Development of castration resistance in prostate cancer patients treated with luteinizing hormone-releasing hormone analogues (LHRHa): results of the ANARESISTANCE study.

PURPOSE: Evaluate the percentage of patients with prostate cancer treated with luteinizing hormone-releasing hormone analogues (LHRHa) that develop castration resistance after a follow-up period of 3 years. The secondary objective is to evaluate the variables potentially related to the progression to castration resistant prostate cancer (CRPC). METHODS: A post-authorization, nation-wide, multicenter, prospective, observational, and longitudinal study that included 416 patients treated with LHRHa between 2012 and 2017 is presented. Patients were followed for 3 years or until development of CRPC, thus completing a per-protocol population of 350 patients. A Cox regression analysis was carried out to evaluate factors involved in progression to CRPC. RESULTS: After 3 years of treatment with LHRHa 18.2% of patients developed CRPC. In contrast, in the subgroup analysis, 39.6% of the metastatic patients developed CRPC, compared with 8.8% of the non-metastatic patients. The patients with the highest risk of developing CRPC were those with a nadir prostate-specific antigen (PSA) > 2 ng/ml (HR 21.6; 95% CI 11.7-39.8; p < 0.001) and those receiving concomitant medication, most commonly bicalutamide (HR 1.8; 95% CI 1-3.1, p = 0.0431). CONCLUSIONS: The proportion of metastatic patients developing CRPC after 3 years of treatment with LHRHa is consistent with what has been previously described in the literature. In addition, this study provides new findings on CRPC in non-metastatic patients. Concomitant medication and nadir PSA are statistically significant predictive factors for the time to diagnosis of CRPC, the nadir PSA being the strongest predictor.

European Biological Variation Study (EuBIVAS): within- and between-subject biological variation estimates of ß-isomerized C-terminal telopeptide of type I collagen (ß-CTX), N-terminal propeptide of type I collagen (PINP), osteocalcin, intact fibroblast growth factor 23 and uncarboxylated-unphosphorylated matrix-Gla protein-a cooperation between the EFLM Working Group on Biological Variation and the International Osteoporosis Foundation-International Federation of Clinical Chemistry Committee on Bone Metabolism.

We have calculated the biological variation (BV) of different bone metabolism biomarkers on a large, well-described cohort of subjects. BV is important to calculate reference change value (or least significant change) which allows evaluating if the difference observed between two consecutive measurements in a patient is biologically significant or not. INTRODUCTION: Within-subject (CVI) and between-subject (CVG) biological variation (BV) estimates are essential in determining both analytical performance specifications (APS) and reference change values (RCV). Previously published estimates of BV for bone metabolism biomarkers are generally not compliant with the most up-to-date quality criteria for BV studies. We calculated the BV and RCV for different bone metabolism markers, namely ß-isomerized C-terminal telopeptide of type I collagen (ß-CTX), N-terminal propeptide of type I collagen (PINP), osteocalcin (OC), intact fibroblast growth factor 23 (iFGF-23), and uncarboxylated-unphosphorylated Matrix-Gla Protein (uCuP-MGP) using samples from the European Biological Variation Study (EuBIVAS). METHODS: In the EuBIVAS, 91 subjects were recruited from six European laboratories. Fasting blood samples were obtained weekly for ten consecutive weeks. The samples were run in duplicate on IDS iSYS or DiaSorin Liaison instruments. The results were subjected to outlier and variance homogeneity analysis before CV-ANOVA was used to obtain the BV estimates. RESULTS: We found no effect of gender upon the CVI estimates. The following CVI estimates with 95% confidence intervals (95% CI) were obtained: ß-CTX 15.1% (14.4-16.0%), PINP 8.8% (8.4-9.3%), OC 8.9% (8.5-9.4%), iFGF23 13.9% (13.2-14.7%), and uCuP-MGP 6.9% (6.1-7.3%). CONCLUSIONS: The EuBIVAS has provided updated BV estimates for bone markers, including iFGF23, which have not been previously published, facilitating the improved follow-up of patients being treated for metabolic bone disease.

Directed, Elliptic, and Higher Order Flow Harmonics of Protons, Deuterons, and Tritons in Au+Au Collisions at sqrt[s_{NN}]=2.4 GeV.

Flow coefficients v_{n} of the orders n=1-6 are measured with the High-Acceptance DiElectron Spectrometer (HADES) at GSI for protons, deuterons, and tritons as a function of centrality, transverse momentum, and rapidity in Au+Au collisions at sqrt[s_{NN}]=2.4 GeV. Combining the information from the flow coefficients of all orders allows us to construct for the first time, at collision energies of a few GeV, a multidifferential picture of the angular emission pattern of these particles. It reflects the complicated interplay between the effect of the central fireball pressure on the emission of particles and their subsequent interaction with spectator matter. The high precision information on higher order flow coefficients is a major step forward in constraining the equation of state of dense baryonic matter.

Strong Absorption of Hadrons with Hidden and Open Strangeness in Nuclear Matter.

We present the first observation of K^{-} and ϕ absorption within nuclear matter by means of π^{-}-induced reactions on C and W targets at an incident beam momentum of 1.7 GeV/c studied with HADES at SIS18/GSI. The double ratio (K^{-}/K^{+})_{W}/(K^{-}/K^{+})_{C} is found to be 0.319±0.009(stat)_{-0.012}^{+0.014}(syst) indicating a larger absorption of K^{-} in heavier targets as compared to lighter ones. The measured ϕ/K^{-} ratios in π^{-}+C and π^{-}+W reactions within the HADES acceptance are found to be equal to 0.55±0.04(stat)_{-0.07}^{+0.06}(syst) and to 0.63±0.06(stat)_{-0.11}^{+0.11}(syst), respectively. The similar ratios measured in the two different reactions demonstrate for the first time experimentally that the dynamics of the ϕ meson in nuclear medium is strongly coupled to the K^{-} dynamics. The large difference in the ϕ production off C and W nuclei is discussed in terms of a strong ϕN in-medium coupling. These results are relevant for the description of heavy-ion collisions and the structure of neutron stars.

Tension hydrothorax: Emergency decompression of a pleural cause of cardiac tamponade.

INTRODUCTION: A tension hydrothorax is defined as a massive pleural effusion presenting with hemodynamic abnormalities secondary to mediastinal compression. In these patients pleural volume increases intrathoracic pressure to the point of compromising diastolic filling and cardiac output simulating a cardiac tamponade physiology. This is an uncommon yet potentially fatal medical emergency that if left untreated may progress to cardiac arrest. Early detection and rapid intervention of these patients prevents cardiorespiratory collapse. CASE PRESENTATION: We present a two-case report of patients presenting with malignant tension hydrothoraxes decompressed with ultrasound-guided thoracentesis and tube thoracostomy in the ED. CONCLUSION: Although these life-saving decompressive interventions appear simple, not having proper training is an independent factor for chest tube and thoracentesis complications. Courses and simulation training can benefit physicians to minimize potential complications when managing emergency conditions such as tension hydrothoraxes which continue to be a medical challenge. Whether thoracentesis or thoracostomy is superior in managing this condition remains in debate and a clinical dilemma.

A new species of Hemibrycon (Characiformes, Characidae, Stevardiinae) from the upper Magdalena River basin in Colombia.

Hemibrycon iqueima sp. nov., is described from small streams in the Magdalena drainage at the foothills of the western slope of the Eastern Cordillera of the Colombian Andes, Suarez municipality, Tolima Department, Colombia. The new species is distinguished from its congeners in the Magdalena-Cauca River basin by a combination of characters related to snout-anal-fin origin length, head length, dorsal-pectoral fin distance, dorsal-fin-hypural distance, postorbital distance, orbital diameter, snout length, number of total vertebrae, pre-dorsal scales, scale rows between anal-fin origin and lateral line, number of branched rays of the anal fin, maxillary teeth number and number and arrangement of hooks on the branched rays of the pectoral and dorsal fins. In addition, the validity of this species is supported by previous molecular analyses that included specimens of the new species that had been erroneously identified. Phylogenetic relationships between the new species and congeners from Pacific coast basins are discussed.

Subthreshold Ξ

Results on the production of the double strange cascade hyperon Ξ^{-} are reported for collisions of p(3.5 GeV)+Nb, studied with the High Acceptance Di-Electron Spectrometer (HADES) at SIS18 at GSI Helmholtzzentrum for Heavy-Ion Research, Darmstadt. For the first time, subthreshold Ξ^{-} production is observed in proton-nucleus interactions. Assuming a Ξ^{-} phase-space distribution similar to that of Λ hyperons, the production probability amounts to P_{Ξ^{-}}=[2.0±0.4(stat)±0.3(norm)±0.6(syst)]×10^{-4} resulting in a Ξ^{-}/(Λ+Σ^{0}) ratio of P_{Ξ^{-}}/P_{Λ+Σ^{0}}=[1.2±0.3(stat)±0.4(syst)]×10^{-2}. Available model predictions are significantly lower than the measured Ξ^{-} yield.

Feature extraction by statistical contact potentials and wavelet transform for predicting subcellular localizations in gram negative bacterial proteins.

Predicting the localization of a protein has become a useful practice for inferring its function. Most of the reported methods to predict subcellular localizations in Gram-negative bacterial proteins make use of standard protein representations that generally do not take into account the distribution of the amino acids and the structural information of the proteins. Here, we propose a protein representation based on the structural information contained in the pairwise statistical contact potentials. The wavelet transform decodes the information contained in the primary structure of the proteins, allowing the identification of patterns along the proteins, which are used to characterize the subcellular localizations. Then, a support vector machine classifier is trained to categorize them. Cellular compartments like periplasm and extracellular medium are difficult to predict, having a high false negative rate. The wavelet-based method achieves an overall high performance while maintaining a low false negative rate, particularly, on "periplasm" and "extracellular medium". Our results suggest the proposed protein characterization is a useful alternative to representing and predicting protein sequences over the classical and cutting edge protein depictions.

Osteochondromas in fibrodysplasia ossificans progressiva: a widespread trait with a streaking but overlooked appearance when arising at femoral bone end.

Metaphyseal bony outgrowths are a well-recognized feature of fibrodysplasia ossificans progressiva (FOP) phenotype, but its genuine frequency, topographic distribution, morphological aspect, and potential implications are not fully established. To better ascertain the frequency and characteristics of osteocartilaginous exostoses in FOP disease, we conducted a cross-sectional radiological study based on all the traceable cases identified in a previous comprehensive national research. Metaphyseal exostoses were present in all the 17 cases of FOP studied. Although most often arising from the distal femoral (where metaphyseal exostoses adopt a peculiar not yet reported appearance) and proximal tibial bones, we have found that they are not restricted to these areas, but rather can be seen scattered at a variety of other skeletal sites. Using nuclear magnetic resonance imaging, we show that these exophytic outgrowths are true osteochondromas. As a whole, these results are in agreement with data coming from the literature review. Our study confirms the presence of metaphyseal osteochondromas as a very frequent trait of FOP phenotype and an outstanding feature of its anomalous skeletal developmental component. In line with recent evidences, this might imply that dysregulation of BMP signaling, in addition to promoting exuberant heterotopic ossification, could induce aberrant chondrogenesis and osteochondroma formation. Unveiling the molecular links between these physiopathological pathways could help to illuminate the mechanisms that govern bone morphogenesis.

Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR), Spanish Society of Emergency and Emergency Medicine (SEMES) and Spanish Society of Otolaryngology, Head and Neck Surgery (SEORL-CCC) Guideline for difficult airway management. Part I.

The Airway Management section of the Spanish Society of Anesthesiology, Resuscitation, and Pain Therapy (SEDAR), the Spanish Society of Emergency Medicine (SEMES), and the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC) present the Guide for the comprehensive management of difficult airway in adult patients. Its principles are focused on the human factors, cognitive processes for decision-making in critical situations, and optimization in the progression of strategies application to preserve adequate alveolar oxygenation in order to enhance safety and the quality of care. The document provides evidence-based recommendations, theoretical-educational tools, and implementation tools, mainly cognitive aids, applicable to airway management in the fields of anesthesiology, critical care, emergencies, and prehospital medicine. For this purpose, an extensive literature search was conducted following PRISMA-R guidelines and was analyzed using the GRADE methodology. Recommendations were formulated according to the GRADE methodology. Recommendations for sections with low-quality evidence were based on expert opinion through consensus reached via a Delphi questionnaire.

Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR), Spanish Society of Emergency and Emergency Medicine (SEMES) and Spanish Society of Otolaryngology, Head and Neck Surgery (SEORL-CCC) Guideline for difficult airway management. Part II.

The Airway Management section of the Spanish Society of Anesthesiology, Resuscitation, and Pain Therapy (SEDAR), the Spanish Society of Emergency Medicine (SEMES), and the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC) present the Guide for the comprehensive management of difficult airway in adult patients. Its principles are focused on the human factors, cognitive processes for decision-making in critical situations, and optimization in the progression of strategies application to preserve adequate alveolar oxygenation in order to enhance safety and the quality of care. The document provides evidence-based recommendations, theoretical-educational tools, and implementation tools, mainly cognitive aids, applicable to airway management in the fields of anesthesiology, critical care, emergencies, and prehospital medicine. For this purpose, an extensive literature search was conducted following PRISMA-R guidelines and was analyzed using the GRADE methodology. Recommendations were formulated according to the GRADE methodology. Recommendations for sections with low-quality evidence were based on expert opinion through consensus reached via a Delphi questionnaire.

Conceptual and quantitative categorization of wave-induced flooding impacts for pedestrians and assets in urban beaches.

Beaches combined with sloping structures are frequently the first element of defense to protect urban areas from the impact of extreme coastal flooding events. However, these structures are rarely designed for null wave overtopping discharges, accepting that waves can pass above the crest and threat exposed elements in hinterland areas, such as pedestrians, urban elements and buildings, and vehicles. To reduce risks, Early Warning Systems (EWSs) can be used to anticipate and minimize the impacts of flooding episodes on those elements. A key aspect of these systems is the definition of non-admissible discharge levels that trigger significant impacts. However, large discrepancies in defining these discharge levels and the associated impacts are found among the existing methods to assess floodings. Due to the lack of standardization, a new conceptual and quantitative four-level (from no-impact to high-impact) categorization of flood warnings (EW-Coast) is proposed. EW-Coast integrates and unifies previous methods and builds on them by incorporating field-based information. Thus, the new categorization successfully predicted the impact level on 70%, 82%, and 85% of the overtopping episodes affecting pedestrians, urban elements and buildings, and vehicles, respectively. This demonstrates its suitability to support EWSs in areas vulnerable to wave-induced flooding.

18F-DCFPyL PET/CT guidelines.

The objective of this guide is to provide to nuclear medicine physicians a tool based on scientific evidence and prepared by consensus of experts, to perform the 18F-DCFPyL PET/CT procedure with safely and efficiently for patients with prostate cancer who present PSMA overexpression. For them, some recommendations will be established for 18F-DCFPyL PET/CT examination: reconstruction parameters, presentation of the images and their interpretation. The possible false positives of the procedure will be analysed, how to interpret them and how to avoid them. Finally, all exploration should lead to the preparation of a report that answers the clinician's question. For this, it is recommended to prepare a structured report that includes the PROMISE criteria as well as the classification of the findings according to PSMA-RADS parameters.

Patterns of extension of gastrointestinal stromal tumors (GIST) treated with imatinib (Gleevec®) by 18F-FDG PET/CT.

BACKGROUND AND AIM: currently it is recognized the usefulness of 18F-FDG PET in assessing response to therapy with imatinib (Gleevec®) in the gastrointestinal tract sarcomas (GIST). To facilitate the follow-up of these studies is important to know the patterns of metastatic spread. The aim of this paper is to describe patterns observed in the 18F-FDG PET/CT. METHOD: retrospective study included 29 patients who underwent 18F-FDG PET/CT after being diagnosed with unresectable or metastatic GIST. In total, 87 PET/CT studies were performed (1-6 controls per patient) with a mean time of follow-up 6-36 months. We analyzed the location of the lesions evidenced in PET, CT and fusion. Images were evaluated visually and semiquantitatively (SUV). In cases in which has been considered necessary, additional images have been undertaken: PET delayed imaging, intravenous contrast CT and inspiratory chest CT. RESULTS: the most common primary site was the stomach (41%), small bowel (35%), and rectum (24%). Significant changes in the location of metastatic disease between pre-treatment and the monitoring were observed, with the appearance of more extra-abdominal disease. CONCLUSIONS: individualization of protocol studies and interpretation of PET, CT and fused images were required for evaluation of treatment response to imatinib. Hybrid 18F-FDG PET/CT provides an accurate determination of the extent of GIST. While the most common metastatic site is the liver and peritoneum, in the following cases are common extra-abdominal disease.

Current practice of rapid sequence induction in adults: A national survey among anesthesiologists in Spain. / Práctica actual de la inducción de secuencia rápida en adultos: una encuesta nacional entre anestesiólogos en España.

BACKGROUND: Rapid sequence induction (RSI) in adults has undergone changes in recent years due to pharmacological and technological advances. The objective of this survey was to evaluate current practice among Spanish anesthesiologists. METHODS: A 31-item questionnaire regarding RSI practice was sent to anesthesiologists working in Spanish public hospitals. Differences in responses according to the type of hospital or experience of the respondent were compared for all data using the chi-square and Fisher's exact test. RESULTS: Approximately 15.89% of Spanish anesthesiologists participated in the survey (1002 questionnaires). The results show considerable heterogeneity in most aspects of RSI. Less than 20% of respondents administer sodium citrate. Sixty-four percent place a nasogastric tube in patients with intestinal obstruction. Gastric residue is assessed by ultrasound in 6% of cases. Only 25% of respondents measure ETO2 to check the effectiveness of preoxygenation, and 22% use nasal oxygen insufflation with nasal prongs or THRIVE. Sixty two percent of respondents apply cricoid pressure, but only 50% release the pressure when encountering intubation difficulty. Up to 40% of respondents reported cases of aspiration despite applying cricoid pressure. Propofol was the most commonly used hypnotic (97.6%), but there was no clear preference in the choice of neuromuscular relaxant (suxamethonium versus rocuronium ratio of approximately 1:1). Only 44% of respondents calculated the dose of sugammadex that would be required for emergency reversal of rocuronium. CONCLUSIONS: The survey showed significant variation in RSI practice, similar to that of other countries. Quality prospective studies are needed to standardize clinical practice.

Systematic review of the biological variation data for diabetes related analytes.

BACKGROUND: Objective interpretation of laboratory test results used to diagnose and monitor diabetes mellitus in part requires the application of biological variation data (BVD). The quality of published BVD has been questioned. The aim of this study was to quality assess publications reporting BVD for diabetes-related analytes using the Biological Variation Data Critical Appraisal Checklist (BIVAC); to assess whether published BVD are fit for purpose and whether the study design and population attributes influence BVD estimates and to undertake a meta-analysis of the BVD from BIVAC-assessed publications. METHODS: Publications reporting data for glucose, HbA1c, adiponectin, C-peptide, fructosamine, insulin like growth factor 1 (IGF-1), insulin like growth factor binding protein 3 (IGFBP-3), insulin, lactate and pyruvate were identified using a systematic literature search. These publications were assessed using the BIVAC, receiving grades A, B, C or D, where A is of highest quality. A meta-analysis of the BVD from the assessed studies utilised weightings based upon BIVAC grades and the width of the data confidence intervals to generate global BVD estimates. RESULTS: BIVAC assessment of 47 publications delivered 1 A, 3 B, 39C and 4 D gradings. Publications relating to adiponectin, C-peptide, IGF-1, IGFBP-3, lactate and pyruvate were all assessed as grade C. Meta-analysis enabled global BV estimates for all analytes except pyruvate, lactate and fructosamine. CONCLUSIONS: This study delivers updated and evidence-based BV estimates for diabetes-related analytes. There remains a need for delivery of new high-quality BV studies for several clinically important analytes.

[Utility of inspiratory diagnostic CT scan after CT/PET study in the detection of pulmonary nodules]. / Utilidad de la TC diagnóstica inspiratoria tras la realización del estudio PET/TC en la detección de nódulos pulmonares.

We present the case of a 57-year old woman diagnosed of papillary thyroid carcinoma and treated with thyroidectomy followed by radioiodine (I-131) on two occasions. Follow-up radioiodine scan showed disease in right cervical region, confirmed by fine needle aspiration (FNA) and treated with lymphadenectomy. Due to thyroglobulin elevation, I-131 scan negative and inconclusive cervical ultrasonography/CT scan, we conducted a CT/PET study that confirmed cervical disease. An additional CT scan that was performed on maximum-inspiration showed four micro-nodules, one of which was not detected by the CT scan on shallow breathing (CT/PET). Post-treatment (I-131) scan confirmed uptake in these localizations. Good fusion between PET and CT images that avoids the errors of attenuation correction, especially in the lung bases, is necessary for correct image interpretation of the CT/PET study. Shallow breathing is necessary in order to obtain optimal image fusion with the CT/PET study, although this is not the best to evaluate pulmonary parenchyma in which an additional inspiratory CT scan improves detection of the pulmonary nodules.

Local mepivacaine before castration of horses under medetomidine isoflurane balanced anaesthesia is effective to reduce perioperative nociception and cytokine release.

BACKGROUND: In horses castration with primary intention healing is usually performed under balanced inhalation anaesthesia. To optimise analgesia, the use of local anaesthesia was tested. OBJECTIVES: To investigate the effect of local mepivacaine before castration with first intention healing under balanced medetomidine-isoflurane anaesthesia and flunixin meglumine, morphine analgesia on perioperative cytokine levels and pain in horses. STUDY DESIGN: Prospective blinded clinical study. METHODS: Twenty stallions were randomly assigned to control or mepivacaine groups. Flunixin meglumine was administered before sedation with medetomidine and followed by ketamine/diazepam intravenously (i.v.). Anaesthesia was maintained with isoflurane and 3.5 µg/kg per hour medetomidine. Mepivacaine horses were given mepivacaine 2% (3.5 mL SC, 1 mL/100 kg intrafunicularly, 2 mL/100 kg intratesticularly) on each side. For recovery, horses were given 2 µg/kg medetomidine i.v. and 0.1 mg/kg morphine i.m. and oral phenylbutazone (0.02 mg/kg q12h) for post-operative analgesia. One hour before premedication and 4, 8 and 24 h post-incision, pain was scored with three different pain scales (Equine Utrecht University Scale for Facial Assessment of Pain, Horse Grimace Scale, Equine Utrecht University Scale for Composite Pain Assessment) and plasma cytokines (interleukin-6 and tumour necrosis factor alpha) were measured. Data were analysed using repeated measures ANOVA, linear regression and unpaired t-test, significance level P≤0.05. RESULTS: Horses in both groups showed a significant increase in pain scores and cytokines compared to baseline. Post-operatively the mepivacaine group exhibited significantly lower pain scores and cytokine levels. Mean heart rate during anaesthesia was significantly lower in the mepivacaine group compared to control group (28.8 ± 1 and 33.2 ± 1.7 respectively). Otherwise there were no differences between the groups. MAIN LIMITATIONS: The decision to provide additional analgesia was based on the attending surgeon's assessment rather than a standardised rescue analgesia plan based on pain scores. The study was only conducted for 24 h post-castration and complications were not recorded. CONCLUSION: Local mepivacaine before castration with primary wound closure improved anaesthesia quality, attenuated post-operative increases in cytokines and reduced post-operative pain despite balanced anaesthesia with multimodal analgesia in control horses.

Palate shape and size and palatal rugae morphology of children with anterior open bite and normal vertical overbite.

PURPOSE: To determine differences between open bite and normal vertical overbite regarding distribution, size and clinical appearance of palatal rugae, depth and length of the palate, intercanine and intermolar widths and arch perimeter. METHODS: A cross-sectional study was performed in 264 superior models were studied with a 3D analysis system. A total of 132 individuals with AOB and 132 individuals with normal vertical overbite were evaluated, chosen from public schools with ages between 8 and 16 years. Palatal anthropometric features were evaluated. Qualitative analysis of palatal rugae was performed, exploring the shape, direction, unification and sensitivity of the palate. The Mann Whitney and Chi Square tests were used for statistical analyses. RESULTS: The average age was 11.37 ± 2.27 years for normal overbite and 11.87 for anterior open bite, with 54.9% of women. No significant differences were found between subjects with AOB and subjects with normal vertical overbite regarding intermolar or intercanine width. The maxillary length and depth and the height and width of palatal rugae were lower in the AOB group. The most common rugae shapes were curved and wavy, predominating in the horizontal direction with a parallel distribution. CONCLUSION: Qualitative evaluation demonstrated asymmetry in the shape, direction and unification of rugae in both groups. Most arch measurements were greater in individuals with AOB.

Transcription factor c-Myb inhibits breast cancer lung metastasis by suppression of tumor cell seeding.

Metastasis accounts for most of cancer-related deaths. Paracrine signaling between tumor cells and the stroma induces changes in the tumor microenvironment required for metastasis. Transcription factor c-Myb was associated with breast cancer (BC) progression but its role in metastasis remains unclear. Here we show that increased c-Myb expression in BC cells inhibits spontaneous lung metastasis through impaired tumor cell extravasation. On contrary, BC cells with increased lung metastatic capacity exhibited low c-Myb levels. We identified a specific inflammatory signature, including Ccl2 chemokine, that was expressed in lung metastatic cells but was suppressed in tumor cells with higher c-Myb levels. Tumor cell-derived Ccl2 expression facilitated lung metastasis and rescued trans-endothelial migration of c-Myb overexpressing cells. Clinical data show that the identified inflammatory signature, together with a MYB expression, predicts lung metastasis relapse in BC patients. These results demonstrate that the c-Myb-regulated transcriptional program in BCs results in a blunted inflammatory response and consequently suppresses lung metastasis.