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1Diagnosis and treatment of diabetes mellitus in chronic pancreatitis显示文摘Diabetes secondary to pancreatic diseases is commonly referred to as pancreatogenic diabetes or type 3c diabetes mellitus.It is a clinically relevant condition with a prevalence of 5%-10%among all diabetic subjects in Western populations.In nearly 80%of all type 3c diabetes mellitus cases,chronic pancreatitis seems to be the underlying disease.The prevalence and clinical importance of diabetes secondary to chronic pancreatitis has certainly been underestimated and underappreciated so far.In contrast to the management of type 1 or type2 diabetes mellitus,the endocrinopathy in type 3c is very complex.The course of the disease is complicated by additional present comorbidities such as maldigestion and concomitant qualitative malnutrition.General awareness that patients with known and/or clinically overt chronic pancreatitis will develop type 3c diabetes mellitus(up to 90%of all cases)is rather good.However,in a patient first presenting with diabetes mellitus,chronic pancreatitis as a potential causative condition is seldom considered.Thus many patients are misdiagnosed.The failure to correctly diagnose type 3 diabetes mellitus leads to a failure to implement an appropriate medical therapy.In patients with type 3c diabetes mellitus treating exocrine pancreatic insufficiency,preventing or treating a lack of fat-soluble vitamins(especially vitamin D)and restoring impaired fat hydrolysis and incretin secretion are key-features of medical therapy.Nils Ewald Philip D Hardt 2013World Journal of Gastroenterology2013,19,42:23
2Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25显示文摘堵住抗体 ipilimumab 的细胞毒素的 T 淋巴细胞 antigen-4 (CTLA-4 ) 在很少的病人导致变形黑瘤的调停免疫者的长期的控制。尽管 ipilimumab 无疑经由 immunostimulation 施加它的治疗学的效果,这样远的临床上有用的、 immunologically 相关的 biomarkers 预言治疗效率是逃犯的。这里,我们显示出 IL-2 的那中立化或堵住 α并且 βIL-2 受体的子单元(CD25 和 CD122,分别地) 否则在现出症状之前的潜的老鼠模型由 CTLA-4 封锁导致了,废除了 antitumor 效果和 intratumoral T 受动器对规章的房间(Tregs ) 的比率的伴随的改进,它是。CTLA-4 封锁导致了在失去了 FoxP3 表示并且在 regressing 肿瘤积累了的 IL-2-producing 受动器房间与伴随物上升表示 Lag3, ICOS, IL-10 和 Egr2 的一个镇压 CD4 + T 房间子集的减小。当 recombinant IL-2 改进了 CTLA-4 封锁的治疗学的功效时,圈套 IL-2 受体 α(IL-2Rα, sCD25 ) 禁止了 CTLA-4 的 anticancer 效果封锁。在收到 ipilimumab 的 262 个变形黑瘤病人, sCD25 的基线浆液集中代表了全面幸存的独立指示物,与预言到治疗的抵抗的高水平。总的来说,这些结果解开为在 CTLA-4 的 anticancer 活动的 IL-2 和 IL-2 受体的一个角色封锁。重要地,我们的学习提供第一 immunologically 相关的 biomarker,也就是提高的浆液 sCD25,那与黑瘤在病人预言抵抗到 CTLA-4 封锁。Dalil Hannani Marie Vetizou David Enot Sylvie Rusakiewicz Nathalie Chaput David Klatzmann Melanie Desbois Nicolas Jacquelot Nadege Vimond Salem Chouaib Christine Mateus James P Allison Antoni Ribas Jedd D Wolchok Jianda Yuan Philip Wong Michael Postow Andrzej Mackiewicz Jacek Mackiewicz Dirk Schadendorff Dirk Jaeger Alan J Korman Keith Bahjat Michele Maio Luana Calabro Michele WL Teng Mark J Smyth Alexander Eggennont Caroline Robert Guido Kroemer Laurence Zitvogel 2015Cell Research2015,25,2:14
3Predictors of suboptimal bowel preparation in asymptomatic patients undergoing average-risk screening colonoscopy显示文摘AIM To identify risk factors for a suboptimal preparation among a population undergoing screening or surveillance colonoscopy.METHODS Retrospective review of the University of Michigan and Veteran's Administration(VA) Hospital records from 2009 to identify patients age 50 and older who underwent screening or surveillance procedure and had resection of polyps less than 1 cm in size and no more than 2 polyps. Patients with inflammatory bowel disease or a family history of colorectal cancer were excluded. Suboptimal procedures were defined as procedure preparations categorized as fair, poor or inadequate by the endoscopist. Multivariable logistic regression was used to identify predictors of suboptimal preparation.RESULTS Of 4427 colonoscopies reviewed, 2401 met our inclusion criteria and were analyzed. Of our population, 16% had a suboptimal preparation. African Americans were 70% more likely to have a suboptimal preparation(95%CI: 1.2-2.4). Univariable analysis revealed that narcotic and tricyclic antidepressants(TCA) use, diabetes, prep type, site(VA vs non-VA), and presence of a gastroenterology(GI) fellow were associated with suboptimal prep quality. In a multivariable model controlling for gender, age, ethnicity, procedure site and presence of a GI fellow, diabetes [odds ratio(OR) = 2.3; 95%CI: 1.6-3.2], TCA use(OR = 2.5; 95%CI: 1.3-4.9), narcotic use(OR = 1.7; 95%CI: 1.2-2.5) and Miralax-Gatorade prep vs 4L polyethylene glycol 3350(OR = 0.6; 95%CI: 0.4-0.9) were associated with a suboptimal prep quality. CONCLUSION Diabetes, narcotics use and TCA use were identified as predictors of poor preparation in screening colonoscopies while Miralax-Gatorade preps were associated with better bowel preparation.Shail M Govani Eric E Elliott Stacy B Menees Stephanie L Judd Sameer D Saini Constantinos P Anastassiades Annette L Urganus Suzanna J Boyce Philip S Schoenfeld 2016World Journal of Gastrointestinal Endoscopy2016,8,17:7
4Risk stratification for ST segment elevation myocardial infarction in the era of primary percutaneous coronary intervention显示文摘Acute coronary syndromes presenting with ST elevation are usually treated with emergency reperfusion/revascularisation therapy. In contrast current evidence and national guidelines recommend risk stratification for non ST segment elevation myocardial infarction(NSTEMI) with the decision on revascularisation dependent on perceived clinical risk. Risk stratification for STEMI has no recommendation. Statistical risk scoring techniques in NSTEMI have been demonstrated to improve outcomes however their uptake has been poor perhaps due to questions over their discrimination and concern for application to individuals who may not have been adequately represented in clinical trials. STEMI is perceived to carry sufficient risk to warrant emergency coronary intervention [by primary percutaneous coronary intervention(PPCI)] even if this results in a delay to reperfusion with immediate thrombolysis. Immediate thrombolysis may be as effective in patients presenting early, or at low risk, but physicians are poor at assessing clinical and procedural risks and currently are not required to consider this. Inadequate data on risk stratification in STEMI inhibits the option of immediate fibrinolysis, which may be cost-effective. Currently the mode of reperfusion for STEMI defaults to emergency angiography and percutaneous coronary intervention ignoring alternative strategies. This review article examines the current risk scores and evidence base for risk stratification for STEMI patients. The requirements for an ideal STEMI risk score are discussed.Richard A Brogan Christopher J Malkin Philip D Batin Alexander D Simms James M McLenachan Christopher P Gale 2014World Journal of Cardiology2014,6,8:6
5The Changing Cold Regions Network:Observation,diagnosis and prediction of environmental change in the Saskatchewan and Mackenzie River Basins,Canada显示文摘Climate change is causing rapid and severe changes to many Earth systems and processes,with widespread cryospheric,ecological,and hydrological impacts globally,and especially in high northern latitudes.This is of major societal concern and there is an urgent need for improved understanding and predictive tools for environmental management.The Changing Cold Regions Network(CCRN)is a Canadian research consortium with a focus to integrate existing and new experimental data with modelling and remote sensing products to understand,diagnose,and predict changing land,water,and climate,and their interactions and feedbacks over the geographic domain of the Mackenzie and Saskatchewan River Basins in Canada.The network operates a set of 14 unique and focused Water,Ecosystem,Cryosphere and Climate(WECC)observatories within this region,which provide opportunities to observe and understand processes and their interaction,as well as develop and test numerical simulation models,and provide validation data for remote sensing products.This paper describes this network and its observational,experimental,and modelling programme.An overview of many of the recent Earth system changes observed across the study region is provided,and some local insights from WECC observatories that may partly explain regional patterns and trends are described.Several of the model products being developed are discussed,and linkages with the local to international user community are reviewed—In particular,the use of WECC data towards model and remote sensing product calibration and validation is highlighted.Some future activities and prospects for the network are also presented at the end of the paper.Chris M DEBEER Howard S WHEATER William L QUINTON Sean K CAREY Ronald E STEWART Murray D MACKAY Philip MARSH 2015Science China Earth Sciences2015,58,1:5
6Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial显示文摘Geert D’Haens Filip Baert Gert van Assche Philip Caenepeel Philippe Vergauwe Hans Tuynman Martine De Vos Sander van Deventer Larry Stitt Allan Donner Severine Vermeire Frank J Van De Mierop Jean-Charles R Coche Janneke van der Woude Thomas Ochsenkühn Ad A 2008The Lancet2008,,9613:5
7Brucella species lacking the major outer membrane protein Omp25 are attenuated in mice and protect against Brucella melitensis and Brucella ovis显示文摘Matthew D Edmonds Axel Cloeckaert Philip H Elzer 2002Veterinary Microbiology2002,,3:3
8Preoperative immunonutrition in patients undergoing liver resection:A prospective randomized trial显示文摘BACKGROUND Preoperative supplementation with immunonutrients, including arginine and n-3 fatty acids, has been shown in a number of systematic reviews to reduce infectious complications in patients who have undergone gastrointestinal surgery. Limited information, however, is available on the benefits of nutritional supplementation enriched with arginine and n-3 fatty acids in patients undergoing liver resection.AIM To evaluate the effects of preoperative nutritional supplementation enriched with arginine and n-3 fatty acids on inflammatory and immunologic markers and clinical outcome in patients undergoing liver resection.METHODS Thirty-four patients undergoing liver resection were randomized to either five days of preoperative Impact? [1020 kcal/d, immunonutrition(IMN) group], or standard care [no supplementation, standard care(STD) group]. Nutritional status was measured at study entry by subjective global assessment(SGA).Functional assessments(grip strength, fatigue and performance status) were carried out at study entry, on the day prior to surgery, and on postoperative day(POD) 7 and 30. Inflammatory and immune markers were measured at study entry, on the day prior to surgery, and POD 1, 3, 5, 7, 10 and 30. Postoperative complications were recorded prospectively until POD30.RESULTS A total of 32 patients(17 IMN and 15 STD) were analysed. All except four patients were SGA class A. The plasma ratio of(eicosapentaenoic acid plus docosahexaenoic acid) to arachidonic acid was higher in IMN patients on the day prior to surgery and POD 1, 3, 5 and 7(P < 0.05). Plasma interleukin(IL)-6 concentrations were elevated in the IMN group(P = 0.017 for POD7). No treatment effect was detected for functional measures, immune response(white cell count and total lymphocytes) or markers of inflammation(C-reactive protein,tumour necrosis factor-α, IL-8, IL-10). There were 10 patients with infectious complications in the IMN group and 4 in the STD group(P = 0.087). Median hospital stay was 9(range 4–49) d in the IMN group and 8(3-34) d in the STD group(P = 0.476).CONCLUSION In well-nourished patients undergoing elective liver resection, this study failed to show any benefit of preoperative immunonutrition.Kylie Russell Han-Guang Zhang Lyn K GillANDers Adam SJR Bartlett Helena L Fisk Philip C Calder Peter J Swan Lindsay D Plank 2019World Journal of Hepatology2019,11,3:3
9Structure of the Ca2+-dependent PP2A heterotrimer and insights into Cdc6 dephosphorylation显示文摘B″蛋白质磷酸酶 2A (PP2A ) 的 /PR72 家庭一个重要 PP2A 家庭涉及多样的细胞的过程,并且特别地由钙绑定调整了到规章的子单元。在这个家庭的 PR70 子单元与房间部门控制 6 交往(Cdc6 ) ,为 DNA 复制的控制重要的一个房间周期管理者。这里,我们在 2.1 和 2.4 Å 的一个决定报导孤立的 PR72 和 trimeric PR70 holoenzyme 的水晶结构;,分别地并且在 Cdc6 dephosphorylation 的 vitro 描述。holoenzyme 结构表明 PR70 钙绑定主题之一直接联系支架子单元,导致在所有 PP2A holoenzymes 之中的最紧缩的支架子单元符合构造。PR70 也在活跃地点附近区别地绑在催化子单元,它被要求让 PR70 向 Cdc6 提高磷酸酶活动。我们的研究为 B″ 的唯一的规定提供一个结构的基础;由钙离子的 /PR72 holoenzymes,并且在 PP2A holoenzymes 之中为底层特性的精确控制建议机制。Nathan Wlodarchak Feng Guo Kenneth A Satyshur Li Jiang Philip D Jeffrey Tingwan Sun Vitali Stanevich Marc C Mumby Yongna Xing 2013Cell Research2013,23,7:3
10Revisiting normal perfusion pressure breakthrough in light of hemorrhage-induced vasospasm显示文摘Cerebral arteriovenous malformations(AVMs) have abnormally enlarged arteries and veins prone to spontaneous hemorrhage.Immediately following surgical excision of a cerebral AVM,even normal brain tissue surrounding the lesion is subject to hemorrhage,a phenomenon termed normal perfusion pressure breakthrough(NPPB) syndrome.According to this theory,arteries supplying cerebral AVMs become dilated and lose their capacity to dilate or constrict to autoregulate pressure.Acutely after removal of a cerebral AVM,excessive blood pressure in these arterial feeders can cause normal brain tissue to bleed.However,this theory remains controversial.We present a patient with a cerebral AVM that demonstrated cerebrovascular reactivity and argues against an assumption underlying the theory of NPPB syndrome.Matthew D Alexander E Sander Connolly Philip M Meyers 2010World Journal of Radiology2010,2,6:3
11Acute coronary syndromes: an old age problem显示文摘在老年的增加的人口将导致他们的更大的数字与急性冠的症候群(交流) 介绍。这在全球保健资源上有含意并且为基于证据的治疗要求更好的管理和选择。老比更年轻的交流是有更重要的治疗好处的一个高风险组。不过,在交流的相关不平等在乎的年龄被认出并且坚持。到某程度,在照顾的这差异被不正常、推迟的演讲的更高的频率在表示在老、不太诊断的心电图解释,加强在交流的延期诊断。在死亡风险在的评价下面由于为生理的脆弱,合作病态,认知 / 心理的缺陷和物理残疾的有限考虑老,由心病学专家和 randomised 的缺乏的更少的输入,指导管理在的控制试用数据老可以进一步使照顾的不平等惊讶。当这些不平等存在时,在那里仍然是一个实质的机会改进年龄相关交流结果。为特定的治疗和药政体的老病人的选择是未答复的。对 randomised 有成长需要,人口更代表性并且与合作病态先进年龄注册那些的控制试用数据。不利事件报导的缺乏,张贴冠的 angiography 例如肾的缺陷,在老进一步的限制风险利益决定。在老交流病人的照顾的实质的改进被要求并且应该被倡导。最终,这些改进是可能的导致更好的结果柱子交流。然而,在结果的改进不是无限的并且将由年龄相关的风险的非可修改的因素有限。Alexander D Simms Philip D Batin John Kurian Nigel Durham Christopher P Gale 2012Journal of Geriatric Cardiology2012,9,2:3
12Preoperative assessment of liver function显示文摘Philip D Schneider 2004Surgical Clinics of North America2004,,2:3
13一种房颤风险评分系统的建立(Framingham心脏研究):基于社区的队列研究显示文摘背景房颤导致了发病率和病死率的显著上升。本研究旨在建立一种预测个体罹患房颤绝对风险的风险评分系统,并提供研究人员评价新危险因素的流程。方法作者评估了Framingham心脏研究中于1968年6月至1987年9月间进行了8044次检测的4764例参与者(55%为女性,年龄45~95岁)。此后,参与者被随访至房颤首发,随访期最长达10年。多变量Coxi回归确认出1(1年内罹患房颤的临床危险因素。次级分析纳入了常规超声心动图检测指标(5152例4参与者,7156次检测)对房颤风险进行再分层评估,并评价超声检测指标能否提高风险预测能力。结果4764例参与者中的457例4(10%)罹患房颤。年龄、性别、体重指数、收缩压、降压治疗、PR间期、有临床意义的心脏杂音及心力衰竭与房颤相关,并被纳入了风险评分模型(除体重指数P=0.08外,其余均为P〈0.05),模型的C统计量为0.78(95%CI0.76~0.80)。10年房颤风险随年龄变化:年龄〈65岁的人群中53例(1%)风险高于15%,而〉65岁的人群中为783例(27%)。为提高预测能力而纳入超声检测指标仅使模型C统计量略微增高,由0.78(95%C10.75~0.80)增至0.79(95%CI0.77~0.82:P=0.005)。超声心动图检测指标并不能改善风险再分层评估(P=0.18)。结论基于社区医疗中易得的临床因素建立的风险评分系统,有助于确认社区个体罹患房颤的风险,评估技术或标志物能否改善风险预测,以及针对高危个体采取预防措施。Renate B Schnabel Lisa M Sullivan Daniel Levy Michael J Pencina Joseph M Massaro Ralph B D'Agostino Sr Christopher Newton-Cheh Jennifer F Yamamoto Jared W Magnani Thomas M Tadros William B Kannel Thomas J Wang Patrick T Ellinor Philip A Wolf Ramachanclran S Vasan Emelia J Benjamin 黄刚(译) 2009世界临床医学2009,,9:2
14Lack of correlation between Treg quantification assays in inflammatory bowel disease patients显示文摘AIM:To compare the number of regulatory T-cells( Tregs) measured by flow cytometry with those obtained using a real-time quantitative PCR(q PCR) method in patients suffering from inflammatory bowel disease(IBD).METHODS:Tregs percentages obtained by both flow cytometry and q PCR methods in 35 adult IBD patients,18 out of them with Crohn′s disease(CD)and 17 with ulcerative colitis(UC)were compared to each other as well as to scores on two IBD activity questionnaires using the Harvey Bradshaw Index(HBI)for CD patients and the Simple Colitis Clinical Activity Index(SCCAI)for UC patients.The Treg percentages by flow cytometry were defined as CD4+CD25highCD127lowFOXP3+cells in peripheral blood mononuclear cells,whereas the Treg percentages by q PCR method were determined as FOXP3 promoter demethylation in genomic DNA.RESULTS:We found an average of 1.56%±0.78%Tregs by using flow cytometry,compared to 1.07%±0.53%Tregs by using q PCR in adult IBD patients.There were no significant correlations between either the percentages of Tregs measured by flow cytometry or q PCR and the HBI or SCCAI questionnaire scores in CD or UC patients,respectively.In addition,there was no correlation between Treg percentages measured by q PCR and those measured by flow cytometry(r=-0.06,P=0.73;Spearman Rho).These data suggest that,either Treg-related immune function or the clinical scores in these IBD patients did not accurately reflect actual disease activity.Until the cause(s)for these differences are more clearly defined,the resultssuggest caution in interpreting studies of Tregs in various inflammatory disorders.CONCLUSION:The two methods did not produce equivalent measures of the percentage of total Tregs in the IBD patients studied which is consistent with the conclusion that Tregs subtypes are not equally detected by these two assays.Gunnar Brandhorst Darinka Todorova Petrova Sebastian Weigand Christoph Eberle Nicolas von Ahsen Jessica Schmitz Frank Christian Schultze Dirk Raddatz Michael Karaus Michael Oellerich Philip D Walson 2015World Journal of Gastroenterology2015,21,11:2
15Acute coronary syndromes in young patients: Presentation, treatment and outcome显示文摘Andreas W. Schoenenberger Dragana Radovanovic Jean-Christophe Stauffer Stephan Windecker Philip Urban Gregor Niedermaier Pierre-Frédéric Keller Felix Gutzwiller Paul Erne 2009International Journal of Cardiology2009,,3:2
16Improved procedures for clearing roots and staining parasitic and vesicular-arbuscular mycorrhizal fungi for rapid assessment of infection显示文摘Philips J M Hayman D S 1970Trans Br Mycol Soc1970,55,:2
17Impact of Atrial Fibrillation on the Risk of Death: The Framingham Heart Study显示文摘Emelia J. Benjamin Philip A. Wolf Ralph B. D’Agostino Halit Silbershatz William B. Kannel Daniel Levy 1998Circulation1998,,10:2
18General Cardiovascular Risk Profile for Use in Primary Care: The Framingham Heart Study显示文摘Ralph B. D’Agostino Ramachandran S. Vasan Michael J. Pencina Philip A. Wolf Mark Cobain Joseph M. Massaro William B. Kannel 2008Circulation2008,,6:2
19Cervical adjacent segment pathology following fusion:Is it due to fusion?显示文摘Adjacent segment pathology affects 25% of patients within ten years of anterior cervical diskectomy and fusion(ACDF). Laboratory studies demonstrate fused segments increase adjacent level stress including elevated intradiscal pressure and increased range of motion. Radiographic adjacent segment pathology(RASP) has been associated to ACDF in multiple statistically significant studies. Randomized controlled trials(RCTs) comparing anterior cervical discectomy and arthroplasty(ACDA) and ACDF have confirmed ACDF accelerates RASP. The question of greatest clinical interest is whether ACDA, artificial disc surgery, results in fewer adjacent level surgeries than ACDF. Current RCT follow up results reveal only non statistically significant trends favoring ACDA yet the post operative periods are only two to four years. Statistically significant increased RASP in ACDF patients however is already documented. The RCT patients' average ages are in the mid forties with an expected longevity of up to forty more years. Early statistically significant increased RASP in the ACDF patients supports our prediction that given sufficient follow up of ten or more years, fusion will lead to statistically significant higher rate of adjacent level surgery compared to artificial disc surgery.Philip Rosenthal Kee D Kim 2013World Journal of Orthopedics2013,4,3:2
20Safety,immunogenicity,and protection provided by unadjuvanted and adjuvanted formulations of a recombinant plant-derived virus-like particle vaccine candidate for COVID-19 in nonhuman primates显示文摘Although antivirals are important tools to control severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,effective vaccines are essential to control the current coronavirus disease 2019(COVID-19)pandemic.Plant-derived virus-like particle(VLP)vaccine candidates have previously demonstrated immunogenicity and efficacy against influenza.Here,we report the immunogenicity and protection induced in rhesus macaques by intramuscular injections of a VLP bearing a SARS-CoV-2 spike protein(CoVLP)vaccine candidate formulated with or without Adjuvant System 03(AS03)or cytidine-phospho-guanosine(CpG)1018.Although a single dose of the unadjuvanted CoVLP vaccine candidate stimulated humoral and cell-mediated immune responses,booster immunization(at 28 days after priming)and adjuvant administration significantly improved both responses,with higher immunogenicity and protection provided by the AS03-adjuvanted CoVLP.Fifteen micrograms of CoVLP adjuvanted with AS03 induced a polyfunctional interleukin-2(IL-2)-driven response and IL-4 expression in CD4 T cells.Animals were challenged by multiple routes(i.e.,intratracheal,intranasal,and ocular)with a total viral dose of 106 plaque-forming units of SARS-CoV-2.Lower viral replication in nasal swabs and bronchoalveolar lavage fluid(BALF)as well as fewer SARS-CoV-2-infected cells and immune cell infiltrates in the lungs concomitant with reduced levels of proinflammatory cytokines and chemotactic factors in the BALF were observed in animals immunized with the CoVLP adjuvanted with AS03.No clinical,pathologic,or virologic evidence of vaccineassociated enhanced disease was observed in vaccinated animals.The CoVLP adjuvanted with AS03 was therefore selected for vaccine development and clinical trials.Stéphane Pillet Prabhu SArunachalam Guadalupe Andreani Nadia Golden Jane Fontenot Pyone Pyone Aye Katharina Röltgen Gabrielle Lehmicke Philipe Gobeil Charlotte Dubé Sonia Trépanier Nathalie Charland Marc-AndréD’Aoust Kasi Russell-Lodrigue Christopher Monjure Robert V.Blair Scott D.Boyd Rudolf P.Bohm Jay Rappaport François Villinger Nathalie Landry Bali Pulendran Brian J.Ward 2022Cellular & Molecular Immunology2022,19,2:2
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