High tumor budding stratifies breast cancer with metastatic properties.

Tumor budding refers to single or small cluster of tumor cells detached from the main tumor mass. In colon cancer high tumor budding is associated with positive lymph nodes and worse prognosis. Therefore, we investigated the value of tumor budding as a predictive feature of lymph node status in breast cancer (BC). Whole tissue sections from 148 surgical resection specimens (SRS) and 99 matched preoperative core biopsies (CB) with invasive BC of no special type were analyzed on one slide stained with pan-cytokeratin. In SRS, the total number of intratumoral (ITB) and peripheral tumor buds (PTB) in ten high-power fields (HPF) were counted. A bud was defined as a single tumor cell or a cluster of up to five tumor cells. High tumor budding equated to scores averaging >4 tumor buds across 10HPFs. In CB high tumor budding was defined as ≥10 buds/HPF. The results were correlated with pathological parameters. In SRS high PTB stratified BC with lymph node metastases (p ≤ 0.03) and lymphatic invasion (p ≤ 0.015). In CB high tumor budding was significantly (p = 0.0063) associated with venous invasion. Pathologists are able, based on morphology, to categorize BC into a high and low risk groups based in part on lymph node status. This risk assessment can be easily performed during routine diagnostics and it is time and cost effective. These results suggest that high PTB is associated with loco-regional metastasis, highlighting the possibility that this tumor feature may help in therapeutic decision-making.

Ellis-van Creveld Syndrome in Grey Alpine Cattle: Morphologic, Immunophenotypic, and Molecular Characterization

Ellis-van Creveld (EvC) syndrome is a human autosomal recessive disorder caused by a mutation in either the EVC or EVC2 gene, and presents with short limbs, polydactyly, and ectodermal and heart defects. The aim of this study was to understand the pathologic basis by which deletions in the EVC2 gene lead to chondrodysplastic dwarfism and to describe the morphologic, immunohistochemical, and molecular hallmarks of EvC syndrome in cattle. Five Grey Alpine calves, with a known mutation in the EVC2 gene, were autopsied. Immunohistochemistry was performed on bone using antibodies to collagen II, collagen X, sonic hedgehog, fibroblast growth factor 2, and Ki67. Reverse transcription polymerase chain reaction was performed to analyze EVC1 and EVC2 gene expression. Autopsy revealed long bones that were severely reduced in length, as well as genital and heart defects. Collagen II was detected in control calves in the resting, proliferative, and hypertrophic zones and in the primary and secondary spongiosa, with a loss of labeling in the resting zone of 2 dwarfs. Collagen X was expressed in hypertrophic zone in the controls but was absent in the EvC cases. In affected calves and controls, sonic hedgehog labeled hypertrophic chondrocytes and primary and secondary spongiosa similarly. FGF2 was expressed in chondrocytes of all growth plate zones in the control calves but was lost in most EvC cases. The Ki67 index was lower in cases compared with controls. EVC and EVC2 transcripts were detected. Our data suggest that EvC syndrome of Grey Alpine cattle is a disorder of chondrocyte differentiation, with accelerated differentiation and premature hypertrophy of chondrocytes, and could be a spontaneous model for the equivalent human disease.

Cosmogenic 180W variations in meteorites and re-assessment of a possible 184Os–180W decay system

We measured tungsten (W) isotopes in 23 iron meteorites and the metal phase of the CB chondrite Gujba in order to ascertain if there is evidence for a large-scale nucleosynthetic heterogeneity in the p-process isotope 180W in the solar nebula as recently suggested by Schulz et al. (2013). We observed large excesses in 180W (up to ≈ 6 ε) in some irons. However, significant within-group variations in magmatic IIAB and IVB irons are not consistent with a nucleosynthetic origin, and the collateral effects on 180W from an s-deficit in IVB irons cannot explain the total variation. We present a new model for the combined effects of spallation and neutron capture reactions on 180W in iron meteorites and show that at least some of the observed within-group variability is explained by cosmic ray effects. Neutron capture causes burnout of 180W, whereas spallation reactions lead to positive shifts in 180W. These effects depend on the target composition and cosmic-ray exposure duration; spallation effects increase with Re/W and Os/W ratios in the target and with exposure age. The correlation of 180W/184W with Os/W ratios in iron meteorites results in part from spallogenic production of 180W rather than from 184Os decay, contrary to a recent study by Peters et al. (2014). Residual ε180W excesses after correction for an s-deficit and for cosmic ray effects may be due to ingrowth of 180W from 184Os decay, but the magnitude of this ingrowth is at least a factor of ≈2 smaller than previously suggested. These much smaller effects strongly limit the applicability of the putative 184Os-180W system to investigate geological problems.

The physiological consequences of crib-biting in horses in response to an ACTH challenge test

Stereotypies are repetitive and relatively invariant patterns of behavior, which are observed in a wide range of species in captivity. Stereotypic behavior occurs when environmental demands produce a physiological response that, if sustained for an extended period, exceeds the natural physiological regulatory capacity of the organism, particularly in situations that include unpredictability and uncontrollability. One hypothesis is that stereotypic behavior functions to cope with stressful environments, but the existing evidence is contradictory. To address the coping hypothesis of stereotypies, we triggered physiological reactions in 22 horses affected by stereotypic behavior (crib-biters) and 21 non-crib-biters (controls), using an ACTH challenge test. Following administration of an ACTH injection, we measured saliva cortisol every 30min and heart rate (HR) continuously for a period of 3h. We did not find any differences in HR or HR variability between the two groups, but crib-biters (Group CB) had significantly higher cortisol responses than controls (Group C; mean±SD: CB, 5.84±2.62ng/ml, C, 4.76±3.04ng/ml). Moreover, crib-biters that did not perform the stereotypic behavior during the 3-hour test period (Group B) had significantly higher cortisol levels than controls, which was not the case of crib-biters showing stereotypic behavior (Group A) (B, 6.44±2.38ng/ml A, 5.58±2.69ng/ml). Our results suggest that crib-biting is a coping strategy that helps stereotypic individuals to reduce cortisol levels caused by stressful situations. We conclude that preventing stereotypic horses from crib-biting could be an inappropriate strategy to control this abnormal behavior, as it prevents individuals from coping with situations that they perceive as stressful.

Contemporary spinal cord protection during thoracic and thoracoabdominal aortic surgery and endovascular aortic repair: a position paper of the vascular domain of the European Association for Cardio-Thoracic Surgery†.

Ischaemic spinal cord injury (SCI) remains the Achilles heel of open and endovascular descending thoracic and thoracoabdominal repair. Neurological outcomes have improved coincidentially with the introduction of neuroprotective measures. However, SCI (paraplegia and paraparesis) remains the most devastating complication. The aim of this position paper is to provide physicians with broad information regarding spinal cord blood supply, to share strategies for shortening intraprocedural spinal cord ischaemia and to increase spinal cord tolerance to transitory ischaemia through detection of ischaemia and augmentation of spinal cord blood perfusion. This study is meant to support physicians caring for patients in need of any kind of thoracic or thoracoabdominal aortic repair in decision-making algorithms in order to understand, prevent or reverse ischaemic SCI. Information has been extracted from focused publications available in the PubMed database, which are cohort studies, experimental research reports, case reports, reviews, short series and meta-analyses. Individual chapters of this position paper were assigned and after delivery harmonized by Christian D. Etz, Ernst Weigang and Martin Czerny. Consequently, further writing assignments were distributed within the group and delivered in August 2014. The final version was submitted to the EJCTS for review in September 2014.

Biomechanical Evaluation of the Stabilizing Function of Three Atlantoaxial Implants Under Shear Loading: A Canine Cadaveric Study

OBJECTIVE: To compare the biomechanical properties of a ventral transarticular lag screw fixation technique, a new dorsal atlantoaxial instability (AAI) clamp, and a new ventral AAI hook plate under sagittal shear loading after transection of the ligaments of the atlantoaxial joint. STUDY DESIGN: Cadaveric biomechanical study. ANIMALS: Canine cadavers (n = 10). MATERIALS AND METHODS: The occipitoatlantoaxial region of Beagles euthanatized for reasons unrelated to the study was prepared leaving only ligamentous structures and the joint capsules between the first 2 cervical vertebrae (C1 and C2). The atlanto-occipital joints were stabilized with 2 transarticular diverging positive threaded K-wires. The occipital bone and the caudal end of C2 were embedded in polymethylmethacrylate and loaded in shear to a force of 50 Newtons. The range of motion (ROM) and neutral zone (NZ) of the atlantoaxial joint were determined after 3 loading cycles with atlantoaxial ligaments intact, after ligament transection, and after fixation with each implant. The testing order of implants was randomly assigned. The implants tested last were subjected to failure testing. RESULTS: All stabilization procedures decreased the ROM and NZ of the atlantoaxial joint compared to transected ligament specimens. Only stabilization with transarticular lag screws and ventral plates produced a significant reduction of ROM compare to intact specimens. CONCLUSION: Fixation with transarticular lag screws and a ventral hook plate was biomechanically similar and provided more rigidity compared to dorsal clamp fixation. Further load cycling to failure tests and clinical studies are required before making clinical recommendations.

Ventilation/perfusion SPECT/CT in patients with pulmonary emphysema. Evaluation of software-based analysing

UNLABELLED The purpose of this study was to evaluate the reproducibility of a new software based analysing system for ventilation/perfusion single-photon emission computed tomography/computed tomography (V/P SPECT/CT) in patients with pulmonary emphysema and to compare it to the visual interpretation. PATIENTS, MATERIAL AND METHODS 19 patients (mean age: 68.1 years) with pulmonary emphysema who underwent V/P SPECT/CT were included. Data were analysed by two independent observers in visual interpretation (VI) and by software based analysis system (SBAS). SBAS PMOD version 3.4 (Technologies Ltd, Zurich, Switzerland) was used to assess counts and volume per lung lobe/per lung and to calculate the count density per lung, lobe ratio of counts and ratio of count density. VI was performed using a visual scale to assess the mean counts per lung lobe. Interobserver variability and association for SBAS and VI were analysed using Spearman's rho correlation coefficient. RESULTS Interobserver agreement correlated highly in perfusion (rho: 0.982, 0.957, 0.90, 0.979) and ventilation (rho: 0.972, 0.924, 0.941, 0.936) for count/count density per lobe and ratio of counts/count density in SBAS. Interobserver agreement correlated clearly for perfusion (rho: 0.655) and weakly for ventilation (rho: 0.458) in VI. CONCLUSIONS SBAS provides more reproducible measures than VI for the relative tracer uptake in V/P SPECT/CTs in patients with pulmonary emphysema. However, SBAS has to be improved for routine clinical use.

Internal bacterial colonization of implants: association with peri-implant bone loss

OBJECTIVES The aim of the present longitudinal study was to investigate bacterial colonization of the internal implant cavity and to evaluate a possible association with peri-implant bone loss. METHODS A total of 264 paper point samples were harvested from the intra-implant cavity of 66 implants in 26 patients immediately following implant insertion and after 3, 4, and 12 months. Samples were evaluated for Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, and Tannerella forsythia as well as total bacterial counts by real-time PCR. Bone loss was evaluated on standardized radiographs up to 25 months after implant insertion. For the statistical analysis of the data, mixed effects models were fitted. RESULTS There was an increase in the frequency of detection as well as in the mean counts of the selected bacteria over time. The evaluation of the target bacteria revealed a significant association of Pr. intermedia at 4 and 12 months with peri-implant bone loss at 25 months (4 months: P = 0.009; 12 months: P = 0.021). CONCLUSIONS The present study could demonstrate a progressive colonization by periodontopathogenic bacteria in the internal cavities of two-piece implants. The results suggest that internal colonization with Pr. intermedia was associated with peri-implant bone loss.

Computer-based summative assessment of clinical reasoning in clerkships: A mixed-method comparison of key feature problems with case-based multiple choice questions

Background: It is yet unclear if there are differences between using electronic key feature problems (KFPs) or electronic case-based multiple choice questions (cbMCQ) for the assessment of clinical decision making. Summary of Work: Fifth year medical students were exposed to clerkships which ended with a summative exam. Assessment of knowledge per exam was done by 6-9 KFPs, 9-20 cbMCQ and 9-28 MC questions. Each KFP consisted of a case vignette and three key features (KF) using “long menu” as question format. We sought students’ perceptions of the KFPs and cbMCQs in focus groups (n of students=39). Furthermore statistical data of 11 exams (n of students=377) concerning the KFPs and (cb)MCQs were compared. Summary of Results: The analysis of the focus groups resulted in four themes reflecting students’ perceptions of KFPs and their comparison with (cb)MCQ: KFPs were perceived as (i) more realistic, (ii) more difficult, (iii) more motivating for the intense study of clinical reasoning than (cb)MCQ and (iv) showed an overall good acceptance when some preconditions are taken into account. The statistical analysis revealed that there was no difference in difficulty; however KFP showed a higher discrimination and reliability (G-coefficient) even when corrected for testing times. Correlation of the different exam parts was intermediate. Conclusions: Students perceived the KFPs as more motivating for the study of clinical reasoning. Statistically KFPs showed a higher discrimination and higher reliability than cbMCQs. Take-home messages: Including KFPs with long menu questions into summative clerkship exams seems to offer positive educational effects.