Effect of TPE vs medical management on patient outcomes in the setting of hypertriglyceridemia-induced acute pancreatitis with severely elevated triglycerides.

OBJECTIVES: Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) accounts for 1 to 10% of pancreatitis cases, and is associated with a more severe clinical course. Therapeutic plasma exchange (TPE) is a potential treatment option for quickly lowering plasma triglycerides (TG). Current ASFA guidelines define HTG-AP as a Category III disorder, indicating the role of apheresis is not firmly established. Here, we examine clinical data regarding its effectiveness on morbidity and mortality in patients with HTG-AP presenting with severely elevated plasma triglycerides (>4000 mg/dl). METHODS: We retrospectively examined clinical data and outcomes from 67 consecutive episodes of HTG-AP over a 5-year period in which either medical management alone or medical management plus adjunct TPE was employed to reduce plasma triglycerides. RESULTS: 16/67 admissions involved TPE, initiated at a mean of 0.7 days from the time of presentation, while 51 received medical management alone. After only one TPE procedure, the mean TG values decreased from 4103 to 1045 mg/dl (a reduction of 74.7%), and those receiving TPE reached plasma TG < 1000 mg/dl 0.99 days faster than the medical group. One patient in the TPE group died. However, when excluding patients with hospital courses complicated by multiple organ dysfunction, there was no significant difference in mortality or hospital length of stay (LOS) between the groups. CONCLUSIONS: In uncomplicated cases of HTG-AP with an absence of multiorgan dysfunction, there is no significant benefit to either mortality or LOS when adding adjunct TPE to medical management, even when patients present with severely elevated levels of TG.

A Survey of LOINC Code Selection Practices Among Participants of the College of American Pathologists Coagulation (CGL) and Cardiac Markers (CRT) Proficiency Testing Programs.

CONTEXT.­: Biomedical terminologies such as Logical Observation Identifiers, Names, and Codes (LOINC) were developed to enable interoperability of health care data between disparate health information systems to improve patient outcomes, public health, and research activities. OBJECTIVE.­: To ascertain the utilization rate and accuracy of LOINC terminology mapping to 10 commonly ordered tests by participants of the College of American Pathologists (CAP) Proficiency Testing program. DESIGN.­: Questionnaires were sent to 1916 US and Canadian laboratories participating in the 2018 CAP coagulation (CGL) and/or cardiac markers (CRT) surveys requesting information on practice setting, instrument(s) and test method(s), and LOINC code selection and usage in the laboratory and electronic health records. RESULTS.­: Ninety of 1916 CGL and/or CRT participants (4.7%) responded to the questionnaire. Of the 275 LOINC codes reported, 54 (19.6%) were incorrect: 2 codes (5934-2 and 12345-1) (0.7%) did not exist in the LOINC database and the highest error rates were observed in the property (27 of 275, 9.8%), system (27 of 275, 9.8%), and component (22 of 275, 8.0%) LOINC axes. Errors in LOINC code selection included selection of the incorrect component (eg, activated clotting time instead of activated partial thromboplastin time); selection of panels that can never be used to obtain an individual analyte (eg, prothrombin time panel instead of international normalized ratio); and selection of an incorrect specimen type. CONCLUSIONS.­: These findings of real-world LOINC code implementation across a spectrum of laboratory settings should raise concern about the reliability and utility of using LOINC for clinical research or to aggregate data.

Impact of Hormone Therapy on Laboratory Values in Transgender Patients.

BACKGROUND: For transgender individuals taking hormone therapy (HT), data on laboratory values are limited, and the effects on laboratory values cannot be easily predicted. We evaluated the impact on common laboratory analytes in transgender individuals before and after initiation of HT. METHODS: We conducted a retrospective chart review of transgender patients identified at transgender-specific clinics at an urban county hospital and community clinic. Laboratory data were collected on hormone concentrations, hematologic parameters, electrolytes, lipids, and liver and renal markers before and after initiation of HT. RESULTS: We identified 183 transgender women (TW) and 119 transgender men (TM) for whom laboratory data were available. In all, 87 TW and 62 TM had baseline laboratory data, and data were also available for 133 TW and 89 TM on HT for >6 months. The most significant changes were seen in red blood cell count, hemoglobin concentration, hematocrit, and creatinine levels after >6 months of HT, which increased in TM and decreased in TW after HT (P < 0.005; d index > 0.6). Alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase levels increased in TM; however, the effect size was small (d index < 0.5). Calcium, albumin, and alkaline phosphatase levels significantly decreased in TW (P < 0.001; d > 0.6). Additionally, TM were found to have increased triglycerides and decreased HDL levels (P < 0.005; d > 0.6). CONCLUSIONS: Changes occur in several common laboratory parameters for patients on HT. Some laboratory values changed to match the gender identity, whereas others remained unchanged or were intermediate from the baseline values. These findings will help guide interpretation of laboratory test results in transgender patients taking HT.

Agreement between cytotechnologists and cytopathologists as a new measure of cytopathologist performance in gynecologic cytology.

BACKGROUND: Although objective measures of cytotechnologist (CT) and cytopathologist (CP) performance exist, challenges remain. Two assumptions deserve examination: CPs' interpretations are correct, and CTs and CPs render interpretations independently of each other. This study presents a CT-CP interpretation comparison and provides insight into these assumptions. METHODS: Every gynecologic cytology specimen examined by both a CT and a CP from December 2004 to March 2015 was extracted from the laboratory information system; glandular interpretations were excluded. Excel and SAS were used for CT-CP pair analysis. CT-CP pairs with fewer than 32 specimens (the lowest quartile) were excluded. For the remaining CT-CP pairs, 30 specimens or 10% of the specimens (whichever was higher) were randomly selected for comparison by a weighted κ statistic. κ values greater than 0.6 represented good agreement within CT-CP pairs. RESULTS: This study evaluated 7116 of 53,241 gynecologic cytology specimens (13.4%) that received CT and CP interpretations. This resulted in 155 pair-specific κ values from 15 CTs and 16 CPs. In aggregate, the κ values had a mean of 0.64, a standard deviation of 0.14, a median of 0.65, and a range of 0.27 to 0.91. Nine CTs exhibited good agreement in the majority of their pair-specific κ values with CPs (high-concordance CTs; 88 pair-specific κ values). This allowed us to identify outlier CPs who did not demonstrate good agreement with high-concordance CTs (16 of 88 pair-specific κ values [18.2%]). CONCLUSIONS: Laboratories can use this κ to determine when CP levels of agreement with CTs depart from those of their peers. Adding this to established metrics can give a more nuanced impression of CP performance. Cancer Cytopathol 2017;125:576-80. © 2017 American Cancer Society.

Metastatic Melanoma to the Bladder: Case Report and Review of the Literature.

A 49-year-old Caucasian woman presented to the dermatology clinic for follow-up of malignant melanoma with a complaint of painless gross hematuria. Two years prior she was diagnosed with malignant melanoma from a skin lesion on her left flank treated with wide excision, negative axillary sentinel lymph node biopsy, and adjuvant radiotherapy. Subsequently, she had no evidence of disease until urologic evaluation of her hematuria revealed two lesions in her bladder and cytopathology demonstrated findings consistent with malignant melanoma. We review literature on melanoma metastatic to the bladder and discuss the potential role of metastasectomy and other treatment strategies in such rare cases.

The ongoing evolution of the core curriculum of a clinical fellowship in pathology informatics.

The Partners HealthCare system's Clinical Fellowship in Pathology Informatics (Boston, MA, USA) faces ongoing challenges to the delivery of its core curriculum in the forms of: (1) New classes of fellows annually with new and varying educational needs and increasingly fractured, enterprise-wide commitments; (2) taxing electronic health record (EHR) and laboratory information system (LIS) implementations; and (3) increasing interest in the subspecialty at the academic medical centers (AMCs) in what is a large health care network. In response to these challenges, the fellowship has modified its existing didactic sessions and piloted both a network-wide pathology informatics lecture series and regular "learning laboratories". Didactic sessions, which had previously included more formal discussions of the four divisions of the core curriculum: Information fundamentals, information systems, workflow and process, and governance and management, now focus on group discussions concerning the fellows' ongoing projects, updates on the enterprise-wide EHR and LIS implementations, and directed questions about weekly readings. Lectures are given by the informatics faculty, guest informatics faculty, current and former fellows, and information systems members in the network, and are open to all professional members of the pathology departments at the AMCs. Learning laboratories consist of small-group exercises geared toward a variety of learning styles, and are driven by both the fellows and a member of the informatics faculty. The learning laboratories have created a forum for discussing real-time and real-world pathology informatics matters, and for incorporating awareness of and timely discussions about the latest pathology informatics literature. These changes have diversified the delivery of the fellowship's core curriculum, increased exposure of faculty, fellows and trainees to one another, and more equitably distributed teaching responsibilities among the entirety of the pathology informatics asset in the network. Though the above approach has been in place less than a year, we are presenting it now as a technical note to allow for further discussion of evolving educational opportunities in pathology informatics and clinical informatics in general, and to highlight the importance of having a flexible fellowship with active participation from its fellows.

Intrapopulation genome size variation in D. melanogaster reflects life history variation and plasticity.

We determined female genome sizes using flow cytometry for 211 Drosophila melanogaster sequenced inbred strains from the Drosophila Genetic Reference Panel, and found significant conspecific and intrapopulation variation in genome size. We also compared several life history traits for 25 lines with large and 25 lines with small genomes in three thermal environments, and found that genome size as well as genome size by temperature interactions significantly correlated with survival to pupation and adulthood, time to pupation, female pupal mass, and female eclosion rates. Genome size accounted for up to 23% of the variation in developmental phenotypes, but the contribution of genome size to variation in life history traits was plastic and varied according to the thermal environment. Expression data implicate differences in metabolism that correspond to genome size variation. These results indicate that significant genome size variation exists within D. melanogaster and this variation may impact the evolutionary ecology of the species. Genome size variation accounts for a significant portion of life history variation in an environmentally dependent manner, suggesting that potential fitness effects associated with genome size variation also depend on environmental conditions.

The 2013 symposium on pathology data integration and clinical decision support and the current state of field.

BACKGROUND: Pathologists and informaticians are becoming increasingly interested in electronic clinical decision support for pathology, laboratory medicine and clinical diagnosis. Improved decision support may optimize laboratory test selection, improve test result interpretation and permit the extraction of enhanced diagnostic information from existing laboratory data. Nonetheless, the field of pathology decision support is still developing. To facilitate the exchange of ideas and preliminary studies, we convened a symposium entitled: Pathology data integration and clinical decision support. METHODS: The symposium was held at the Massachusetts General Hospital, on May 10, 2013. Participants were selected to represent diverse backgrounds and interests and were from nine different institutions in eight different states. RESULTS: The day included 16 plenary talks and three panel discussions, together covering four broad areas. Summaries of each presentation are included in this manuscript. CONCLUSIONS: A number of recurrent themes emerged from the symposium. Among the most pervasive was the dichotomy between diagnostic data and diagnostic information, including the opportunities that laboratories may have to use electronic systems and algorithms to convert the data they generate into more useful information. Differences between human talents and computer abilities were described; well-designed symbioses between humans and computers may ultimately optimize diagnosis. Another key theme related to the unique needs and challenges in providing decision support for genomics and other emerging diagnostic modalities. Finally, many talks relayed how the barriers to bringing decision support toward reality are primarily personnel, political, infrastructural and administrative challenges rather than technological limitations.

Polypectomy is adequate treatment for adenoma-like dysplastic lesions (DALMs) in Crohn's disease.

BACKGROUND: The purpose of this study was to reevaluate the clinical and pathologic features and outcomes in patients with Crohn's disease with an adenoma-like dysplasia-associated lesion or mass (DALMs) to determine if polypectomy is adequate treatment. METHODS: The clinical, endoscopic and pathologic features, and outcomes of 50 patients with Crohn's disease, each with ≥1 adenoma-like DALM were evaluated. The median length of follow-up was 39 months (range: 0.5-156 months). RESULTS: Of the 50 patients with Crohn's disease (male to female ratio, 30:20; median age: 53 years; median duration of disease: 83 months), 11 had ileal disease, 26 had colonic disease, and 13 had both ileal and colonic disease. Approximately 43% of polyps occurred within areas of previous or concurrent colitis, whereas 57% occurred in areas not previously involved by colitis. Most polyps had tubular architecture and contained low-grade dysplasia. Of the patients who had polypectomy followed by surveillance, 45% developed new adenoma-like DALMs, but none developed flat dysplasia and only 1 had adenocarcinoma at the time of resection, which was within 3 months of polypectomy. There were no differences in the clinical or pathologic features or outcomes in patients who had adenoma-like DALMs within versus outside areas of previous or concurrent colitis, except that the former showed a higher risk of developing new polyps within areas of colitis and near the site of the original polyp compared with the latter. CONCLUSIONS: Patients with Crohn's disease who develop an adenoma-like DALM, regardless of its location in relationship to previous or concurrent colitis, may be treated safely with polypectomy and continued surveillance.

Tissue array construction: pitfalls, problems, and progress.

The tissue array is an economical and efficient tool for translational research. An important factor in constructing tissue arrays is the ability to reliably transfer the pathologic feature of interest from the donor block to the array block. The precision of this transfer is undermined by the distortion of dotted routine sections, which serve as the primary feature-finding device for manual array construction, and by certain tissues such as breast, colon, and skin that prove resistant to being punched. To evaluate and improve this transfer process, with a focus on breast tissue, we investigated a series of waterbath temperatures best suited to minimize microtomy-induced section distortion of breast tissue, and a novel donor block pretreatment before array construction. Our results show that routine sections deviate least from their blocks when transferred to slides in 46 degrees C waterbaths, but also that attention be paid to the crushing effect of the microtome. Core transfer rates are highest when donor blocks are stored at 4 degrees C before punching and when 0.6-mm diameter cores are taken from donor blocks.

Differential expression of interleukin-8 and its receptors in the neuroendocrine and non-neuroendocrine compartments of prostate cancer.

Hormonal therapy (androgen ablation and/or inhibition of androgen action) is the treatment of choice for advanced prostate cancer. After an initial response in most patients, tumors invariably progress to an androgen-independent state. It is unclear how prostate cancer cells proliferate without androgen. Recent studies suggest that interleukin-8 may promote androgen-independent proliferation, but the source of interleukin-8 in the prostate is unknown. Using immunohistochemistry, we show that interleukin-8 was expressed by the neuroendocrine tumor cells in human prostate cancer tissue. Expression of the interleukin-8 receptor CXCR1 was negative or low in benign prostatic tissue and was frequently increased in malignant cells of high-grade prostatic intraepithelial neoplasia and prostate cancer; however, CXCR1 was not detected in the neuroendocrine tumor cells, suggesting a paracrine mechanism by which interleukin-8 produced by neuroendocrine tumor cells stimulates androgen-independent proliferation of prostate cancer. Neuroendocrine tumor cells expressed another type of interleukin-8 receptor, CXCR2, suggesting an autocrine mechanism by which interleukin-8 regulates the differentiation or function of the neuroendocrine cells. These results, combined with previous reports that neuroendocrine differentiation is induced by hormonal therapy, suggest that neuroendocrine cells play an important role in promoting androgen-independent growth of prostate cancer through interleukin-8 signaling.