bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear Magnetic Resonance (NMR)–Based Serum Metabolic Profiles: Impact of Fasting Status
Authors: Smy Laura , Lee Megan , Biase Irene De , Genzen Jon , Yuzyuk Tatiana 
Published: September 2019

Abstract

Introduction
Measurement of lipoprotein subclass concentration (-c), particle number (-p), and size (-s) by nuclear magnetic resonance (NMR) has gained traction recently in the clinical laboratory due to associations between smaller lipid particle sizes and atherogenic risk, especially for LDL-p. Since patients may not comply with the clinician’s recommendation of fasting before sample collection, our objective was to evaluate the impact of fasting status on NMR-based lipid and amino acid determinations.

Methods
Fifty self-reported healthy participants were recruited using an internal review board-approved protocol: males (n = 25; 41.3 ± 10.5 years; BMI 27.7 ± 4.6 kg/m2) and females (n = 25; 35.6 ± 9.1 years; BMI 25.3 ± 5.4 kg/m2). Blood was collected after overnight fast and 4 hours after a high-fat meal. Samples were analyzed using the AXINON lipoFIT by NMR assay (Numares) with an Avance III NMR spectrometer and Ascend 600 MHz magnet (Bruker). This assay included measurements of triglycerides, total cholesterol, IDL-c, and LDL, HDL, VLDL concentrations; particle numbers; and sizes. Additionally, NMR-based glucose, alanine, valine, leucine, and isoleucine concentrations were acquired. Conventional lipid parameters were obtained using cobas 8000 chemistry system (Roche). Fasting and postprandial results were compared for significant differences.

Results
As expected, mean triglycerides increased after the meal (53%, P < .0001). Increases were also observed for VLDL-c (22%, P < .0001) and large VLDL-p (56%, P < .0001), as well as LDL-s, HDL-s, and VLDL-s (all <3.5%, P < .005). In contrast, LDL-p, small LDL-p, large LDL-p, HDL-p, small HDL-p, glucose, total cholesterol, and LDL, HDL, and IDL cholesterols demonstrated at most an 11% decrease (all P < .002). Valine, leucine, and isoleucine also increased after the meal (31%-46%, P < .0001 for all). Differences in individual lipids or amino acids were not sufficient to distinguish between fasting vs postprandial states, although incorporation of valine into a ratio with VLDL-c and LDL cholesterol (Valine*VLDL-c/LDL cholesterol) provided adequate differentiation (ROC analysis: AUC 0.91 [SD 0.03, P < .0001]). A cutoff of 75 for the ratio had a sensitivity of 88.9% (95% CI, 76.0%-96.3%) and specificity of 85.4% (95% CI, 72.2%-93.9%). Interference with NMR results occurred for three participants’ postprandial samples. These individuals had significantly higher fasting triglycerides, LDL-p, small LDL-p, large VLDL-p, VLDL-s, VLDL-c, IDL-c and lower LDL-s, and HDL-s compared to other participants.

Conclusions
The clinical impact on results from postprandial samples warrants further evaluation prior to accepting nonfasting samples for NMR analysis. Considering a subpar compliance with fasting, algorithms to differentiate fasting and postprandial specimens may be useful in identifying suboptimal specimens.
The Correlation Between DPYD*9A(c.85T>C) Genotype and Dihydropyrimidine Dehydrogenase Deficiency Phenotype in Patients With Gastrointestinal Malignancies Treated With Fluoropyrimidines
Authors: Maharjan Anu S , McMillin Gwendolyn , Khushman Moh’d , Patel Girijesh 
Published: September 2019

Abstract

Introduction
The correlation between DPYD*9A (c.85T>C) genotype and dihydropyrimidine dehydrogenase (DPD) deficiency phenotype is controversial. In a cohort of 28 patients, DPYD*9A was the most commonly diagnosed variant (46%) and there was a noticeable genotype-phenotype correlation. Here we genotyped a larger cohort of a mixed racial background to explore the incidence of DPYD*9A variant and to further study the genotype-phenotype correlation.

Methods
Genotyping for high-risk DPYD variants (DPYD*2A, DPYD*13, and DPYD*9B) and the DPYD*9A variant was performed on 113 patients with gastrointestinal malignancies (GI) treated with fluoropyrimidines, using TaqMan chemistry. The prevalence of different DPYD variants was further analyzed in 1,283 retrospective data from ARUP laboratories. Fluoropyrimidines-associated toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (v 5.0). Fisher’s exact test was used for statistical analysis.

Results
In total, 1,283 were retrospectively reviewed for DPYD variants. Four patients (0.31%) carried DPYD c.-1590T>C, 10 patients (0.55%) carried DPYD c.1679T>G (*13), 36 patients (2.8%) carried DPYD c.2846A>T, and 527 patients (41.1%) carried DPYD c.85T>C (*9A). In the GI cancer cohort, DPYD variants were identified in 61 patients (54%), showing similar prevalence as the retrospective analysis. Caucasians represented 54% and African Americans represented 43%. Twenty-eight patients (46%) were females. Heterozygous DPYD*9A was identified in 46 patients (41%) and homozygous DPYD*9A was identified in 11 patients (10%). DPYD*2A was identified in 3 patients and DPYD*9B was identified in 2 patients (one patient had double heterozygous *9A and *9B). Grade 3 to 4 toxicities were experienced in 26 patients with mutant DPYD*9A (3 patients had homozygous DPYD*9A) and in 20 patients with no identified DPYD mutation (P = .7035). In patients who received full-dose fluoropyrimidines (N = 85), grade 3 to 4 toxicities were experienced in 22 patients with mutant DPYD*9A (2 patients had homozygous DPYD*9A) and in 17 patients with no identified DPYD mutation (P = .8275).

Conclusion
In the GI cancer population, the DPYD*9A variant was identified in 54% of patients. The correlation between DPYD*9A variant and DPD clinical phenotype was not significant. The noticeable correlation that was previously reported is likely due to small sample size and selection bias.
Stop Waiting for Tomorrow: Early Disk Diffusion—An Accurate Method for Antimicrobial Susceptibility Testing With Reduced Turnaround Time
Authors: Webber Daniel , Wallace Meghan , Burnham Carey-Ann 
Published: September 2019

Abstract

Background
Disk diffusion is a slow but reliable reference method for measuring antimicrobial susceptibility. Our objective was to improve the turnaround time for this method by reducing the culture incubation period prior to disk diffusion testing (referred to as early disk diffusion [eDD] testing).

Methods
Clinical isolates (n = 13) and quality control (QC) strains (n = 8) of bacteria, including 6 Staphylococcus aureus, 3 Enterococcus faecium, 3 Enterococcus faecalis, 3 Escherichia coli, 3 Pseudomonas aeruginosa, 2 Klebsiella pneumoniae, and 1 Enterobacter cloacae, were inoculated on blood agar by quadrant streaking and were incubated at 35○C for 6 hours (eDD6), 10 hours (eDD10), or 24 hours (standard [sDD]) before disk diffusion testing was set up in accordance with CLSI guidelines using Mueller Hinton Agar (Hardy Diagnostics) and clinically appropriate antimicrobial agents (total: 24). Experiments were performed sequentially in triplicate with zones measured by two independent readers.

Results
Examination of 6-hour blood agar plates showed limited growth in the first 1 to 2 quadrants while 10-hour growth plates had 4-quadrant growth and individual colonies in most cases. Despite limited growth on 6-hour plates, there were adequate bacteria to produce a 0.5 McFarland standard for disk diffusion testing for all 126 eDD replicates. Results were evaluable for 1,206 of 1,206 (100%) of eDD and 603 of 603 (100%) of standard disk diffusion (sDD). A comparison of early vs standard disk diffusion showed that eDD6 had 3 of 154 (1.9%) very major errors and 6 of 449 (1.3%) major errors, whereas eDD10 had no very major errors and 3 of 449 (0.7%) minor errors. Very major errors in eDD6 included a 1-mm difference between eDD6 and sDD for cefoxitin inhibition of S aureus as well as 4- and 6-mm differences between eDD6 replicates and sDD for nitrofurantoin inhibition of E cloacae. There was similar categorical agreement of eDD6 (96.7%) and eDD10 (96.7%) with sDD. Overall, there was a very good correlation of eDD6 (r2 = 0.98) and eDD10 (r2 = 0.99) with sDD. When grouping results by bacterial species, there was no more than 1-mm difference in median antimicrobial inhibition between eDD6, eDD10, and sDD. Of note, 5 of 7 bacterial species had the same median zone size when comparing eDD6 or eDD10 with sDD. There was also very little difference between early and standard methods when examining bacteria-drug combinations, with a similar zone size (difference in mode <2 mm) in 67 of 69 (97%) eDD6 and 66 of 69 (96%) eDD10 compared to sDD. Test results for QC isolates agreed with the CLSI recommended ranges in 97 of 99 (98%) eDD6, 97 of 99 (98%) eDD10, and 96 of 99 (97%) sDD.

Conclusion
Early disk diffusion testing is a simple and accurate method of antimicrobial susceptibility testing that can reduce time to results by as much as 18 hours with no additional cost.
Effect of Long-Term Storage on Hematopoietic Progenitor Cell Transplant Product Quality
Authors: Mattis Aidas , Sempek Diane , Thibodeaux Suzanne 
Published: September 2019

Abstract
Hematopoietic progenitor cell (HPC) transplant product quality indicators after prolonged cryopreservation are variable. A recent study in Europe demonstrated wide variability of cryopreservation times, from 1 to >20 years, with most centers storing products for 5 or 10 years. Thawed HPC viability using various ex vivo means and in vivo by studying neutrophil and platelet engraftment has generally supported preservation of CD34+ viability with prolonged storage. However, sample size, methods, and timepoints varied, and clear guidelines currently do not exist regarding how long HPCs can be stored. This study’s objectives include an evaluation of HPC quality indicators over time and if HPC product age and/or viability correlates with HPC engraftment. Retrospective record review was conducted on 837 HPC products thawed between January 1, 2011, and December 31, 2018. HPC products were sampled and characterized at thawing by flow cytometry for total nucleated cell (TNC) recovery, CD34+ recovery, and CD34+ viability (by 7-AAD). Preestablished acceptability criteria for TNC recovery, CD34+ recovery, and CD34+ viability were >80%, >40%, and >60%, respectively. If available, products with ANC engraftment data were further analyzed to correlate data with time to HPC engraftment. HPC products were stored between 3 and 5,943 days; 816 products were infused, ranging from 3 to 5,273 days in storage. Most (81%) HPC transplants occurred within the first year, 47 infusions occurred after storage >5 years, and 4 infusions occurred after storage >10 years. CD34 viability and percent recovery of TNC and CD34 were not significantly different as time in storage increased. Given sample paucity, 19 samples stored for >10 years were analyzed in individual years and grouped. In total, 96.5% samples stored for <1 year and 68% in samples stored >10 years met acceptability criteria for >60% CD34+ recovery; 98.9% samples stored <1 year met the >60% CD34+ viability acceptability threshold versus 90% of samples stored for >10 years. The oldest sample infused after storage of 5,273 days (14.4 years) showed 42% TNC recovery, 19% CD34+ recovery, and 84% CD34 viability; ANC engraftment data were not available. Sixty-five samples containing ANC engraftment data showed that time to ANC engraftment ranged from 9 to 15 days. No clear trend was present for viability or CD34 recovery when compared with days to engraftment based on limited data. Although rare, infusion of HPC products of extended duration occurs. This study suggests that HPC product quality may decrease after extended cryopreservation based on preestablished acceptability criteria. The oldest sample infused had preserved CD34+ viability despite significantly less TNC and CD34+ recovery, suggesting thawing might select for more robust HPCs. More studies with older samples are needed to determine the clinical impact of cryopreservation and if modification of current quality indicators could be useful clinically.
Evaluation of Positive T- and B-Cell Gene Rearrangement Studies Among Patients Without a Definitive Diagnosis by Other Assays
Authors: Mendoza Hadrian , Tormey Christopher , Siddon Alexa 
Published: September 2019

Abstract
In the evaluation of bone marrow (BM) and peripheral blood (PB) for hematologic malignancy, positive immunoglobulin heavy chain (IG) or T-cell receptor (TCR) gene rearrangement results may be detected despite unrevealing results from morphologic, flow cytometric, immunohistochemical (IHC), and/or cytogenetic studies. The significance of positive rearrangement studies in the context of otherwise normal ancillary findings is unknown, and as such, we hypothesized that gene rearrangement studies may be predictive of an emerging B- or T-cell clone in the absence of other abnormal laboratory tests. Data from all patients who underwent IG or TCR gene rearrangement testing at the authors’ affiliated VA hospital between January 1, 2013, and July 6, 2018, were extracted from the electronic medical record. Date of testing; specimen source; and morphologic, flow cytometric, IHC, and cytogenetic characterization of the tissue source were recorded from pathology reports. Gene rearrangement results were categorized as true positive, false positive, false negative, or true negative. Lastly, patient records were reviewed for subsequent diagnosis of hematologic malignancy in patients with positive gene rearrangement results with negative ancillary testing. A total of 136 patients, who had 203 gene rearrangement studies (50 PB and 153 BM), were analyzed. In TCR studies, there were 2 false positives and 1 false negative in 47 PB assays, as well as 7 false positives and 1 false negative in 54 BM assays. Regarding IG studies, 3 false positives and 12 false negatives in 99 BM studies were identified. Sensitivity and specificity, respectively, were calculated for PB TCR studies (94% and 93%), BM IG studies (71% and 95%), and BM TCR studies (92% and 83%). Analysis of PB IG gene rearrangement studies was not performed due to the small number of tests (3; all true negative). None of the 12 patients with false-positive IG/TCR gene rearrangement studies later developed a lymphoproliferative disorder, although 2 patients were later diagnosed with acute myeloid leukemia. Of the 14 false negatives, 10 (71%) were related to a diagnosis of plasma cell neoplasms. Results from the present study suggest that positive IG/TCR gene rearrangement studies are not predictive of lymphoproliferative disorders in the context of otherwise negative BM or PB findings. As such, when faced with equivocal pathology reports, clinicians can be practically advised that isolated positive IG/TCR gene rearrangement results may not indicate the need for closer surveillance.
Performance of the Procalcitonin Test in Diagnosing Pneumonia in Real-World Practice
Authors: Ayala-Lopez Nadia , Ghaedi Mahboobe , Peaper David , Harb Roa 
Published: September 2019

Abstract

Background
Procalcitonin (PCT) rises early upon bacterial infection and has a long-half life, making it useful in the diagnosis of infections and antibiotic stewardship. We sought to determine the utility of PCT in diagnosing pneumonia (PNU) in the patient population presenting to our hospital during real-world clinical practice.

Methods
PCT results from patients in 2015 were reviewed retrospectively. Patients were eligible for inclusion if all of following criteria were met: PCT in 2015 and a lower respiratory tract culture, respiratory virus testing, chest x-ray, and white blood cell (WBC) count within 1 day of the PCT. Patients who opted out of research and those with mycobacterial infections and culture-positive infections of body sites other than urine and lower respiratory tract were excluded from further analysis.

Results
A total of 400 patients remained with 413 eligible PCT results across the ED (109), ICU (134), and inpatient (167) and outpatient (3) areas with a mean (SD) age of 66.2 (18.1). PCT was higher in patients with multiple pathogens reported on their respiratory cultures, direct fluorescence antibody (DFA), or PCR-based tests (mean ± SD = 2.43 ± 0.74 ng/mL; N = 32), than those with no pathogens reported (3.25 ± 1.13 ng/mL; N = 224; P < .05). Patients were grouped for the presence or absence of clinically defined PNU, according to a modification of the Centers for Disease Control (CDC) PNU1 criteria incorporating (1) chest x-ray results, (2) altered WBC number/altered mental status/fever, and (3) respiratory/breathing signs. PCT was higher in patients with clinically defined PNU, and the high PCTs were consistent with positive chest x-rays (criterion 1), and positive criterion 2 but not criterion 3. Incorporation of an elevated PCT >0.1 ng/mL into the PNU score slightly improved the area under the ROC curve (AUC) for the algorithm’s detection of PNU against the final clinical diagnosis (0.73 without PCT vs 0.76 with PCT). Furthermore, higher PCT was associated with higher 30-day and 1-year mortality.

Conclusion
PCT results were largely consistent with other markers of PNU such as imaging and CDC criterion 2, which suggests that PCT can be useful in evaluating for the presence of PNU. However, the PCT may not add additional information to assist in decision making above the already commonly ordered tests.
Alveolar Soft Part Sarcoma Presenting as a Uterine Polyp
Authors: Gomez Mariangela , Whiting Kerry 
Published: September 2019

Abstract

Background
Alveolar soft part sarcoma (ASPS) is a rare malignant soft tissue tumor, mainly localized in the extremities, occurring principally in adolescents and young adults. ASPS is uncommon in the female genital tract.

Case report
We here report a case of ASPS in a 20-year-old nullipara, presenting with vaginal bleeding and profound anemia requiring blood transfusions. Ultrasonographic examination revealed a polyp in the lower uterine segment. Surgical resection of the polyp was performed, and pathological evaluation showed the typical histological, immunohistochemical, and molecular features consistent with ASPS. At the time of this report, the patient was scheduled for total hysterectomy with promising results.

Conclusion
Given the infrequency of ASPS, pathological evaluation is or utmost importance in order to establish an accurate diagnosis. When presenting as a primary tumor, complete excision is fundamental in the treatment.
Tumors With Neuroectodermal Differentiation of the Uterus and Ovary: A Series of 12 Cases and Review of the Literature
Authors: Ge Li , Zhou Amy , Maksem John , Gennette Sarah , Schimp Veronica 
Published: September 2019

Abstract

Objectives
Primitive neuroectodermal tumors (PNETs) are a group of small round cell tumors most commonly found in the central nervous system, soft tissue, or bone. Such tumors arising in the uterus or ovary are rare. In this study, we describe the clinicopathologic features from a series of gynecological tumors with neuroectodermal differentiation.

Methods
In a retrospective review, 5 years of departmental archives were searched for gynecological tumors diagnosed at Orlando Health’s Department of Pathology. Clinicopathological information was analyzed, including age at diagnosis, tumor size, depth of invasion, other component, pathologic stage, FIGO stage, immunohistochemical stains, months of follow-up, and current disease status.

Results
Twelve fully staged tumors with neuroectodermal differentiation were identified. Eleven were of uterine origin and one was of ovarian origin. Ages at diagnosis ranged from 38 to 78 years (median 65). Neuroectodermal component was variable in morphology, including lymphocyte-like small cells in sheets, perivascular pseudorosettes, or cords; larger cells with prominent nucleoli with or without cystic change; and giant cells resembling megakaryocytes. Components other than neuroectodermal differentiation included carcinosarcoma, dedifferentiated endometrioid carcinoma, and high-grade serous carcinoma. Membranous and/or paranuclear dot-like CD99 immunoreactivity were in all cases. Ten patients were deceased due to disease at 1 to 33 months follow-up, while one patient was alive without evidence of disease after 61 months follow-up, possibly due to being able to tolerate a different therapeutic protocol for peripheral PNET.

Conclusion
Neuroectodermal differentiation may be found as components of other gynecological tumors, especially those with an aggressive phenotype and high-stage disease. The neuroectodermal component comprises a spectrum of cytohistological features. Because of its presentation in the shadow of other components, it may be more common than is generally assumed. Mortality remains high, but recognition of neuroectodermal differentiation in gynecologic tumors might introduce a different therapeutic approach and potentially improve clinical outcomes.
Loss of WT1 Expression After Chemotherapy in a Primary Peritoneal Serous Carcinoma: A Case Report
Authors: De Los Reyes Francia Victoria 
Published: September 2019

Abstract

Objectives
Primary peritoneal serous carcinoma (PPSC) is defined as a high-grade malignant neoplasm with widespread peritoneal involvement in the setting of normal-sized ovaries that contain small surface tumoral implants and no other identifiable source of malignant serous neoplasm elsewhere in the gynecologic tract.

Methods
The aim of this case report is to contribute to the understanding of tumor immunophenotype and describe the behavior of a primary peritoneal serous carcinoma in relation to the conversion of the tumor’s WT1 immunohistochemistry expression from positive to negative after chemotherapy.

Results
This is a case of a 72-year-old female that presented with a history of increasing abdominal girth of 12 months. She underwent biopsy of the omentum and was diagnosed to have metastatic carcinoma that was positive for WT1, PAX8, CK7, and ER. The patient was initially diagnosed and managed as a case of ovarian serous carcinoma with metastasis to the omentum. She underwent neoadjuvant platinum-based chemotherapy and en-bloc total abdominal hysterectomy with bilateral salpingo-oophorectomy and low anterior resection, with metastasis resection. The criteria of PPSC were fulfilled due to the normal-sized ovaries and minimal ovarian involvement with normal fallopian tubes.
Immunohistochemistry of the resection specimen showed negative WT1 and PAX8, and positive ER, CK, and p16 expression, with null p53 expression.

Conclusion
Following the concept that WT1 expression portends a poorer prognosis, the loss of WT1 expression may be a positive response to the chemotherapy and should be correlated with the time to recurrence. The patient was noted to be recurrence free for 1 year and still does not show signs of the disease at present.
This is the first documented case of a previously WT1-positive primary peritoneal serous carcinoma that converted to a negative WT1 expression. This may provide insight on the role of chemotherapy in silencing protein expression.