bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the Clinical Utility of Factor V, VII, and VIII Assays in Assessment of DIC
Authors: Carll Timothy , Mikrut Krzysztof , Wool Geoffrey 
Published: September 2019

Abstract
Disseminated intravascular coagulation (DIC) is a hematologic emergency that requires prompt diagnosis and intervention. The International Society of Thrombosis and Hemostasis (ISTH) has developed a scoring system to diagnose life-threatening DIC, which is based upon routine coagulation lab assays, including PT, D-dimer, fibrinogen, and platelet count. Laboratory assays for coagulation factors V (FV) and VII (FVII) are commonly used to evaluate for abnormal liver function in patients with abnormally elevated PT/INR. They are also frequently ordered as part of workup for DIC, in combination with factor VIII (FVIII), at UChicago Medicine. However, these coagulation factors are not part of the guideline-based DIC workup, and their utility in the evaluation of DIC is not clearly defined. A retrospective review of orders containing at least factors V, VII, and VIII was performed at UChicago Medicine ranging from December 1, 2016, through November 30, 2017. Results for corresponding coagulation lab results, anticoagulation therapy, and factor-replenishing therapy (vitamin K, plasma, cryoprecipitate, and factor concentrates) were pooled. Patient charts were reviewed for DIC diagnosis by clinical suspicion (defined by keyword searches of clinician documentation) and by ISTH scoring. In total, 117 patients were reviewed. Only 47 had complete coagulation data to perform ISTH scoring. Of these, 30 met ISTH criteria for DIC (64%). No patient was diagnosed with DIC based on abnormal coagulation factor assays in the absence of abnormal screening coagulation results. The most common underlying diagnosis in those meeting ISTH criteria was sepsis. A statistically significant lower FV level was observed in those meeting ISTH criteria (P < .001, one-tail), but no such differences were observed in FVII or FVIII levels (P = .059, .224). FVIII was only reduced in 2 of the 117 reviewed patients (2%), and FVIII levels were rarely repeated to trend for any decrease in FVIII levels. FVII was reduced in 88 patients, of which 57 also showed reduced FV levels. Twenty-eight patients received factor replenishing therapy shortly before their initial lab draw for factor testing. Of the 88 patients with reduced FVII, 61 received factor-replenishing therapy within 3 days following the lab draw. We concluded that at this institution, factor level assays are often ordered without first obtaining complete screening coagulation assays, which represents poor utilization of laboratory resources due to cost and time constraints placed by factor assay testing. Factors VII and VIII are ineffective at evaluation of DIC, and factor VIII levels as currently utilized are of particularly little value given its near-universal elevation in the inpatient setting and lack of repeat testing for trend. We also took this opportunity to review the clinical response to abnormal testing results and found that the majority of abnormal factor testing results in the reviewed setting prompted therapeutic correction.
Prothrombin Complex Concentrate Versus Plasma in Patients With Liver Disease
Authors: Knoeckel Christopher , Roberts Sammie , Pokrandt Paul , Stokes Amber , Berg Mary 
Published: September 2019

Abstract
Prothrombin complex concentrate (PCC) is FDA approved for warfarin reversal but is often used for coagulopathy and hemorrhage in patients with liver disease. While studies have explored its use during liver transplant, less is known about its safety and efficacy for other indications in patients with liver disease. Our objective was to retrospectively compare INR and mortality in patients with liver disease treated with PCC versus plasma. After obtaining institutional review board approval, we conducted retrospective chart review of patients with liver disease who received PCC. Control patients with liver disease who received plasma alone were matched based on indication for treatment. Outcomes were first post-PCC or post-plasma INR and mortality during admission. Twenty-one patients with liver disease who received PCC were identified; 21 who received plasma alone were matched. Two PCC patients and 1 plasma patient were excluded due to insufficient data in the medical record to calculate MELD scores. Statistics were calculated in Microsoft Excel (Version 1901). The most frequent indications were coagulopathy reversal and hemorrhage. The most common liver disease etiologies in both groups were alcohol and hepatitis C. The mean MELD score for the PCC group was higher than that for the plasma group (35 ± 7 vs 27 ± 9, P = .01). Mean baseline INR was similar between groups (PCC group, 4.0 ± 2.8 vs plasma group, 3.8 ± 3.8, P = .88). While INR decreased somewhat without a significant difference between groups (PCC group, 2.8 ± 1.5 vs plasma group, 2.4 ± 1.2, P = .44), mortality during admission was significantly higher in patients who received PCC (15 [71%] vs 5 [33%], P < .01). Of the 15 PCC patients who died, 5 died with hemorrhage as a contributing factor, 3 with disseminated intravascular coagulopathy, and 1 with both; 1 other patient died with TIPS thrombus as a contributing factor. Of the 5 plasma patients who died during admission, 2 died with hemorrhage as a contributing factor, and none died with clotting complications. The difference in mortality between groups is likely confounded by more severe disease in the PCC group as evidenced by higher mean MELD score. It is unclear whether the higher number of bleeding and clotting complications in the PCC group is related to PCC administration or is a consequence of more advanced liver disease in these patients. The higher mean MELD score in the PCC group may reflect a tendency for providers to prescribe PCC for patients with more severe liver disease, who may not tolerate the large fluid boluses required for coagulopathy reversal with plasma. In conclusion, PCC does not appear to be superior to plasma for INR reversal in patients with liver disease. Further study is needed to determine efficacy and safety of PCC in patients with liver disease and should include comparison of patient groups with similar disease severity.
Automated Clinical Chemistry Platform Performance Across Two Academic Medical Centers
Authors: Brown Megan , Colby Jennifer , Feldhammer Matthew , Nichols James 
Published: September 2019

Abstract
Our objective was to define the performance of automated chemistry platforms at two large academic medical centers by calculating and comparing sigma metrics for 28 analytes. Performance characteristics of chemistry assays on two Roche Cobas analyzers and four Abbott Architect analyzers were estimated using 12 months of Bio-Rad quality control (QC) data at two concentrations. Method imprecision was calculated as the cumulative QC coefficient of variation (CV) across analyzers at each QC concentration and percent bias was calculated by comparison of analyzer QC mean to peer group means. Sigma values were calculated for each method as [(TEa – Bias%)/CV%] using allowable total error (TEa) from two sources: the CLIA evaluation limits and desirable biological variation. Average sigma values were generated for each site and graded as optimal, >6 sigma; good, 5 to 6 sigma; marginal, 3 to 5 sigma; or poor, <3 sigma. Analysis of NIST SRM1950 standards for a subset of analytes allowed an estimation of absolute bias. Sigma metrics were highly comparable across both study sites. Considering CLIA TEa, just over half (Roche 57%; Abbott 54%) of the 28 analytes met the six-sigma standard of performance. The highest performing groups to meet or exceed the six-sigma standard were lipids (cholesterol, LDL, HDL, and triglycerides) and enzymes (ALP, ALT, AST, CK, GGT, LDH, and lipase). Electrolytes (Na, K, Cl, Mg) and metabolites (total bilirubin, BUN, CO2) failed to meet six-sigma. Notably, there were dramatic differences in sigma values calculated using CLIA and Ricos TEa criteria. Almost 40% of the analytes had at least one QC that performed poorly using Ricos criteria. Only 4 of the 28 assays (CK, GGT, lipase, and triglycerides) demonstrated optimal performance at both study sites using Ricos and CLIA criteria. Overall, 11 analytes at each institution exhibited unacceptable performance using Ricos criteria as opposed to only two analytes with the CLIA TEa limits. Analysis of NIST SRM1950 at both study sites gave comparable sigmas for all analytes except total bilirubin, cholesterol, Mg, and total protein. Neither Abbott nor Roche analyzers met six-sigma quality standards for all analytes tested. Overall assay performance across these two platforms at two major academic medical centers was almost identical. CLIA TEa and RICOS TEa criteria are significantly different, with wider limits of acceptability for CLIA. Variations between individual analyzers and manufacturers and limitations in automation would make tailored QC rules based on sigma metrics difficult to implement in a high-volume laboratory.
Amylase and Lipase Co-ordering in the Workup of Pancreatic Disorders Is Unnecessary and Costly: An Institutional Lab Utilization Study
Authors: Hupp Meghan , Peterson Nicholas , Buchner Sasha , Karger Amy B 
Published: September 2019

Abstract

Background
Acute pancreatitis is the most common gastrointestinal cause of hospitalization in the United States. Amylase and lipase are commonly ordered together in the workup of suspected pancreatitis at our institution (a large academic medical center), despite meta-analyses and evidence-based guidelines that recommend the use of lipase alone. Lipase has more diagnostic accuracy, rises earlier, and stays elevated longer than amylase. Co-ordering amylase has not been shown to increase sensitivity or specificity. This study aims to explore how well amylase and lipase correlate in our patient population, and which marker more accurately detects acute pancreatitis when the results are discrepant.

Methods
The laboratory information system was queried for co-orders of amylase and lipase during a 2-month period (November 1, 2016, to December 31, 2016). The overall agreement and Cohen’s kappa were calculated. Discrepant results were separated from concordant results. Clinical data were extracted from the electronic medical record, including the rationale for ordering and relevant diagnosis code.

Results
There were 962 instances of amylase and lipase co-orders in the 2-month period. Of these, 138 had high amylase and lipase, and 694 had normal amylase and lipase concentrations. The overall agreement was 86.5% and Cohen’s kappa was 0.596 (moderate agreement) (P < .0001). There were 88 cases in which the lipase was elevated and the amylase was normal. Of these, 12 were acute pancreatitis and 76 were not. There were 42 cases in which the amylase was elevated and the lipase was normal; only one case out of 42 was acute pancreatitis. Further investigation into this case revealed that the patient was approximately 7 months status-post pancreas transplant. During this admission, he was diagnosed with “graft pancreatitis” and, while amylase remained elevated above the reference range for longer than lipase after treatment, both enzymes were increased at diagnosis (lipase 831 U/L [73-393 U/L] and amylase 194 U/L [30-110 U/L]). These data show that, had only lipase been ordered, no cases of acute pancreatitis would have been missed.

Conclusion
Amylase has been shown to be an inferior marker of acute pancreatitis compared to lipase, and many guidelines recommend the use of lipase alone. However, these tests are commonly co-ordered at our institution; in a given 2-month period, there were 962 co-order events. Of these, there were no cases of pancreatitis that would have been missed by ordering lipase alone. Our laboratory charges $50 per amylase assay; therefore $48,100 was spent on unnecessary amylase orders during the 2 months of this study. Lab test overutilization has been identified as an important problem; if addressed and curtailed, labs and hospitals can increase efficiency and cost savings.
Trends of Fecal Calprotectin and Lactoferrin Results for Infants
Authors: Goold Eric , Johnson Lisa 
Published: September 2019

Abstract
Calprotectin and lactoferrin can be measured in stool to test for inflammation in the gastrointestinal tract associated with inflammatory bowel disease (IBD) versus irritable bowel syndrome (IBS). The clinical specificity of these markers decreases in children versus adults because of the broader differential diagnosis for intestinal inflammation in children. Surprisingly, these tests are frequently ordered for infants (age = 0 years). Therefore, we wanted to assess our historical data in order to understand how infant calprotectin and lactoferrin concentrations change over time and review literature for the potential differential diagnosis for intestinal inflammation in infants. Data were analyzed on 19,543 infants/toddlers ages 0 to 2 years who had a stool test result of either the quantitative ELISA calprotectin PhiCal assay (Eurospital) or qualitative ELISA Lactoferrin Chek assay (Techlab). For the quantitative calprotectin test, the averages and medians were graphed over time in infants. And for the qualitative lactoferrin test, the positivity rate was graphed over time in infants. Both were compared to toddlers of ages 1 to 2 years old. The average level of calprotectin in neonates (0-1 months old) was 336 ± 348 μg/g with a median of 192 μg/g. While these values were dramatically above the adult normal reference range of 0 to 50 μg/g, the average level decreased over time to 119 ± 218 μg/g with a median of 39 μg/g for toddlers 2 years old. The presence of elevated lactoferrin was detected in 89% of neonates versus 34% of toddlers age 2 years. These trends demonstrate that both calprotectin and lactoferrin may be elevated early in life for many infants, but rapidly decline with time. Ordering trends show that, for infants/toddlers age 0 to 2 years, fecal calprotectin ordering has grown rapidly, whereas fecal lactoferrin has remained stable. In conclusion, while fecal calprotectin and lactoferrin are widely used markers of pathologic intestinal inflammation in adults, results in infants must be interpreted with great care. An elevated calprotectin or lactoferrin concentration in infant stool may be pathological, perhaps due to necrotizing enterocolitis or food-associated enteropathy, but is also associated with nonpathological reasons such as intestinal exposure to food antigens or commensal bacteria. Literature studies have shown associations of elevated calprotectin or lactoferrin with diet, gestational age at birth, and even mode of delivery. Thus, it is essential that clinicians interpret calprotectin levels or the presence of elevated lactoferrin in the context of the entire clinical picture and understand the lack of specificity of these markers for pathological conditions in infants.
Invasive Mammary Paget Disease Without an Underlying Breast Cancer: A Case Report
Authors: Bousamra Alexis , Khatoon Nazia , Sandhu Ariel , Silverman Jan , Malay Mary Beth 
Published: September 2019

Abstract
Mammary Paget disease (MPD) is a malignant lesion of the nipple-areolar complex and considered an intraepidermal sign of an underlying invasive or in situ carcinoma. In rare instances, mammary Paget cells can invade the dermis. Comprehensive literature review identified 33 such cases. Here, we report a case of a 48-year-old female with invasive MPD, without an associated underlying breast cancer. Only five such presentations are reported. With a presentation of right nipple-areolar excoriation for 2 years, skin punch biopsy was performed and reported as “Paget disease.” Further evaluation with bilateral mammograms failed to show any primary mass or calcifications. Bilateral breast MRI revealed focal nonmass enhancement in upper outer quadrant in both breast, the biopsy of which showed benign breast tissue. Right breast nipple areolar complex resection demonstrated MPD extensively involving the epidermis. Multiple foci of invasive ductal carcinoma are present, growing downward into the nipple dermis, the largest focus being 0.2 cm in greatest dimension. No lymphovascular invasion is identified. The mammary Paget cells are positive for Cam 5.2 and epithelial membrane antigen (EMA) and negative for keratins 7 and 20. The invasive tumor cells are strongly positive for estrogen receptor (100%) and progesterone receptor (75%) and equivocal (2+) for Her2/Neu. FISH analysis showed amplification for HER2 (HER2/CEP17 ratio: 2.75). Four right axillary sentinel lymph nodes are negative for carcinoma. Two of the five patients with invasive MPD described in the literature, and without underlying breast cancer, had a sentinel lymph node biopsy performed. Isolated tumor clusters were present in one of these two cases. In summary, we describe a rare case of invasive MPD without an underlying breast cancer. Although sentinel lymph nodes are important to assess metastasis, further cases are required to evaluate the significance and prognosis of this rare entity.
Malignant Biphasic Adenomyoepithelioma: A Rare Entity
Authors: Law Timothy , Veran-Taguibao Sonia , Ibe Ifegwu , Goreal Wamda 
Published: September 2019

Abstract

Objectives
Adenomyoepithelioma of the breast is an uncommon biphasic breast lesion characterized by a cytologically bland epithelial and myoepithelial proliferation. It is often considered benign and thought to represent a variant of intraductal papilloma. However, rare cases of adenomyoepitheliomas have been reported to show malignant transformation. Features that favor malignancy include increased mitoses, necrosis, atypia, cellular pleomorphism, and infiltrative borders. Most reported cases of malignant adenomyoepithelioma demonstrate carcinomas arising in a benign adenomyoepithelioma.

Methods
A 74-year-old woman presented to the hospital with an 8-month history of a palpable right breast mass. Mammogram demonstrated an irregular marginated mass, and a needle core biopsy of the mass showed atypical sclerosing adenosis. A lumpectomy revealed a firm, tan-white, ill-defined 2.7-cm mass abutting the anterior and posterior margins.

Results
Histologic examination showed an infiltrative proliferation of epithelial-lined tubules surrounded by myoepithelial cells with clear cytoplasm. There were focal areas of hypercellularity with marked cytologic atypia in both the epithelial and myoepithelial components. Focal necrosis and increased mitoses (12/10 HPF) were also identified. On immunohistochemical studies, the epithelial cells were positive for CK7 while the myoepithelial cells were highlighted by p63, SMMHC, SMA, and CK5/6. Ki-67 showed an increased proliferative index (35%). ER, PR, and HER-2 immunostains were negative. The overall histologic and immunohistochemical findings support a diagnosis of malignant biphasic adenomyoepithelioma. No in situ carcinoma was identified. After the diagnosis was reported, a follow-up reexcision with axillary sentinel lymph node excision was performed. Both specimens were negative for malignancy.

Conclusion
Malignant adenomyoepithelioma of the breast is an uncommon entity and it is strongly associated with local recurrence and distant metastases. Awareness of its distinctive histologic and immunohistochemical features will be helpful in initiating the appropriate medical management for patients with this entity, which is crucial for improving prognosis and overall survival.
Invasive Mammary Carcinoma With Paneth Cell–Like Eosinophilic Cytoplasmic Granules: Is It an Entity?
Authors: Sakshi Sakshi , Persidsky Yuri , Reilly Kathleen , Taraif Suad 
Published: September 2019

Abstract
Breast carcinomas with Paneth cell–like eosinophilic cytoplasmic granules are rare and commonly reported in association with acinic cell carcinoma or microglandular adenosis. Paneth cell–like differentiation has been described outside the GI tract, including lung, liver, pancreas, lacrimal glands, and prostate. Very little is known about the significance of these granules and whether they represent a metaplastic or possibly a therapy-related change. There are only 45 reported cases involving the breast, mostly individual case reports or 2 to 3 case series. Although the clinical experience is limited, most of the reported cases seem clinically indolent.
Here we present a 74-year-old female with a mammographically detected 1.1-cm left breast retroareolar mass for which she underwent a biopsy and subsequent lumpectomy with axillary dissection. Histology revealed an invasive ductal carcinoma, with Paneth cell–like eosinophilic PAS-positive cytoplasmic granules in the background of extensive ductal carcinoma in situ (DCIS). Similar granules were seen in some ducts involved by DCIS. Invasive carcinoma and DCIS were present throughout the 5.5-cm lumpectomy beyond the grossly measured 4.0-cm mass. There was extensive lymphovascular invasion and tumor was present at all the surgical resection margins. Twelve of the 13 axillary lymph nodes had macrometastases. The tumor was ER and PR positive and HER2 negative. Clinically, there were extensive bony metastases involving the skull, spine, sternum, iliac bones, and femur. There were also multiple lung nodules and mediastinal lymph nodes that were positive for metastasis on biopsy. The patient is still undergoing chemotherapy and radiotherapy 6 months following surgical excision.
Our case demonstrates the heterogeneity of this entity as the clinical course in our patient has been very aggressive. A collaborative effort must be established to compile a larger case series to better our understanding of this increasingly reported histological observation and whether it represents a distinct entity.
Can You Detect Spread Through Air Spaces (STAS) in Lung Needle Core Biopsies? An Initial Investigation
Authors: Pillappa Raghavendra , Robila Valentina , King Caleb , Kraft Adele 
Published: September 2019

Abstract

Objectives
The debate of spread through air spaces (STAS) as a newly described pattern of invasion in lung cancer is ongoing. Some authors argue that the inclusion of STAS in the CAP synoptic template is premature and controversial as it is difficult to exclude an artifactual process. However, assessment of STAS in needle core biopsies has not been pursued. Hence, we intended to evaluate STAS in needle core biopsies, with an added emphasis on the specimen requirements for detection. Finally, correlation with the corresponding available resections was performed.

Methods
Fifty-four needle core biopsies of adenocarcinomas were examined by three pathologists. For each case, the extent of both tumor (1-12 mm) and nonneoplastic alveolated parenchyma (NNT) (2-6 mm) was measured. STAS was defined as presence of only micropapillary clusters, solid nests, and single cells in NNT adjacent to the main tumor. Corresponding lung resections available in 12 cases were also examined.

Results
Nests highly suspicious for STAS were demonstrated in 4 (7%) cases, predominantly micropapillary clusters and single cells. Of those, only one case had a surgical resection and showed STAS. When the NNT was present, then absence of STAS was determined in 20/54 (37%) tumors, all exhibiting a lepidic/acinar growth pattern. Finally, the presence of STAS could not be evaluated in 30 (55%) cases. This was due to extensive core fragmentation, sampling only from the center of the tumor, with no adjacent NNT, necrosis, or fibrotic background.

Conclusion
STAS evaluation may be performed in core needle biopsies and depends on the core quality and tumor/NNT content. Despite appropriate material, STAS was not identified in approximately one-third of cases. Rare cases with small groups suspicious for STAS were seen. These findings may provide additional information for further therapeutic/surgical guidance.