Clopidogrel Administration Impairs Post-Stroke Learning and Memory Recovery in Mice.

Clopidogrel, which is one of the most prescribed antiplatelet medications in the world, is given to stroke survivors for the prevention of secondary cardiovascular events. Clopidogrel exerts its antiplatelet activity via antagonism of the P2Y12 receptor (P2RY12). Although not widely known or considered during the initial clinical trials for clopidogrel, P2RY12 is also expressed on microglia, which are the brain's immune cells, where the receptor facilitates chemotactic migration toward sites of cellular damage. If microglial P2RY12 is blocked, microglia lose the ability to migrate to damaged sites and carry out essential repair processes. We aimed to investigate whether administering clopidogrel to mice post-stroke was associated with (i) impaired motor skills and cognitive recovery; (ii) physiological changes, such as survival rate and body weight; (iii) changes in the neurovascular unit, including blood vessels, microglia, and neurons; and (iv) changes in immune cells. Photothrombotic stroke (or sham surgery) was induced in adult male mice. From 24 h post-stroke, mice were treated daily for 14 days with either clopidogrel or a control. Cognitive performance (memory and learning) was assessed using a mouse touchscreen platform (paired associated learning task), while motor impairment was assessed using the cylinder task for paw asymmetry. On day 15, the mice were euthanized and their brains were collected for immunohistochemistry analysis. Clopidogrel administration significantly impaired learning and memory recovery, reduced mouse survival rates, and reduced body weight post-stroke. Furthermore, clopidogrel significantly increased vascular leakage, significantly increased the number and appearance of microglia, and significantly reduced the number of T cells within the peri-infarct region post-stroke. These data suggest that clopidogrel hampers cognitive performance post-stroke. This effect is potentially mediated by an increase in vascular permeability post-stroke, providing a pathway for clopidogrel to access the central nervous system, and thus, interfere in repair and recovery processes.

Central and left division hepatectomies in two dogs.

OBJECTIVE: To describe the management of extensive hepatectomy in 2 dogs. ANIMALS: A 10-year-old female intact mixed-breed dog (case 1) and an 11-year-old male castrated mixed-breed dog (case 2) were presented for surgical evaluation following diagnosis of a hepatic mass. CLINICAL PRESENTATION, PROGRESSION, AND PROCEDURES: 16 months before presentation, case 1 had undergone a left lateral liver lobectomy, which resulted in an incomplete resection of hepatocellular carcinoma. Both dogs underwent surgical excision of the liver mass. TREATMENT AND OUTCOME: In case 1, surgery consisted of the removal of the remaining left medial lobe, as well as the central division. Case 2 received a complete left and central division hepatectomy. Histopathology confirmed a diagnosis of hepatocellular carcinoma in both dogs. Liver enzyme resolution and lack of tumor recurrence were confirmed with chemistry panel and abdominal ultrasonography in both dogs. CLINICAL RELEVANCE: This case report describes, for the first time, the clinical management and outcome of extensive hepatectomy in 2 dogs. We propose that extensive hepatectomy, staged or synchronous, is possible in a clinical setting.

Characterization of exercise-induced hemolysis in endurance horses.

Exercise-induced hemolysis occurs as the result of intense physical exercise and is caused by metabolic and mechanical factors including repeated muscle contractions leading to capillary vessels compression, vasoconstriction of internal organs and foot strike among others. We hypothesized that exercise-induced hemolysis occurred in endurance racehorses and its severity was associated with the intensity of exercise. To provide further insight into the hemolysis of endurance horses, the aim of the study was to deployed a strategy for small molecules (metabolites) profiling, beyond standard molecular methods. The study included 47 Arabian endurance horses competing for either 80, 100, or 120 km distances. Blood plasma was collected before and after the competition and analyzed macroscopically, by ELISA and non-targeted metabolomics with liquid chromatography-mass spectrometry. A significant increase in all hemolysis parameters was observed after the race, and an association was found between the measured parameters, average speed, and distance completed. Levels of hemolysis markers were highest in horses eliminated for metabolic reasons in comparison to finishers and horses eliminated for lameness (gait abnormality), which may suggest a connection between the intensity of exercise, metabolic challenges, and hemolysis. Utilization of omics methods alongside conventional methods revealed a broader insight into the exercise-induced hemolysis process by displaying, apart from commonly measured hemoglobin and haptoglobin, levels of hemoglobin degradation metabolites. Obtained results emphasized the importance of respecting horse limitations in regard to speed and distance which, if underestimated, may lead to severe damages.

Oral metagenomes from Native American Ancestors reveal distinct microbial lineages in the pre-contact era.

OBJECTIVES: Limited studies have focused on how European contact and colonialism impacted Native American oral microbiomes, specifically, the diversity of commensal or opportunistically pathogenic oral microbes, which may be associated with oral diseases. Here, we studied the oral microbiomes of pre-contact Wichita Ancestors, in partnership with the Descendant community, The Wichita and Affiliated Tribes, Oklahoma, USA. MATERIALS AND METHODS: Skeletal remains of 28 Wichita Ancestors from 20 archeological sites (dating approximately to 1250-1450 CE) were paleopathologically assessed for presence of dental calculus and oral disease. DNA was extracted from calculus, and partial uracil deglycosylase-treated double-stranded DNA libraries were shotgun-sequenced using Illumina technology. DNA preservation was assessed, the microbial community was taxonomically profiled, and phylogenomic analyzes were conducted. RESULTS: Paleopathological analysis revealed signs of oral diseases such as caries and periodontitis. Calculus samples from 26 Ancestors yielded oral microbiomes with minimal extraneous contamination. Anaerolineaceae bacterium oral taxon 439 was found to be the most abundant bacterial species. Several Ancestors showed high abundance of bacteria typically associated with periodontitis such as Tannerella forsythia and Treponema denticola. Phylogenomic analyzes of Anaerolineaceae bacterium oral taxon 439 and T. forsythia revealed biogeographic structuring; strains present in the Wichita Ancestors clustered with strains from other pre-contact Native Americans and were distinct from European and/or post-contact American strains. DISCUSSION: We present the largest oral metagenome dataset from a pre-contact Native American population and demonstrate the presence of distinct lineages of oral microbes specific to the pre-contact Americas.

Upregulation of PARG in prostate cancer cells suppresses their malignant behavior and downregulates tumor-promoting genes.

Post-translational modification of nuclear proteins through the addition of poly(ADP-ribose) (pADPr) moieties is upregulated in many metastatic cancers, where the high levels of pADPr have often been associated with poor cancer prognosis. Although the inhibitors of poly(ADP-ribose) polymerases (PARPs) have been utilized as potent anti-cancer agents, their efficacy in clinical trials varied among patient groups and has often been unpredictable. Such outcome cannot be interpreted solely by the inability to keep PARP-driven DNA repair in check. The focus of studies on PARP-driven tumorigenesis have recently been shifted toward PARP-dependent regulation of transcription. Here we utilized the controlled overexpression of poly(ADP-ribose) glycohydrolase (PARG), a sole pADPr-degrading enzyme, to investigate pADPr-dependent gene regulation in prostate cancer PC-3 cells. We demonstrated that PARG upregulation reduces pADPr levels and inhibits the expression of genes in key tumor-promoted pathways, including TNFα/NF-kB, IL6/STAT3, MYC, and KRAS signaling, the genes involved in inflammation response, especially chemokines, and endothelial-mesenchymal transition. The observed effect of PARG on transcription was consistent across all tested prostate cancer cell lines and correlates with PARG-induced reduction of clonogenic potential of PC-3 cells in vitro and a significant growth inhibition of PC-3-derived tumors in nude mice in vivo.

Comparing Psychoanalytic Process in Consulting Room and Teleconference: A Naturally Occurring Controlled Experiment.

BACKGROUND: In response to COVID-19, clinicians migrated psychoanalyses to videoconference platforms, creating an opportunity for a controlled empirical study in which only the site varied. HYPOTHESES: There will be no differences in the quality of the psychoanalytic process (QAP) in the consulting room (CR) and in videoconference (VC). Individuals' defensive functioning (adaptive style) will be associated with their capacity to maintain the analytic process when treatment moves from CR to VC. Underlying was the concept that empirical research of clinical psychoanalysis is possible. PARTICIPANTS AND METHODS: Forty psychoanalysts of all ranks in the Accreditation Council for Psychoanalytic Education, Inc., accredited programs contributed 50 cases. Participants scored QAP at each site on a 0-to-100 scale. They reported patients' characteristic defense mechanisms using the Defensive Functioning Scale (DFS). DATA ANALYSIS: To minimize bias, investigators calculated median DFS scores from data provided by clinicians. They compared QAP scores in CR and VC for the entire group without and with DFS scores, and for each DFS level (when feasible) using the related-samples Wilcoxon signed-rank test. FINDINGS: There was no difference in QAP between CR and VC for the group as a whole; but QAP of the Minor Image Distorting group degraded significantly from CR to VC. This was the only group showing a significant difference. CONCLUSIONS: While statistical significance may not reflect clinical significance, individual differences in adaptation to telepsychoanalysis warrant further study. Empirical research of phenomena occurring naturally in clinical psychoanalysis appears feasible.

Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries.

INTRODUCTION: The target of a class of antiplatelet medicines, P2Y12R inhibitors, exists both on platelets and on brain immune cells (microglia). This protocol aims to describe a causal (based on a counterfactual model) approach for analysing whether P2Y12R inhibitors prescribed for secondary prevention poststroke may increase the risk of cognitive disorder or dementia via their actions on microglia, using real-world evidence. METHODS AND ANALYSIS: This will be a cohort study nested within the Swedish National Health and Medical Registers, including all people with incident stroke from 2006 to 2016. We developed directed acyclic graphs to operationalise the causal research question considering potential time-independent and time-dependent confounding, using input from several experts. We developed a study protocol following the components of the target trial approach described by Hernan et al and describe the data structure that would be required in order to make a causal inference. We also describe the statistical approach required to derive the causal estimand associated with this important clinical question; that is, a time-to-event analysis for the development of cognitive disorder or dementia at 1, 2 and 5-year follow-up, based on approaches for competing events to account for the risk of all-cause mortality. Causal effect estimates and the precision in these estimates will be quantified. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of the University of Gothenburg and Confidentiality Clearance at Statistics Sweden with Dnr 937-18, and an approved addendum with Dnr 2019-0157. The analysis and interpretation of the results will be heavily reliant on the structure, quality and potential for bias of the databases used. When we implement the protocol, we will consider and document any biases specific to the dataset and conduct appropriate sensitivity analyses. Findings will be disseminated to local stakeholders via conferences, and published in appropriate scientific journals.

The Role of Impulsivity and Stress Mind-Set in Understanding the Mindfulness-Intimate Partner Aggression Relationship.

Perpetration of relational aggression, which is estimated to occur in 60% to 90% of relationships, has been demonstrated to have lasting negative effects both systemically and for its victims. Relational aggression has also been demonstrated to be impacted, in part by impulsivity, stress mind-set, and mindfulness. The present study examined a path analysis model of the relation between mindfulness and relational aggression, utilizing impulsivity as the mediating variable. Furthermore, the present study incorporated an examination of the potential moderating effects of stress mind-set on the relation between impulsivity and relational aggression. Three hundred eighty-three participants were recruited from across the United States, using Facebook ads. Participants completed online questionnaires assessing key study variables. We hypothesized that the negative urgency aspect of impulsivity would mediate the relation between the five facets of mindfulness and relational aggression, and further that this relationship would be moderated by stress mind-set, such that a stress mind-set which conceptualizes stress as negative would make the relation between impulsivity and relational aggression stronger. We hypothesized that the negative urgency aspect of impulsivity would mediate the relation between mindfulness and relational aggression. Furthermore, we hypothesized that the relation between impulsivity and aggression would be moderated by stress mind-set. Results indicated that the negative urgency component of impulsivity mediated the relation between all five facets of mindfulness and perpetration of relational aggression. Furthermore, stress mind-set moderated the relation between negative urgency and relational aggression, such that a lower stress mind-set was related to a stronger association between negative urgency and aggression. Implications for clinical intervention and future research efforts are discussed.

Assessing Challenges with Access to Care for Patients Presenting to the Emergency Department for Non-Emergent Complaints.

INTRODUCTION: Emergency department (ED) utilization continues to climb nationwide resulting in overcrowding, increasing wait times, and a surge in patients with non-urgent conditions. Patients frequently choose the ED for apparent non-emergent medical issues or injuries that after-the-fact could be cared for in a primary care setting. We seek to better understand the reasons why patients choose the ED over their primary care managers. METHODS: We prospectively surveyed patients that signed into the ED at the Brooke Army Medical Center as an emergency severity index of 4 or 5 (non-emergent triage) regarding their visit. We then linked their survey data to their ED visit including interventions, diagnoses, diagnostics, and disposition by using their electronic medical record. We defined their visit to be non-urgent and more appropriate for primary care, or primary care eligible, if they were discharged home and received no computed tomography (CT) imaging, ultrasound, magnetic resonance imaging (MRI), intravenous (IV) medications, or intramuscular (IM) controlled substances. RESULTS: During the 2-month period, we collected data on 208 participants out of a total of 252 people offered a survey (82.5%). There were 92% (n=191) that were primary care eligible within our respondent pool. Most reported very good (38%) or excellent (21%) health at baseline. On survey assessing why they came, inability to get a timely appointment (n=73), and a self-reported emergency (n=58) were the most common reported reasons. Most would have utilized primary care if they had a next-morning appointment available (n=86), but many reported they would have utilized the ED regardless of primary care availability (n=77). The most common suggestion for improving access to care was more primary care appointment availability (n=96). X-rays were the most frequent study (37%) followed by laboratory studies (20%). Before coming to the ED, 38% (n=78) reported trying to contact their primary care for an appointment. Before coming to the ED, 22% (n=46) reported contacting the nurse advice line. Based on our predefined model, 92% (n=191) of our respondents were primary care eligible within our respondent pool. CONCLUSIONS: Patient perceptions of difficulty obtaining appointments appear to be a major component of the ED use for non-emergent visits. Within our dataset, most patients surveyed stated they had difficulty obtaining a timely appointment or self-reported as an emergency. Data suggests most patients surveyed could be managed in the primary care setting.

Indexing cerebrovascular health using near-infrared spectroscopy.

Near-infrared spectroscopy (NiRS) is a relatively new technology of brain imaging with its potential in the assessment of cerebrovascular health only recently discovered. Encouraging early results suggest that NiRS can be used as an inexpensive and portable cerebrovascular health tracking device using a recently proposed pulse relaxation function (PReFx). In this paper, we propose a new NiRS timing index, [Formula: see text], of cerebrovascular health. [Formula: see text] is a novel use of the NiRS technology. [Formula: see text] is motivated by the previously proved relationship of the timing of the reflected wave with vascular resistance and compliance in the context of pressure waveforms. We correlated both [Formula: see text] and PReFx against age, a non-exercise cardiorespiratory fitness (CRF) index, and two existing indices of cerebrovascular health, namely transcranial Doppler (TCD) augmentation index, [Formula: see text], and magnetic resonance imaging (MRI) blood flow pulsatility index, [Formula: see text]. The [Formula: see text] correlations with Age, CRF, [Formula: see text] and [Formula: see text] all are significant, i.e., [Formula: see text] ([Formula: see text]), [Formula: see text] ([Formula: see text]), [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]), respectively. PReFx, however, did not have significant correlations with any of the vascular health factors. The proposed timing index is a reliable indicator of cerebrovascular aging factors in the NiRS waveform.

Corticosterone Administration Alters White Matter Tract Structure and Reduces Gliosis in the Sub-Acute Phase of Experimental Stroke.

White matter tract (WMT) degeneration has been reported to occur following a stroke, and it is associated with post-stroke functional disturbances. White matter pathology has been suggested to be an independent predictor of post-stroke recovery. However, the factors that influence WMT remodeling are poorly understood. Cortisol is a steroid hormone released in response to prolonged stress, and elevated levels of cortisol have been reported to interfere with brain recovery. The objective of this study was to investigate the influence of corticosterone (CORT; the rodent equivalent of cortisol) on WMT structure post-stroke. Photothrombotic stroke (or sham surgery) was induced in 8-week-old male C57BL/6 mice. At 72 h, mice were exposed to standard drinking water ± CORT (100 µg/mL). After two weeks of CORT administration, mice were euthanised and brain tissue collected for histological and biochemical analysis of WMT (particularly the corpus callosum and corticospinal tract). CORT administration was associated with increased tissue loss within the ipsilateral hemisphere, and modest and inconsistent WMT reorganization. Further, a structural and molecular analysis of the WMT components suggested that CORT exerted effects over axons and glial cells. Our findings highlight that CORT at stress-like levels can moderately influence the reorganization and microstructure of WMT post-stroke.

Exploring How Low Oxygen Post Conditioning Improves Stroke-Induced Cognitive Impairment: A Consideration of Amyloid-Beta Loading and Other Mechanisms.

Cognitive impairment is a common and disruptive outcome for stroke survivors, which is recognized to be notoriously difficult to treat. Previously, we have shown that low oxygen post-conditioning (LOPC) improves motor function and limits secondary neuronal loss in the thalamus after experimental stroke. There is also emerging evidence that LOPC may improve cognitive function post-stroke. In the current study we aimed to explore how exposure to LOPC may improve cognition post-stroke. Experimental stroke was induced using photothrombotic occlusion in adult, male C57BL/6 mice. At 72 h post-stroke animals were randomly assigned to either normal atmospheric air or to one of two low oxygen (11% O2) exposure groups (either 8 or 24 h/day for 14 days). Cognition was assessed during the treatment phase using a touchscreen based paired-associate learning assessment. At the end of treatment (17 days post-stroke) mice were euthanized and tissue was collected for subsequent histology and biochemical analysis. LOPC (both 8 and 24 h) enhanced learning and memory in the 2nd week post-stroke when compared with stroke animals exposed to atmospheric air. Additionally we observed LOPC was associated with lower levels of neuronal loss, the restoration of several vascular deficits, as well as a reduction in the severity of the amyloid-beta (Aß) burden. These findings provide further insight into the pro-cognitive benefits of LOPC.

Data set for reporting carcinoma of the thyroid: recommendations from the International Collaboration on Cancer Reporting.

Thyroid cancer therapy is increasingly tailored to patients' risk of recurrence and death, placing renewed importance on pathologic parameters. The International Collaboration on Cancer Reporting (ICCR), an organization promoting evidence-based, internationally agreed-upon standardized pathology data sets, is the ideal conduit for the development of a pathology reporting protocol aimed at improving the care of patients with thyroid carcinomas. An international expert panel reviewed each element of thyroid pathology reporting. Recommendations were made based on the most recent literature and expert opinion.The data set uses the most recent World Health Organization (WHO) classification for the purpose of a more clinically and prognostically relevant nomenclature. One example is the restriction of the term minimally invasive follicular carcinoma to tumors with capsular invasion only. It reinforces the already established criteria for blood vessel invasion adopted by the most recent WHO classification and Armed Forces Institute of Pathology fascicle. It emphasizes the importance of the extent of blood vessel invasion and extrathyroid extension to better stratify patients for appropriate therapy. It is the first data set that requires pathologists to use the more recently recognized prognostically powerful parameters of mitotic activity and tumor necrosis. It highlights the importance of assessing nodal disease volume in predicting the risk of recurrence.The ICCR thyroid data set provides the tools to generate a report that will guide patient treatment in a more rational manner aiming to prevent the undertreatment of threatening malignancies and spare patients with indolent tumors the morbidity of unnecessary therapy. We recommend its routine use internationally for reporting thyroid carcinoma histology.

Clinical Decision Support Tools for Predicting Outcomes in Patients Undergoing Total Knee Arthroplasty: A Systematic Review.

BACKGROUND: Total knee arthroplasty is the standard surgical treatment for end-stage osteoarthritis. Although widely accepted as a successful procedure, approximately 30% of patients are not satisfied due to non-optimal postoperative outcomes. Clinical decision support tools that are able to accurately predict post-surgery outcomes would assist in providing individualized advice or services to help alleviate possible issues, resulting in significant benefits to both the healthcare system and individuals. METHODS: Five databases (Ovid Medline, Ovid EMBASE, CINAHL complete, Cochrane Library, and Scopus) were searched for the key phrases "knee replacement" or "knee arthroplasty" and "decision support tool," "decision tool," "predict∗ tool," "predict∗ model," "algorithm" or "nomogram." Searches were limited to peer-reviewed journal articles published between January 2000 and June 2019. Reference lists of included articles were examined. Authors came to a consensus on the final list of included articles. RESULTS: Eighteen articles were included for review. Most models reported low predictive success and inability to externally validate. Both candidate and final predictor variables were inconsistent between studies. Only 1 model was considered strongly predictive (AUROC >0.8), and only 2 studies were able to externally validate their developed model. In general, models that performed well used large patient numbers, were tested on similar demographics, and used either nonlinear input transformations or a completely nonlinear model. CONCLUSION: Some models do show promise; however, there remains the question of whether the reported predictive success can continue to be replicated. Furthermore, clinical applicability and interpretation of predictive tools should be considered during development.

Monitoring Rates of Malnutrition Risk in Outpatient Cancer Centers Utilizing the Malnutrition Screening Tool Embedded into the Electronic Health Record.

BACKGROUND: The risk of malnutrition in patients with cancer is well documented. However, screening to identify patients at risk in ambulatory cancer centers is not standardized nor uniform. The 2-question Malnutrition Screening Tool (MST) is validated in the ambulatory oncology setting and endorsed by the Academy of Nutrition and Dietetics. OBJECTIVE: To test the feasibility of operationalizing and standardizing malnutrition risk assessment across 2 large ambulatory cancer centers by embedding the MST into the electronic health record (EHR) with the goal of identifying and quantifying the prevalence of malnutrition risk in outpatient settings. DESIGN: A Quality Assurance Performance Improvement project was conducted to evaluate malnutrition screening practices by leveraging the EHR. Work standards were developed, implemented, and evaluated to assess the feasibility of utilizing de-identified MST data, entered as discrete variables in an EHR flowsheet, to track monthly MST completion rates and to identify and quantify patients being treated for cancer scoring at risk for impaired nutritional status. PARTICIPANTS/SETTING: Data from 2 large adult ambulatory community cancer centers in the upper Midwest were collected between April 2017 and December 2018. RESULTS: Over a 20-month period, the average monthly MST completion rate was 74%. Of those with completed MST screens, the average percentage of patients identified at nutritional risk (MST score ≥2) was 5% in medical oncology and 12% in radiation oncology. CONCLUSION: It is feasible to (1) integrate and standardize data collection of the MST into existing EHR flowsheets and (2) identify and quantify patients at risk for malnutrition on a consistent basis.

Pathology data set for reporting parathyroid carcinoma and atypical parathyroid neoplasm: recommendations from the International Collaboration on Cancer Reporting.

Standardized pathologic reporting for cancers improves patient care and prognostic determination. However, access in many countries is limited. To address this issue, the International Collaboration on Cancer Reporting (ICCR), a not-for-profit organization, has the mission to develop and disseminate standardized data sets for global use. Within endocrine organs, the parathyroid gland has rarely been included in formal pathologic data sets. Utilizing an expert international panel of eleven members, an evidence-based data set was developed for parathyroid carcinoma and atypical parathyroid neoplasms. This data set consists of sixteen core (required) elements viewed as essential for documentation of these conditions. Characterizing parathyroid carcinomas and atypical neoplasms begins with correlative clinical information, the operative procedure, specimens submitted, and site of the disease. The pathologic features essential to document include parathyroid weight, size, classification, and, when a carcinoma, the tumor grade. Histologic grade of parathyroid carcinoma incorporates other core elements including necrosis, mitotic count, perineural invasion, and lymphovascular invasion. Documenting the extent of disease locally into adjacent organs, regionally, and distally is critical for staging. Pathologic staging is now included as part of the American Joint Committee on Cancer 8th edition and is included in this data set. Ancillary studies should be recorded when performed as noncore elements. Standardized pathologic data sets for endocrine organs including the parathyroid gland are now available through the ICCR website. These essential resources enhance international standardization for documenting these rare tumors for both patient care and future guidelines.

A human factor event-based learning assessment tool for assessment of errors and diagnostic accuracy in histopathology and cytopathology.

This review article summarises systems for categorisation of diagnostic errors in pathology and cytology with regard to diagnostic accuracy and the published information on human factors (HFs) in pathology to date. A 12-point event-based checklist for errors of diagnostic accuracy in histopathology and cytopathology is proposed derived from Dupont's 'Dirty Dozen' HF checklist, as used in the aerospace industry for aircraft maintenance. This HF checklist comprises 12 HFs; (1) Failure of communication. (2) Complacency. (3) Lack of knowledge. (4) Distractions. (5) Lack of teamwork. (6) Fatigue. (7) Lack of resources. (8) Pressure. (9) Lack of assertiveness. (10) Stress. (11) Norms. (12) Lack of awareness. The accompanying article explains practical examples of how each of these 12 HFs may cause errors in diagnostic accuracy in pathology. This checklist could be used as a template for analysis of accuracy and risk of diagnostic error in pathology either retrospectively 'after the event' or prospectively at the time of diagnosis. There is a need for further evaluation and validation of this proposed 12-point HF checklist and similar systems for categorisation of diagnostic errors and diagnostic accuracy in pathology based on HF principles.

Measures to reduce diagnostic error and improve clinical decision making in thyroid FNA aspiration cytology: A proposed framework.

Thyroid fine-needle aspiration cytology (FNA) and histopathology can be subjective areas of medical diagnosis and subject to different interpretations. On the basis of the authors' personal experience, 12 recommendations with potential to improve clinical decision making, ensure quality, and reduce diagnostic error in thyroid FNAC and histopathology are presented. 1) use a standardized reporting terminology for thyroid FNAC; 2) understand and explain to service users the limitations of cytology and the standardized thyroid FNAC reporting terminology used; 3) the cytopathologist should review all relevant clinical and ultrasound findings, if feasible; 4) include the risk of malignancy in all FNAC reports if feasible; 5) collect data to calculate the local institutional risk of malignancy for FNAC if feasible; 6) accept that nondiagnostic FNAC will include small numbers of carcinomas; 7) use rapid on-site evaluation and/or educational sessions for aspirators if the nondiagnostic aspiration rate is high; 8) know the diagnostic pitfalls of both cytology and histopathology; 9) use special immunohistochemical and molecular techniques that are evidence-based; 10) make use of second opinions, either in-house or interinstitutional; 11) multidisciplinary discussion of cases before surgery or therapy is invaluable; and, finally, 12) manage patient and clinician expectations of thyroid cytology and histopathology. These 12 recommendations may assist in quality-improvement initiatives and may reduce diagnostic errors in thyroid cytology and histopathology. Thyroid multidisciplinary case discussion remains the principal, overarching method for error reduction and for providing high-quality clinical decision making.

Fork-tip needle biopsy versus fine-needle aspiration in endoscopic ultrasound-guided sampling of solid pancreatic masses: a randomized crossover study.

BACKGROUND: A novel fork-tip fine-needle biopsy (FNB) needle has recently been introduced for endoscopic ultrasound (EUS)-guided sampling. The aim of this study was to compare the performance of fork-tip FNB histology and standard fine-needle aspiration (FNA) cytology in the diagnosis of solid pancreatic masses. METHODS: A randomized crossover study was performed in patients referred for EUS-guided sampling. Three passes were taken with each needle in a randomized order. Only samples reported as diagnostic of malignancy were considered positive. The primary end point was the sensitivity of diagnosis of malignancy. Secondary end points included the amount of sample obtained, ease of diagnosis, duration of tissue sampling, pathologist viewing time, and cost. RESULTS: 108 patients were recruited. Median age was 69 years (range 30 - 87) and 57 were male; 85.2 % had a final diagnosis of malignancy. There were statistically significant differences in sensitivity (82 % [95 % confidence interval (CI) 72 % to 89 %] vs. 71 % [95 %CI 60 % to 80 %]), accuracy (84 % [95 %CI 76 % to 91 %] vs. 75 % [95 %CI 66 % to 83 %]), proportion graded as a straightforward diagnosis (69 % [95 %CI 60 % to 78 %] vs. 51 % [95 %CI 41 % to 61 %]), and median pathology viewing time (188 vs. 332 seconds) (P < 0.001) between FNB and FNA needles, respectively. There was no significant difference in cost between an FNB or FNA strategy. CONCLUSION: The diagnostic performance of the fork-tip FNB needle was significantly better than that of FNA; it was associated with ease of diagnosis, shorter pathological viewing times, and was cost neutral.