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1帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析显示文摘背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PEMBRO-RT研究和Ⅰ/Ⅱ期MDACC研究中,患有转移性非小细胞肺癌(NSCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NSCLC患者的免疫治疗应答。方法PEMBRO-RT和MDACC研究纳入标准:患者年龄≥18岁,患有转移性NSCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PEMBRO-RT研究纳入曾接受过化疗患者,MDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PEMBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为<10年组和≥10年组)。MDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PEMBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在MDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFS)和总生存期(OS)。2个研究的意向治疗(ITT)人群均纳入分析。PEMBRO-RT研究(NCT02492568)和MDACC研究(NCT02444741)均在ClinicalTrials.gov上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFS中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;OS中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NSCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。陈大卫(翻译) 于金明(校对) Willemijn S M E Theelen Vivek Verma Brian P Hobbs Heike M U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia M de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoulidis Steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh 2021中华肿瘤防治杂志2021,28,24:49
2Total knee arthroplasty and fractures of the tibial plateau显示文摘Tibial plateau fractures are common injuries that occur in a bimodal age distribution. While there are various treatment options for displaced tibial plateau fractures, the standard of care is open reduction and internal fixation(ORIF). In physiologically young patients with higher demand and better bone quality, ORIF is the preferred method of treating these fractures. However, future total knee arthroplasty(TKA) is a consideration in these patients as post-traumatic osteoarthritis is a common long-term complication of tibial plateau fractures. In older, lower demand patients, ORIF is potentially less favorable for a variety of reasons, namely fixation failure and the need for delayed weight bearing. In some of these patients, TKA can be considered as primary mode of treatment. This paper will review the literature surrounding TKA as both primary treatment and as a salvage measure in patients with fractures of the tibial plateau. The outcomes, complications, techniques and surgical challenges are also discussed.Kenneth A Softness Ryan S Murray Brian G Evans 2017World Journal of Orthopedics2017,8,2:15
3Medical management of gastric cancer:A 2014 update显示文摘Gastric cancer represents a serious health problem on a global scale. It is the second leading cause of cancer-related death worldwide. Novel therapeutic targets are desperately needed because the meager improvement in the cure rate of about 10% realized by adjunctive treatments to surgery is unacceptable as > 50% patients with localized gastric cancer succumb to their disease. Either postoperative chemoradiotherapy(United States),pre-and post-operative chemotherapy(Europe),and adjuvant chemotherapy after a D2 resection(Asia) can all be regarded as standards of care in the localized gastric cancer management. In metastatic disease the addition of trastuzumab to chemotherapy is standard of care in Her2 positive disease. In the HER2 negative population,the treatments remain limited.In the first line setting,the standard of care is a combination of fluoropyrimidine and platinum containing chemotherapy,with or without epirubicin or docetaxel.The results of targeted therapy trials have by and large been disappointing,but none of these trials looked at an appropriately enriched population.Finally there is a meager overall survival benefit in treating patients with metastatic disease in the second line setting,with either irinotecan,docetaxel or ramucirumab however none of these drugs have been compared head to head in a well-powered randomized controlled trial.Elena Elimova Hironori Shiozaki Roopma Wadhwa Kazuki Sudo Qiongrong Chen Jeannelyn S Estrella Mariela A Blum Brian Badgwell Prajnan Das Shumei Song Jaffer A Ajani 2014World Journal of Gastroenterology2014,20,38:10
4Mycophenolate mofetil for drug-induced vanishing bile duct syndrome显示文摘Amoxicillin/clavulanate is associated with liver injury, mostly of a cholestatic pattern. While outcomes are usually benign, progression to cirrhosis and death has been reported. The role of immunosuppressive therapy for patients with a protracted course is unclear. We report the case of an elderly patient who developed prolonged cholestasis secondary to amoxicillin/clavulanate. Vanishing bile duct syndrome was confirmed by sequential liver biopsies. The patient responded to prednisone treatment, but could not be weaned off corticosteroids, even when azathioprine was added. Complete withdrawal of both prednisone and azathioprine was possible by using mycophenolate mofetil, an inosine monophosphate dehydrogenase inhibitor. Sustained remission has been maintained for more than 3 years with low-dose mycophenolate mofetil.S Simona Jakab A Brian West Dennis M Meighan Robert S Brown Jr William B Hale 2007World Journal of Gastroenterology2007,13,45:8
5Current protective strategies in liver surgery显示文摘During liver resection surgery for cancer or liver transplantation,the liver is subject to ischaemia (reduction in blood flow) followed by reperfusion (restoration of blood flow),which results in liver injury [ischemiareperfusion (IR) or IR injury]. Modulation of IR injury can be achieved in various ways. These include hypothermia,ischaemic preconditioning (IPC) (brief cycles of ischaemia followed by reperfusion of the organ before the prolonged period of ischaemia i.e. a conditioning response),ischaemic postconditioning (conditioning after the prolonged period of ischaemia but before the reperfusion),pharmacological agents to decrease IR injury,genetic modulation of IR injury,and machine perfusion (pulsatile perfusion). Hypothermia decreases the metabolic functions and the oxygen consumption of organs. Static cold storage in University of Wisconsin solution reduces IR injury and has prolonged organ storage and improved the function of transplanted grafts. There is currently no evidence for any clinical advantage in the use of alternate solutions for static cold storage. Although experimental data from animal models suggest that IPC,ischaemic postconditioning,various pharma-cological agents,gene therapy,and machine perfusion decrease IR injury,none of these interventions can be recommended in clinical practice. This is because of the lack of randomized controlled trials assessing the safety and efficacy of ischaemic postconditioning,gene therapy,and machine perfusion. Randomized controlled trials and systematic reviews of randomized controlled trials assessing the safety and efficacy of IPC and various pharmacological agents have demonstrated biochemical or histological improvements but this has not translated to clinical benefit. Further well designed randomized controlled trials are necessary to assess the various new protective strategies in liver resection.Kurinchi S Gurusamy Hector D Gonzalez Brian R Davidson 2010World Journal of Gastroenterology2010,16,48:7
6Endoscopic retrograde cholangiography for pediatric choledocholithiasis: Assessing the need for endoscopic intervention显示文摘AIM:To assess pediatric patients for choledocholithiasis.We applied current adult guidelines to identify predictivefactors in children.METHODS:A single-center retrospective analysis was performed at a tertiary children's hospital.We evaluated 44 consecutive pediatric patients who underwent endoscopic retrograde cholangiography(ERCP) for suspected choledocholithiasis.Patients were stratified into those with common bile duct stones(CBDS) at ERCP vs those that did not using the American Society of Gastrointestinal Endoscopy(ASGE) guidelines(Very Strong and Strong criteria) for suspected CBDS.RESULTS:CBDS were identified in 84% at the time of ERCP.Abdominal ultrasound identified CBDS in 36% of patients.Conjugated bilirubin ≥ 0.5 mg/d L was an independent risk factor for CBDS(P = 0.003).The Very Strong(59.5%) and Strong(48.6%) ASGE criteria identified the majority of patients(P = 0.0001).A modified score using conjugated bilirubin had a higher sensitivity(81.2% vs 59.5%) and more likely to identify a stone than the standard criteria,odds ratio of 25.7 compared to 8.8.Alanine aminotransferase and gamma-glutamyl transferase values identified significant differences in a subset of patients with odds ratio of 4.1 and 3.25,respectively.CONCLUSION:Current adult guidelines identified the majority of pediatric patients with CBDS,but specific pediatric guidelines may improve detection,thus decreasing risks and unnecessary procedures.Douglas S Fishman Bruno P Chumpitazi Isaac Raijman Cynthia Man-Wai Tsai E O’Brian Smith Mark V Mazziotti Mark A Gilger 2016World Journal of Gastrointestinal Endoscopy2016,8,11:6
7Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial显示文摘Stephen B Hanauer Brian G Feagan Gary R Lichtenstein Lloyd F Mayer S Schreiber Jean Frederic Colombel Daniel Rachmilewitz Douglas C Wolf Allan Olson Weihang Bao Paul Rutgeerts 2002The Lancet2002,,9317:6
8Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models显示文摘AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD).Nicha Wongjarupong Gabriela M Negron-Ocasio Roongruedee Chaiteerakij Benyam D Addissie Essa A Mohamed Kristin C Mara William S Harmsen J Paul Theobald Brian E Peters Joseph G Balsanek Melissa M Ward Nasra H Giama Sudhakar K Venkatesh Denise M Harnois Michael R Charlton Hiroyuki Yamada Alicia Algeciras-Schimnich Melissa R Snyder Terry M Therneau Lewis R Roberts 2018World Journal of Gastroenterology2018,24,12:5
9Advances in endovascular aneurysm management: coiling and adjunctive devices显示文摘Endovascular coil embolisation continues to evolve and remains a valid modality in managing ruptured and unruptured cerebral aneurysms.Technological advances in coil properties,adjunctive devices and interventional techniques continue to improve long-term aneurysm occlusion rates.This review elaborates on the latest advances in next-generation endovascular coils and adjunctive coiling techniques for treating cerebral aneurysms.Jessica K Campos Brian V Lien Alice S Wang Li-Mei Lin 2020Stroke & Vascular Neurology2020,5,1:5
10Primary total elbow arthroplasty in complex fractures of the distal humerus显示文摘AIM:To evaluate short-to medium term outcome of total elbow arthroplasty(TEA)in complex fractures of the distal humerus.METHODS:A consecutive series of 24 complex distal humerus fractures operated with TEA in the period2006-2012 was evaluated with the Mayo Elbow Performance score(MEPS),plain radiographs,complications and overall satisfaction.The indications for surgery were 1:AO type B3 or C3 or Sheffield type 3 fracture and age above 65 or 2:fracture and severe rheumatoid arthritis.Mean follow-up time was 21 mo.RESULTS:Twenty patients were followed up.Four patients,of which 3 had died,were lost to follow up.According to the AO classification there were 17 C3,1B2 and 2 A2 fractures.Mean follow-up was 21 months(range 4-54).Mean MEPS was 94(range 65-100).Mean flexion was 114 degrees(range 80-140).According to MEPS there were 15 excellent,4 good and 1 fair result.Patient satisfaction:8 excellent,10 good,2 fair and 1poor.There were two revisions due to infection treated successfully with revision and three months of antibiotics.In two patients the locking split had loosened.One was referred to re-insertion and one chose yearly con-trols.Two patients had persistent dysaesthesia of their5th finger,but were able to discriminate between sharp and blunt.CONCLUSION:Our study suggests that TEA in complex fractures of the distal humerus in elderly patients can result in acceptable short-to medium term outcome.Brian Weng S?rensen Stig Brorson Bo Sanderhoff Olsen 2014World Journal of Orthopedics2014,5,3:5
11Diagnosis and management of iatrogenic endoscopic perforations: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement显示文摘Gregorios Paspatis Jean-Marc Dumonceau Marc Barthet S?ren Meisner Alessandro Repici Brian Saunders Antonios Vezakis Jean Gonzalez Stine Turino Zacharias Tsiamoulos Paul Fockens Cesare Hassan 2014Endoscopy2014,,:4
12Laparoscopic vs open partial colectomy in elderly patients:Insights from the American College of Surgeons- National Surgical Quality Improvement Program database显示文摘AIM: To compare the outcomes between the laparoscopic and open approaches for partial colectomy in elderly patients aged 65 years and over using the American College of Surgeons- National Surgical Quality Improvement Program(ACS NSQIP) database. METHODS: The ACS NSQIP database for the years 2005-2011 was queried for all patients 65 years and above who underwent partial colectomy. 1:1 propensity score matching using the nearest- neighbor method was performed to ensure both groups had similar preoperative comorbidities. Outcomes including postoperative complications, length of stay and mortality were compared between the laparoscopic and open groups. χ2 and Fisher's exact test were used for discrete variables and Student's t-test for continuous variables. P < 0.05 was considered significant and odds ratios with 95%CI were reported when applicable. RESULTS: The total number of patients in the ACS NSQIP database of the years 2005-2011 was 1777035. We identified 27604 elderly patients who underwent partial colectomy with complete data sets. 12009(43%) of the cases were done laparoscopically and15595(57%) were done with open. After propensity score matching, there were 11008 patients each in the laparoscopic(LC) and open colectomy(OC) cohorts. The laparoscopic approach had lower post-operative complications(LC 15.2%, OC 23.8%, P < 0.001), shorter length of stay(LC 6.61 d, OC 9.62 d, P < 0.001) and lower mortality(LC 1.6%, OC 2.9%, P < 0.001). CONCLUSION: Even after propensity score matching, elderly patients in the ACS NSQIP database having a laparoscopic partial colectomy had better outcomes than those having open colectomies. In the absence of specific contraindications, elderly patients requiring a partial colectomy should be offered the laparoscopic approach.Umashankkar Kannan Vemuru Sunil K Reddy Amar N Mukerji Vellore S Parithivel Ajay K Shah Brian F Gilchrist Daniel T Farkas 2015World Journal of Gastroenterology2015,21,45:3
13Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse显示文摘Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC binding.Using primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA synthesis.Furthermore,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production.Similar effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th subset.These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell binding.We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation.These data point to a pivotal role for HA in DC–T cell interactions at the IS.Paul L Bollyky Stephen P Evanko Rebecca P Wu Susan Potter-Perigo S Alice Long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng Christina K Chan Kathy R Braun John A Gebe Gerald T Nepom Thomas N Wight 2010Cellular & Molecular Immunology2010,7,3:3
14Measles-mumps-rubella vaccination timing and autism among young african american boys: a reanalysis of CDC data显示文摘Background:A significant number of children diagnosed with autism spectrum disorder suffer a loss of previously-acquired skills,suggesting neurodegeneration or a type of progressive encephalopathy with an etiological basis occurring after birth.The purpose of this study is to investigate the effectof the age at which children got their first Measles-Mumps-Rubella(MMR)vaccine on autism incidence.This is a reanalysis of the data set,obtained from the U.S.C enters for Disease C ontrol and Protection(CDC),used for the Destefano et al.2004 publication on the timing of the first MMR vaccine and autism diagnoses.Methods:The author embarked on the present study to evaluate whether a relationship exists between child age when the first MMR vaccine was administered among cases diagnosed with autism and controls born between 1986 through 1993 among school children in metropolitan Atlanta.The Pearson's chisquared method was used to assess relative risks of receiving an autism diagnosis within the total cohort as well as among different race and gender categories.Results:When comparing cases and controls receiving their first MMR vaccine before and after 36 months of age,there was a statistically significant increase in autism cases specifically among African American males who received the first MMR prior to 36 months of age.Relative risks for males in general and African American males were 1.69(p=0.0138)and 3.36(p=0.0019),respectively.Additionally,African American males showed an odds ratio of 1.73(p=0.0200)for autism cases in children receiving their first MMR vaccine prior to 24 months of age versus 24 months of age and thereafter.Conclusions:The present study provides new epidemiologic evidence showing that African American males receiving the MMR vaccine prior to 24 months of age or 36 months of age are more likely to receive an autism diagnosis.Brian S Hooker 2014Translational Neurodegeneration2014,3,1:3
15Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity显示文摘Corbin Amie S Agarwal Anupriya Loriaux Marc Cortes Jorge Deininger Michael W Druker Brian J 2011Journal of Clinical Investigation2011,,1:3
16Role of MRI in the diagnosis and treatment of osteomyelitis in pediatric patients显示文摘Osteomyelitis is a significant cause of morbidity in children throughout the world. Multiple imaging modalities can be used to evaluate for suspected osteomyelitis, however magnetic resonance imaging(MRI) has distinct advantages over other modalities given its ability to detect early changes related to osteomyelitis, evaluate the true extent of disease, depict extraosseous spread of infection, and help guide surgical manage-ment. MRI has assumed a greater role in the evaluation of osteomyelitis with the increase in musculoskeletal infections caused by methicillin-resistant Staphylococ-cus aureus which have unique imaging features that are well-demonstrated with MRI. This review focuses primarily on the use of MRI in the evaluation of osteo-myelitis in children and will include a discussion of the clinically important and characteristic findings on MRI of acute bacterial osteomyelitis and related conditions.Brian S Pugmire Randheer Shailam Michael S Gee 2014World Journal of Radiology2014,6,8:3
17Positron emission tomography scanning in the evaluation of hepatocellular carcinoma显示文摘M.Akram Khan Connie S Combs Elizabeth M Brunt Val J Lowe Michael K Wolverson Harvey Solomon Brian T Collins Adrian M.Di Bisceglie 2000Journal of Hepatology2000,,5:2
18Advances in cellulose ester performance and application显示文摘Kevin J Edgar Charles M Buchanan John S Debenham Paul A Rundquist Brian D Seiler Michael C Shelton Debra Tindall 2001Progress in Polymer Science2001,,9:2
19Urban Modification of Thunderstorms: An Observational Storm Climatology and Model Case Study for the Indianapolis Urban Region*显示文摘Niyogi Dev Pyle Patrick Lei Ming Arya S Pal Kishtawal Chandra M Shepherd Marshall Chen Fei Wolfe Brian 2011Journal of Applied Meteorology and Climatology2011,,5:2
20The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: the first 4 years显示文摘Mark R Nelson Christine Katlama Julio S Montaner David A Cooper Brian Gazzard Bonaventura Clotet Adriano Lazzarin Knud Schewe Joep Lange Christina Wyatt Sue Curtis Shan-Shan Chen Stephen Smith Norbert Bischofberger James F Rooney 2007AIDS2007,,10:2
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