Tall cell papillary thyroid carcinoma: new diagnostic criteria and mutations in BRAF and TERT

The tall cell (TC) variant of papillary thyroid carcinoma (PTC) has an unfavorable prognosis. The diagnostic criteria remain inconsistent, and the role of a minor TC component is unclear. Molecular diagnostic markers are not available; however, there are two potential candidates: BRAF V600E and telomerase reverse transcriptase (TERT) promoter mutations. Using a novel approach, we enriched a collective with PTCs that harbored an adverse outcome, which overcame the limited statistical power of most studies. This enabled us to review 125 PTC patients, 57 of which had an adverse outcome. The proportion of TCs that constituted a poor prognosis was assessed. All of the tumors underwent sequencing for TERT promoter and BRAF V600E mutational status and were stained with an antibody to detect the BRAF V600E mutation. A 10% cutoff for TCs was significantly associated with advanced tumor stage and lymph node metastasis. Multivariate analysis showed that TCs above 10% were the only significant factor for overall, tumor-specific, and relapse-free survival. Seven percent of the cases had a TERT promoter mutation, whereas 61% demonstrated a BRAF mutation. The presence of TC was significantly associated with TERT promoter and BRAF mutations. TERT predicted highly significant tumor relapse (P<0.001). PTCs comprised of at least 10% TCs are associated with an adverse clinical outcome and should be reported accordingly. BRAF did not influence patient outcome. Nevertheless, a positive status should encourage the search for TCs. TERT promoter mutations are a strong predictor of tumor relapse, but their role as a surrogate marker for TCs is limited.

Identifying observable criteria defining a critical situation involving football fans: an expert focus group study

Critical situations (CSs) involving football fans is a well-researched phenomenon with most studies examining factors leading to an escalation of violence (e.g. Braun & Vliegenthart, 2008). However, research so far has fallen short of analysing CSs that do not escalate (e.g. Hylander & Guvå, 2010) as well as establishing observable criteria that constitute such CSs. Granström et al. (2009), for instance, put forward a definition of a CS describing such situations as characterised by a discrepancy between peace and war-making behaviours between police and demonstrators. Still, this definition remains vague and does not provide concrete, defining criteria that can be identified on site. The present study looks beyond fans’ violent acts per se and focuses on these situations with a potentially – but not necessarily - violent outcome. The aim of this preliminary study is to identify observable criteria defining such a CS involving football fans. This focus group comprised of five experts working with football fans in the German-speaking area of Switzerland who discussed observable characteristics of a CS. Inductive content analysis led to the identification of specific criteria such as, “arrest of a fan”, “insufficient distance (<30m) between fans and police” and “fans mask themselves”. These criteria were then assigned to four phases of a CS highlighting the dynamic aspect of this phenomenon: Antecedents, Causes, Reactions, Consequence. Specifically, Causes, Reactions and Consequences are observable on site, while Antecedents include relevant, background information directly influencing a CS. This study puts forward a working definition of a CS that can facilitate the assessment of actual situations in the football context as well as for further research on fan violence prevention and control. These results also highlight similarities with studies investigating fan violence in other European countries while acknowledging unique characteristics of the Swiss German fan culture.

Twelve-month psychosis-predictive value of the ultra-high risk criteria in children and adolescents

Objective The validity of current ultra-high risk (UHR) criteria is under-examined in help-seeking minors, particularly, in children below the age of 12 years. Thus, the present study investigated predictors of one-year outcome in children and adolescents (CAD) with UHR status. Method Thirty-five children and adolescents (age 9–17 years) meeting UHR criteria according to the Structured Interview for Psychosis-Risk Syndromes were followed-up for 12 months. Regression analyses were employed to detect baseline predictors of conversion to psychosis and of outcome of non-converters (remission and persistence of UHR versus conversion). Results At one-year follow-up, 20% of patients had developed schizophrenia, 25.7% had remitted from their UHR status that, consequently, had persisted in 54.3%. No patient had fully remitted from mental disorders, even if UHR status was not maintained. Conversion was best predicted by any transient psychotic symptom and a disorganized communication score. No prediction model for outcome beyond conversion was identified. Conclusions Our findings provide the first evidence for the predictive utility of UHR criteria in CAD in terms of brief intermittent psychotic symptoms (BIPS) when accompanied by signs of cognitive impairment, i.e. disorganized communication. However, because attenuated psychotic symptoms (APS) related to thought content and perception were indicative of non-conversion at 1-year follow-up, their use in early detection of psychosis in CAD needs further study. Overall, the need for more in-depth studies into developmental peculiarities in the early detection and treatment of psychoses with an onset of illness in childhood and early adolescence was further highlighted.

Expected impact of applying new 2013 AHA/ACC cholesterol guidelines criteria on the recommended lipid target achievement after acute coronary syndromes.

BACKGROUND 2013 AHA/ACC guidelines on the treatment of cholesterol advised to tailor high-intensity statin after ACS, while previous ATP-III recommended titration of statin to reach low-density lipoprotein cholesterol (LDL-C) targets. We simulated the impact of this change of paradigm on the achievement of recommended targets. METHODS Among a prospective cohort study of consecutive patients hospitalized for ACS from 2009 to 2012 at four Swiss university hospitals, we analyzed 1602 patients who survived one year after recruitment. Targets based on the previous guidelines approach was defined as (1) achievement of LDL-C target < 1.8 mmol/l, (2) reduction of LDL-C ≥ 50% or (3) intensification of statin in patients who did not reach LDL-C targets. Targets based on the 2013 AHA/ACC guidelines approach was defined as the maximization of statin therapy at high-intensity in patients aged ≤75 years and moderate- or high-intensity statin in patients >75 years. RESULTS 1578 (99%) patients were prescribed statin at discharge, with 1120 (70%) at high-intensity. 1507 patients (94%) reported taking statin at one year, with 909 (57%) at high-intensity. Among 482 patients discharged with sub-maximal statin, intensification of statin was only observed in 109 patients (23%). 773 (47%) patients reached the previous LDL-C targets, while 1014 (63%) reached the 2013 AHA/ACC guidelines targetsone year after ACS (p value < 0.001). CONCLUSION The application of the new 2013 AHA/ACC guidelines criteria would substantially increase the proportion of patients achieving recommended lipid targets one year after ACS. Clinical trial number, NCT01075868.

Implications of proposed fibromyalgia criteria across other functional pain syndromes

OBJECTIVES In 2010, the American College of Rheumatology (ACR) proposed new criteria for the diagnosis of fibromyalgia (FM) in the context of objections to components of the criteria of 1990. The new criteria consider the Widespread Pain Index (WPI) and the Symptom Severity Score (SSS). This study evaluated the implications of the new diagnostic criteria for FM across other functional pain syndromes. METHOD A cohort of 300 consecutive in-patients with functional pain syndromes underwent a diagnostic screen according to the ACR 2010 criteria. Additionally, systematic pain assessment including algometric and psychometric data was carried out. RESULTS Twenty-five patients (8.3%) had been diagnosed with FM according to the ACR 1990 criteria. Twenty-one of them (84%) also met the new ACR 2010 criteria. In total, 130 patients (43%) fulfilled the new ACR 2010 criteria. A comparison of new vs. old cases showed a high degree of conformity in most of the pain characteristics. The new FM cases, however, revealed a pronounced heterogeneity in the anatomical pain locations, including several types of localized pain syndromes. Furthermore, patients fulfilling the ACR 2010 FM criteria differed from those with other functional pain syndromes; they had increased pain sensitivity scores and increased psychometric values for depression, anxiety, and psychological distress (p<0.01). CONCLUSIONS FM according to the ACR 2010 criteria describes the 'severe half' of the spectrum of functional pain syndromes. By dropping the requirement of 'generalized pain', these criteria result in a blurring of the distinction between FM and more localized functional pain syndromes.

Evaluation of New Cone-beam Computed Tomographic Criteria for Radiographic Healing Evaluation after Apical Surgery: Assessment of Repeatability and Reproducibility.

INTRODUCTION Conventional 2-dimensional radiography uses defined criteria for outcome assessment of apical surgery. However, these radiographic healing criteria are not applicable for 3-dimensional radiography. The present study evaluated the repeatability and reproducibility of new cone-beam computed tomographic (CBCT)-based healing criteria for the judgment of periapical healing 1 year after apical surgery. METHODS CBCT scans taken 1 year after apical surgery (61 roots of 54 teeth in 54 patients, mean age = 54.4 years) were evaluated by 3 blinded and calibrated observers using 4 different indices. Reformatted buccolingual CBCT sections through the longitudinal axis of the treated roots were analyzed. Radiographic healing was assessed at the resection plane (R index), within the apical area (A index), of the cortical plate (C index), and regarding a combined apical-cortical area (B index). All readings were performed twice to calculate the intraobserver agreement (repeatability). Second-time readings were used for analyzing the interobserver agreement (reproducibility). Various statistical tests (Cohen, kappa, Fisher, and Spearman) were performed to measure the intra- and interobserver concurrence, the variability of score ratios, and the correlation of indices. RESULTS For all indices, the rates of identical first- and second-time scores were always higher than 80% (intraobserver Cohen κ values ranging from 0.793 to 0.963). The B index (94.0%) showed the highest intraobserver agreement. Regarding interobserver agreement, the highest rate was found for the B index (72.1%). The Fleiss' κ values for R and B indices exhibited substantial agreement (0.626 and 0.717, respectively), whereas the values for A and C indices showed moderate agreement (0.561 and 0.573, respectively). The Spearman correlation coefficients for R, A, C, and B indices all exhibited a moderate to very strong correlation with the highest correlation found between C and B indices (rs = 0.8069). CONCLUSIONS All indices showed an excellent intraobserver agreement (repeatability). With regard to interobserver agreement (reproducibility), the B index (healing of apical and cortical defects combined) and the R index (healing on the resection plane) showed substantial congruence and thus are to be recommended in future studies when using buccolingual CBCT sections for radiographic outcome assessment of apical surgery.

Use of a modified Delphi panel to identify and weight criteria for prioritization of zoonotic diseases in Switzerland

Zoonotic diseases have a significant impact on public health globally. To prevent or reduce future zoonotic outbreaks, there is a constant need to invest in research and surveillance programs while updating risk management strategies. However, given the limited resources available, disease prioritization based on the need for their control and surveillance is important. This study was performed to identify and weight disease criteria for the prioritization of zoonotic diseases in Switzerland using a semi-quantitative research method based on expert opinion. Twenty-eight criteria relevant for disease control and surveillance, classified under five domains, were selected following a thorough literature review, and these were evaluated and weighted by seven experts from the Swiss Federal Veterinary Office using a modified Delphi panel. The median scores assigned to each criterion were then used to rank 16 notifiable and/or emerging zoonoses in Switzerland. The experts weighted the majority of the criteria similarly, and the top three criteria were Severity of disease in humans, incidence and prevalence of the disease in humans and treatment in humans. Based on these weightings, the three highest ranked diseases were Avian Influenza, Bovine Spongiform Encephalitis, and Bovine Tuberculosis. Overall, this study provided a preliminary list of criteria relevant for disease prioritization in Switzerland. These were further evaluated in a companion study which involved a quantitative prioritization method and multiple stakeholders.

Do multiple true-false items beat the commonly used one-best-answers questions regarding to the Ottawa Criteria for Good Assessment? Results of a literature review

Background: Multiple True-False-Items (MTF-Items) might offer some advantages compared to one-best-answer-questions (TypeA) as they allow more than one correct answer and may better represent clinical decisions. However, in medical education assessment MTF-Items are seldom used. Summary of Work: With this literature review existing findings on MTF-items and on TypeA were compared along the Ottawa Criteria for Good Assessment, i.e. (1) reproducibility, (2) feasibility, (3) validity, (4) acceptance, (5) educational effect, (6) catalytic effects, and (7) equivalence. We conducted a literature research on ERIC and Google Scholar including papers from the years 1935 to 2014. We used the search terms “multiple true-false”, “true-false”, “true/false”, and “Kprim” combined with “exam”, “test”, and “assessment”. Summary of Results: We included 29 out of 33 studies. Four of them were carried out in the medical field Compared to TypeA, MTF-Items are associated with (1) higher reproducibility (2) lower feasibility (3) similar validity (4) higher acceptance (5) higher educational effect (6) no studies on catalytic effects or (7) equivalence. Discussion and Conclusions: While studies show overall good characteristics of MTF items according to the Ottawa criteria, this type of question seems to be rather seldom used. One reason might be the reported lower feasibility. Overall the literature base is still weak. Furthermore, only 14 % of literature is from the medical domain. Further studies to better understand the characteristics of MTF-Items in the medical domain are warranted. Take-home messages: Overall the literature base is weak and therefore further studies are needed. Existing studies show that: MTF-Items show higher reliability, acceptance and educational effect; MTF-Items are more difficult to produce

Evaluating the Utility of Clinical Criteria for the Identification of Lynch Syndrome among Endometrial Cancer Patients

Background: Lynch Syndrome (LS) is a familial cancer syndrome with a high prevalence of colorectal and endometrial carcinomas among affected family members. Clinical criteria, developed from information obtained from familial colorectal cancer registries, have been generated to identify individuals at elevated risk for having LS. In 2007, the Society of Gynecologic Oncology (SGO) codified criteria to assist in identifying women presenting with gynecologic cancers at elevated risk for having LS. These criteria have not been validated in a population-based setting. Materials and Methods: We retrospectively identified 412, unselected endometrial cancer cases. Clinical and pathologic information were obtained from the electronic medical record, and all tumors were tested for expression of the DNA mismatch repair proteins through immunohistochemistry. Tumors exhibiting loss of MSH2, MSH6 and PMS2 were designated as probable Lynch Syndrome (PLS). For tumors exhibiting immunohistochemical loss of MLH1, we used the PCR-based MLH1 methylation assay to delineate PLS tumors from sporadic tumors. Samples lacking methylation of the MLH1 promoter were also designated as PLS. The sensitivity and specificity for SGO criteria for detecting PLS tumors was calculated. We compared clinical and pathologic features of sporadic tumors and PLS tumors. A simplified cost-effectiveness analysis was also performed comparing the direct costs of utilizing SGO criteria vs. universal tumor testing. Results: In our cohort, 43/408 (10.5%) of endometrial carcinomas were designated as PLS. The sensitivity and specificity of SGO criteria to identify PLS cases were 32.7 and 77%, respectively. Multivariate analysis of clinical and pathologic parameters failed to identify statistically significant differences between sporadic and PLS tumors with the exception of tumors arising from the lower uterine segment. These tumors were more likely to occur in PLS tumors. Cost-effectiveness analysis showed clinical criteria and universal testing strategies cost $6,235.27/PLS case identified and $5,970.38/PLS case identified, respectively. Conclusions: SGO 5-10% criteria successfully identify PLS cases among women who are young or have significant family history of LS related tumors. However, a larger proportion of PLS cases occurring at older ages with less significant family history are not detected by this screening strategy. Compared to SGO clinical criteria, universal tumor testing is a cost effective strategy to identify women presenting with endometrial cancer who are at elevated risk for having LS.

Classification criteria and commercial profile re-definition of the Family Farm Agriculture in Chile, Maule region

In Chile, small-scale farmers are classified according to old approaches from 1993 that do not include changes occurred in the last two decades. Maule is the region with most rural population in Chile which represents a significant stratum for development, innovation and competitiveness. This study explores a new approach of small-scale farmers -associated with Family Farm Agriculture (AFC) - classification in Chile and it describes a commercial profile or AFC-1 for famers of the Maule Region. A Cluster analysis to determine AFC-1 farmers is used. The analysis includes four association variables: Total Assets, Farm Income, Production Costs and Management Indicators. The results suggest that 16.4% of the farmers have a commercial profile and they could stay out support provided by the National Institute for Agricultural Development (INDAP). This group of farmers would not belong to AFC in short terms. This fact could bring restriction to AFC-1 farmers such as lack of credit access, less investment incentives and technical assistance. Thus, it would expect low process of technology adoption and welfare improvement. New agrarian policies must be warranted to support this important group of famers with a commercial profile.