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1帕博利珠单抗治疗伴脑转移NSCLC患者的一项非随机、开放Ⅱ期试验的长期随访结果和生物标志物分析显示文摘背景与目的我们开展了一项帕博利珠单抗用于伴未治疗脑转移的非小细胞肺癌(non-small cell lung cancer,NSCLC)或黑色素瘤患者的疗效和安全性的II期试验,旨在评估程序性死亡受体1(programmed cell death 1,PD-1)抑制剂在中枢神经系统(central nervous system,CNS)中的疗效。中期结果已发表,现报道对NSCLC队列的更新分析结果。方法这是一项开放性、单中心、II期试验。纳入标准:年龄≥18岁,诊断为晚期NSCLC并伴有≥1个5 mm-20 mm脑转移病灶,既往从未治疗或之前放疗后进展,无神经系统症状,不需要激素治疗且美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)<2分。患者每2周接受一次帕博利珠单抗(10 mg/kg)治疗。队列1为程序性死亡配体1(programmed cell death ligand 1,PD-L1)≥1%的患者,队列2为PD-L1<1%或未评估的患者。主要终点是脑转移患者缓解比例。所有经治患者均纳入疗效与安全性终点的分析。该研究已结束入组,并于Clinicaltrials.gov登记注册,注册号为NCT02085070。结果2014年3月31日-2018年5月21日,共42例患者接受治疗。中位随访时间为8.3个月(IQR:4.5个月-26.2个月)。队列1的37例患者中11例有脑转移缓解[29.7%(95%CI:15.9%-47.0%)]。队列2未观察到缓解。治疗相关的3级-4级不良事件(adverse events,AEs)包括2例肺炎、1例全身症状、1例结肠炎、1例肾上腺皮质功能不全、1例高血糖症和1例低钾血症。6例(14%)患者发生了治疗相关的严重不良事件,包括肺炎、急性肾损伤、低钾血症和肾上腺皮质功能不全。没有观察到治疗相关死亡病例。结论帕博利珠单抗治疗PD-L1≥1%的NSCLC伴脑转移患者有效,且对所有纳入的未经治疗的脑转移患者安全。需要进一步探索免疫治疗用于NSCLC合并CNS转移。Sarah B GOLDBERG Kurt A SCHALPER Scott N GETTINGER Amit MAHAJAN Roy S HERBST Anne C CHANG Rogerio LILENBAUM Frederick H WILSON Sacit Bulent OMAY James B YU Lucia JILAVEANU Thuy TRAN Kira PAVLIK Elin ROWEN Heather GERRSH Annette KOMLO Richa GUPTA Hailey WYATT Matthew RIBEIRO Yuval KLUGER Geyu ZHOU Wei WEI Veronica L CHANG Harriet M KLUGER 董晓荣(翻译/校对) 2021中国肺癌杂志2021,24,9:34
2Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome显示文摘Polycystic ovary syndrome(PCOS) is the most common endocrine disorder in reproductive-aged women. Women with PCOS frequently have metabolic complications including insulin resistance(IR), early diabetes, hypertension and dyslipidemia. Recent studies have demonstrated an association between PCOS and another metabolic complication: nonalcoholic fatty liver disease(NAFLD). NAFLD occurs as a result of abnormal lipid handling by the liver, which sensitizes the liver to injury and inflammation. It can progress to nonalcoholic steatohepatitis(NASH), which is characterized by hepatocyte injury and apoptosis. With time and further inflammation, NASH can progress to cirrhosis. Thus, given the young age at which NAFLD may occur in PCOS, these women may be at significant risk for progressive hepatic injury over the course of their lives. Many potential links between PCOS and NAFLD have been proposed, most notably IR and hyperandrogenemia. Further studies are needed to clarify the association between PCOS and NAFLD. In the interim, clinicians should be aware of this connection and consider screening for NAFLD in PCOS patients who have other metabolic risk factors. The optimal method of screening is unknown. However, measuring alanine aminotransferase and/or obtaining ultrasound on high-risk patients can be considered. First line treatment consists of lifestyle interventions and weight loss, with possible pharmacologic interventions in some cases.Carly E Kelley Ann J Brown Anna Mae Diehl Tracy L Setji 2014World Journal of Gastroenterology2014,20,39:11
3Molecular targets in the treatment of alcoholic hepatitis显示文摘Alcohol related costs to health and society are high. One of the most serious complications of alcohol misuse to the individual is the development of alcoholic hepatitis (AH), a clinical syndrome of jaundice and progressive inflammatory liver injury in patients with a history of recent heavy alcohol use. It has a poor outcome and few existing successful therapies. The use of glucocorticoids in patients with severe AH is still controversial and there remains a group of patients with glucocorticoid-resistant disease. However, as our understanding of the pathogenesis of the condition improves there are opportunities to develop new targeted therapies with specific actions to control liver inflammation without having a detrimental effect on the immune system as a whole. In this article we review the molecular mechanisms of AH concentrating on the activation of the innate and adaptive immune response. We consider existing treatments including glucocorticoids, anti-tumor necrosis factor therapy and pentoxifylline and their limitations. Using our knowledge of the disease pathogenesis we discuss possible novel therapeutic approaches. New targets include pro-inflammatory cytokines such as interleukin (IL)-17, chemokines and their receptors (for example IL-8, CXCL9 and CXCR3) and augmentation of anti-inflam- matory molecules such as IL-10 and IL-22. And there is also future potential to consider combination therapy to selectively modulate the immune response and gain control of disease.Ashwin D Dhanda Richard WL Lee Peter L Collins C Anne McCune 2012World Journal of Gastroenterology2012,18,39:9
4Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach: Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)显示文摘Inzucchi Silvio E Bergenstal Richard M Buse John B Diamant Michaela Ferrannini Ele Nauck Michael Peters Anne L Tsapas Apostolos Wender Richard Matthews David R 2012EN2012,,3:6
5Parenting preschoolers with autism: Socioeconomic influences on wellbeing and sense of competence显示文摘BACKGROUND Previous research suggests that parents raising a child with autism experience higher levels of psychological distress than parents of typically developing children and parents of children with other developmental disorders. Little is known, however, about the intersection between the effects of socioeconomic status(SES) on the wellbeing and sense of parental competency of parents of preschoolers with autism and how it relates to child symptom severity.AIM To examine the relationship between their child's symptom severity, SES, as measured by neighbourhood advantage and occupational status, on the psychological wellbeing and perceived parenting competence among parents of preschoolers with autism.METHODS Parents of 117 preschool-aged children with a diagnosis of autism spectrum disorder(ASD), 107 mothers and 54 fathers, completed questionnaires about their child's symptoms of ASD and functioning, their own perceptions of their wellbeing and parental competence on entry to an early intervention program in Sydney, Australia. Parents also provided demographic information pertaining to their occupation, level of education attained and address(postcode). All children were also assessed for their severity of symptoms using the Autism Diagnostic Observation Schedule. The Australian Socioeconomic Index of occupationalstatus as a measure of familial SES and the Index of Relative Socio-economic Advantage and Disadvantage as a measure of neighbourhood advantage were used to examine the impact of SES on parental sense of competence and wellbeing.RESULTS Compared to normative populations, both mothers and fathers in our sample reported significantly higher levels of parenting sense of efficacy but lower levels of interest in the parenting role. Mothers also displayed higher levels of satisfaction. Both mothers and fathers displayed higher levels of depression than normative populations with mothers also reporting greater levels of stress and anxiety. Child symptom severity was associated with maternal parenting competency with these relationships amplified among mothers with higher familial SES and who lived in areas of greater neighbourhood advantage.Increased adaptive functioning was associated with better maternal wellbeing,particularly among mothers who lived in areas of greater neighbourhood advantage. Contrastingly, paternal parenting competence was generally not influenced by child adaptive functioning or symptom severity, although for those in higher familial SES brackets, children's symptom severity and maladaptive symptoms were negatively related to paternal sense of parenting efficacy. There was a trend towards moderate relationships between lower familial SES and greater depression, stress and anxiety among fathers, but no relationship with their child's ASD symptom severity or functioning.CONCLUSION SES differentially impacts wellbeing and sense of parenting competence and its relationship to the impact of child symptoms for mothers and fathers of preschoolers with autism.Nisha E Mathew Karen L O Burton Anne Schierbeek Rudi ?rn?ec Amelia Walter Valsamma Eapen 2019World Journal of Psychiatry2019,9,2:6
6Colonoscopy surveillance for high risk polyps does not always prevent colorectal cancer显示文摘AIM To determine the frequency and risk factors for colorectal cancer(CRC) development among individuals with resected advanced adenoma(AA)/traditional serrated adenoma(TSA)/advanced sessile serrated adenoma(ASSA). METHODS Data was collected from medical records of 14663 subjects found to have AA, TSA, or ASSA at screening or surveillance colonoscopy. Patients with inflammatory bowel disease or known genetic predisposition for CRC were excluded from the study. Factors associated with CRC developing after endoscopic management of high risk polyps were calculated in 4610 such patients who had at least one surveillance colonoscopy within 10 years following the original polypectomy of the incident advanced polyp. RESULTS84/4610(1.8%) patients developed CRC at the polypectomy site within a median of 4.2 years(mean 4.89 years), and 1.2%(54/4610) developed CRC in a region distinct from the AA/TSA/ASSA resection site within a median of 5.1 years(mean 6.67 years). Approximately, 30%(25/84) of patients who developed CRC at the AA/TSA/ASSA site and 27.8%(15/54) of patients who developed CRC at another site had colonoscopy at recommended surveillance intervals. Increasing age; polyp size; male sex; right-sided location; high degree of dysplasia; higher number of polyps resected; and piecemeal removal were associated with an increased risk for CRC developmentat the same site as the index polyp. Increasing age; right-sided location; higher number of polyps resected and sessile endoscopic appearance of the index AA/TSA/ASSA were significantly associated with an increased risk for CRC development at a different site. CONCLUSION Recognition that CRC may develop following AA/TSA/ASSA removal is one step toward improving our practice efficiency and preventing a portion of CRC related morbidity and mortality.Mohamad A Mouchli Lidia Ouk Marianne R Scheitel Alisha P Chaudhry Donna Felmlee-Devine Diane E Grill Shahrooz Rashtak Panwen Wang Junwen Wang Rajeev Chaudhry Thomas C Smyrk Ann L Oberg Brooke R Druliner Lisa A Boardman 2018World Journal of Gastroenterology2018,24,8:5
7Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study显示文摘Laurent Beaugerie Nicole Brousse Anne Marie Bouvier Jean Frédéric Colombel Marc Lémann Jacques Cosnes Xavier Hébuterne Antoine Cortot Yoram Bouhnik Jean Pierre Gendre Tabassome Simon Marc Maynadié Olivier Hermine Jean Faivre Fabrice Carrat 2009The Lancet . 2009 (9701)2009,,:4
8Is liver biopsy necessary in the management of alcoholic hepatitis?显示文摘Acute alcoholic hepatitis(AAH)is characterised by deep jaundice in patients with a history of heavy alcohol use,which can progress to liver failure.A clinical diagnosis of AAH can be challenging to make in patients without a clear alcohol history or in the presence of risk factors for other causes of acute liver failure.Other causes of acute on chronic liver failure such as sepsis or variceal haemorrhage should be considered.Liver biopsy remains the only reliable method to make an accurate diagnosis.However,there is controversy surrounding the use of liver biopsy in patients with AAH because of the risks of performing a percutaneous biopsy and limitations in access to transjugular biopsy.We review the existing literature and find there are few studies directly comparing clinical and histological diagnosis of AAH.In the small number of studies that have been conducted the correlation between a clinical and histological diagnosis of AAH is poor.Due to this lack of agreement together with difficulties in accessing transjugular liver biopsy outside tertiary referral centres and research institutions,we cannot advocate universal biopsy for AAH but there remains a definite role for liver biopsy where there is clinical diagnostic doubt or dual pathology.Italso adds value in a clinical trial context to ensure a homogeneous trial population and to further our understanding of the disease pathology.Further prospective studies are required to determine whether non-invasive markers can be used to accurately diagnose AAH.Ashwin D Dhanda Peter L Collins C Anne McCune 2013World Journal of Gastroenterology2013,19,44:4
9Analysis of a Successful Immune Response against Hepatitis C Virus显示文摘Stewart Cooper Ann L Erickson Erin J Adams Joe Kansopon Amy J Weiner David Y Chien Michael Houghton Peter Parham Christopher M Walker 1999Immunity1999,,4:3
10Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial显示文摘David N Krag Stewart J Anderson Thomas B Julian Ann M Brown Seth P Harlow Joseph P Costantino Takamaru Ashikaga Donald L Weaver Eleftherios P Mamounas Lynne M Jalovec Thomas G Frazier R Dirk Noyes André Robidoux Hugh MC Scarth Norman Wolmark 2010Lancet Oncology2010,,10:3
11Wilson’s disease显示文摘Aftab Ala Ann P Walker Keyoumars Ashkan James S Dooley Michael L Schilsky 2007The Lancet . 2007 (9559)2007,,9559:3
12Increased Risk for Nonmelanoma Skin Cancers in Patients Who Receive Thiopurines for Inflammatory Bowel Disease显示文摘Laurent Peyrin–Biroulet Kiarash Khosrotehrani Fabrice Carrat Anne–Marie Bouvier Jean–Baptiste Chevaux Tabassome Simon Frank Carbonnel Jean–Frédéric Colombel Jean–Louis Dupas Philippe Godeberge Jean–Pierre Hugot Marc Lémann Stéphane Nahon Jean–Marc Sabaté 2011Gastroenterology2011,,5:3
13Relationship between the severity of hepatitis C virus-related liver disease and the presence of Helicobacter species in the liver: A prospective study显示文摘AIM: To determine the presence of Helicobacter species DNA in the liver of chronic hepatitis C (CHC) patients with and without cirrhosis as compared to controls, and to identify the bacterial species involved. METHODS: Seventy-nine consecutive patients (HBV and HIV negative) with a liver sample obtained after liver biopsy or hepatic resection were studied: 41 with CHC without cirrhosis, 12 with CHC and cirrhosis, and 26 controls (HCV negative). Polymerase chain reactions (PCRs) targeting Helicobacter 16S rDNA and species- specific were performed on DNA extracted from the liver. A gastric infection with H pylori was determined by serology and confirmed by 13C-urea breath test. RESULTS: Overall, Helicobacter 16S rDNA was found in 16 patients (20.2%). Although positive cases tended to be higher in CHC patients with cirrhosis (41.6%) than in those without cirrhosis (17.0%) or in controls (15.4%), the difference was not statistically significant (P =0.08). H pylori-like DNA was identified in 12 cases and H. pullorum DNA in 2, while 2 cases remained unidenti- fied. Gastric infection with H pylori was found in only 2 of these patients. CONCLUSION: Our results do not confirm the associ- ation of Helicobacter species DNA in the liver of CHC patients with advanced liver disease. The lack of correlation between positive H pylori serology and the presence of H pylori-like DNA in the liver may indicate the presence of a variant of this species.Laurent Castéra Anne Pedeboscq Marcia Rocha Brigitte Le Bail Corinne Asencio Victor de Lédinghen Pierre-Henri Bernard Christophe Laurent Marie-Edith Lafon Maylis Capdepont Patrice Couzigou Paulette Bioulac-Sage Charles Balabaud FrancisMégraud Armelle Ménard 2006World Journal of Gastroenterology2006,12,45:3
14用传统方法与计算机辅助精液分析软件CRISMAS分析166名丹麦青年男性精液样本的结果比较显示文摘本研究以166名丹麦青年男性精液为样本,通过评估精于浓度和活力来比较传统精液分析与计算机辅助精液分析方法(CASA)(哥本哈根Rigshospitalet图像屋精子运动分析系统,CRISMAS软件4.6版本)。CRISMAS软件测定精子的浓度把精子活力分为三类。传统分析方法将精子活力分为四种状态。为了便于二者的比较,本文将传统的四种状态根据精子速度等级重新分为三个状态:rapidly progressive(A),slowly progressive(B)和non-progressive(C+D)。两种方法所研究的参数之间都有显著差异(P〈0.001)。与传统方法相比,CRISMAS高估了精子浓度以及快速运动精子的比例,因而低估了慢速运动和非运动精子。为分析研究结果是否会随精液分析时间而起伏变动,将精液分析结果按分析同期分为四个层次。结果表明CRISMAS对活力的分析结果比传统分析方法稳定,但两种方法都未表现出任何趋势。显然,无法比较CRISMAS CASA和传统分析方法在精子浓度和精子活力方面的分析结果。在临床上使用该软件时以及用其研究这些精子特性时需要说明这一点。Anne Vested Cecilia H Ramlau-Hansen Jens P Bonde Ane M Thulstrup Susanne L Kristensen Gunnar Toft 2011Asian Journal of Andrology2011,13,3:3
15Noninvasive In Vivo Liver Fibrosis Evaluation Using Supersonic Shear Imaging: A Clinical Study on 113 Hepatitis C Virus Patients显示文摘éric Bavu Jean-Luc Gennisson Mathieu Couade Jeremy Bercoff Vincent Mallet Mathias Fink Anne Badel Ana?s Vallet-Pichard Bertrand Nalpas Micka?l Tanter Stanislas Pol 2011Ultrasound in Medicine & Biology2011,,9:3
16Pediatric Nd:YAG laser capsulotomy in the operating room: review of 87 cases显示文摘AIM: To report a large series of children having Nd:YAG laser capsulotomy in the operating room using the lateral decubitus position. METHODS: Medical records of children who underwent Nd:YAG laser capsulotomy in the operating room at Ann & Robert H. Lurie Children's Hospital of Chicago between September 2008 and April 2017 were reviewed. Induction of general anesthesia and intubation was performed in the supine position after which the patient was placed in lateral decubitus position. The Nd:YAG laser capsulotomy was performed using a standard protocol. At the completion of the procedure, the patient was turned back into the supine position and extubated. RESULTS: This study included 87 eyes of 60 patients. Patient's age ranged from 1 to 18 y(mean 6.4±4.1 y). In most cases(84/87, 97%), the procedure was performed under general anesthesia. In all cases, good focus on the membrane was achieved, and the procedure was performed successfully. There were no intraoperative ocular or anesthesia-related complications. CONCLUSION: When performing Nd:YAG laser capsulotomy in the operating room, the lateral decubitus position allowsan easy and safe approach without the risk of potentially devastating complications that have been associated with the previously described sitting and prone positions.Michael Kinori Narasimhan Jagannathan Anne M Langguth Marjorie A Sasso Marilyn B Mets Bahram Rahmani Hawke Yoon Rebecca Mets-Halgrimson Sudhi P Kurup Janice L Zeid 2019International Journal of Ophthalmology(English edition)2019,12,5:2
17Natural History of Intraductal Papillary Mucinous Tumors of the Pancreas: Actuarial Risk of Malignancy显示文摘Philippe Lévy Vincent Jouannaud Dermot O’Toole Anne Couvelard Marie Pierre Vullierme Laurent Palazzo Alain Aubert Philippe Ponsot Alain Sauvanet Frédérique Maire Olivia Hentic Pascal Hammel Philippe Ruszniewski 2006Clinical Gastroenterology and Hepatology2006,,4:2
18B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: Application to autoimmune disease therapy显示文摘Vijay K Kuchroo Mercy Prabhu Das Julia A Brown Ann M Ranger Scott S Zamvil Raymond A Sobel Howard L Weiner Nasrin Nabavi Laurie H Glimcher 1995Cell1995,,5:2
19Hierarchical porous induced competent removal of low concentration azo dye molecules by generating a leachy crystalline structure H-MIL-53(Fe)显示文摘The development in technology of synthetic azo dyes,has led to excessive water resources pollution.Eve n at lower concentration they can impart the quality of water and human life.Herein,we have developed a novel synthesis strategy via introducing salicylic acid(SA)for the synthesis of a leachy crystalline material H-MIL-53(Fe)with hierarchical pores(HP)and exposed coordination unsaturated sites(CUS),which had higher surface area and larger pore volume than the as synthesized MIL-53(Fe).Due to these characteristics,H-MIL-53(Fe)was competent removal of orange G(OG,one of the frequently used azo dyes)with equilibrium in 300 min and the maximum adsorption capacity of 163.9 mg/g.The adsorption mechanism of OG onto H-MIL-53(Fe)was mostly based on electrostatic attraction between CUS of HMIL-53(Fe)along with HP as active species to OG diffusion and bind.By comparing H-MIL-53(Fe)with other adsorbents for OG adsorption,it is undoubtedly that H-MIL-53(Fe)can be used as a promising adsorbent for OG removal from aqueous solutions.Tao Feng Jean Pierre Bavumiragira Mumbi Anne Wambui Daniel Manaye Kabtamu Krisztina László Ying Wang Fengting Li 2020Chinese Chemical Letters2020,31,10:2
20Folate and vitamin B12 in idiopathic male infertility显示文摘尽管 methylenetetrahydrofolate reductase,叶酸的酶基因,与自发的男不孕被联系了,很少研究检验了另外的叶酸相关的代谢物和基因。我们调查了自发的男不孕是否与变体被联系在叶酸,维生素 B 12(B12 ) 和全部的 homocysteine (tHcy ) 联系了基因并且在血测量了这些代谢物。我们进行了与自发的不孕和在生育力中心和胎儿的照顾中心招募的 184 肥沃的男控制包括了 153 个人的盒子控制研究,大学医院, Malmö并且 Lund,瑞典。浆液叶酸的、红房间叶酸(RCF ) ,浆液 B12,血浆 tHcy 和精液质量被测量。题目是为在与 folate/B12/homocysteine 新陈代谢有关的 12 基因的 20 普通变体的 genotyped。代谢物集中和遗传型分布为 covariates 与调整用线性、逻辑的回归在案例和控制之间被作比较。phosphatidylethanolamine N-methyltransferase (PEMT ) M175V 和 TCblR rs173665 多型性显著地与不孕被联系(P=0.01 和 P=0.009,分别地) ,然而并非与精液质量。在补充的非用户之中,有的不肥沃的人降低浆液叶酸的集中比肥沃的人(12.89 对 14.73   nmol l −1 ;P=0.02 ) ,但是在 RCF, B12 或 tHcy 没有重要差别。叶酸, B12 和 tHcy 集中没与任何精液参数被相关。这研究几乎不提供小支持为低叶酸或在自发的男不孕的致病的 B12 地位。尽管另外的数据被需要证实这些起始的调查结果,我们的结果建议那 PEMT 和 TCblR,基因在胆碱和 B12 新陈代谢包含了,在自发的男不孕应得进一步的调查。Laurel E Murphy James L Mills Anne M Molloy Cong Qian Tonia C Carter Helena Strevens Dag Wide-Swensson Aleksander Giwercman Richard J Levine 2011Asian Journal of Andrology2011,13,6:2
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