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Detection of Helicobacter pylori resistance to clarithromycin and fluoroquinolones in Brazil:A national survey

World Journal of Gastroenterology 2016年第33期22卷 7587-7594页

作者： Bruno Squarcio Sanches Gustavo Miranda Martins Karine Lima Bianca Cota Luciana Dias Moretzsohn Laercio Tenorio Ribeiro Helenice P Breyer Ismael Maguilnik Aline Bessa Maia Joffre Rezende-Filho Ana Carolina Meira Henrique Pinto Edson Alves Ramiro Mascarenhas Raissa Passos Julia Duarte de Souza Osmar Reni Trindade Luiz Gonzaga Coelho Instituto Alfa de Gastroenterologia Hospital das ClínicasUniversidade Federal de Minas Gerais Unigastro e Clínica Santa Fé hospital de Clínicas Universidade Federal do Rio Grande do Sul fundacao hospital adriano jorge hospital das Clínicas Universidade Federal de Goiás hospital Geral Roberto Santos

AIM To evaluate bacterial resistance to clarithromycin and fluoroquinolones in Brazil using molecular methods.METHODS The primary antibiotic resistance rates of Helicobacter pylori(H. pylori) were determined from November 2012 to March 2015 in the Southern,South-Eastern,Northern,North-Eastern,and Central-Western regions of Brazil. Four hundred ninety H. pylori patients [66% female,mean age 43 years(range: 18-79)] who had never been previously treated for this infection were enrolled. All patients underwent gastroscopy with antrum and corpus biopsies and molecular testing using Geno Type Helico DR(Hain Life Science,Germany). This test was performed to detect the presence of H. pylori and to identify point mutations in the genes responsible for clarithromycin and fluoroquinolone resistance. The molecular procedure was divided into three steps: DNA extraction from the biopsies,multiplex amplification,and reverse hybridization. RESULTS Clarithromycin resistance was found in 83(16.9%) patients,and fluoroquinolone resistance was found in 66(13.5%) patients. There was no statistical difference in resistance to either clarithromycin or fluoroquinolones(P = 0.55 and P = 0.06,respectively) among the different regions of Brazil. Dual resistance to clarithromycin and fluoroquinolones was found in 4.3%(21/490) of patients. The A2147 G mutation was present in 90.4%(75/83),A2146 G in 16.9%(14/83) and A2146 C in 3.6%(3/83) of clarithromycin-resistant patients. In 10.8%(9/83) of clarithromycin-resistant samples,more than 01 mutation in the 23 S r RNA gene was noticed. In fluoroquinolone-resistant samples,37.9%(25/66) showed mutations not specified by the Geno Type Helico DR test. D91 N mutation was observed in 34.8%(23/66),D91 G in 18.1%(12/66),N87 K in 16.6%(11/66) and D91 Y in 13.6%(9/66) of cases. Among fluoroquinolone-resistant samples,37.9%(25/66) showed mutations not specified by the Geno Type Helico DR test. CONCLUSION The H. pylori clarithromycin resistance rate in Brazil is at the borderline(15%-20%) for applying the sta

关键词： Helicobacter pylori Microbial drug resistance Clarithromycin Fluoroquinolones Molecular diagnostic techniques

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Gastric Neoplasia during Anti-TNF Therapy for Crohn’s Disease: Casual Event?

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Journal of Cancer Therapy 2015年第8期6卷 743-747页

作者： F. M. L. Fortes B. C. Silva B. C. Silva M. C. Lyra A. M. Pimentel G. O. Santana hospital Geral Roberto Santos Salvador Brasil hospital Universitário Prof. Edgard Santos (UFBA) Salvador Brasil fundacao Monte Tabor Hospital Sao Rafael Salvador Brasil

The increase risk of cancer development in patients with inflammatory intestinal disease (IBD) has already studied for decades. The anti-TNF therapy has changed the treatment strategy of IBD. By using on a larger scale and for a longer time, the anti-TNF raised concern over its potential adverse events. A male Crohn’s disease (CD) patient, 55 years old, diagnosed for nine years, treated with infliximab for 6 years. In 2011, he underwent a nupper endoscopy (UE) which showed flat erosive gastritis with moderate intensity in antrum, gastric polyps and gastric erosion. Pathological examination revealed a chronic gastritis in erosive activity and search for Helicobacter pylori resulted positive. In May 2014, the patient was asymptomatic, when it held UE, which showed suggestive lesion of early gastric cancer, measuring 1.5 cm and search for Helicobacter pylori negative. Histopathological exams confirmed the adenocarcinoma. The patient underwent to a laparoscopic surgery (total gastrectomy with lymphadenectomy and reconstruction Roux-en-Y). Risk factors for the development of gastric cancer in general population are already well defined. However studying a possible association among CD and the different therapeutic modalities used in the treatment of this disease with gastric cancer appearance is important to set specific assessment strategies, prevention and follow-up. While there is no consensus on a proper monitoring for gastric cancer prevention in these patients, individualized conduct, taking into account individual characteristics, family record and other risk factors, should be adopted to avoid unfavorable outcomes in CD patients.

关键词： Crohn’s Disease Risk for Neoplasm Gastric Neoplasm Anti-TNF

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Risk Factors for Cervical Cancer in a Sample Comprising Three Generations of Brazilian Women

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Journal of Cancer Therapy 2017年第1期8卷 12-25页

作者： Ilce Ferreira da Silva Rosalina jorge Koifman Virgilio Augusto Gomes Parreira Simone Soares Sergio Koifman Instituto Fernandes Figueira Fundacao Oswaldo Cruz Rio de Janeiro Brazil Escola Nacional de Saúde Pública Fundacao Oswaldo Cruz Rio de Janeiro Brazil hospital do Cancer-II Instituto Nacional do Cancer Rio de Janeiro Brazil

Background: Cervical cancer is the main cause of cancer deaths in some developing countries. Age-related cervical cancer incidence has been fundamental for understanding the different stages of carcinogenesis concepts. No Brazilian study explored the environmental risk factors involved on cervical cancer, according to age groups taking 70’s sexual revolution in Brazil as reference. Aim: To determine the prevalence of epidemiological and clinical aspects related to cervical cancer development in a sample of three age groups of Brazilian women based on 70’s sexual revolution. Methods: A cross-section study was proceeded in a hospital-based cohort of women with altered Pap-test refereed to the National Cancer Institute for Colposcopy and treatment from October 2004 to May 2006. Two register nurses interviewed all patients ascertaining risk factors and clinical characteristics. Biopsy, partial ablation were used for CIN-1, and conization was the treatment for CIN-2/3. Results: From 318 women included in the study, 42.8% were 18 - 30 years old (born after 1975), 43.4% were 31 - 49 years old (born 1955-1975), and 13.8% were 50 - 68 years old (born 1936-1954). Pregnancies (OR = 1.16;CI95%: 1.01 - 1.34) and menarche under 12 years old (OR = 1.95;CI95%: 1.17 - 3.25) were independently associated to CIN2- 3/cancer in 18 - 30 age group;menopause age (OR = 1.21;CI95%: 1.04 - 1.41) and current smoking habit (OR = 1.37;CI95%: 1.10 - 1.70) were associated to CIN2- 3/cancer in 31 - 49 age group;no statistical significance was observed for 50 - 68 age group. Conclusion: Brazilian women present distinct risk for cervical cancer according to the generation they belong, when taking the Brazilian sexual revolution on 70’s as a reference.

关键词： Cervical Cancer Cross-Section Study Epidemiology Sexual Revolution Brazil

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Antipsychotics preserve telomere length in peripheral blood mononuclear cells after acute oxidative stress injury

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Neural Regeneration Research 2022年第5期17卷 1156-1160页

作者： Gabriel B.Polho Giancarlo M.Cardillo Daniel S.Kerr Thais Chile Wagner F.Gattaz Orestes V.Forlenza Helena P.Brentani Vanessa J.De-Paula Laboratório de Neurociências(LIM-27) Departamento e Instituto de PsiquiatriaHospital das Clinicas HCFMUSPFaculdade de MedicinaUniversidade de São PauloSPBrasil Laboratório de Psicobiologia(LIM-23) Departamento e Instituto de PsiquiatriaHospital das Clinicas HCFMUSPFaculdade de MedicinaUniversidade de São PauloSPBrasil

Antipsychotics may prolong or retain telomere length,affect mitochondrial function,and then affect the metabolism of nerve cells.To validate the hypothesis that antipsychotics can prolong telomere length after oxidative stress injury,leukocytes from healthy volunteers were extracted using Ficoll-Histopaque density gradient.The mononuclear cells layer was resuspended in cell culture medium.Oxidative stress was induced with hydrogen peroxide in cultured leukocytes.Four days later,leukocytes were treated with aripiprazole,haloperidol or clozapine for 7 days.Real-time PCR revealed that treatments with aripiprazole and haloperidol increased the telomere length by 23%and 20%in peripheral blood mononuclear cells after acute oxidative stress injury.These results suggest that haloperidol and aripiprazole can reduce the damage to telomeres induced by oxidative stress.The experiment procedure was approved by the Ethics Committee of Faculty of Medicine of the University of Sao Paulo(FMUSP/CAAE approval No.52622616.8.0000.0065).

关键词： antipsychotic aripiprazole cell culture clozapine haloperidol oxidative stress peripheral blood mononuclear cell telomere length

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Neuroscience for Architecture:How Building Design Can Influence Behaviors and Performance

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Journal of Civil Engineering and Architecture 2018年第2期12卷 132-138页

作者： Andréa de Paiva fundacao Getulio Vargas FGVInstitute for Educational DevelopmentSao Paulo 01310-100Brazil

The purpose of this paper is to discuss recent findings in neuroscience that can be useful to architecture.Knowing the working patterns of the brain and how space affects cerebral functions can help architects design buildings that improve the user’s behavior,performance and well-being.The built environment has a direct impact on the human brain.Social relations,focus,cognition,creativity,memory and well-being can be influenced by the surrounding physical space.Although it is not possible to create the perfect room,the space can be used in a strategic way,depending on the task that individuals are supposed to do there and depending on the people(age,gender,culture)who will make use of the space.Schools can be designed in a way to improve cognition,learning and memorization;hospital buildings can help improving recovery;workspaces can improve performance,creativity and collaboration.Above all,all spaces of long occupation should be designed in a way to improve well-being.How can architecture change automatic behaviors and nudge people to behave in a healthier way?Can architects create buildings and cities that improve socialization and happiness?Can criminality levels drop due to changes on the way the environments are designed?These are some of the questions that will be discussed in this paper.

关键词： Architecture brain neuroarchitecture neuroscience behavior performance well-being design

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Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease

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World Journal of Gastroenterology 2007年第7期13卷 1067-1073页

作者： Andre Castro lyra Milena Botelho Pereira Soares luiz Flavio Maia da Silva Marcos Fraga Fortes André Goyanna Pinheiro Silva Augusto César de Andrade Mota Sheilla A Oliveira Eduardo lorens Braga Wilson Andrade de Carvalho Bernd Genser Ricardo Ribeiro dos Santos luiz Guilherme Costa lyra Hos-pital Sao Rafael Salvador Bahia Brazil Centro de Pesquisas Goncalo Moniz Fundacao Oswaldo Cruz Salvador Bahia Brazil BGStats Consulting Graz Austria

AIM: To evaluate the safety and feasibility of bone marrow cell (BMC) transplantation in patients with chronic liver disease on the waiting list for liver transplantation. METHODS: Ten patients (eight males) with chronic liver disease were enrolled to receive infusion of autologous bone marrow-derived cells. Seven patients were classified as Child-Pugh B and three as Child-Pugh C. Baseline assessment included complete clinical and laboratory evaluation and abdominal MRI. Approximately 50 ml of bone marrow aspirate was prepared by centrifugation in a ficoll-hypaque gradient. At least of 100 millions of mononuclear-enriched BMCs were infused into the hepatic artery using the routine technique for arterial chemoembolization for liver tumors. Patients were followed up for adverse events up to 4 mo. RESULTS: The median age of the patients was 52 years (range 24-70 years). All patients were discharged 48 h after BMC infusion. Two patients complained ofmild pain at the bone marrow needle puncture site. No other complications or specific side effects related to the procedure were observed. Bilirubin levels were lower at 1 (2.19 ± 0.9) and 4 mo (2.10 ± 1.0) after cell transplantation that baseline levels (2.78 ± 1.2). Albumin levels 4 mo after BMC infusion (3.73 ± 0.5) were higher than baseline levels (3.47 ± 0.5). International normalized ratio (INR) decreased from 1.48 (SD = 0.23) to 1.43 (SD = 0.23) one month after cell transplantation. CONCLUSION: BMC infusion into hepatic artery of patients with advanced chronic liver disease is safe and feasible. In addition, a decrease in mean serum bilirubin and INR levels and an increase in albumin levels are observed. Our data warrant further studies in order to evaluate the effect of BMC transplantation in patients with advanced chronic liver disease.

关键词：可行性分析安全性能自体骨髓干细胞细胞移植慢性肝疾病

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Local bone metabolism balance regulation via double-adhesive hydrogel for fixing orthopedic implants

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Bioactive Materials 2022年第6期7卷 169-184页

作者： Wei Jiang Fushan Hou Yong Gu Qimanguli Saiding Pingping Bao Jincheng Tang Liang Wu Chunmao Chen Cailiang Shen Catarina Leite Pereira Marco Sarmento Bruno Sarmento Wenguo Cui Liang Chen Department of Orthopaedic Surgery Orthopedic InstituteThe First Affiliated Hospital of Soochow University708 Renmin RdSuzhouJiangsu215006PR China Department of Orthopedics The Second Hospital of Shanxi Medical UniversityNo.382 Wuyi RoadTaiyuanShanxi030001PR China Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai200025PR China Department of Electrocardiography The First Affiliated Hospital of Anhui Medical University218 Jixi RoadShushan DistrictHefeiAnhui230022PR China Department of Orthopedics The First Affiliated Hospital of Anhui Medical University218 Jixi RoadShushan DistrictHefeiAnhui230022PR China i3S-Instituto de Investigacao e Inovacao em Saude and INEB-dica Universidade do PortoRua Alfredo Allen 2084200-393PortoPortugal CESPU-Institute for Research and Advanced Training in Health Sciences and Technologies Rua Central de Gandra 13174585-116GandraPortugal Faculty of Medicine Universidade de LisboaAvenida Professor Egas Moniz1649-028LisboaPortugal

The effective osteointegration of orthopedic implants is a key factor for the success of orthopedic surgery.However,local metabolic imbalance around implants under osteoporosis condition could jeopardize the fixation effect.Inspired by the bone structure and the composition around implants under osteoporosis condition,alendronate(A)was grafted onto methacryloyl hyaluronic acid(H)by activating the carboxyl group of methacryloyl hyaluronic acid to be bonded to inorganic calcium phosphate on trabecular bone,which is then integrated with aminated bioactive glass(AB)modified by oxidized dextran(O)for further adhesion to organic collagen on the trabecular bone.The hybrid hydrogel could be solidified on cancellous bone in situ under UV irradiation and exhibits dual adhesion to organic collagen and inorganic apatite,promoting osteointegration of orthopedic implants,resulting in firm stabilization of the implants in cancellous bone areas.In vitro,the hydrogel was evidenced to promote osteogenic differentiation of embryonic mouse osteoblast precursor cells(MC3T3-E1)as well as inhibit the receptor activator of nuclear factor-κB ligand(RANKL)-induced osteoclast differentiation of macrophages,leading to the upregulation of osteogenic-related gene and protein expression.In a rat osteoporosis model,the bone-implant contact(BIC)of the hybrid hydrogel group increased by 2.77,which is directly linked to improved mechanical stability of the orthopedic implants.Overall,this organic-inorganic,dual-adhesive hydrogel could be a promising candidate for enhancing the stability of orthopedic implants under osteoporotic conditions.

关键词： Hydrogels Osteoporosis Osseointegration Dual-functional Peri-implant

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Changes in cellular proliferation and plasma products are associated with liver failure

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World Journal of Hepatology 2016年第32期8卷 1370-1383页

作者： Juliana Gil Melgaco Frederico Marianetti Soriani Pedro Henrique Ferreira Sucupira Leonardo Assaf Pinheiro Yasmine Rangel Vieira Jaqueline Mendes de Oliveira Lia Laura Lewis-Ximenez Cristina Carvalho Vianna Araújo Lúcio Filgueiras Pacheco-Moreira Gustavo Batista Menezes Oswaldo Goncalves Cruz Claudia Lamarca Vitral Marcelo Alves Pinto Departamento de Microbiologia e Parasitologia Universidade Federal Fluminense Instituto Oswaldo Cruz/Fiocruz Laboratório de Desenvolvimento Tecnológico em Virologia Departamento de Biologia Geral Instituto de Ciencias BiologicasUniversidade Federal de Minas Gerais Instituto Oswaldo Cruz/Fiocruz Ambulatório de Hepatites Virais hospital Federal de Bonsucesso Laboratório de Imunofarmacologia Departamento de Bioquímica e ImunologiaInstituto de Ciencias BiológicasUniversidade Federal de Minas Gerais fundacao Oswaldo Cruz Programa de Computacao Científica

AIM To study the differences in immune response and cytokine profile between acute liver failure and selflimited acute hepatitis.METHODS Forty-six patients with self-limited acute hepatitis(AH), sixteen patients with acute liver failure(ALF), and twenty-two healthy subjects were involved in this study. The inflammatory and anti-inflammatory products in plasma samples were quantified using commercial enzyme-linked immunoassays and quantitative real-time PCR. The cellular immune responses were measured by proliferation assay using flow cytometry. The groups were divided into viral- and non-viral-induced selflimited AH and ALF. Thus, we worked with five groups: Hepatitis A virus(HAV)-induced self-limited acute hepatitis(HAV-AH), HAV-induced ALF(HAV-ALF), nonviral-induced self-limited acute hepatitis(non-viral AH), non-viral-induced acute liver failure(non-viral ALF), and healthy subjects(HC). Comparisons among HAV and non-viral-induced AH and ALF were performed.RESULTS The levels of mitochondrial DNA(mt DNA) and the cytokines investigated [interleukin(IL)-6, IL-8, IL-10, interferon gamma, and tumor necrosis factor] were significantly increased in ALF patients, independently of etiology(P < 0.05). High plasma mt DNA and IL-10 were the best markers associated with ALF [mt DNA: OR = 320.5(95%CI: 14.42-7123.33), P < 0.0001; and IL-10: OR = 18.8(95%CI: 1.38-257.94), P = 0.028] and death [mt DNA: OR = 12.1(95%CI: 2.57-57.07), P = 0.002; and IL-10: OR = 8.01(95%CI: 1.26-50.97), P = 0.027]. In the cellular proliferation assay, NK^(bright), NKT and regulatory T cells(TReg) predominated in virusspecific stimulation in HAV-induced ALF patients with an anergic behavior in the cellular response to mitotic stimulation. Therefore, in non-viral-induced ALF, anergic behavior of activated T cells was not observed after mitotic stimulation, as expected and as described by the literature. CONCLUSION mt DNA and IL-10 may be predictors of ALF and death. TReg cells are involved in immunological disturbance in HAV-induced ALF.

关键词： Acute liver failure Cytokines Mitochondrial DNA Cellular immune response Hepatitis A virus

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Cardiac Myeloperoxidase Activity Is Elevated in Hypertensive Pregnant Rats

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2017年第6期37卷 904-909页

作者：朱明林赵金平崔凝 Victor H.Goncalves-Rizzi Jose S.Possomato-Vieira Regina A.Nascimento Carlos A.Dias-Junior Department of Thoracic and Cardiovascular Surgery Zhongnan HospitalWuhan University Department of Gastroenterology Renmin Hospital of Wuhan University Department of Pharmacology Biosciences Institute of BotucatuSao Paulo State University (UNESP)

Myeloperoxidase（MPO） is released from activated neutrophils. The inflammation in preeclampsia was found to be associated with endothelial dysfunction. We hypothesized that cardiac and circulating MPO levels are elevated in hypertensive pregnancy. Systolic and diastolic blood pressure and heart rate were measured on pregnancy days 14, 16, 18 and 20 in normal pregnant and hypertensive pregnant rats. Left and right ventricle weights, the number of viable fetuses, litter size, fetal and placenta weights were recorded on gestational day 21. Circulating and cardiac MPO activities, soluble fms-like tyrosine kinase-1（sFlt-1） and vascular endothelial growth factor（VEGF） and nitric oxide（NO） were detected. The results showed increases in cardiac（left, but not right ventricle） and circulating MPO activities, and concomitantly lower number of viable fetuses, litter size, and fetal and placenta weights, and decreases in NO in hypertensive pregnant rats. Also, the increases in circulating sFlt-1 and VEGF were found in hypertensive pregnant group. In conclusion, maternal and fetal detrimental changes along with increases in circulating sFlt-1 and VEGF in hypertensive pregnancy may be associated with increases in cardiac and circulating MPO activities, confirming the causative role of inflammatory response in preeclampsia.

关键词： hypertensive pregnancy preeclampsia rats myeloperoxidase

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Foveal thickness reduction after anti-vascular endothelial growth factor treatment in chronic diabetic macular edema

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International Journal of Ophthalmology(English edition) 2017年第5期10卷 760-764页

作者： Gabriel Willmann Antonio Brunno Nepomuceno Katharina Messias Leticia Barroso Ingrid U.Scott André Messias Rodrigo jorge Centre for Ophthalmology University of Tübingen Eye hospital Katharinen Hospital Department of Ophthalmology Ribeirao Preto School of Medicine University of Sao Paulo Departments of Ophthalmology and Public Health Sciences Penn State College of Medicine

AIM：To report foveal thickness reduction in eyes with resolution of macular edema and recovery of a foveal depression after one-year of anti-vascular endothelial growth factor（anti-VEGF） therapy for center-involving diabetic macular edema（DME）.METHODS：Foveal thickness was assessed with optical coherence tomography to determine the central subfield foveal thickness（CSFT） and macular volume in 42 eyes with DME（CSFT〉275 μm）. Evaluations also included measurement of best-corrected visual acuity（BCVA）, and were performed at baseline, and upon foveal depression recovery achieved after 12 monthly intravitreal injections of either 1.5 mg/0.06 mL bevacizumab（n=21） or 0.5 mg/0.05 mL ranibizumab（n=21）. Data was compared to 42 eyes of normally sighted, non-diabetic, healthy individuals with similar age, gender and race distributions.RESULTS：Mean baseline BCVA was 0.59±0.04 and 0.32± 0.03 log MAR（P〈0.001） after treatment and resolution of DME, with all, but 3 eyes, showing BCVA improvement. Mean CSFT before treatment was 422.0±20.0 μm, and after treatment, decreased to 241.6±4.6 μm（P〈0.001）, which is significantly thinner than CSFT found in control subjects（272.0±3.4 μm; P〈0.001）. Moreover, in 33/42 DM eyes（79%）, CSTF was thinner than the matched control eye. Macular volume showed comparable results, but with lower differences between groups（control：8.5±0.4 mm^3; DME：8.2±1.0 mm^3; P=0.0267）.CONCLUSION：DME eyes show significantly lower foveal thickness than matched controls after DME resolution achieved with one-year anti-VEGF therapy. Further investigation into the reasonsfor this presumable retinal atrophy using fluorescein angiography and functional parameters as well as establishing possible predictors is warranted. This finding should be considered during the treatment of DME.

关键词： diabetes macular edema bevacizumab ranibizumab optical coherence tomography central subfield foveal thickness diabetic retinopathy

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