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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 |
| 2 | Mechanosignaling activation of TGFβmaintains intervertebral disc homeostasis显示文摘Intervertebral disc(IVD) degeneration is the leading cause of disability with no disease-modifying treatment.IVD degeneration is associated with instable mechanical loading in the spine, but little is known about how mechanical stress regulates nucleus notochordal(NC) cells to maintain IVD homeostasis. Here we report that mechanical stress can result in excessive integrin α_vβ_6-mediated activation of transforming growth factor beta(TGFβ), decreased NC cell vacuoles, and increased matrix proteoglycan production, and results in degenerative disc disease(DDD). Knockout of TGFβ type II receptor(TβRII) or integrin α_v in the NC cells inhibited functional activity of postnatal NC cells and also resulted in DDD under mechanical loading.Administration of RGD peptide, TGFβ, and α_vβ_6-neutralizing antibodies attenuated IVD degeneration. Thus,integrin-mediated activation of TGFβ plays a critical role in mechanical signaling transduction to regulate IVD cell function and homeostasis. Manipulation of this signaling pathway may be a potential therapeutic target to modify DDD. | Qin Bian Lei Ma Amit Jain Janet L Crane Khaled Kebaish Mei Wan Zhengdong Zhang X Edward Guo Paul D Sponseller Cheryle A Seguin Lee H Riley Yongjun Wang Xu Cao | 2017 | Bone Research2017，5，1： | 9 |
| 3 | Management of hypersplenism in non-cirrhotic portal hypertension:a surgical series显示文摘BACKGROUND:Hypersplenism is commonly seen in patients with non-cirrhotic portal hypertension(NCPH).While a splenectomy alone can effectively relieve the hypersplenism,it does not address the underlying portal hypertension.The present study was undertaken to analyze the impact of shunt and non-shunt operations on the resolution of hypersplenism in patients with NCPH.The relationship of symptomatic hypersplenism,severe hypersplenism and number of peripheral cell line defects to the severity of portal hypertension and outcome was also assessed.METHODS:A retrospective analysis of NCPH patients with hypersplenism managed surgically between 1999 and 2009 at our center was done.Of 252 patients with NCPH,64(45 with extrahepatic portal vein obstruction and 19 with non-cirrhotic portal fibrosis) had hypersplenism and constituted the study group.Statistical analysis was done using GraphPad InStat.Categorical and continuous variables were compared using the chi-square test,ANOVA,and Student's t test.The MannWhitney U test and Kruskal-Wallis test were used to compare non-parametric variables.RESULTS:The mean age of patients in the study group was 21.81±6.1 years.Hypersplenism was symptomatic in 70.3% with an incidence of spontaneous bleeding at 26.5%,recurrent anemia at 34.4%,and recurrent infection at 29.7%.The mean duration of surgery was 4.16±1.9 hours,intraoperative blood loss was 457±126(50-2000) mL,and postoperative hospital stay 5.5±1.9 days.Following surgery,normalization of hypersplenism occurred in all patients.On long-term followup,none of the patients developed hepatic encephalopathy and 4 had a variceal re-bleeding(2 after a splenectomy alone,1 each after an esophago-gastric devascularization and proximal splenorenal shunt).Patients with severe hypersplenism and those with defects in all three peripheral blood cell lineages were older,had a longer duration of symptoms,and a higher incidence of variceal bleeding and postoperative morbidity.In addition,patients with triple cell line defects had elevated portal pressure(P=0.001),portal biliopathy(P=0.02),portal gastropathy(P=0.005) and intraoperative blood loss(P=0.001).CONCLUSIONS:Hypersplenism is effectively relieved by both shunt and non-shunt operations.A proximal splenorenal shunt not only relieves hypersplenism but also effectively addresses the potential complications of underlying portal hypertension and can be safely performed with good long-term outcome.Patients with hypersplenism who have defects in all three blood cell lineages have significantly elevated portal pressures and are at increased risk of complications of variceal bleeding,portal biliopathy and gastropathy. | Rajesh Rajalingam Amit Javed Dharmanjay Sharma Puja Sakhuja Shivendra Singh Hirdaya H Nag Anil K Agarwal | 2012 | Hepatobiliary & Pancreatic Diseases International2012，11，2： | 7 |
| 4 | Retrograde-viewing device improves adenoma detection rate in colonoscopies for surveillance and diagnostic workup显示文摘AIM:To determine which patients might benefit most from retrograde viewing during colonoscopy through subset analysis of randomized,controlled trial data.METHODS:The Third Eye Retroscope Randomized Clinical Evaluation(TERRACE) was a randomized,controlled,multicenter trial designed to evaluate the efficacy of a retrograde-viewing auxiliary imaging device that is used during colonoscopy to provide a second video image which allows viewing of areas on the proximal aspect of haustral folds and flexures that are difficult to see with the colonoscope's forward view.We performed a post-hoc analysis of the TERRACE data to determine whether certain subsets of the patient population would gain more benefit than others from use of the device.Subjects were patients scheduled for colonoscopy for screening,surveillance or diagnostic workup,and each underwent same-day tandem examinations with standard colonoscopy(SC) and Third Eye colonoscopy(TEC),randomized to SC followed by TEC or vice versa.RESULTS:Indication for colonoscopy was screening in 176/345 subjects(51.0%),surveillance after previous polypectomy in 87(25.2%) and diagnostic workup in 82(23.8%).In 4 subjects no indication was specified.Previously reported overall results had shown a net additional adenoma detection rate(ADR) with TEC of 23.2% compared to SC.Relative risk(RR) of missing adenomas with SC vs TEC as the initial procedure was 1.92(P = 0.029).Post-hoc subset analysis shows additional ADRs for TEC compared to SC were 4.4% for screening,35.7% for surveillance,55.4% for diagnostic and 40.7% for surveillance and diagnostic combined.The RR of missing adenomas with SC vs TEC was 1.11(P = 0.815) for screening,3.15(P = 0.014) for surveillance,8.64(P = 0.039) for diagnostic and 3.34(P = 0.003) for surveillance and diagnostic combined.Although a multivariate Poisson regression suggested gender as a possibly significant factor,subset analysis showed that the difference between genders was not statistically significant.Age,bowel prep quality and withdrawal time did not significantly affect the RR of missing adenomas with SC vs TEC.Mean sizes of adenomas detected with TEC and SC were similar at 0.59 cm and 0.56 cm,respectively(P = NS).CONCLUSION:TEC allows detection of significantly more adenomas compared to SC in patients undergoing surveillance or diagnostic workup,but not in screening patients(ClinicalTrials.gov Identifier:NCT01044732). | Peter D Siersema Amit Rastogi Anke M Leufkens Paul A Akerman Kassem Azzouzi Richard I Rothstein Frank P Vleggaar Alessandro Repici Giacomo Rando Patrick I Okolo Olivier Dewit Ana Ignjatovic Elizabeth Odstrcil James East Pierre H Deprez Brian P Saunders Anthony N Kalloo Bradley Creel Vikas Singh Anne Marie Lennon Daniel C DeMarco | 2012 | World Journal of Gastroenterology2012，18，26： | 6 |
| 5 | Coagonist of glucagon-like peptide-1 and glucagon receptors ameliorates kidney injury in murine models of obesity and diabetes mellitus显示文摘AIM To investigate the role of glucagon-like peptide-1(GLP-1)/glucagon receptors coagonist on renal dysfunction associated with diabetes and obesity. METHODS Chronic high-fat diet fed C57 BL/6 J mice, streptozotocintreated high-fat diet fed C57 BL/6 J mice and diabeticC57 BLKS/J db/db mice were used as models of diabetes-induced renal dysfunction. The streptozotocintreated high-fat diet fed mice and db/db mice were treated with the GLP-1 and glucagon receptors coagonist(Aib2 C24 Chimera2, 150 μg/kg, sc) for twelve weeks, while in chronic high-fat diet fed mice, coagonist(Aib2 C24 Chimera2, 150 μg/kg, sc) treatment was continued for forty weeks. Kidney function, histology, fibrosis, inflammation, and plasma biochemistry were assessed at the end of the treatment. RESULTS Coagonist treatment decreased body weight, plasma lipids, insulin resistance, creatinine, blood urea nitrogen, urinary albumin excretion rate and renal lipids. In kidney, expression of lipogenic genes(SREBP-1 C, FAS, and SCD-1) was decreased, and expression of genes involved in β-oxidation(CPT-1 and PPAR-α) was increased due to coagonist treatment. In plasma, coagonist treatment increased adiponectin and FGF21 and decreased IL-6 and TNF-?. Coagonist treatment reduced expression of inflammatory(TNF-α, MCP-1, and MMP-9) and pro-fibrotic(TGF-β, COL1 A1, and α-SMA) genes and also improved histological derangement in renal tissue.CONCLUSION Coagonist of GLP-1 and glucagon receptors alleviated diabetes and obesity-induced renal dysfunction by reducing glucose intolerance, obesity, and hyperlipidemia. | Vishal J Patel Amit A Joharapurkar Samadhan G Kshirsagar Brijesh K Sutariya Maulik S Patel Hiren M Patel Dheerendra K Pandey Rajesh H Bahekar Mukul R Jain | 2018 | World Journal of Diabetes2018，9，6： | 5 |
| 6 | Use of omental patch and endoscopic closure technique as an alternative to surgery after endoscopic full thickness resection of gastric intestinal stromal tumors: A series of cases显示文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)originate from interstitial cells of Cajal.GISTs can occur anywhere along the gastrointestinal tract.Large lesions have traditionally been removed surgically.However,with recent innovations in advanced endoscopy,GISTs located within the stomach are now removed endoscopically.We describe a new innovative endoscopic technique to close large and hard to access defects after endoscopic full-thickness resection of gastric GISTs.CASE SUMMARY We present a series of three patients who were diagnosed with a gastric GIST.All patients underwent full-thickness endoscopic resection.In all cases,for closure of the surgical bed,conventional endoscopic techniques including hemoclips,endoloop and suturing were unsuccessful.We performed a new technique in which we pulled omental fat into the gastric lumen and completely closed the defect using endoscopic devices.All patients performed well post-procedure and computed tomography was carried out one day after the procedures which showed no extravasation of contrast.CONCLUSION The omental plug technique may be used as an alternative to surgery in selected cases of gastric perforation. | Amit H Sachdev Shahzad Iqbal Igor Braga Ribeiro Diogo Turiani Hourneaux de Moura | 2020 | World Journal of Clinical Cases2020，8，1： | 2 |
| 7 | Acute bleeding after argon plasma coagulation for weight regain after gastric bypass: A case report显示文摘Roux-en-Y gastric bypass(RYGB)is the most commonly performed surgical procedure used to treat obesity worldwide.Despite satisfactory results in terms of weight loss,over time many patients experience weight regain.There are many factors that contribute to weight regain after RYGB,including the diameter of the gastric-jejunal anastomosis(GJA).One of the most commonly performed endoscopic procedures for weight regain after RYGB is argon plasma coagulation(APC).We report a case of hematemesis after outlet revision with APC.We highlight several treatment modalities that can be used to treat this complication.CASE SUMMARY A 45-year-old female with a history of weight regain after RYGB was referred for possible endoscopic treatment for weight regain.On endoscopic evaluation,the diameter of the GJA was 22 mm.Due to the dilated GJA,treatment with APC was performed.Several months later she reported a return of poor satiety and an increased appetite.A repeat endoscopy was then performed.The GJA was approximately 15 mm and was incompetent.APC was performed.One day post procedure she had four episodes of hematemesis.An endoscopy was performed and a large ulcer with a visible arterial vessel was visualized at the GJA.Coagulation was attempted using a Coagrasper and after initial contact with the vessel,the vessel started oozing.Due to fibrosis and the depth of ulceration in the area,clips and repeat APC could not be used.Therefore,an attempt to inject epinephrine injection was made.However,persistent oozing was noted.As a result,hemostatic powder was applied to the region of the bleeding vessel.Subsequently,no more bleeding was observed.On follow-up,the patient remained hemodynamically stable and a second look endoscopy was not performed.The patient was discharged three days later.CONCLUSION APC revision of the GJA is known to be a relatively safe and effective strategy to manage weight regain post RYGB.Anastomotic site bleeding is an infrequent and potentially life-threatening complication associated with this therapy.Endoscopic management is the first line therapy used to achieve hemostasis in these cases. | Diogo Turiani Hourneaux de Moura Amit H Sachdev Po-Wen Lu Igor Braga Ribeiro Christopher C Thompson | 2019 | World Journal of Clinical Cases2019，7，15： | 1 |
| 8 | Human feeder layers for human embryonic stem cells显示文摘 | Amit M Margulets V Segev H | 2003 | Biol Reprod2003，68，6： | 1 |
| 9 | Human feeder layers for human embryonic stem cells 显示文摘 | AMIT M MARGULETS V SEGEV H | 2003 | Biol Reprod2003，68，： | 1 |
| 10 | Bloodstream infectionsamong carriers of carbapenem-resistant Klebsiella pneumoni-ae:etiology,incidence and predictors显示文摘 | Amit S Mishali H Kotlovsky T | 2015 | Clin Microbiol In-fect2015，21，1： | 1 |
| 11 | Strategic assets and organizational rent显示文摘 | Amit R Schoemaker P J H | 1993 | Strategic Management Journal1993，14，1： | 1 |
| 12 | Strategic Assets and Organizational Rent 显示文摘 | AMIT P J H SCHOEMAKER | 1993 | Strategic Management Journal1993，，14： | 1 |
| 13 | Strategic assets and or- ganizational rent 显示文摘 | AMIT R SHOEMAKER P J H | 1993 | Strategic Management Journal1993，14，1： | 1 |
| 14 | Human feeder layers for human embryonic stem cells显示文摘 | Margulets V Segev H | 2003 | Biol Reprod2003，68，6： | 1 |
| 15 | Effects of tobacco smoke on immunity, inflammation and autoimmunity 显示文摘 | Arnson Y Shoenfeld Y Amital H | 2010 | J Autoimmun2010，34，3： | 1 |
| 16 | Seismic behavior and modeling of high-strength composite concrete-filled steel tube beam-columns显示文摘 | Amit H V James M R Richard S | 2002 | Journal of Constructional Steel Research2002，58，7： | 1 |
| 17 | Strategic assets and organizational rent显示文摘 | Amit Raphael Paul J H Schoemaker | 1993 | Strategic Management Journal1993，，1： | 1 |
| 18 | Strategic Assets and Organizational Rent显示文摘 | Amit R Schoemaker P J H | 1993 | Strategic Management Journal1993，14，1： | 1 |
| 19 | Effects of tobacco smoke on immunity, inflammation and autoimmunity 显示文摘 | Arnson Y Shoenfeld Y Amital H | 2010 | J Autoimmun2010，34，3： | 1 |
| 20 | Influence of processing parameters on PZT thick films显示文摘 | Oliver H Amit B Susmita B | 2005 | Mater Sci Eng B2005，116，： | 1 |
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