the intermediate (hazard ratio [HR] = 1.68, 95% confidence interval [CI], 1.06-2.68; P = .03) and adverse (HR = 2.50, 95% CI, 1.54-4.06; P < .001) risk groups compared to the favorable risk group. Similarly, LFS was worse in the intermediate (HR = 1.63, 95%, CI 1.06-2.53; P = .03) and adverse (HR 2.23, 95% CI, 1.41-3.54; P < .001) risk groups while relapse was higher in the adverse risk group (HR = 2.36, 95% CI, 1.28-4.35; P = .006) as compared to the favorable risk group. These data highlight the prognostic impact of the 2017 ELN genetic risk stratification on the survival of AML patients after alloHCT. Patients in the adverse risk group had the highest risk of relapse and worst survival. Thus the 2017 ELN prognostic system can help identify AML patients who may benefit from clinical trials offering relapse mitigation strategies to improve transplant outcomes.
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http://dx.doi.org/10.1016/j.jtct.2020.12.021DOI Listing
March 2021

Hypofractionated stereotactic re-irradiation with pembrolizumab and bevacizumab in patients with recurrent high-grade gliomas: results from a phase I study.

Neuro Oncol 2021 04;23(4):677-686

H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Background: Radiotherapy may synergize with programmed cell death 1 (PD1)/PD1 ligand (PD-L1) blockade. The purpose of this study was to determine the recommended phase II dose, safety/tolerability, and preliminary efficacy of combining pembrolizumab, an anti-PD1 monoclonal antibody, with hypofractionated stereotactic irradiation (HFSRT) and bevacizumab in patients with recurrent high-grade gliomas (HGGs).

Methods: Eligible subjects with recurrent glioblastoma or anaplastic astrocytoma were treated with pembrolizumab (100 or 200 mg based on dose level Q3W) concurrently with HFSRT (30 Gy in 5 fractions) and bevacizumab 10 mg/kg Q2W.

Results: Thirty-two patients were enrolled (bevacizumab-naïve, n = 24; bevacizumab-resistant, n = 8). The most common treatment-related adverse events (TRAEs) were proteinuria (40.6%), fatigue (25%), increased alanine aminotransferase (25%), and hypertension (25%). TRAEs leading to discontinuation occurred in 1 patient who experienced a grade 3 elevation of aspartate aminotransferase. In the bevacizumab-naïve cohort, 20 patients (83%) had a complete response or partial response. The median overall survival (OS) and progression-free survival (PFS) were 13.45 months (95% CI: 9.46-18.46) and 7.92 months (95% CI: 6.31-12.45), respectively. In the bevacizumab-resistant cohort, PR was achieved in 5 patients (62%). Median OS was 9.3 months (95% CI: 8.97-18.86) with a median PFS of 6.54 months (95% CI: 5.95-18.86). The majority of patients (n = 20/26; 77%) had tumor-cell/tumor-microenvironment PD-L1 expression <1%.

Conclusions: The combination of HFSRT with pembrolizumab and bevacizumab in patients with recurrent HGG is generally safe and well tolerated. These findings merit further investigation of HFSRT with immunotherapy in HGGs.
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http://dx.doi.org/10.1093/neuonc/noaa260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041351PMC
April 2021

The Probable, Possible, and Novel Functions of ERp29.

Front Physiol 2020 8;11:574339. Epub 2020 Sep 8.

Cystic Fibrosis Center, The Children's Hospital of Philadelphia, Philadelphia, PA, United States.

The luminal endoplasmic reticulum (ER) protein of 29 kDa (ERp29) is a ubiquitously expressed cellular agent with multiple critical roles. ERp29 regulates the biosynthesis and trafficking of several transmembrane and secretory proteins, including the cystic fibrosis transmembrane conductance regulator (CFTR), the epithelial sodium channel (ENaC), thyroglobulin, connexin 43 hemichannels, and proinsulin. ERp29 is hypothesized to promote ER to Golgi cargo protein transport COP II machinery through its interactions with the KDEL receptor; this interaction may facilitate the loading of ERp29 clients into COP II vesicles. ERp29 also plays a role in ER stress (ERS) and the unfolded protein response (UPR) and is implicated in oncogenesis. Here, we review the vast array of ERp29's clients, its role as an ER to Golgi escort protein, and further suggest ERp29 as a potential target for therapies related to diseases of protein misfolding and mistrafficking.
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http://dx.doi.org/10.3389/fphys.2020.574339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506106PMC
September 2020

Managing a Large-Scale Multiomics Project: A Team Science Case Study in Proteogenomics.

Methods Mol Biol 2021 ;2194:187-221

Department of Molecular Oncology/Pathology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Highly collaborative scientists are often called on to extend their expertise to different types of projects and to expand the scope and scale of projects well beyond their previous experience. For a large-scale project involving "big data" to be successful, several different aspects of the research plan need to be developed and tested, which include but are not limited to the experimental design, sample collection, sample preparation, metadata recording, technical capability, data acquisition, approaches for data analysis, methods for integration of different data types, recruitment of additional expertise as needed to guide the project, and strategies for clear communication throughout the project. To capture this process, we describe an example project in proteogenomics that built on our collective expertise and experience. Key steps included definition of hypotheses, identification of an appropriate clinical cohort, pilot projects to assess feasibility, refinement of experimental designs, and extensive discussions involving the research team throughout the process. The goal of this chapter is to provide the reader with a set of guidelines to support development of other large-scale multiomics projects.
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http://dx.doi.org/10.1007/978-1-0716-0849-4_11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771375PMC
March 2021

Neutrophil to lymphocyte ratio, not platelet to lymphocyte or lymphocyte to monocyte ratio, is predictive of patient survival after resection of early-stage pancreatic ductal adenocarcinoma.

BMC Cancer 2020 Aug 11;20(1):750. Epub 2020 Aug 11.

Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL, 33612, USA.

Background: NLR, PLR, and LMR have been associated with pancreatic ductal adenocarcinoma (PDAC) survival. Prognostic value and optimal cutpoints were evaluated to identify underlying significance in surgical PDAC patients.

Methods: NLR, PLR, and LMR preoperative values were available for 277 PDAC patients who underwent resection between 2007 and 2015. OS, RFS, and survival probability estimates were calculated by univariate, multivariable, and Kaplan-Meier analyses. Continuous and dichotomized ratio analysis determined best-fit cutpoints and assessed ratio components to determine primary drivers.

Results: Elevated NLR and PLR and decreased LMR represented 14%, 50%, and 50% of the cohort, respectively. OS (P = .002) and RFS (P = .003) were significantly decreased in resected PDAC patients with NLR ≥5 compared to those with NLR < 5. Optimal prognostic OS and RFS cutpoints for NLR, PLR, and LMR were 4.8, 192.6, and 1.7, respectively. Lymphocytes alone were the primary prognostic driver of NLR, demonstrating identical survival to NLR.

Conclusions: NLR is a significant predictor of OS and RFS, with lymphocytes alone as its primary driver; we identified optimal cutpoints that may direct future investigation of their prognostic value. This study contributes to the growing evidence of immune system influence on outcomes in early-stage pancreatic cancer.
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http://dx.doi.org/10.1186/s12885-020-07182-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422564PMC
August 2020

Dexmedetomidine: A Multipurpose Tool Which Is Difficult to Analyze.

Pediatr Crit Care Med 2020 07;21(7):704-705

Department of Pharmacy, Nationwide Children's Hospital, Columbus, OH.

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http://dx.doi.org/10.1097/PCC.0000000000002353DOI Listing
July 2020

The Association of Mutation with Tumor Mutation Burden and Its Prognostic Implications in Cutaneous Melanoma.

Cancer Epidemiol Biomarkers Prev 2020 09 1;29(9):1792-1799. Epub 2020 Jul 1.

Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Background: is a mucin marker that is frequently mutated in melanoma, but whether mutations could be useful as a surrogate biomarker for tumor mutation burden (TMB) remains unclear.

Methods: This study rigorously evaluates the mutation as a clinical biomarker in cutaneous melanoma by utilizing genomic and clinical data from patient samples from The Cancer Genome Atlas (TCGA) and two independent validation cohorts. We further extended the analysis to studies with patients treated with immunotherapies.

Results: Analysis results showed that samples with mutations had a higher TMB than the samples of wild-type, with strong statistical significance ( < 0.001) in all melanoma cohorts tested. Associations between mutations and TMB remained statistically significant after adjusting for potential confounding factors in the TCGA cohort [OR, 9.28 (95% confidence interval (CI), 5.18-17.39); < 0.001], Moffitt cohort [OR, 31.95 (95% CI, 8.71-163.90); < 0.001], and Yale cohort [OR, 8.09 (95% CI, 3.12-23.79); < 0.01]. mutations were also found to be associated with overall survival in the TCGA [HR, 0.62; (95% CI, 0.45-0.85); < 0.01] and Moffitt cohorts [HR, 0.49 (95% CI, 0.28-0.87); = 0.014]. Strikingly, is the only top frequently mutated gene for which prognostic significance was observed. mutations were also found valuable in predicting anti-CTLA-4 and anti-PD-1 therapy responses.

Conclusions: mutation appears to be a useful predictive marker of global TMB and patient survival in melanoma.

Impact: This is, to the best of our knowledge, the first systematic evaluation of mutation as a clinical biomarker and a predictive biomarker for immunotherapy in melanoma.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483810PMC
September 2020

Diffusion-Weighted MR Imaging of Primary and Secondary Lung Cancer: Predictive Value for Response to Transpulmonary Chemoembolization and Transarterial Chemoperfusion.

J Vasc Interv Radiol 2020 Feb 30;31(2):301-310. Epub 2019 Dec 30.

Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, Frankfurt am Main 60590, Germany.

Purpose: To examine predictive value of apparent diffusion coefficient (ADC) in diffusion-weighted imaging (DWI) for response of patients with primary and secondary lung neoplasms undergoing transpulmonary chemoembolization (TPCE) and transarterial chemoperfusion (TACP) treatment.

Materials And Methods: Thirty-one patients (mean age ± SD 64 ± 12.4 y) with 42 lung target lesions (13 primary and 29 secondary) underwent DWI and subsequent ADC analysis on a 1.5T MR imaging scanner before and 30.3 days ± 6.4 after first session of TPCE or TACP. After 3.1 treatment sessions ± 1.4 performed in 2- to 4-week intervals, morphologic response was analyzed by comparing tumor diameter and volume before and after treatment on unenhanced T1-weighted MR images. On a per-lesion basis, response was classified according to Response Evaluation Criteria In Solid Tumors.

Results: Threshold ADC increase of 20.7% indicated volume response with 88% sensitivity and 78% specificity (area under the curve [AUC] = 0.84). Differences between ADC changes in volume response groups were significant (P = .002). AUC for volume response predicted by ADC before treatment was 0.77. Median ADC before treatment and mean ADC change were 1.09 × 10 mm/second and 0.36 × 10 mm/second ± 0.23, 1.45 × 10 mm/second and 0.14 × 10 mm/second ± 0.16, and 1.30 × 10 mm/second and 0.06 × 10 mm/second ± 0.19 in partial response, stable disease, and progressive disease groups. In primary lung cancer lesions, strong negative correlation of ADC change with change in diameter (ρ = -.87, P < .001) and volume (ρ = -.66, P = .016) was found. In metastases, respective correlation coefficients were ρ = -.18 (P = .356) and ρ = -.35 (P = .061).

Conclusions: ADC quantification shows considerable diagnostic value for predicting response and monitoring TPCE and TACP treatment of patients with primary and secondary lung neoplasms.
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http://dx.doi.org/10.1016/j.jvir.2019.08.027DOI Listing
February 2020

Significant effect of HIV/HAART on oral microbiota using multivariate analysis.

Sci Rep 2019 12 27;9(1):19946. Epub 2019 Dec 27.

Center of Excellence in Oral and Craniofacial Biology, Louisiana State University Health Sciences Center School of Dentistry, New Orleans, LA, USA.

Persons infected with HIV are particularly vulnerable to a variety of oral microbial diseases. Although various study designs and detection approaches have been used to compare the oral microbiota of HIV-negative and HIV-positive persons, both with and without highly active antiretroviral therapy (HAART), methods have varied, and results have not been consistent or conclusive. The purpose of the present study was to compare the oral bacterial community composition in HIV-positive persons under HAART to an HIV-negative group using 16S rRNA gene sequence analysis. Extensive clinical data was collected, and efforts were made to balance the groups on clinical variables to minimize confounding. Multivariate analysis was used to assess the independent contribution of HIV status. Eighty-nine HIV-negative participants and 252 HIV-positive participants under HAART were sampled. The independent effect of HIV under HAART on the oral microbiome was statistically significant, but smaller than the effect of gingivitis, periodontal disease, smoking, caries, and other clinical variables. In conclusion, a multivariate comparison of a large sample of persons with HIV under HAART to an HIV-negative control group showed a complex set of clinical features that influenced oral bacterial community composition, including the presence of HIV under HAART.
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http://dx.doi.org/10.1038/s41598-019-55703-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934577PMC
December 2019

Proteogenomic landscape of squamous cell lung cancer.

Nat Commun 2019 08 8;10(1):3578. Epub 2019 Aug 8.

Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.

How genomic and transcriptomic alterations affect the functional proteome in lung cancer is not fully understood. Here, we integrate DNA copy number, somatic mutations, RNA-sequencing, and expression proteomics in a cohort of 108 squamous cell lung cancer (SCC) patients. We identify three proteomic subtypes, two of which (Inflamed, Redox) comprise 87% of tumors. The Inflamed subtype is enriched with neutrophils, B-cells, and monocytes and expresses more PD-1. Redox tumours are enriched for oxidation-reduction and glutathione pathways and harbor more NFE2L2/KEAP1 alterations and copy gain in the 3q2 locus. Proteomic subtypes are not associated with patient survival. However, B-cell-rich tertiary lymph node structures, more common in Inflamed, are associated with better survival. We identify metabolic vulnerabilities (TP63, PSAT1, and TFRC) in Redox. Our work provides a powerful resource for lung SCC biology and suggests therapeutic opportunities based on redox metabolism and immune cell infiltrates.
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http://dx.doi.org/10.1038/s41467-019-11452-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687710PMC
August 2019

The Predominant Oral Microbiota Is Acquired Early in an Organized Pattern.

Sci Rep 2019 07 22;9(1):10550. Epub 2019 Jul 22.

The Ohio State University, College of Dentistry, 4126 Postle Hall, 305 W. 12th Ave, Columbus, OH, 43210, USA.

The human oral cavity is sterile prior to birth, and we have limited knowledge of how complex oral communities are assembled. To examine bacterial acquisition and community assembly over the first year of life, oral samples from a cohort of nine infants and their mothers were collected, and bacterial community composition was studied by 16S rRNA gene sequencing. Exogenous species including skin and environmental bacteria were present initially, but were quickly replaced by a small, shared microbial community of species common to all infants and adults. Subsequent ordered microbial succession and the formation of increasingly complex communities was observed. By one year of age oral microbial community composition converged to a profile that was remarkably similar among children. The introduction of new nutrient sources, but not tooth eruption, was associated with increasing complexity. Infants had fewer species than mothers, mostly accounted for by the lack of certain anaerobes, and showing that the acquisition and assembly of oral microbial communities continues past infancy. When relative abundance was considered, a shared set of species accounted for the majority of the microbial community at all ages, indicating that the dominant structure of the oral microbiome establishes early, and suggesting that it persists throughout life.
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http://dx.doi.org/10.1038/s41598-019-46923-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646312PMC
July 2019

Ultrasound characterization for thyroid nodules with indeterminate cytology: inter-observer agreement and impact of combining pattern-based and scoring-based classifications in risk stratification.

Endocrine 2019 11 12;66(2):278-287. Epub 2019 Jul 12.

Department of Head and Neck-Endocrine Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA.

Background: The American Thyroid Association (ATA) sonographic patterns stratify the risk of malignancy of cytologically indeterminate thyroid nodules (ITNs). This study aimed to (1) assess inter-observer agreement for sonographic features and patterns; (2) identify potential sources of disagreement; and (3) evaluate whether the number of suspicious features risk-stratifies non-ATA and high-suspicion patterns.

Methods: Three observers independently reviewed the ultrasound images of 463 ITNs with histological follow-up consecutively evaluated between October 2008 and June 2015 at an academic cancer center. Each observer evaluated individual sonographic features. ATA sonographic patterns were derived from the interpretation of sonographic features. Nodules not fitting into any of the proposed patterns were clustered into a non-ATA pattern.

Results: The inter-observer agreement for ATA sonographic patterns and echogenicity was fair, moderate for margins, good for composition and echogenic foci, and very good for extrathyroidal extension and lymph node metastasis. The interpretation of each sonographic feature was significantly different between observers, and there was complete disagreement in at least one of the features in 104 (22%) nodules. A total of 169 nodules (37%) were classified into the non-ATA pattern. The number of suspicious features allowed risk stratifying nodules with non-ATA and high-suspicion sonographic patterns. Most Non-invasive Follicular Thyroid Neoplasms with Papillary-like Nuclear Features had 0-1 suspicious features and none had >2.

Conclusions: Echogenicity interpretation was the greatest source of disagreement. The number of suspicious features risk-stratifies ITNs with non-ATA or high-suspicion patterns. Future studies attempting to objectivize the interpretation of echogenicity and heterogeneity are needed.
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http://dx.doi.org/10.1007/s12020-019-02000-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771547PMC
November 2019

The Homeobox gene, HOXB13, Regulates a Mitotic Protein-Kinase Interaction Network in Metastatic Prostate Cancers.

Sci Rep 2019 07 4;9(1):9715. Epub 2019 Jul 4.

Department of Surgery, Washington University in St. Louis, MO, USA.

HOXB13, a homeodomain transcription factor, is linked to recurrence following radical prostatectomy. While HOXB13 regulates Androgen Receptor (AR) functions in a context dependent manner, its critical effectors in prostate cancer (PC) metastasis remain largely unknown. To identify HOXB13 transcriptional targets in metastatic PCs, we performed integrative bioinformatics analysis of differentially expressed genes (DEGs) in the proximity of the human prostate tumor-specific AR binding sites. Unsupervised Principal Component Analysis (PCA) led to a focused core HOXB13 target gene-set referred to as HOTPAM9 (HOXB13 Targets separating Primary And Metastatic PCs). HOTPAM9 comprised 7 mitotic kinase genes overexpressed in metastatic PCs, TRPM8, and the heat shock protein HSPB8, whose levels were significantly lower in metastatic PCs compared to the primary disease. The expression of a two-gene set, CIT and HSPB8 with an overall balanced accuracy of 98.8% and a threshold value of 0.2347, was sufficient to classify metastasis. HSPB8 mRNA expression was significantly increased following HOXB13 depletion in multiple metastatic CRPC models. Increased expression of HSPB8 by the microtubule inhibitor Colchicine or by exogenous means suppressed migration of mCRPC cells. Collectively, our results indicate that HOXB13 promotes metastasis of PCs by coordinated regulation of mitotic kinases and blockade of a putative tumor suppressor gene.
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http://dx.doi.org/10.1038/s41598-019-46064-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609629PMC
July 2019

IV Acetaminophen-As Benign As We Thought?

Pediatr Crit Care Med 2019 06;20(6):574-575

Department of Pharmacy, Nationwide Children's Hospital, Columbus, OH.

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http://dx.doi.org/10.1097/PCC.0000000000001904DOI Listing
June 2019

Medical Cannabis Use in Glioma Patients Treated at a Comprehensive Cancer Center in Florida.

J Palliat Med 2019 10 13;22(10):1202-1207. Epub 2019 May 13.

Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Glioma is a devastating primary tumor of the central nervous system with difficult-to-manage symptoms. Cannabis products have been postulated to potentially benefit glioma patients. Recent state legalization allowed investigators an opportunity to study glioma patients' adoption of medical marijuana (MM). Our goals were to: (1) determine the prevalence of marijuana use, both through physician recommendation and self-medication, and (2) evaluate its perceived risks and benefits in glioma patients. Self-report data were collected and descriptive analyses were conducted. Participants were adult, English-speaking patients undergoing treatment for primary non-recurrent malignant glioma in neuro-oncology clinics at an NCI-designated Comprehensive Cancer Center. The survey on MM was adapted from previous research and included questions on knowledge and attitudes toward MM; use, frequency, type, and sourcing of MM; and reasons for use of MM and perceived symptom relief among users. A total of 73 patients were surveyed. The majority of participants were aware that MM was legal in the state, and most reported learning of this through the media. Over 70% of participants reported having considered using MM, and a third reported using marijuana products after their diagnosis. Most received recommendations from friends/family rather than a medical provider, and only half of the users had obtained a physician's recommendation. Users generally reported benefits. With the increasing national conversation that accompanies legalization, glioma patients are pursuing marijuana for the treatment for their symptoms. More research and education is needed to bring health care providers into the conversation.
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http://dx.doi.org/10.1089/jpm.2018.0528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364313PMC
October 2019

Survey of the Current Use of Dexmedetomidine and Management of Withdrawal Symptoms in Critically Ill Children.

J Pediatr Pharmacol Ther 2019 Jan-Feb;24(1):16-21

Objectives: Dexmedetomidine use for sedation in the pediatric intensive care units (PICUs) has increased since its initial US Food and Drug Administration (FDA) approval in adults. However, there is limited evidence to direct providers regarding current usage, dosing, and monitoring for withdrawal symptoms in pediatric patients. This study sought to determine the utilization of dexmedetomidine and management of dexmedetomidine withdrawal symptoms among PICU physicians.

Methods: A questionnaire survey was distributed to all members of the American Academy of Pediatrics Section on Critical Care. It assessed the practice site demographics, indication, dosing, and duration of dexmedetomidine infusion, unit protocol, and strategies for management of dexmedetomidine withdrawal.

Results: A total of 147 surveys (21.1%) were returned and analyzed. The reported uses for dexmedetomidine were as a primary sedative (59.9%), adjunctive agent for sedation (82.3%), and adjunctive agent to assist weaning sedation (62.6%) or from mechanical ventilation (70.1%). One hundred twenty-nine respondents (87.8%) had concerns over dexmedetomidine withdrawal, with 59 respondents becoming concerned after 120 hours of infusion (45.7%). Most respondents reported managing dexmedetomidine withdrawal symptoms via a regimented wean and initiation of clonidine (81%). Units with >1000 admissions per year were more likely to have a protocol related to dexmedetomidine use (p = 0.021). Units with >1000 admissions per year reported using clonidine for withdrawal at a higher rate, whereas units with ≤1000 admissions per year used a systematic wean of dexmedetomidine (p = 0.014).

Conclusions: Dexmedetomidine use in the PICU is varied among pediatric intensive care physicians. Intensivists have withdrawal concerns after dexmedetomidine discontinuation, and the primary management of this withdrawal phenomenon is the initiation of clonidine with a regimented dexmedetomidine wean.
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http://dx.doi.org/10.5863/1551-6776-24.1.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397011PMC
March 2019

Iodine quantification based on rest / stress perfusion dual energy CT to differentiate ischemic, infarcted and normal myocardium.

Eur J Radiol 2019 Mar 16;112:136-143. Epub 2019 Jan 16.

Division of Cardiovascular Imaging, Medical University of South Carolina, Department of Radiology and Radiological Science, Division of Cardiovascular Imaging, Charleston, SC, USA; Emory University, Department of Radiology and Imaging Sciences, Atlanta, GA, USA. Electronic address:

Background: The aim of this study was to assess the potential of rest-stress DECT iodine quantification to discriminate between normal, ischemic, and infarcted myocardium.

Methods: Patients who underwent rest-stress DECT on a 2nd generation dual-source system and cardiac magnetic resonance (CMR) were retrospectively included from a prospective study cohort. CMR was performed to identify ischemic and infarcted myocardium and categorize patients into ischemic, infarcted, and control groups. Controls were analyzed on a per-slice and per-segment basis. Regions of interest (ROIs) were placed in ischemic and infarcted areas based on CMR. Additionally, ROIs were placed in the septal area to assess normal and remote myocardium.

Results: We included 42 patients: 10 ischemic, 17 infarcted, and 15 controls. Iodine concentrations showed no significant between segments in controls. Iodine concentrations for normal myocardium increased significantly from rest to stress (median 3.7 mg/mL (interquartile range 3.5-3.9) vs. 4.5 mg/mL (4.3-4.9)) (p < 0.001). Iodine concentrations in diseased myocardium were significantly lower than in normal myocardium; 1.3 mg/mL (0.9-1.8) and 0.6 mg/mL (0.4-0.8) at rest and stress in ischemic myocardium, and 0.3 mg/mL (0.3-0.5) and 0.5 mg/mL (0.5-0.7) at rest and stress in infarcted myocardium (p < 0.005 and p < 0.001). At rest only, iodine concentrations were significantly lower in infarcted vs. ischemic myocardium (p < 0.001). The optimal threshold for differentiating diseased from normal myocardium was 2.5 mg/mL and 2.1 mg/mL for rest and stress (AUC 1.00). To discriminate ischemic from infarcted myocardium, the optimal threshold was 1.0 mg/ml (AUC 0.944) at rest.

Conclusion: DECT iodine concentration from rest-stress imaging can potentially differentiate between normal, ischemic, and infarcted myocardium.
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http://dx.doi.org/10.1016/j.ejrad.2019.01.017DOI Listing
March 2019

Dexmedetomidine-Associated Fever in a Critically Ill Obese Child.

J Pediatr Pharmacol Ther 2018 Nov-Dec;23(6):486-489

Dexmedetomidine use in the pediatric intensive care unit has increased in recent years. Reports of dexmedetomidine-associated drug fever have been described in adult patients; however, this has not been reported in the pediatric population. We report a case of persistent fever that resolved with the discontinuation of dexmedetomidine and successful transition to clonidine. This is the first report of dexmedetomidine drug fever in a pediatric patient.
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http://dx.doi.org/10.5863/1551-6776-23.6.486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336172PMC
January 2019

Vancomycin Pharmacokinetics During Extracorporeal Membrane Oxygenation and Dosing Targets-A Constantly Moving Target?

Pediatr Crit Care Med 2018 10;19(10):1002-1003

Department of Pharmacy, Nationwide Children's Hospital, Columbus, OH.

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http://dx.doi.org/10.1097/PCC.0000000000001689DOI Listing
October 2018

Association of Tumor Size With Histologic and Clinical Outcomes Among Patients With Cytologically Indeterminate Thyroid Nodules.

JAMA Otolaryngol Head Neck Surg 2018 09;144(9):788-795

Department of Head and Neck-Endocrine Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Importance: Tens of thousands of unnecessary operations are performed each year for diagnostic purposes among patients with cytologically indeterminate thyroid nodules. Whereas a diagnostic lobectomy is recommended for most patients with solitary indeterminate thyroid nodules, a total thyroidectomy is preferred for nodules larger than 4 cm.

Objective: To determine whether histologic or clinical outcomes of indeterminate thyroid nodules 4 cm or larger are worse than those for nodules smaller than 4 cm, thus justifying a more aggressive initial surgical approach.

Design, Setting, And Participants: In this retrospective cohort study, 652 indeterminate thyroid nodules (546 nodules <4 cm and 106 nodules ≥4 cm) with surgical follow-up were consecutively evaluated at an academic cancer center from October 1, 2008, through April 30, 2016.

Exposure: Tumor size.

Main Outcomes And Measures: Differences in cancer rates, rates of invasive features, cancer aggressiveness, and response to therapy between indeterminate thyroid nodules smaller than 4 cm and 4 cm or larger.

Results: A total of 652 indeterminate thyroid nodules (546 nodules <4 cm and 106 nodules ≥4 cm) from 589 patients (mean [SD] age, 53.1 [13.8] years; 453 [76.9%] female) were studied. No differences were found in the baseline characteristics of patients or nodules between the 2 size groups. Tumor size was not associated with the cancer rate as a categorical (140 of 546 [25.6%] for nodules <4 cm and 33 of 106 [31.1%] for nodules ≥4 cm; effect size, 0.05; 95% CI, 0.002-0.12) or continuous (odds ratio [OR], 1.03; 95% CI, 0.92-1.15) variable. No association was found between nodule size and prevalence of extrathyroidal extension, positive margins, lymphovascular invasion, lymph node metastasis, or distant metastasis. Most malignant tumors were low risk in both size groups (70% in the nodules <4 cm and 72% in the nodules ≥4 cm), and tumor size was not associated with tumor aggressiveness as a categorical (effect size, 0.10; 95% CI, 0.03-0.31) or continuous variable (OR for intermediate-risk cancer, 0.91; 95% CI, 0.72-1.14; OR for high-risk cancer, 1.43; 95% CI, 0.96-2.15). At the last follow-up visit, 88 of 105 patients (83.8%) with malignant tumors in the smaller than 4 cm group and 21 of 25 (84.0%) in the 4 cm or greater group had no evidence of disease, and tumor size was not associated with response to therapy (effect size, 0.13; 95% CI, 0.07-0.33).

Conclusions And Relevance: Most indeterminate thyroid nodules are benign or low-risk malignant tumors regardless of tumor size. In the absence of other indications for total thyroidectomy, this study suggests that a thyroid lobectomy is sufficient initial treatment for most solitary cytologically indeterminate thyroid nodules independent of the tumor size.
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http://dx.doi.org/10.1001/jamaoto.2018.1070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233620PMC
September 2018

Thyroid Nodules with Indeterminate Cytology: Utility of the American Thyroid Association Sonographic Patterns for Cancer Risk Stratification.

Thyroid 2018 08 17;28(8):1004-1012. Epub 2018 Jul 17.

1 Department of Head and Neck-Endocrine Oncology, H. Lee Moffitt Cancer Center and Research Institute , Tampa, Florida.

Background: The 2015 American Thyroid Association (ATA) guidelines recommend using a classification based on sonographic patterns to set the size threshold for biopsies. Each pattern is associated with a distinct estimated rate of malignancy that it was hypothesized should stratify the risk of malignancy of cytologically indeterminate thyroid nodules (ITNs).

Methods: Ultrasound images of 463 ITNs (38% atypia/follicular lesions of undetermined significance; 62% follicular neoplasms) with histological follow-up consecutively evaluated between October 2008 and June 2015 at the authors' academic cancer center were independently evaluated by three observers and classified into one of the five sonographic patterns proposed by the ATA. Nodules with sonographic patterns not defined in the classification were grouped into a non-ATA pattern category. Differences in clinical and histological findings between the sonographic patterns were assessed. The prevalence of malignancy and odds ratio for malignancy were calculated for each sonographic pattern (low and intermediate patterns were collapsed for the analysis).

Results: The distribution of size and cytological diagnosis was significantly different between sonographic patterns (p < 0.001). The overall rate of malignancy was 27%. The rate of malignancy for the very low, low/intermediate, high, and non-ATA patterns were 0%, 19%, 56%, and 36%, respectively, and were all significantly different. Compared to the low/intermediate suspicion patterns, the odds ratios for malignancy were 2.35 for the non-ATA and 5.18 for the high suspicion patterns (p < 0.001). The odds ratio of the non-ATA pattern was 0.45 over the high suspicion pattern (p = 0.04). Results were similar in both cytological categories and for each observer separately. Sonographic patterns were associated with distinct histopathological profiles (p < 0.001).

Conclusions: ATA sonographic patterns are associated with distinct clinical features and pathological outcomes, and effectively stratify the cancer risk in ITNs. Thus, the ATA sonographic patterns should be used not only to set the size threshold for biopsy, but also to personalize management after the biopsy.
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http://dx.doi.org/10.1089/thy.2018.0085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916126PMC
August 2018

Survival of patients with non-resectable, chemotherapy-resistant colorectal cancer liver metastases undergoing conventional lipiodol-based transarterial chemoembolization (cTACE) palliatively versus neoadjuvantly prior to percutaneous thermal ablation.

Eur J Radiol 2018 May 14;102:138-145. Epub 2018 Mar 14.

Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. Electronic address:

Purpose: To determine overall (OS) and progression-free survival (PFS) for cTACE alone and in combination with percutaneous thermal ablation in patients with non-resectable, chemotherapy-resistant colorectal cancer liver metastases (CRLM).

Material And Methods: The study included 452 patients undergoing 2654 repetitive cTACE treatments of CRLM. 233 patients were treated palliatively using only cTACE, whereas 219 patients were treated with cTACE in a neoadjuvant intend with subsequent thermal ablation (either microwave ablation or laser-induced thermotherapy). The chemotherapeutics agents used, in either single-, double-, or triple-combinations, included MitomycinC, Gemcitabine, Irinotecan, and Cisplatin. Several factors were analysed to determine their prognostic value in terms of OS and PFS.

Results: Palliative use of cTACE resulted in a median OS and PFS of 12.6 and 5.9 months, whereas the neoadjuvant use of cTACE showed a median OS and PFS of 25.8 and 10.8 months. The differences in OS and PFS between the two groups were statistically significant (p < 0.001). Extrahepatic metastases were a significant prognostic factor in the OS and PFS analysis of the palliative and neoadjuvant group. In addition, number, location, and mean size of metastases were significant prognostic factors for OS and PFS in the neoadjuvant group. Sex, primary tumor location, T- and N-parameters of the TNM staging system, time of liver metastases appearance, ablation method, and patient age did not significantly impact OS and PFS in either patient group. The most distinct response to cTACE was observed in metastases that were treated with a triple-combination of chemotherapeutics (p = 0.021).

Conclusion: cTACE is an effective treatment option in advanced non-resectable CRLM. Chemoembolization followed by ablation further increases survival rates. A triple combination of chemotherapeutics improves response to cTACE.
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http://dx.doi.org/10.1016/j.ejrad.2018.03.015DOI Listing
May 2018

Impact of oncogene panel results on surgical management of cytologically indeterminate thyroid nodules.

Head Neck 2018 08 6;40(8):1812-1823. Epub 2018 Apr 6.

Department of Head and Neck-Endocrine Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Background: The impact of oncogene panel results on the surgical management of indeterminate thyroid nodules (ITNs) is currently unknown.

Methods: Surgical management of 649 patients consecutively evaluated from October 2008 to April 2016 with a single nodule biopsied and indeterminate cytology (193 evaluated with and 456 without oncogene panels) was assessed and compared. Histological features of 629 consecutively resected ITNs (164 evaluated with and 465 without oncogene panels) were also characterized and compared.

Results: Oncogene panel evaluation was associated with higher rates of total thyroidectomy (45% vs 28%; P = .006), and central lymph node dissection (19% vs 12%; P = .03) without increasing the yield of malignancy or decreasing the rate of completion thyroidectomy. Most malignancies (64%), including 83% of those with driver mutation identified, were low-risk cancers for which a lobectomy could have been sufficient initial treatment.

Conclusion: Current oncogene panel results seem insufficient to guide the surgical extent of solitary ITNs.
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http://dx.doi.org/10.1002/hed.25165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771319PMC
August 2018

High-pitch low-voltage CT coronary artery calcium scoring with tin filtration: accuracy and radiation dose reduction.

Eur Radiol 2018 Jul 5;28(7):3097-3104. Epub 2018 Feb 5.

Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA.

Objectives: To investigate diagnostic accuracy and radiation dose of high-pitch CT coronary artery calcium scoring (CACS) with tin filtration (Sn100kVp) versus standard 120kVp high-pitch acquisition.

Methods: 78 patients (58% male, 61.5±9.1 years) were prospectively enrolled. Subjects underwent clinical 120kVp high-pitch CACS using third-generation dual-source CT followed by additional high-pitch Sn100kVp acquisition. Agatston scores, calcium volume scores, Agatston score categories, percentile-based risk categorization and radiation metrics were compared.

Results: 61/78 patients showed coronary calcifications. Median Agatston scores were 34.9 [0.7-197.1] and 41.7 [0.7-207.2] and calcium volume scores were 34.1 [0.7-218.0] for Sn100kVp and 35.7 [1.1-221.0] for 120kVp acquisitions, respectively (both p<0.0001). Bland-Altman analysis revealed underestimated Agatston scores and calcium volume scores with Sn100kVp versus 120kVp acquisitions (mean difference: 16.4 and 11.5). However, Agatston score categories and percentile-based risk categories showed excellent agreement (ĸ=0.98 and ĸ=0.99). Image noise was 25.8±4.4HU and 16.6±2.9HU in Sn100kVp and 120kVp scans, respectively (p<0.0001). Dose-length-product was 9.9±4.8mGy*cm and 40.9±14.4mGy*cm with Sn100kVp and 120kVp scans, respectively (p<0.0001). This resulted in significant effective radiation dose reduction (0.13±0.07mSv vs. 0.57±0.2mSv, p<0.0001) for Sn100kVp acquisitions.

Conclusion: CACS using high-pitch low-voltage tin-filtered acquisitions demonstrates excellent agreement in Agatston score and percentile-based cardiac risk categorization with standard 120kVp high-pitch acquisitions. Furthermore, radiation dose was significantly reduced by 78% while maintaining accurate risk prediction.

Key Points: • Coronary artery calcium scoring with tin filtration reduces radiation dose by 78%. • There is excellent correlation between high-pitch Sn100kVp and standard 120kVp acquisitions. • Excellent agreement regarding Agatston score categories and percentile-based risk categorization was achieved. • No cardiac risk reclassifications were observed using Sn100kVp coronary artery calcium scoring.
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http://dx.doi.org/10.1007/s00330-017-5249-2DOI Listing
July 2018

Handedness and the risk of glioma.

J Neurooncol 2018 May 13;137(3):639-644. Epub 2018 Jan 13.

Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612-9416, USA.

Gliomas are the most common type of malignant primary brain tumor and few risk factors have been linked to their development. Handedness has been associated with several pathologic neurological conditions such as schizophrenia, autism, and epilepsy, but few studies have evaluated a connection between handedness and risk of glioma. In this study, we examined the relationship between handedness and glioma risk in a large case-control study (1849 glioma cases and 1354 healthy controls) and a prospective cohort study (326,475 subjects with 375 incident gliomas). In the case-control study, we found a significant inverse association between left handedness and glioma risk, with left-handed persons exhibiting a 35% reduction in the risk of developing glioma [odds ratio (OR) = 0.65, 95% confidence interval (CI) 0.51-0.83] after adjustment for age, gender, race, education, and state of residence; similar inverse associations were observed for GBM (OR = 0.69, 95% CI 0.52-0.91), and non-GBM (OR = 0.59, 95% CI 0.42-0.82) subgroups. The association was consistent in both males and females, and across age strata, and was observed in both glioblastoma and in lower grade tumors. In the prospective cohort study, we found no association between handedness and glioma risk (hazards ratio = 0.92, 95% CI 0.67-1.28) adjusting for age, gender, and race. Further studies on this association may help to elucidate mechanisms of pathogenesis in glioma.
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http://dx.doi.org/10.1007/s11060-018-2759-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5924459PMC
May 2018

Microwave ablation of pancreatic tumors.

Minim Invasive Ther Allied Technol 2018 Feb 26;27(1):33-40. Epub 2017 Dec 26.

a Department of Diagnostic and Interventional Radiology , Frankfurt-University Hospital , Frankfurt am Main , Germany.

Objectives: To evaluate the clinical performance of percutaneous microwave ablation (MWA) for treatment of locally-advanced-pancreatic-cancer (LAPC).

Material And Methods: Twenty-two MWA sessions (August 2015-March 2017) in 20 patients with primary pancreatic cancer (13 men, 7 women, mean-age: 59.9 ± 8.6 years, range: 46-73 years), who had given informed consent, were retrospectively evaluated. All procedures were performed percutaneously under CT-guidance using the same high-frequency (2.45-GHz) MWA device. Tumor location and diameter, ablation diameter and volume, roundness, duration, technical success and efficacy, output energy, complications, and local tumor progression defined as a tumor focus connected to the edge of a previously technically efficient ablation zone were collected.

Results: Seventeen pancreatic malignant tumors (77.3%) were located in the pancreatic head and five (22.7%) in the pancreatic tail. Initial Mean Tumor Diameter was 30 ± 6 mm. Technical success and efficacy were idem (100%). No major complications occurred. Two patients (9.1%) showed minor complications of severe local pain related to MWA. Post-ablation diameter was on average 34.4 ± 5.8 mm. Mean ablation volume was 7.8 ± 3.8 cm³. The mean transverse roundness index was 0.74 ± 0.14. Mean ablation time was 2.6 ± 0.96 min. The mean applied energy per treatment was 9627 ± 3953 J. Local tumor progression was documented in one case (10%) of the 10/22 available three-month follow-up imaging studies.

Conclusion: High-frequency (2.45 GHz) microwave ablation (MWA) for treatment of unresectable and non-metastatic locally-advanced-pancreatic-cancer (LAPC) shows promising results regarding feasibility and safety of percutaneous approach after short-term follow-up and should be further evaluated.
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http://dx.doi.org/10.1080/13645706.2017.1420664DOI Listing
February 2018

Gene Expression Signature-Based Prediction of Lymph Node Metastasis in Patients With Endometrioid Endometrial Cancer.

Int J Gynecol Cancer 2018 02;28(2):260-266

Objective: This study aimed to develop a prediction model for lymph node metastasis using a gene expression signature in patients with endometrioid-type endometrial cancer.

Methods: Newly diagnosed endometrioid-type endometrial cancer cases in which the patients had undergone lymphadenectomy during a surgical staging procedure were identified from a national dataset (N = 330). Clinical and pathologic data were extracted from patient medical records, and gene expression datasets of their tumors were used to create a 12-gene predictive model for lymph node metastasis. We used principal components analysis on a training set (n = 110) to develop multivariate logistic models to predict low-risk patients having a probability of lymph node metastasis of less than 4%. The model with the highest prediction performance was selected for an evaluation set (n = 112), which, in turn, was validated in an independent validation set (n = 108).

Results: The model applied to the evaluation set showed 100% sensitivity (90% confidence interval [CI], 74%-100%) and 42% specificity (90% CI, 34%-51%), which resulted in 100% negative predictive value (90% CI, 89%-100%). In the validation set, we confirmed that the model consistently showed 100% sensitivity (90% CI, 88%-100%), 42% specificity (90% CI, 32%-50%), and 100% negative predictive value (90% CI, 88%-100%).

Conclusions: Our 12-gene signature model is a useful tool for the identification of patients with endometrioid-type endometrial cancer at low risk of lymph node metastasis, particularly given that it can be used to analyze histologic tissue before surgery and used to tailor surgical options.
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http://dx.doi.org/10.1097/IGC.0000000000001152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780243PMC
February 2018

Cancer Risk Associated with Nuclear Atypia in Cytologically Indeterminate Thyroid Nodules: A Systematic Review and Meta-Analysis.

Thyroid 2018 02 21;28(2):210-219. Epub 2017 Dec 21.

1 Department of Head and Neck-Endocrine Oncology, H. Lee Moffitt Cancer Center and Research Institute , Tampa, Florida.

Background: Indeterminate categories of thyroid cytopathology (categories B-III and B-IV of the Bethesda system) are integrated by a heterogeneous spectrum of cytological scenarios that are generally clustered for analysis and management recommendations. It has been suggested that aspirates exhibiting nuclear atypia have a higher risk of malignancy. This study aimed to assess whether cytologically indeterminate thyroid nodules with nuclear atypia have a significantly higher cancer risk than those without nuclear atypia.

Methods: On June 30, 2016, PubMed and EMBASE were searched for articles in English or Spanish using a search strategy developed by an endocrinologist and a librarian. Case reports were excluded, and no date limits were used. The references of all included studies were also screened for relevant missing studies. Studies were included if the prevalences of malignancy of cytologically indeterminate thyroid nodules with histological confirmation with and without nuclear atypia were reported. Studies were excluded if they had: (i) nodules suspicious for malignancy; (ii) nodules with non-indeterminate (B-III or B-IV) cytology on repeated biopsy, if performed; (iii) nodules not consecutively evaluated; or (iv) cohorts overlapping with another larger series. Two investigators independently assessed the eligibility and risk of bias of the studies. PRISMA and MOOSE guidelines were followed. Summary data were extracted from published reports by one investigator and independently reviewed by another. Data were pooled using a random-effects model. Heterogeneity was explored using subgroup analysis and mixed-effect model meta-regression. The odds ratio for malignancy of cytologically indeterminate thyroid nodules with nuclear atypia over cytologically indeterminate thyroid nodules without nuclear atypia was calculated.

Results: Of 2571 retrieved studies, 20 were eligible. The meta-analysis was conducted on summary data of 3532 cytologically indeterminate thyroid nodules: 1162 with and 2370 without nuclear atypia. The odds ratio for malignancy in cytologically indeterminate thyroid nodules with nuclear atypia was 3.63 [confidence interval 3.06-4.35]. There was no evidence of publication bias, and heterogeneity was insignificant (I < 0.01%, p = 0.40).

Conclusions: Nuclear atypia is a significant indicator of malignancy in cytologically indeterminate thyroid nodules and needs to be standardized and implemented into clinical practice.
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http://dx.doi.org/10.1089/thy.2017.0419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869885PMC
February 2018

Decreasing the Time to Oral Antibiotics in a University Hospital Pediatric Emergency Department.

J Pediatr Pharmacol Ther 2017 Jul-Aug;22(4):272-275

Objectives: To compare time to administration of oral antibiotics in the pediatric emergency department (ED) when antibiotics are stored in the pediatric ED versus when they were dispensed by central pharmacy services within an academic medical center.

Methods: This was a retrospective review of patients who received a one-time dose of oral antibiotics within the pediatric ED and were subsequently discharged home. Two 3-month time periods were compared to determine the metrics of providing oral antibiotics before and after these medications were stocked in the pediatric ED automated dispensing cabinet (ADC). The primary outcome was to compare the time to administration. Secondary outcomes were to assess wastage of stocked medications and time to ED discharge.

Results: In the ADC time period (n = 74), the median time to administration was 17.5 minutes versus 57 minutes in the central pharmacy time period (n = 34) (p < 0.001). The ED length of stay during the ADC time period was 188.5 minutes versus 228.5 minutes (p = 0.094). 35.4% of doses from the ADC expired resulting in a wholesale acquisition cost of $53.14 wasted.

Conclusion: Stocking commonly used oral antibiotics in the pediatric ED led to a significant decrease in the time to medication administration. This decreased time to administration has the potential to lead to improved patient and nursing satisfaction. Routine surveillance is needed after implementation to ensure compliance and to minimize wastage.
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http://dx.doi.org/10.5863/1551-6776-22.4.272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562207PMC
September 2017