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Treat to target in Crohn’s disease:A practical guide for clinicians

World Journal of gastroenterology 2024年第1期30卷 50-69页

作者： Ashish R Srinivasan Department of gastroenterology Austin HealthVictoriaMelbourne 3083Australia Department of gastroenterology Eastern HealthVictoriaMelbourne 3128Australia Department of Medicine University of MelbourneVictoriaMelbourne 3052Australia

A treat-to-target(T2T)approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease.The Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)-II guidelines specify short,intermediate,and long-term treatment goals,documenting specific treatment targets to be achieved at each of these timepoints.Scheduled appraisal of Crohn’s disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified.Consensus treatment targets in Crohn’s disease comprise combination clinical and patient-reported outcome remission,in conjunction with biomarker normalisation and endoscopic healing.Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing,clinicians must consider that this may not always be appropriate,acceptable,or achievable in all patients.This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets.The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques,particularly intestinal ultrasound,holds great promise;as do emerging treatment targets such as transmural healing.Two randomised clinical trials,namely,CALM and STARDUST,have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn’s disease.Findings from these studies reflect that patient subgroups and Crohn’s disease characteristics likely to benefit most from a T2T approach,remain to be clarified.Moreover,outside of clinical trials,data pertaining to the real-world effectiveness of a T2T approach remains scare,highlighting the need for pragmatic real-world studies.Despite the obvious promise of a T2T approach,a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake.This highlights the need to describe strategies,processes,and models of care capable of

关键词： Treat to target Inflammatory bowel disease Crohn’s disease Treatment targets Endoscopic remission Transmural healing Time to response Intestinal ultrasound

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The value of the INFECTIONS scoring system in identifying bacterial infections among patients presenting at the emergency department of a middle-income country:A pilot study

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Chinese Journal of Traumatology 2024年第2期27卷 77-82页

作者： Dooshanveer C.Nuckchady Department of Internal Medicine Victoria HospitalCandosMauritius

Purpose:To investigate which scoring system is the most accurate tool in predicting mortality among the infected patients who present to the emergency department in a middle-income country,and to validate a new scoring system to predict bacterial infections.Methods:This was a retrospective,single-center study among patients who were admitted via the emergency department of a public hospital.All patients who were started on antibiotics were included in the study,while patients agedg patients'demographics,vital signs and basic laboratory parameters like white blood cell count and creatinine.The sensitivity and specificity of different scoring systems were calculated as well as their negative and positive predictive values.Logistic regression was used to derive a novel early warning system for bacterial infections.The area under the receiver operating characteristic(AUROC)was computed for each scoring model.Results:In total,109 patients were included in this study.The quick sequential organ failure assessment(qSOFA),search out severity and rapid acute physiology score had the highest AUROC(≥0.89)for predicting mortality,while qSOFA and universal vital assessment were the simplest scoring systems with an AUROC>0.85;however,these scoring systems failed to predict whether patients were truly infected.The INFECTIONS(short for impaired mental status,not conscious,fast heart rate,elevated creatinine,high temperature,on inotrope,low oxygen,high neutrophils and high sugar)model reached an AUROC of 0.88 to more accurately predict the infectious state of a patient.Conclusions:Middle-income countries should use the qSOFA or universal vital assessment score to identify the sickest patients in emergency department.The INFECTIONS score may help recognize patients with bacterial infections,but it should be further validated in multiple countries prior to widely use.

关键词： Prognosis Mortality Bacterial infection INFECTIONS scoring system Sequential organ failure assessment Prediction

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Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care

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World Journal of Hepatology 2024年第4期16卷 650-660页

作者： Dorothy Liu Mark M Youssef Josephine A grace Marie Sinclair Department of gastroenterology Austin HealthMelbourne 3084VictoriaAustralia victorian Liver Transplant Unit Austin HealthMelbourne 3084VictoriaAustralia Department of Medicine University of MelbourneMelbourne 3084VictoriaAustralia

BACKgROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients.Cumulative immunosuppression has been shown to contribute to post-transplant malignancy(PTM)risk.There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of immunosuppression.Calcineurin inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(MPA),the active metabolite of mycophenolate mofetil,may limit tumour progression.Liver transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort.However,there is limited clinical data on this subject in both LT and other solid organ transplant recipients.AIM To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation.METHODS A literature search was conducted using MEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022.Related terms,synonyms and explosion of MeSH terms,Boolean operators and truncations were also utilised in the search.Reference lists of retrieved articles were also reviewed to identify any additional articles.Excluding duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in detail.Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria.RESULTS A total of 6 studies were included in this review.All studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol used.Overall,there was no clear difference demonst

关键词： Immunosuppression Solid organ transplantation Liver transplantation Carcinogenicity Tacrolimus Mycophenolate

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Influence of laser parameters on the microstructures and surface properties in laser surface modification of biomedical magnesium alloys

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Journal of Magnesium and Alloys 2024年第1期12卷 72-97页

作者： Chee Ying Tan Cuie Wen Hua Qian Ang School of Engineering RMIT UniversityMelbourneVictoria 3001Australia

Biodegradable implants from magnesium(Mg)alloys have emerged in the biomedical field especially in the orthopedic and cardiovascular stent applications owing to their low density,high specific strength,excellent machinability,good biocompatibility,and biodegradability.The primary shortcoming of Mg-based implants is their low corrosion resistance in the physiological environment,which results in premature mechanical integrity loss before adequate healing and the production of excessive hydrogen gas,which is harmful to the body tissues and negatively affects the biocompatibility of the implant.Laser surface modification has recently received attention because it can improve the surface properties such as surface chemistry,roughness,topography,corrosion resistance,wear resistance,hydrophilicity,and thus cell response to the surface of the material.The composition and microstructures including textures and phases of laser-treated surfaces depend largely on the laser processing parameters(input laser power,laser scan velocity,frequency,pulse duration,pressure,gas circulation,working time,spot size,beam focal position,and laser track overlap)and the thermophysical properties of the substrate(solubility,melting point,and boiling point).This review investigates the impacts of various laser surface modification techniques including laser surface melting,laser surface alloying,laser cladding,laser surface texturing,and laser shock peening,and highlights their significance in improving the surface properties of biodegradable Mg alloys for implant applications.Additionally,we explore how different laser process parameters affect its composition,microstructure,and surface properties in each laser surface modification technique.

关键词： Biocompatibility Biodegradability Corrosion Implant applications Laser surface modification Magnesium alloys

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Refining safety considerations for intradialytic blood flow restriction exercise. Commentary on “Concerns on the application of blood-flow restriction resistance exercise and thrombosis risk in hemodialysis patients”

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Journal of Sport and Health Science 2024年第4期13卷 455-456页

作者： Matthew J.Clarkson Institute for Health and Sport Victoria UniversityMelbourneVIC 8001Australia

I read with great interest the article“Concerns on the application of blood flow restriction resistance exercise and thrombosis risk in hemodialysis patients”by Correa et al.1 The study presents complementary data from a previous randomized controlled trial,2 exploring the application of intradialytic blood flow restriction exercise for hemodialysis patients.

关键词： patients hemodialysis al.

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Comparison of methods for deriving phenotypes from incomplete observation data with an application to age at puberty in dairy cattle

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Journal of Animal Science and Biotechnology 2024年第2期15卷 535-545页

作者： Melissa A.Stephen Chris R.Burke Jennie E.Pryce Nicole M.Steele Peter R.Amer Susanne Meier Claire V.C.Phyn Dorian J.garrick DairyNZ Ltd 605 Ruakura RoadHamilton 3240New Zealand AL Rae Centre for genetics and Breeding-Massey University RuakuraHamilton 3214New Zealand Agriculture victoria Research AgriBioCentre for AgriBioscienceBundooraVictoria 3083Australia School of Applied Systems Biology La Trobe UniversityBundooraVictoria 3083Australia AbacusBio DunedinNew Zealand

Background Many phenotypes in animal breeding are derived from incomplete measures,especially if they are challenging or expensive to measure precisely.Examples include time-dependent traits such as reproductive status,or lifespan.Incomplete measures for these traits result in phenotypes that are subject to left-,interval-and rightcensoring,where phenotypes are only known to fall below an upper bound,between a lower and upper bound,or above a lower bound respectively.Here we compare three methods for deriving phenotypes from incomplete data using age at first elevation(>1 ng/mL)in blood plasma progesterone(AgEP4),which generally coincides with onset of puberty,as an example trait.Methods We produced AgEP4 phenotypes from three blood samples collected at about 30-day intervals from approximately 5,000 Holstein–Friesian or Holstein–Friesian×Jersey cross-bred dairy heifers managed in 54 seasonal-calving,pasture-based herds in New Zealand.We used these actual data to simulate 7 different visit scenarios,increasing the extent of censoring by disregarding data from one or two of the three visits.Three methods for deriving phenotypes from these data were explored:1)ordinal categorical variables which were analysed using categorical threshold analysis;2)continuous variables,with a penalty of 31 d assigned to right-censored phenotypes;and 3)continuous variables,sampled from within a lower and upper bound using a data augmentation approach.Results Credibility intervals for heritability estimations overlapped across all methods and visit scenarios,but estimated heritabilities tended to be higher when left censoring was reduced.For sires with at least 5 daughters,the correlations between estimated breeding values(EBVs)from our three-visit scenario and each reduced data scenario varied by method,ranging from 0.65 to 0.95.The estimated breed effects also varied by method,but breed differences were smaller as phenotype censoring increased.Conclusion Our results indicate that using some methods,phenotypes derived from one observ

关键词： Cattle gibbs sampler Markov-chain Monte Carlo(MCMC) Puberty

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Approach to loss of response to advanced therapies in inflammatory bowel disease

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World Journal of gastroenterology 2024年第22期30卷 2902-2919页

作者： Nikil Vootukuru Abhinav Vasudevan Department of gastroenterology and Hepatology Eastern HealthVictoriaBox Hill 3128Australia Eastern Health Clinical School Monash UniversityVictoriaBox Hill 3128Australia

BACKgROUND Remarkable progress over the last decade has equipped clinicians with many options in the treatment of inflammatory bowel disease.Clinicians now have the unique opportunity to provide individualized treatment that can achieve and sustain remission in many patients.However,issues of primary non-response(PNR)and secondary loss of response(SLOR)to non-tumour necrosis factor inhibitor(TNFi)therapies remains a common problem.Specific issues include the choice of optimization of therapy,identifying when dose optimization will recapture response,establishing optimal dose for escalation and when to switch therapy.AIM To explores the issues of PNR and SLOR to non-TNFi therapies.METHODS This review explores the current evidence and literature to elucidate management options in cases of PNR/SLOR.It will also explore potential predictors for response following SLOR/PNR to therapies including the role of therapeutic drug monitoring(TDM).RESULTS In the setting of PNR and loss of response to alpha-beta7-integrin inhibitors and interleukin(IL)-12 and IL-23 inhibitors dose optimization is a reasonable option to capture response.For Janus kinase inhibitors dose optimization can be utilized to recapture response with loss of response.CONCLUSION The role of TDM in the setting of advanced non-TNFi therapies to identify patients who require dose optimization and as a predictor for clinical remission is not yet established and this remains an area that should be addressed in the future.

关键词： Inflammatory bowel disease Ulcerative colitis Crohn Biologics Interleukin-12 and interleukin-23 inhibitors Alpha-beta7-integrin inhibitors Janus kinase inhibitors Sphingosine-1-phosphate receptor modulators

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Asynchronous Learning-Based Output Feedback Sliding Mode Control for Semi-Markov Jump Systems: A Descriptor Approach

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IEEE/CAA Journal of Automatica Sinica 2024年第6期11卷 1358-1369页

作者： Zheng Wu Yiyun Zhao Fanbiao Li Tao Yang Yang Shi Weihua gui School of Automation Central South UniversityChangsha 410083China Power Electronics Machines and Control GroupThe University of NottinghamNottingham NG72RDUK Department of Mechanical Engineering University of VictoriaVictoria BC V8W 3P6Canada IEEE

This paper presents an asynchronous output-feed-back control strategy of semi-Markovian systems via sliding mode-based learning technique.Compared with most literature results that require exact prior knowledge of system state and mode information,an asynchronous output-feedback sliding sur-face is adopted in the case of incompletely available state and non-synchronization phenomenon.The holonomic dynamics of the sliding mode are characterized by a descriptor system in which the switching surface is regarded as the fast subsystem and the system dynamics are viewed as the slow subsystem.Based upon the co-occurrence of two subsystems,the sufficient stochastic admissibility criterion of the holonomic dynamics is derived by utilizing the characteristics of cumulative distribution functions.Furthermore,a recursive learning controller is formulated to guarantee the reachability of the sliding manifold and realize the chattering reduction of the asynchronous switching and sliding motion.Finally,the proposed theoretical method is substantia-ted through two numerical simulations with the practical contin-uous stirred tank reactor and F-404 aircraft engine model,respectively.

关键词： Asynchronous switching learning-based control output feedback semi-Markovian jump systems sliding mode con-trol(SMC).

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Co-Optimization of Behind-the-Meter and Front-of-Meter Value Streams in Community Batteries

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Journal of Modern Power Systems and Clean Energy 2024年第2期12卷 334-345页

作者： Carmen Bas Domenech Antonella Maria De Corato Pierluigi Mancarella University of Melbourne Parkville 2010VictoriaAustralia Department of Electrical and Electronic Engineering The University of ManchesterManchesterU.K. IEEE

Community batteries(CBs)are emerging to support and even enable energy communities and generally help consumers,especially space-constrained ones,to access potential techno-economic benefits from storage and support local grid decarbonization.However,the economic viability of CB projects is often uncertain.In this regard,typical feasibility studies assess CB value for behind-the-meter(BTM)operation or whole-sale market participation,i.e.,front-of-meter(FOM).This work proposes a novel techno-economic operational framework that allows systematic assessment of the different options and introduces a two-meter architecture that co-optimizes both BTM and FOM benefits.A real CB project application in Australia is used to demonstrate the significant two-meter co-optimization opportunities that could enhance the business case of CB and energy communities by multi-service provision and value stacking.

关键词： Behind-the-meter community battery distributed energy resource(DER) energy community front-of-meter value stacking

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Impact of scandium and terbium on the mechanical properties,corrosion behavior,and biocompatibility of biodegradable Mg-Zn-Zr-Mn alloys

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Journal of Magnesium and Alloys 2024年第2期12卷 546-572页

作者： Khurram Munir Jixing Lin Xian Tong Arne Biesiekierski Yuncang Li Cuie Wen School of Engineering RMIT UniversityMelbourneVictoria 3001Australia School and Hospital of Stomatology Wenzhou Medical UniversityWenzhou 325027China

Magnesium(Mg)-based bone implants degrade rapidly in the physiological environment of the human body which affects their structural integrity and biocompatibility before adequate bone repair.Rare earth elements(REEs)have demonstrated their effectiveness in tailoring the corrosion and mechanical behavior of Mg alloys.This study methodically investigated the impacts of scandium(Sc)and terbium(Tb)in tailoring the corrosion resistance,mechanical properties,and biocompatibility of Mg–0.5Zn–0.35Zr–0.15Mn(MZZM)alloys fabricated via casting and hot extrusion.Results indicate that addition of Sc and Tb improved the strength of MZZM alloys via grain size reduction and solid solution strengthening mechanisms.The extruded MZZM–(1–2)Sc–(1–2)Tb(wt.%)alloys exhibit compressive strengths within the range of 336–405 MPa,surpassing the minimum required strength of 200 MPa for bone implants by a significant margin.Potentiodynamic polarization tests revealed low corrosion rates of as–cast MZZM(0.25 mm/y),MZZM–2Tb(0.45 mm/y),MZZM–1Sc–1Tb(0.18 mm/y),and MZZM–1Sc–2Tb(0.64 mm/y),and extruded MZZM(0.17 mm/y),MZZM–1Sc(0.15 mm/y),MZZM-2Sc(0.45 mm/y),MZZM-1Tb(0.17 mm/y),MZZM-2Tb(0.10 mm/y),MZZM–1Sc-1Tb(0.14 mm/y),MZZM-1Sc-2Tb(0.40 mm/y),and MZZM–2Sc–2Tb(0.51 mm/y)alloys,which were found lower compared to corrosion rate of high-purity Mg(~1.0 mm/y)reported in the literature.Furthermore,addition of Sc,or Tb,or Sc and Tb to MZZM alloys did not adversely affect the viability of SaOS2 cells,but enhanced their initial cell attachment,proliferation,and spreading shown via polygonal shapes and filipodia.This study emphasizes the benefits of incorporating Sc and Tb elements in MZZM alloys,as they effectively enhance corrosion resistance,mechanical properties,and biocompatibility simultaneously.

关键词： Corrosion property In vitro cytotoxicity Magnesium alloys Mechanical property Rare earth elements

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