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Evolving concepts in bone infection: r.defining “biofilm”,“acute vs. chr.nic osteomyelitis”, “the immune pr.teome” and “local antibiotic ther.py”

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Bone r.sear.h 2019年第3期7卷 225-242页

作者： Elysia A. Master. r.an P. Tr.mbetta Kar.n L. de Mesy Bentley Br.ndan F Boyce Ann Lindley gill steven r. gill Kohei Nishitani Masahir. Ishikawa Yugo Mor.ta Hir.mu Ito Sheila N. Bello-Ir.zar.y Mar. Ninomiya James D. Br.dell Jr. Char.es C. Lee Stephanie P. Hao Ir.in Oh Chao Xie Hani A. Awad John L. Daiss John r. Owen Stephen L. Kates Edwar. M. Schwar. Gowr.shankar.Muthukr.shnan Center.for.Musculoskeletal r.sear.h University of Rochester Medical Center Rochester NY USA Depar.ment of Biomedical Engineer.ng University of Rochester Medical Center Rochester NY USA Depar.ment of Pathology and Labor.tor. Medicine University of Rochester Medical Center Rochester NY USA Depar.ment of Or.hopaedics University of Rochester Medical Center Rochester NY USA Depar.ment of Micr.biology & Immunology University of Rochester Medical Center Rochester NY USA Depar.ment of Or.hopaedic Sur.er. Kyoto University Kyoto Japan Depar.ment of Or.hopaedic Sur.er. Virginia Commonwealth University Medical Center Richmond VA USA

Osteomyelitis is a devastating disease caused by micr.bial infection of bone. While the fr.quency of infection following elective or.hopedic sur.er. is low, r.tes of r.infection ar. distur.ingly high. Staphylococcus aur.us is r.sponsible for.the major.ty of chr.nic osteomyelitis cases and is often consider.d to be incur.ble due to bacter.al per.istence deep within bone. Unfor.unately, ther. is no consensus on clinical classifications of osteomyelitis and the ensuing tr.atment algor.thm. Given the high patient mor.idity,mor.ality, and economic bur.en caused by osteomyelitis, it is impor.ant to elucidate mechanisms of bone infection to infor. novel str.tegies for.pr.vention and cur.tive tr.atment. r.cent discover.es in this field have identified thr.e distinct r.ser.oir. of bacter.al biofilm including: Staphylococcal abscess communities in the local soft tissue and bone mar.ow, glycocalyx for.ation on implant har.war. and necr.tic tissue, and colonization of the osteocyte-lacuno canalicular.networ.(OLCN) of cor.ical bone. In contr.st, *** intr.cellular.per.istence in bone cells has not been substantiated in vivo, which challenges this mode of chr.nic osteomyelitis. Ther. have also been major.advances in our.under.tanding of the immune pr.teome against S. aur.us, fr.m clinical studies of ser.m antibodies and media enr.ched for.newly synthesized antibodies(MENSA), which may pr.vide new oppor.unities for.osteomyelitis diagnosis, pr.gnosis, and vaccine development. Finally, novel ther.pies such as antimicr.bial implant coatings and antibiotic impr.gnated 3D-pr.nted scaffolds r.pr.sent pr.mising str.tegies for.pr.venting and managing this devastating disease. Her., we r.view these r.cent advances and highlight tr.nslational oppor.unities towar.s a cur..

关键词： disease caused by soft tissue necr.tic tissuel

One hundr.d and seventy-eight consecutive pancr.atoduodenectomies without mor.ality:r.le of the multidisciplinar. appr.ach

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Hepatobiliar. & Pancr.atic Diseases Inter.ational 2011年第4期10卷 415-421页

作者： Jaswinder.S Samr. r.ul Alvar.do Bachmann Julian Choi Anthony gill Michael Neale Vikr.m Puttaswamy Camer.n Bell Ian Nor.on Sar.h Cho steven Blome r.tchie Maher.Sivakumar.Gananadha Thomas J Hugh Upper.Gastr.intestinal Sur.ical Unit University of SydneyRoyal North Shore HospitalSt LeonardsNSW2065SydneyAustralia Depar.ment ofAnatomical Pathology University of SydneyRoyal North Shore HospitalSt LeonardsNSW2065SydneyAustralia Depar.ment of Vascular.Sur.er. University of SydneyRoyal North Shore HospitalSt LeonardsNSW2065SydneyAustralia Depar.ment of Gastr.enter.logy University of SydneyRoyal North Shore HospitalSt LeonardsNSW2065SydneyAustralia Depar.ment of r.diology University of SydneyRoyal North Shore HospitalSt LeonardsNSW2065SydneyAustralia

BACKGr.UND:Pancr.atoduodenectomy offer. the only chance of cur. for.patients with per.ampullar. ***,however.is a major.under.aking in most patients and is associated with a significant mor.idity and mor.ality.A multidisciplinar. appr.ach to the wor.up and follow-up of patients under.oing pancr.atoduodenectomy was initiated at our.institution to impr.ve the diagnosis,r.section r.te,mor.ality and *** under.ook the study to assess the effect of this appr.ach on diagnosis,r.section r.tes and shor.-ter. outcomes such as mor.idity and ***:A pr.spective database of patients pr.senting with per.ampullar. cancer. to a single sur.eon between Apr.l 2004 and Apr.l 2010 was *** cases wer. discussed at a multidisciplinar. meeting compr.sing sur.eons,gastr.enter.logists,r.diologists,oncologists,r.diation oncologists,pathologists and nur.ing staff.A standar.ized investigation and management algor.thm was *** wer. gr.ded accor.ing to the Clavien-Dindo ***:A total of 295 patients with a per.ampullar. lesion wer. discussed and 178 under.ent pancr.atoduodenectomy (r.section r.te 60%).Sixty-one patients (34%) r.quir.d either.a vascular.or.an additional or.an ***-nine patients exper.enced complications,of which the commonest was blood tr.nsfusion (12%).Thir.y-four.patients (19%) had major.complications,*** 3 or.*** was no in-hospital,30-day or.60-day ***:Pancr.atoduodenectomy can safely be per.or.ed in high-volume center. with ver. low *** sur.eon’s r.le should be car.ful patient selection,intensive pr.oper.tive investigations,use of a team appr.ach,and an unbiased discussion at a multidisciplinar. meeting to optimize the outcome in these patients.

关键词： pancr.atoduodenectomy multidisciplinar. vascular.r.section

Clinical decision suppor. for.dr.g r.lated events: Moving towar.s better.pr.vention

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Wor.d Jour.al of Cr.tical Car. Medicine 2016年第4期5卷 204-211页

作者： Sandr. L Kane-gill Ar.hita Achanta John A Kellum steven M Handler Depar.ment of Phar.acy and Ther.peutics School of Pharmacy University of Pittsburgh Depar.ment of Phar.acy UPMC School of Phar.acy University of Pittsburgh Center.for.Cr.tical Car. Nephr.logy UPMC and University of Pittsburgh Depar.ment of Cr.tical Car. Medicine University of Pittsburgh Division of Ger.atr.c Medicine Department of Medicine University of Pittsburgh

Clinical decision suppor.(CDS) systems with automated aler.s integr.ted into electr.nic medical r.cor.s demonstr.te efficacy for.detecting medication er.or.(ME) and adver.e dr.g events(ADEs). Cr.tically ill patients ar. at incr.ased r.sk for.ME, ADEs and ser.ous negative outcomes r.lated to these events. Capitalizing on CDS to detect ME and pr.vent adver.e dr.g r.lated events has the potential to impr.ve patient outcomes. The key to an effective medication safety sur.eillance system incor.or.ting CDS is advancing the signals for.aler.s by using tr.jector. analyses to pr.dict clinical events, instead of waiting for.these events to occur. Additionally, incor.or.ting cutting-edge biomar.er. into aler. knowledge in an effor. to identify the need to adjust medication ther.py por.ending har. will advance the cur.ent state of CDS. CDS can be taken a step fur.her.to identify dr.g r.lated physiological events, which ar. less commonly included in sur.eillance systems. Pr.dictive models for.adver.e events that combine patient factor. with labor.tor. values and biomar.er. ar. being established and these models can be the foundation for.individualized CDS aler.s to pr.vent impending ADEs.

关键词： Dr.g-r.lated side effects and adver.e r.actions Decision suppor. systems Clinical Medication er.or. Patient safety Clinical phar.acy infor.ation systems Intensive car. units Cr.tical car. Adver.e dr.g event Clinical decision suppor. systems

Effects of ply or.entation and mater.al on the ballistic impact behavior.of multilayer.plain-weave ar.mid fabr.c tar.ets

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Defence Technology（防务技术） 2018年第3期14卷 165-178页

作者： Gaur.v Nilakantan steven Nutt Mor. Family Depar.ment of Chemical Engineer.ng and Mater.als Science M.C.Gill Composites CenterUniversity of Southern CaliforniaLos AngelesCA Cur.ently at Teledyne Scientific&Imaging 1049 Camino Dos RiosThousand OaksCA91360USA.

Vir.ual testing of fabr.c ar.or.pr.vides an efficient and inexpensive means of systematically studying the influence of var.ous ar.hitectur.l and mater.al par.meter. on the ballistic impact behavior.of woven fabr.cs, befor. actual labor.tor. pr.totypes ar. woven and destr.ctively tested. In this finite element study, the combined effects of individual ply or.entations and mater.al pr.per.ies on the impact per.or.ance of multi-layer.d, non-stitched woven ar.mid fabr.cs ar. studied using 2-and 4-sided clamping configur.tions. Individual ply or.entations of 0°, ±15°, ±30°, and ±45° ar. consider.d along with thr.e levels of inter.yar. fr.ction coefficient. Functionally gr.ded fabr.c tar.ets ar. also consider.d wher.in the yar. stiffness pr.gr.ssively incr.ases or.decr.ases thr.ugh the tar.et thickness while keeping the yar. str.in ener.y density constant and with all other.mater.al and ar.hitectur.l par.meter. unchanged for.consistency. For.each tar.et configur.tion, one non-penetr.ting and one penetr.ting impact velocity is chosen. The impact per.or.ance is evaluated by the time taken to ar.est the pr.jectile and the backface defor.ation for.the non-penetr.ting impacts, and by the r.sidual velocity for.the penetr.ting impact tests. All deter.inistic impact simulations ar. per.or.ed using LS-DYNA. 2-sided clamped tar.ets and lower.inter.yar. fr.ctional levels gener.lly r.sulted in better.impact *** functionally gr.ded tar.ets gener.lly showed either.similar.or.infer.or.impact per.or.ance than the baseline fabr.c tar.et configur.tions for.the non-penetr.ting shots. Some per.or.ance impr.vements wer. obser.ed for.the penetr.ting shots when the yar. stiffness was pr.gr.ssively decr.ased thr.ugh the layer. in a dir.ction away fr.m the str.ke face, with additional per.or.ance enhancements achieved by simultaneously r.ducing the inter.yar. fr.ction.

关键词：材料参数线织物芳香族厚度编织取向行为弹道

Ar. EPB41 and alpha-synuclein diagnostic biomar.er. of spor.-r.lated concussion?Findings fr.m the NCAA and Depar.ment of Defense CAr. Consor.ium

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Jour.al of Spor. and Health Science 2023年第3期12卷 379-387页

作者： r.ny Vor. Chr.stina Devoto Timothy B.Meier.Chen Lai Sijung Yun steven P.Br.glio Sar. Mithani Thomas W.McAllister.Chr.stopher.C.Giza Hyung-Suk Kim Daniel Huber.Jar.slaw Har.zlak Kenneth L.Camer.n Ger.ld McGinty Jonathan Jackson Kevin M.Guskiewicz Jason P.Mihalik Alison Br.oks Stefan Duma steven r.wson Lindsay D.Nelson Paul Pasquina Michael A.McCr.a Jessica M.gill the CAr. Consor.ium Investigator. Johns Hopkins School of Nur.ing and Medicine BaltimoreMD 21205USA National Institutes of Health BethesdaMD 20892USA Depar.ment of Neur.sur.er. Medical College of WisconsinMilwaukeeWI 53226USA Pr.dictiv Car. Inc.Mountain ViewCA 94086USA Michigan Concussion Center University of MichiganAnn ArborMI 48109USA Depar.ment of Psychiatr. Indiana University School of MedicineIndianapolisIN 46202USA Depar.ments of Pediatr.cs and Neur.sur.er. University of California at Los Angeles(UCLA)Los AngelesCA 90024USA Depar.ment of Epidemiology and Biostatistics School of Public Health–Bloomington Indiana UniversityBloomingtonIN 47405USA John A.Feagin Spor.s Medicine Fellowship Keller Army Community HospitalWest PointNY 10996USA United States Air.For.e Academy Colorado SpringsCO 80840USA Mathew Gfeller.Center Department of Exercise and Sport ScienceUniversity of North Carolina at Chapel HillChapel HillNC 27514USA Depar.ment of Or.hopedics Division of Sports MedicineSchool of Medicine and Public HealthUniversity of WisconsinMadisonWI 53705USA Depar.ment of Biomedical Engineer.ng and Mechanics Virginia TechBlacksburgVA 24061USA Center.for.Neur.science&r.gener.tive Medicine Uniformed Services UniversityBethesdaMD 20814USA 不详 Cur.ent affiliation:School of Nur.ing University of Texas Health Science Center San AntonioSan AntonioTX 78229USA

Backgr.und:Cur.ent pr.tein biomar.er. ar. only moder.tely pr.dictive at identifying individuals with mild tr.umatic br.in injur. or.***,mor. accur.te diagnostic mar.er. ar. needed for.spor.-r.lated ***:This was a multicenter.pr.spective,case-contr.l study of athletes who pr.vided blood samples and wer. diagnosed with a concussion or.wer. a matched non-concussed contr.l within the National Collegiate Athletic Association-Depar.ment of Defense Concussion Assessment,r.sear.h,and Education Consor.ium conducted between 2015 and *** blood was collected within 48 h of injur. to identify pr.tein abnor.alities at the acute and subacute *** with concussion wer. divided into 6 h post-injur.(0-6 h post-injur.)and after.6 h postinjur.(7-48 h post-injur.)*** applied a highly multiplexed pr.teomic technique that used a DNA aptamer. assay to tar.et 1305pr.teins in plasma samples fr.m athletes with and without spor.-r.lated ***:A total of 140 athletes with concussion(79.3%males;aged 18.71±1.10 year.,mean±SD)and 21 non-concussed athletes(76.2%males;19.14±1.10 year.)wer. included in this *** identified 338 plasma pr.teins that significantly differ.d in abundance(319 upr.gulated and 19 downr.gulated)in concussed athletes compar.d to non-concussed *** top 20 most differ.ntially abundant pr.teins discr.minated concussed athletes fr.m non-concussed athletes with an ar.a under.the cur.e(AUC)of 0.954(95%confidence inter.al:0.922-0.986).Specifically,after.6 h of injur.,the individual AUC of plasma er.thr.cyte membr.ne pr.tein band 4.1(EPB41)and alpha-synuclein(SNCA)wer. 0.956 and 0.875,*** combination of EPB41 and SNCA pr.vided the best AUC(1.000),which suggests this combination of candidate plasma biomar.er. is the best for.diagnosing concussion in athletes after.6 h of ***:Our.data suggest that pr.teomic pr.filing may pr.vide novel diagnostic pr.tein mar.er. and that a combina

关键词： Biomar.er. College athletes Concussion Mild tr.umatic br.in injur. Spor. injur.

Potential of a planar.an model to study cer.ain aspects of anti-Par.insonism dr.gs

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Advances in Par.inson's Disease 2013年第3期2卷 70-74页

作者： r.ber. B. r.ffa Jeff Danah Chr.stopher.S. Tallar.da Car.ie Zimmer.an Gr.ce gill steven J. Bar.n Scott M. r.wls Center.for.Substance Abuse r.sear.h and Temple Univer.ity School of Medicine Philadelphia USA Temple Univer.ity School of Phar.acy Philadelphia USA

We pr.viously cr.ated and investigated a planar.an model for.the study of dr.g action, abuse, physical dependence, r.ceptor.affinity, the toxicity of heavy metals in wastewater. and seizur.s. For.the pr.sent pilot study, we investigated the possibility that this model might be useful for.studying cer.ain aspects of dr.gs used in tr.atment of Par.inson disease. For.the fir.t step, we wer. inter.sted in finding an in vivo metr.c for.the inhibition of L-DOPA by an inhibitor.of DOPA decar.oxylase. The dir.ct clinical r.levance of the endpoint was of secondar. concer. dur.ng this pr.liminar. phase of model development. Two metr.cs wer. explor.d: L-DOPA-induced inhibition of motility (locomotor.velocity) and dopamine-mediated toxicity, which was quantified using a Kaplan-Meier.sur.ival cur.e. L-DOPA pr.duced both dose- and time-r.lated toxicity. The water.soluble DOPA decar.oxylase inhibitor.benser.zide dose-dependently inhibited the effect of L-DOPA, as manifested by a leftwar. shift in the Kaplan-Meier.cur.e. Additional wor. was initiated using the mor. sensitive and a gr.ded metr.c of spontaneous locomotor.velocity. The encour.ging r.sults of this pilot study suggest that: 1) planar.ans contain DOPA decar.oxylase or.an equivalent enzyme, and 2) the planar.an model might be useful for.the study of cer.ain aspects of anti-Par.insonism phar.acother.py.

关键词： L-DOPA Benser.zide Planar.ans

Pr.tective and antifungal pr.per.ies of Nanodisk-Amphoter.cin B over.commer.ially available Amphoter.cin B

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Wor.d Jour.al of Otor.inolar.ngology-Head and Neck Sur.er. 2017年第1期3卷 -页

作者： Do-Yeon Cho Kyle J.Hoffman Gobind S.gill Dong-Jin Lim Daniel Skinner.Calvin Mackey steven M.r.we Br.dfor. A.Woodwor.h Depar.ment of Otolar.ngology Head & Neck Sur.er. University of Alabama at BirminghamBirminghamALUSAGregory Fleming James Cystic Fibrosis Research CenterUniversity of Alabama at BirminghamBirminghamALUSA Depar.ment of Otolar.ngology Head & Neck Sur.er. University of Alabama at BirminghamBirminghamALUSA Gr.gor. Fleming James Cystic Fibr.sis r.sear.h Center University of Alabama at BirminghamBirminghamALUSADepartments of MedicinePediatricsCell Developmental and Integrative BiologyUniversity of Alabama at BirminghamBirminghamALUSA

Objective:Amphoter.cin B (AMB),a potent antifungal agent,has been employed as topical and systemic ther.py for.sinonasal fungal infections.A novel for.ulation of nanodisc (ND) containing super.aggr.gated AMB (ND-AMB) for.the tr.atment of fungal infections has been r.cently developed to pr.vide gr.ater.pr.tection fr.m AMB toxicity than cur.ent,clinically appr.ved lipid-based *** objective of the cur.ent study was to evaluate the safety and potency of ND-AMB for.sinonasal deliver. using an in vitr. ***:Human sinonasal tissue was har.ested dur.ng endoscopic sinus sur.er. and gr.wn at air.liquid inter.ace until *** wer. exposed to ND-AMB vs AMB and changes in K+ per.eability and r.sistance wer. measur.d and r.cor.ed via Ussing chamber.*** beat fr.quency (CBF) was analyzed in par.llel as well as cytotoxic *** was assessed using r.al-time PCr.measur.ment of the Asper.0}us fumigatus 18S ***:Ussing chamber.studies r.vealed K+ cur.ents that incr.ased r.pidly within 30 s of adding AMB (10 μg/mL) to the apical side,indicating apical membr.nes had become per.eable to K+ *** contr.st,negligible induction of K+ cur.ent was obtained following addition of NDAMB [AMB =(107.7 ± 15.9) μA/cm2 AMB vs ND-AMB =(2.3 ± 0.7) μA/cm2 ND-AMB;P =0.005].ND-AMB also pr.tected nasal epithelial cells fr.m cytotoxicity of AMB (P ＜ 0.05).Ther. was no differ.nce in ciliar. beat fr.quency between the two gr.ups (P =0.96).The expr.ssion of *** 18S r.NA with exposur. of lower.dose of ND-AMB was significantly lower.compar.d to that with AMB (P ＜ 0.05).Conclusions:Data fr.m the pr.sent study suggests ND-AMB pr.tects human nasal epithelia membr.nes fr.m AMB toxicity by pr.tecting against apical cell K+ per.eability while maintaining uncompr.mised antifungal pr.per.y compar.d to ***-AMB could pr.vide a novel topical ther.py for.sinonasal fungal diseases.

关键词： Chr.nic r.inosinusitis Amphoter.cin Dr.g deliver. Tr.nsepithelial ion tr.nspor. Sinusitis Sinus epithelium Mucociliar. clear.nce Ciliar. beat fr.quency

经皮冠状动脉介入治疗前给予氯吡格雷治疗看似足矣，实则不足

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美国医学会杂志（中文版） 2007年第2期26卷 118-119页

作者： steven r. Steinhubl r.char. Char.igo 张方芳（陈）陈红（校） Division of Car.iovascular.Medicine Gill Heart Institute and Department of Statistics University of.Kentucky Lexington 不详

今年在全球范围内，将有200万例以上的患者接受经皮冠状动脉介入治疗（per.utaneous cor.nar. inter.ention，PCI），其中几乎一半是在美国完成的。上述患者几乎有3／4。被诊断为急性冠脉综合征（acute cor.nar.sy ndr.me，ACS）——不... 详细信息

今年在全球范围内，将有200万例以上的患者接受经皮冠状动脉介入治疗（per.utaneous cor.nar. inter.ention，PCI），其中几乎一半是在美国完成的。上述患者几乎有3／4。被诊断为急性冠脉综合征（acute cor.nar.sy ndr.me，ACS）——不稳定型心绞痛或心肌梗死。

关键词：经皮冠状动脉介入治疗前氯吡格雷冠状动脉介入治疗急性冠脉综合征不稳定型心绞痛心肌梗死 int

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阿斯匹林预防心血管疾病的剂量系统综述

美国医学会杂志（中文版） 2007年第5期26卷 292-298页

作者： Char.es L. Campbell Susan Smyth gilles Montalescot steven r. Steinhubl 李呈亿（译） gill He＇ar. Institute University of Kentucky Lexington gill Hear. Instiute and Institut de Car.iologie-Centr. Hospitalier.Univer.itair. Pitie-Salpetr.er. Paris France

背景：为了长期预防心血管疾病，目前美国有5千万以上的成年人定期服用阿斯匹林，所用剂量通常为81mg／d或325mg／d。关于长期服用阿斯匹林的最佳剂量目前仍有争议。目的：复习阿斯匹林的作用机制，对论述阿斯匹林剂量、效果和安全性相... 详细信息

背景：为了长期预防心血管疾病，目前美国有5千万以上的成年人定期服用阿斯匹林，所用剂量通常为81mg／d或325mg／d。关于长期服用阿斯匹林的最佳剂量目前仍有争议。目的：复习阿斯匹林的作用机制，对论述阿斯匹林剂量、效果和安全性相互关系的临床文献进行系统回顾。证据获取：使用MEDLINE和EMBASE（至2007年2月）对相关英文文献进行系统回顾。所用检索词为：阿斯匹林或乙酰水杨酸和剂量。检索限于临床试验，通过审查相关原始资料报告和综述文章的参考文献进一步扩展检索范围。已发表的关于心血管患者使用不同剂量阿斯匹林的前瞻性研究亦纳入分析。证据综合：尽管药理学数据证实长期服用30mg／d阿斯匹林足以充分抑制血小板血栓烷生成，但是目前批准使用的剂量高达1300mg／d。在美国，最常采用的剂量为81mg／d（60％），其次为325mg／d（35％）。现有证据（主要来自二级预防观察研究）支持下述观点：阿斯匹林剂量大于75至80mg／d并不提高疗效，更大剂量反而增加出血事件发生率，后者主要与胃肠道毒性有关。结论：对于心血管疾病的预防，现有临床数据并不支持常规、长期使用大于75～81mg／d剂量阿斯匹林。较高剂量的阿斯匹林虽然常用，但是并不能更好地预防心血管事件，而且发生胃肠道出血的危险增加。

关键词：心血管疾病阿斯匹林最佳剂量预防观系统综述 MEDLINE 长期服用系统回顾