Can white-light endoscopy or narrow-band imaging avoid biopsy of colorectal endoscopic mucosal resection scars? A multicenter randomized single-blind crossover trial.

BACKGROUND : Current guidelines suggest that routine biopsy of post-endoscopic mucosal resection (EMR) scars can be abandoned, provided that a standardized imaging protocol with virtual chromoendoscopy is used. However, few studies have examined the accuracy of advanced endoscopic imaging, such as narrow-band imaging (NBI) vs. white-light endoscopy (WLE) for prediction of histological recurrence. We aimed to assess whether NBI accuracy is superior to that of WLE and whether one or both techniques can replace biopsies. METHODS : The study was a multicenter, randomized, pathologist-blind, crossover trial, with consecutive patients undergoing first colonoscopy after EMR of lesions ≥ 20 mm. Computer-generated randomization and opaque envelope concealed allocation. Patients were randomly assigned to scar examination with NBI followed by WLE (NBI + WLE), or WLE followed by NBI (WLE + NBI). Histology was the reference method, with biopsies being performed for all tissues. RESULTS : The study included 203 scars (103 in the NBI + WLE group, 100 in the WLE + NBI group). Recurrence was confirmed histologically in 29.6 % of the scars. The diagnostic accuracy of NBI was not statistically different from that of WLE (95 % [95 %CI 92 %-98 %] vs. 94 % [95 %CI 90 %-97 %]; P = 0.48). The negative predictive values (NPVs) were 96 % (95 %CI 93 %-99 %) for NBI and 93 % (95 %CI 89 %-97 %) for WLE (P = 0.06). CONCLUSIONS : The accuracy of NBI for the diagnosis of recurrence was not superior to that of WLE. Endoscopic assessment of EMR scars with WLE and NBI achieved an NPV that would allow routine biopsy to be avoided in cases of negative optical diagnosis.

An unexpected location for a metastasis from esophageal squamous carcinoma.

We report the case of a 69-year-old male with a relevant alcohol consumption and a history of prostate cancer who underwent screening upper gastrointestinal endoscopy and colonoscopy. The upper gastrointestinal endoscopy revealed an ulcerated mass in the middle esophagus occupying half the circumference. Histologic examination was compatible with a squamous cell carcinoma. Staging with endoscopic ultrasound and computed tomography of the neck, chest and abdomen was consistent with a T3N1M0.

Duodenal lymphangiectasias - The first sign of pancreatic adenocarcinoma.

A 41-year-old caucasian female, with past medical history of pituitary adenoma medicated with cabergoline, presented with worsening dyspepsia and unintentional weight loss of 5%. Physical exam and laboratory results were unremarkable for pathological findings. Esophagogastroduodenoscopy revealed an oedematous and exuberant lymphangiectasia appearance in the duodenum, with no ulceration or suspected infiltration component. However, duodenal biopsies revealed infiltration by poorly differentiated carcinoma. In the meantime, infection and inflammatory/autoimmune causes were ruled out. A CT scan was performed revealing a thickened and enlarged pancreas with ill-defined limits and several intra-abdominal adenopathies, raising suspicion of pancreatic lymphoproliferative disease. EUS with FNB was performed with biopsy of the pancreas and one of the larger adenopathy. EUS also revealed an enlarged, non-nodular pancreas and a thickened duodenal wall. Mild ascites was detected. Both EUS-biopsies were concordant on the diagnosis of carcinoma with gastric or pancreatic-biliary origin, highly aggressive (Ki67 > 80 %). Therefore, the diagnosis of pancreatic adenocarcinoma was assumed (cT4N1Mx). The patient is currently on palliative chemotherapy and remains paucisymptomatic.

Aortic stenosis calcium scoring in a racially mixed sample.

Aortic stenosis (AS) is common and increasing in prevalence as the population ages. Using computed tomography (CT) to quantify aortic valve calcification (AVC) it has been reported that men have greater degrees of calcification than women among subjects with severe AS. These data, however, were derived in largely Caucasian populations and have not been verified in non-Caucasian subjects. This retrospective study identified 137 patients with severe AS who underwent valve replacement and had CT scans within 6 months prior to surgery. AVC scores were compared between men and women, both in the entire sample and in racial subgroups. 52% of subjects were male and 62.8% were non-Caucasian. Mean AVC score for the entire cohort was 3062.08±2097.87 with a range of 428-13,089. Gender differences in aortic valve calcification were found to be statistically significant with an average AVC score of 3646±2422 in men and 2433±1453 in women (p=0.001). On multivariate analysis, gender remained significantly associated with AVC score both in the entire sample (p=0.014) and in the non-Caucasian subgroup (p=0.008). Mean AVA was significantly greater in males than females but this difference disappeared when AVA was indexed to BSA (p=0.719). AVA was not different between racial groups (p=0.369). In this research we observed that among subjects with severe AS men have higher AVC scores than women regardless of racial background. This is consistent with previous studies in predominantly Caucasian populations.

Proteomic identification and purification of seed proteins from native Amazonian species displaying antifungal activity.

MAIN CONCLUSION: Seeds of native species from the rain forest (Amazon) are source of chitinases and their protein extracts exhibited strong and broad antifungal activity. Numerous plant species native to the Amazon have not yet been chemically studied. Studies of seeds are scarcer, since adversities in accessing study areas and seasonality pose constant hurdles to systematic research. In this study, proteins were extracted from seeds belonging to endemic Amazon species and were investigated for the first time. Proteolytic activity, peptidase inhibitors, and chitinases were identified, but chitinolytic activity predominated. Four proteins were purified through chromatography and identified as lectin and chitinases by MS/MS analyses. The proteins were examined for inhibition of a phytopathogen (Fusarium oxysporum). Analyses by fluorescence microscopy suggested binding of propidium iodide to DNA of fungal spores, revealing that spore integrity was lost when accessed by the proteins. Further structural and functional analyses of defensive proteins belonging to species facing highly complex ecosystems such as Amazonia should be conducted, since these could provide new insights into specificity and synergism involving defense proteins of plants submitted to a very complex ecosystem.

Premedication with simethicone and N-acetylcysteine in improving visibility during upper endoscopy: a double-blind randomized trial.

Background and study aim Upper endoscopy is the most common method for the diagnosis of upper gastrointestinal tract diseases. The aim of this study was to determine whether premedication with simethicone or N-acetylcysteine improves mucosal visualization during upper endoscopy. Patients and methods This was a randomized, double-blind, placebo-controlled study of 297 patients scheduled for upper endoscopy who were premedicated 15 - 30 minutes before the procedure with: 100 mL of water (placebo, group A); water plus 100 mg simethicone (group B); water plus 100 mg simethicone plus 600 mg N-acetylcysteine (group C). The primary outcome measure was the quality of mucosal visualization (score: excellent, adequate or inadequate). Results The addition of simethicone (group B) or simethicone plus N-acetylcysteine to the water (group C) improved the visualization scores of endoscopies compared with water alone (group A). In particular, groups B and C produced a significantly higher percentage of endoscopies with excellent visualization for the esophagus (91.1 % and 86.7 %, respectively, vs. 71.4 % in group A; P < 0.001) and stomach (76.2 % and 74.5 % vs. 38.8 % in group A; P < 0.001). For the duodenum, the use of simethicone also showed an increase in the endoscopies with excellent visualization compared with water alone (85.1 % vs. 73.5 %; P = 0.042). There were no significant differences in scores between groups B and C or between gastric scores in patients with previous subtotal gastrectomy (B and C vs. A): 60.0 % and 42.1 % vs. 28.6 % (P = 0.14). The rate of reported lesions was higher in group B but without statistical significance. Conclusions Premedication with simethicone resulted in better mucosal visibility. Such premedication might improve diagnostic yield, and should be considered for standard practice. Trial registered at ClinicalTrials.gov (NCT02357303).

Diversity patterns, research trends and mismatches of the investigative efforts to amphibian conservation in Brazil.

The number of papers on biology of amphibians has increased in the recent years. A detailed overview of the publications on amphibians can be very useful in assessing the status of our knowledge about this taxonomic group. Due to the large number of articles published, we aimed to assess the scientific contribution of herpetological researches carried out between the years 2001 and 2010 on Brazilian amphibians, considering the diversity patterns, the threats and the research topics that have been published most often. We applied scientometric attention indexes in the reviewed studies from seven scientific databases. To examine the relationship between the numbers of species recorded locally and regionally at different spatial scales, we used an additive partitioning of diversity in three hierarchical levels (i.e., states, geographic regions and biomes). We evaluated 892 articles and 914 species, which showed that 65 % of the total diversity of Brazilian amphibian species was represented by the beta diversity among the biomes. We identified many differences in the allocation of research efforts for taxonomic groups, threats categories, geographic regions, and research topics, highlighting the main research trends conducted and the priority themes for investigation of further papers on Brazilian amphibians.

The Effect of Oral Simethicone in a Bowel Preparation in a Colorectal Cancer Screening Colonoscopy Setting: A Randomized Controlled Trial.

Introduction: Current guidelines suggest adding oral simethicone to bowel preparation for colonoscopy. However, its effect on key quality indicators for screening colonoscopy remains unclear. The primary aim was to assess the rate of adequate bowel preparation in split-dose high-volume polyethylene glycol (PEG), with or without simethicone. Methods: This is an endoscopist-blinded, randomized controlled trial, including patients scheduled for colonoscopy after a positive faecal immunochemical test. Patients were randomly assigned to 4 L of PEG split dose (PEG) or 4 L of PEG split dose plus 500 mg oral simethicone (PEG + simethicone). The Boston Bowel Preparation Scale (BBPS) score, the preparation quality regarding bubbles using the Colon Endoscopic Bubble Scale (CEBuS), ADR, CIR, and the intraprocedural use of simethicone were recorded. Results: We included 191 and 197 patients in the PEG + simethicone group and the PEG group, respectively. When comparing the PEG + simethicone group versus the PEG group, no significant differences in adequate bowel preparation rates (97% vs. 93%; p = 0.11) were found. However, the bubble scale score was significantly lower in the PEG + simethicone group (0 [0] versus 2 [5], p < 0.01), as well as intraprocedural use of simethicone (7% vs. 37%; p < 0.01). ADR (62% vs. 61%; p = 0.86) and CIR (98% vs. 96%, p = 0.14) did not differ between both groups. Conclusion: Adding oral simethicone to a split-bowel preparation resulted in a lower incidence of bubbles and a lower intraprocedural use of simethicone but no further improvement on the preparation quality or ADR.

Introdução: As normas de orientação atuais sugerem a adição de simeticone oral à preparação intestinal para colonoscopia. Contudo, o seu efeito nos indicadores de qualidade no âmbito da colonoscopia de rastreio não está comprovado. O objetivo principal foi avaliar a taxa de preparação adequada usando polietilenoglicol (PEG) em dose dividida com e sem simeticone oral. Métodos: Estudo randomizado controlado, cego para o endoscopista, incluindo doentes admitidos para colonoscopia após teste fecal imunoquímico positivo. Os doentes foram aleatoriamente alocados para 4 litros de PEG em dose dividida (PEG) ou 4 litros de PEG em dose divida + simeticone oral (PEG + simeticone). Foram avaliados: Boston Bowel Preparation Scale (BBPS), qualidade da preparação relativa às bolhas através da Colon Endoscopic Bubble Scale (CEBuS) scale, ADR, CIR e uso de simeticone durante o procedimento. Resultados: Foram incluídos 191 e 197 doentes nos grupos PEG + simeticone e PEG, respetivamente. Comparando os grupos PEG + simeticone versus PEG, não se registaram diferenças de significado estatístico relativamente à taxa de preparação intestinal adequada (97% vs. 93%; p = 0,01) mas o score da escala de bolhas foi significativamente inferior no grupo PEG + simeticone [0 (0) versus 2 (5), p < 0.01], assim como o uso de simeticone durante o procedimento (7% vs. 37%; p < 0,01). A ADR (62% vs. 61%; p = 0,86) e a CIR (98% vs. 96%, p = 0,14) não diferiram significativamente entre os dois grupos, respetivamente. Discussão/Conclusão: Adicionar simeticone oral à preparação intestinal em dose dividida permitiu menor incidência de bolhas e menor utilização de simeticone durante o procedimento, mas não se associa a melhor preparação intestinal ou melhor ADR.

Differentiated thyroid carcinoma: what the nonspecialists needs to know.

Differentiated thyroid carcinoma (DTC) accounts for most cases of thyroid cancer, and the heterogeneity of DTC requires that management decisions be taken by a multidisciplinary team involving endocrinologists, head and neck surgeons, nuclear medicine physicians, pathologists, radiologists, radiation oncologists, and medical oncologists. It is important for nonspecialists to recognize and refer patients with DTC who will benefit from a specialized approach. Recent advances in knowledge and changes in management of DTC call for the need to raise awareness on the part of these nonspecialist physicians, including general endocrinologists and medical oncologists at large. We provide an overview of diagnostic and therapeutic principles in DTC, especially those that bear direct implication on day-to-day management of these patients by generalists. Patients with DTC may be broadly categorized as having localized, locally persistent/recurrent, or metastatic disease. Current recommendations for DTC include a three-tiered system that classifies patients with localized disease into low, intermediate, or high risk of persistent or recurrent disease. Risk stratification should be performed at baseline and repeated on an ongoing basis, depending on clinical evolution. One of the overarching goals in the management of DTC is the need to personalize treatment by tailoring its modality and intensity according to ongoing prognostic stratification, evolving knowledge about the disease, and patient characteristics and preference. In metastatic disease that is refractory to radioactive iodine, thyroid tumors are being reclassified into molecular subtypes that better reflect their biological properties and for which molecular alterations can be targeted with specific agents.

Time-dependent modulation of AMPA receptor phosphorylation and mRNA expression of NMDA receptors and glial glutamate transporters in the rat hippocampus and cerebral cortex in a pilocarpine model of epilepsy.

The pilocarpine model in rodents reproduces the main features of mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) in humans. It has been demonstrated in this model that the phosphorylation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR1 subunit is increased 1 h after pilocarpine treatment. Moreover, alterations in the levels of glutamate transporters have been associated with chronic epilepsy in humans. Despite these studies, the profile of these changes has not yet been addressed. We analyzed the protein content and phosphorylation profile of the AMPA receptor GluR1 subunit by western blotting. We also used quantitative real-time polymerase chain reaction to analyze the expression of glial glutamate transporters and the N-methyl-D-aspartate receptor NR1 subunit in the hippocampus (Hip) and cerebral cortex (Ctx) at different time points after pilocarpine-induced status epilepticus (Pilo-SE) in male adult Wistar rats. Biochemical analysis was performed in the Hip and Ctx at 1, 3, 12 h (acute period), 5 days (latent period), and 50 days (chronic period) after Pilo-SE. Key findings include an increase in the phosphorylation of GluR1-Ser(845) in the Ctx and GluR1-Ser(831) in the Hip at different times during the acute period, and a decrease in the total content of the GluR1 subunit in the Ctx in the latent period. There was a down-regulation of the mRNA expression and protein levels of EAAT1 and EAAT2, and a decrease of the NR1 mRNA expression, in the Ctx during the latent period. Notably, during the chronic period, the EAAT2 mRNA expression and protein levels decreased while the NR1 mRNA levels increased in the Hip. Taken together, our findings suggest a time- and structure-dependent imbalance of glutamatergic transmission in response to Pilo-SE, which might be associated with either epileptogenesis or the seizure threshold in MTLE-HS.

Diagnostic accuracy of lugol chromoendoscopy in the oesophagus in patients with head and neck cancer.

BACKGROUND AND AIM: patients with head and neck squamous cell malignancies have a higher risk of oesophageal squamous cell carcinomas. Lugol chromoendoscopy in oesophagus is a simple technique with a high diagnostic yield in premalignant lesions. The objective was to analyze its diagnostic accuracy in dysplasia and carcinoma of the oesophagus in high-risk patients. METHODS: prospective study from April/2008 to January/2012 using lugol chromoendoscopy with biopsies of suspicious lugol voiding areas > or = 5 mm. Patients with head and neck malignancies were included, except the ones with iodine allergy, oesophageal varices and contra-indications to standard endoscopy. The reference method was histopathology. RESULTS: 89 patients were enrolled (mean age 62.8 + or - 13.3 years, 87 % men). Primary tumour was located in oropharynx in 37 (41.6 %), in oral cavity in 29 (32.6 %) and in the larynx in 23 (25.8 %) cases. 40.4 % patients had previous treatments and 87 % reported alcohol or tobacco addition. All exams performed without anaesthesia or complications. Nine suspicious lugol voiding areas were observed and biopsied. Histopathological analysis revealed high-grade dysplasia in 2 (2.2 %) and inflammation or normal findings in the others. The sensitivity and specificity for detecting high-grade dysplasia were 100 % and 92 % (95 % CI: 87-97), respectively. Diagnostic accuracy of the test was 92 % (95 % CI: 86-98). CONCLUSION: lugol staining of the oesophagus during endoscopy seems to be a feasible, safe and justified procedure in high-risk populationas it enhances the detection of premalignant lesions.

Raynaud Phenomenon of the Nipple: A Clinical Case Report.

Objective: In Raynaud's phenomenon of the nipple there is a change in color, accompanied by pain or discomfort during breastfeeding. Case report: A 29-years old female patient, breastfeeding, develops a severe bilateral nipple pain during and after breastfeeding and biphasic change in nipple color, with difficulties in the breastfeeding technique. She was medicated with nifedipine and recommended application of warm compresses to the nipples and use of electric breast pump, showing complete resolution after four weeks of treatment. Conclusion: Raynaud's phenomenon of the nipple should be considered in breastfeeding women who report nipple pain or discomfort. In clinical practice, nipple pain is a very frequent complaint, and responsible for many cases of early abandonment of breastfeeding. It is therefore essential to make an early diagnosis and implement a correct and immediate treatment.

Antimony Selenide Solar Cells Fabricated by Hybrid Reactive Magnetron Sputtering.

The fabrication of Sb2Se3 thin-film solar cells deposited by a pulsed hybrid reactive magnetron sputtering (PHRMS) was proposed and examined for different growth conditions. The influence of growth temperature and Se pulse period were studied in terms of morphology, crystal structure, and composition. The Sb2Se3 growth showed to be dependent on the growth temperature, with a larger crystal size for growth at 270 °C. By controlling the Se pulse period, the crystal structure and crystal size could be modified as a function of the supplied Se amount. The solar cell performance for Sb2Se3 absorbers deposited at various temperatures, Se pulse periods and thicknesses were assessed through current-voltage characteristics. A power conversion efficiency (PCE) of 3.7% was achieved for a Sb2Se3 solar cell with 900 nm thickness, Sb2Se3 deposited at 270 °C and Se pulses with 0.1 s duration and period of 0.5 s. Finally, annealing the complete solar cell at 100 °C led to a further improvement of the Voc, leading to a PCE of 3.8%, slightly higher than the best reported Sb2Se3 solar cell prepared by sputtering without post-selenization.

Cap-Assisted Endoscopic Mucosal Resection for Rectal Neuroendocrine Tumors: An Effective Option.

Introduction: The incidence of rectal neuroendocrine tumors (r-NETs) is increasing, and most small r-NETs can be treated endoscopically. The optimal endoscopic approach is still debatable. Conventional endoscopic mucosal resection (EMR) leads to frequent incomplete resection. Endoscopic submucosal dissection (ESD) allows higher complete resection rates but is also associated with higher complication rates. According to some studies, cap-assisted EMR (EMR-C) is an effective and safe alternative for endoscopic resection of r-NETs. Aims: This study aimed to evaluate the efficacy and safety of EMR-C for r-NETs ≤10 mm without muscularis propria invasion or lymphovascular infiltration. Methods: Single-center prospective study including consecutive patients with r-NETs ≤10 mm without muscularis propria invasion or lymphovascular invasion confirmed by endoscopic ultrasound (EUS), submitted to EMR-C between January 2017 and September 2021. Demographic, endoscopic, histopathologic, and follow-up data were retrieved from medical records. Results: A total of 13 patients (male: 54%; n = 7) with a median age of 64 (interquartile range: 54-76) years were included. Most lesions were located at the lower rectum (69.2%, n = 9), and median lesion size was 6 (interquartile range: 4.5-7.5) mm. On EUS evaluation, 69.2% (n = 9) of tumors were limited to muscularis mucosa. EUS accuracy for the depth of invasion was 84.6%. We found a strong correlation between size measurements by histology and EUS (r = 0.83, p < 0.01). Overall, 15.4% (n = 2) were recurrent r-NETs and had been pretreated by conventional EMR. Resection was histologically complete in 92% (n = 12) of cases. Histologic analysis revealed grade 1 tumor in 76.9% (n = 10) of cases. Ki-67 index was inferior to 3% in 84.6% (n = 11) of cases. The median procedure time was 5 (interquartile range: 4-8) min. Only 1 case of intraprocedural bleeding was reported and was successfully controlled endoscopically. Follow-up was available in 92% (n = 12) of cases with a median follow-up of 6 (interquartile range: 12-24) months with no evidence of residual or recurrent lesion on endoscopic or EUS evaluation. Conclusion: EMR-C is fast, safe, and effective for resection of small r-NETs without high-risk features. EUS accurately assesses risk factors. Prospective comparative trials are needed to define the best endoscopic approach.

Introdução: Os tumores neuroendócrinos do reto (r-NETs) apresentam incidência crescente. A maioria dos tumores de pequenas dimensões pode ser excisada endoscopicamente, no entanto, a abordagem ótima é controversa. A mucosectomia convencional associa-se, frequentemente, a resseção endoscópica incompleta. A disseção endoscópica submucosa (ESD) permite elevadas taxas de resseção completa, mas é tecnicamente complexa e associa-se a maior número de complicações. Alguns estudos sugerem a mucosectomia assistida por cap (EMR-C) como uma alternativa eficaz e segura. Objetivo: Este estudo pretendeu avaliar a eficácia e segurança da mucosectomia com cap na resseção de r-NETs com dimensões ≤10 mm, sem invasão da muscularis própria nem infiltração linfovascular. Material e Métodos: Estudo prospetivo unicêntrico incluindo consecutivamente r-NETs com ≤10 mm, sem invasão da muscularis própria ou linfovascular confirmada em ultrassonografia endoscópica (EUS), submetidos a mucosectomia assistida cap entre janeiro de 2017 e setembro de 2021. Colheita de dados demográficos, clínicos e histopatológicos através de registos médicos eletrónicos. Resultados: Incluídos 13 doentes (género masculino: 54%; n = 7) com idade mediana de 64 (intervalo interquartil [IIQ]: 54­76) anos. A maioria das lesões localizava-se no reto inferior (69.2%; n = 9) e apresentava tamanho mediano de 6 (IIQ: 4.5­7.5) mm. Na avaliação por EUS, 69.2% (n = 9) encontravam-se limitados à muscularis mucosa. A acuidade da EUS na avaliação do envolvimento das camadas da parede retal foi de 84.6% e o tamanho avaliado por EUS correlacionou-se fortemente com o medido na histologia (r = 0.83, p < 0.01). Dois casos (15.4%) corresponderam a recorrências de mucosectomias convencionais prévias. A resseção foi macroscópica e histologicamente completa em 92% (n = 12) dos casos. A análise histológica revelou 76.9% (n = 10) tumores de grau 1. O índice Ki-67 foi inferior a 3% em 84.6% (n = 11) dos casos. O tempo mediano de procedimento foi 5 (IIQ: 4­8) minutos. Verificou-se apenas um caso de hemorragia intraprocedimento resolvida endoscopicamente. O seguimento de 92% dos casos (n = 12) com mediana de 6 (IIQ:12­24) meses não revelou lesão residual ou recorrência em avaliações endoscópica e ultrassonográfica. Discussão/Conclusão: A EMR-C é uma técnica endoscópica segura, rápida e efetiva para a resseção de r-TNEs pequenos sem fatores de alto risco. A EUS apresenta elevada acuidade na avaliação dos fatores de risco. Estudos comparativos prospetivos são necessários para estabelecimento da abordagem endoscópica mais profícua.

The impacts of population subdivision on the viability of Brachyteles hypoxanthus.

Habitat loss and fragmentation turn continuous large populations into metapopulations of smaller populations, more prone to the negative effects of stochastic processes. We modeled scenarios simulating the subdivision of Brachyteles hypoxanthus populations under different dispersal rates. Results show the existence of a population subdivision threshold, below which subdivision causes the metapopulation structure to collapse. Management should target first the increase in local populations through habitat restoration/protection, and only after populations are sufficiently large, connectivity strategies should take place.

Validation of aortic valve calcium quantification thresholds measured by computed tomography in Asian patients with calcific aortic stenosis.

AIMS: Sex-specific thresholds of aortic valve calcification (AVC) have been proposed and validated in Caucasians. Thus, we aimed to validate their accuracy in Asians. METHODS AND RESULTS: Patients with calcific aortic stenosis (AS) from seven international centres were included. Exclusion criteria were ≥moderate aortic/mitral regurgitation and bicuspid valve. Optimal AVC and AVC-density sex-specific thresholds for severe AS were obtained in concordant grading and normal flow patients (CG/NF). We included 1263 patients [728 (57%) Asians, 573 (45%) women, 837 (66%) with CG/NF]. Mean gradient was 48 (26-64) mmHg and peak aortic velocity 4.5 (3.4-5.1) m/s. Optimal AVC thresholds were: 2145 Agatston Units (AU) in men and 1301 AU in women for Asians; and 1885 AU in men and 1129 AU in women for Caucasians. Overall, accuracy (% correctly classified) was high and comparable either using optimal or guidelines' thresholds (2000 AU in men, 1200 AU in women). However, accuracy was lower in Asian women vs. Caucasian women (76-78% vs. 94-95%; P < 0.001). Accuracy of AVC-density (476 AU/cm2 in men and 292 AU/cm2 in women) was comparable to absolute AVC in Caucasians (91% vs. 91%, respectively, P = 0.74), but higher than absolute AVC in Asians (87% vs. 81%, P < 0.001). There was no interaction between AVC/AVC-density and ethnicity (all P > 0.41) with regards to AS haemodynamic severity. CONCLUSION: AVC thresholds defining severe AS are comparable in Asian and Caucasian populations, and similar to those proposed in the guidelines. However, accuracy of AVC to identify severe AS in Asians (especially women) is sub-optimal. Therefore, the use of AVC-density is preferable in Asians.