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Hepatocardiorenal syndrome in liver cirrhosis:Recognition of a new entity?

World Journal of Gastroenterology 2024年第2期30卷 128-136页

作者： Henry H L Wu Amina Rakisheva Arvind Ponnusamy Rajkumar Chinnadurai Renal Research Kolling Institute of Medical ResearchRoyal North Shore Hospital&The University of SydneySt.Leonards(Sydney)2065New South WalesAustralia Department of Cardiology City Cardiological CenterAlmaty 050000Kazakhstan Department of Renal Medicine Royal Preston HospitalPreston PR29HTUnited Kingdom Donal O’Donoghue Renal Research Centre&Department of Renal Medicine Northern Care Alliance National Health Service Foundation TrustSalford M68HDUnited Kingdom

Emerging evidence and perspectives have pointed towards the heart playing an important role in hepatorenal syndrome(HRS),outside of conventional understanding that liver cirrhosis is traditionally considered the sole origin of a cascade of pathophysiological mechanisms directly affecting the kidneys in this context.In the absence of established heart disease,cirrhotic cardiomyopathy may occur more frequently in those with liver cirrhosis and kidney disease.It is a specific form of cardiac dysfunction characterized by blunted contractile responsiveness to stress stimuli and altered diastolic relaxation with electrophysiological abnormalities.Despite the clinical description of these potential cardiac-related complications of the liver,the role of the heart has traditionally been an overlooked aspect of circulatory dysfunction in HRS.Yet from a physiological sense,temporality(prior onset)of cardiorenal interactions in HRS and positive effects stemming from portosystemic shunting demonstrated an important role of the heart in the development and progression of kidney dysfunction in cirrhotic patients.In this review,we discuss current concepts surrounding how the heart may influence the development and progression of HRS,and the role of systemic inflammation and endothelial dysfunction causing circulatory dysfunction within this setting.The temporality of heart and kidney dysfunction in HRS will be discussed.For a subgroup of patients who receive portosystemic shunting,the dynamics of cardiorenal interactions following treatment is reviewed.Continued research to determine the unknowns in this topic is anticipated,hopefully to further clarify the intricacies surrounding the liver-heart-kidney connection and improve strategies for management.

关键词： Hepatorenal syndrome Cardiorenal syndrome Cirrhosis Cardiac dysfunction Circulatory dysfunction

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Multiphasic scaffolds for the repair of osteochondral defects:Outcomes of preclinical studies

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Bioactive Materials 2023年第9期27卷 505-545页

作者： Rouyan Chen Jasmine Sarah Pye Jiarong Li Christopher B.Little Jiao Jiao Li kolling institute Faculty of Medicine and HealthThe University of SydneyNSW2065Australia School of Electrical and Mechanical Engineering Faculty of SciencesEngineering and TechnologyThe University of AdelaideSA5005Australia School of Biomedical Engineering Faculty of Engineering and ITUniversity of Technology SydneyNSW2007Australia

Osteochondral defects are caused by injury to both the articular cartilage and subchondral bone within skeletal joints. They can lead to irreversible joint damage and increase the risk of progression to osteoarthritis. Current treatments for osteochondral injuries are not curative and only target symptoms, highlighting the need for a tissue engineering solution. Scaffold-based approaches can be used to assist osteochondral tissue regeneration, where biomaterials tailored to the properties of cartilage and bone are used to restore the defect and minimise the risk of further joint degeneration. This review captures original research studies published since 2015, on multiphasic scaffolds used to treat osteochondral defects in animal models. These studies used an extensive range of biomaterials for scaffold fabrication, consisting mainly of natural and synthetic polymers. Different methods were used to create multiphasic scaffold designs, including by integrating or fabricating multiple layers, creating gradients, or through the addition of factors such as minerals, growth factors, and cells. The studies used a variety of animals to model osteochondral defects, where rabbits were the most commonly chosen and the vast majority of studies reported small rather than large animal models. The few available clinical studies reporting cell-free scaffolds have shown promising early-stage results in osteochondral repair, but long-term follow-up is necessary to demonstrate consistency in defect restoration. Overall, preclinical studies of multiphasic scaffolds show favourable results in simultaneously regenerating cartilage and bone in animal models of osteochondral defects, suggesting that biomaterials-based tissue engineering strategies may be a promising solution.

关键词： Osteochondral defects Tissue engineering Multiphasic scaffolds Biomaterials Animal models

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Epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China:a hospital-based retrospective study

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Neural Regeneration Research 2024年第5期19卷 1126-1132页

作者： Hengxing Zhou Yongfu Lou Lingxiao Chen Yi Kang Lu Liu Zhiwei Cai David BAnderson Wei Wang Chi Zhang Jinghua Wang Guangzhi Ning Yanzheng Gao Baorong He Wenyuan Ding Yisheng Wang Wei Mei Yueming Song Yue Zhou Maosheng Xia Huan Wang Jie Zhao Guoyong Yin Tao Zhang Feng Jing Rusen Zhu Bin Meng Li Duan Zhongmin Zhang Desheng Wu Zhengdong Cai Lin Huang Zhanhai Yin Kainan Li Shibao Lu Shiqing Feng Department of Orthopedics The Second HospitalCheeloo College of MedicineShandong UniversityShandongChina Department of Orthopedics Shandong University Center for OrthopedicsQilu HospitalCheeloo College of MedicineShandong UniversityShandongChina Department of Orthopedics Tianjin Medical University General HospitalInternational Science and Technology Cooperation Base of Spinal Cord InjuryTianjin Key Laboratory of Spine and Spinal CordTianjinChina Faculty of Medicine and Health The Back Pain Research TeamSydney Musculoskeletal HealthThe Kolling InstituteUniversity of SydneySydneyNSWAustralia Department of Spine Surgery Honghui HospitalXi’an Jiaotong UniversityXi’anShaanxi ProvinceChina Department of Burns and Plastic Surgery The Fourth Medical Center of Chinese PLA General HospitalBeijingChina Faculty of Medicine and Health School of Health SciencesUniversity of SydneyNSWAustralia Sydney Spine institute BurwoodSydneyNSWAustralia Laboratory of Epidemiology Tianjin Neurological InstituteDepartment of NeurologyTianjin Medical University General Hospital&Tianjin Neurological InstituteKey Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous SystemMinistry of Education and Tianjin CityTianjinChina Department of Orthopedics Henan Provincial People’s HospitalZhengzhouHenan ProvinceChina Department of Spinal Surgery The Third Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina Department of Orthopedics The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Department of Spine Surgery Zhengzhou Orthopedics HospitalZhengzhouHenan ProvinceChina Department of Orthopedic Surgery and Orthopedic Research institute West China HospitalSichuan UniversityChengduSichuan ProvinceChina Department of Orthopedics Xinqiao HospitalArmy Medical UniversityChongqingChina Department of Orthopedics The First Affiliated Hospital of China Medical UniversityShenyangLiaoning ProvinceChina Department of Spinal Surgery Shengj

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimot

关键词： China clinical features costs epidemiology methylprednisolone sodium succinate methylprednisolone retrospective study traumatic spinal cord injury treatment

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Lessons from zebrafish on reprogramming the epigenetic ：ode after fertilisation

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Asian Journal of Andrology 2013年第5期15卷 582-583页

作者： Chris O'Neill Centre for Developmental and Regenerative Medicine Kolling Institute for Medical Research Sydney MedicalSchool University of Sydney NSW 2065 Australia

Methylation of cytosine bases encodes epigenetic information that governs lineage-specific patterns of gene expression. Remodelling the methylated genome accompanies major transitions during embryo development, including fertilisation, blastulation and gastrulation. The first whole genome epigenetic maps of this modification across these embryonic transitions in a metazoan has been reported in the zebrafish,

关键词： Lessons zebrafish fertilisation

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Targeting chronic lymphocytic leukemia cells in the tumor microenviroment: A review of the in vitro and clinical trials to date

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World Journal of Clinical Cases 2015年第8期3卷 694-704页

作者： Kyle Crassini Stephen P Mulligan O Giles Best Northern Blood Research Centre and CLL Australian Research Consortium Kolling Institute of Medical Research Royal North Shore Hospital

Chronic lymphocytic leukemia(CLL) is the most common leukemia in the western world. Despite significantadvances in therapy over the last decade CLL remains incurable. Current front-line therapy often consists of chemoimmunotherapy-based regimens, most commonly the fludarabine, cyclophosphamide plus rituximab combination, but rates of relapse and refractory disease are high among these patients. Several key signaling pathways are now known to mediate the survival and proliferation of CLL cells in vivo, the most notable of which are the pathways mediated by the B-cell receptor(BCR) and cytokine receptors. A better understanding of the pathogenesis of the disease, the underlying biology of the CLL-cell and the roles of the tumour microenvironment has provided the rationale for trials of a range of novel, more targeted therapeutic agents. In particular, clinical trials of ibrutinib and idelalisib, which target the Brutons tyrosine kinase and the delta isoform of phosphoinositol-3 kinase components of the BCR signaling pathway respectively, have shown extremely promising results. Here we review the current literature on the key signaling pathways and interactions of CLL cells that mediate the survival and proliferation of the leukemic cells. For each we describe the results of the recent clinical trials and in vitro studies of novel therapeutic agents.

关键词： Chronic lymphocytic leukemia Therapy Microenvironment Leukemia Novel

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COVID-19 and hepatorenal syndrome

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World Journal of Gastroenterology 2022年第39期28卷 5666-5678页

作者： Henry H L Wu Varinder S Athwal Philip A Kalra Rajkumar Chinnadurai kolling institute of Medical Research Royal North Shore HospitalSydney 2065New South WalesAustralia Faculty of Biology Medicine&Health(Division of DiabetesMetabolism&Gastroenterology)The University of ManchesterManchester M139PLUnited Kingdom Department of Renal Medicine Northern Care Alliance NHS Foundation TrustSalford M68HDUnited Kingdom

Coronavirus disease 2019(COVID-19)is a highly infectious disease which emerged into a global pandemic.Although it primarily causes respiratory symptoms for affected patients,COVID-19 was shown to have multi-organ manifestations.Elevated liver enzymes appear to be commonly observed during the course of COVID-19,and there have been numerous reports of liver injury secondary to COVID-19 infection.It has been established that patients with pre-existing chronic liver disease(CLD)are more likely to have poorer outcomes following COVID-19 infection compared to those without CLD.Co-morbidities such as diabetes,hypertension,obesity,cardiovascular and chronic kidney disease frequently co-exist in individuals living with CLD,and a substantial population may also live with some degree of frailty.The mechanisms of how COVID-19 induces liver injury have been postulated.Hepatorenal syndrome(HRS)is the occurrence of kidney dysfunction in patients with severe CLD/fulminant liver failure in the absence of another identifiable cause,and is usually a marker of severe decompensated liver disease.Select reports of HRS following acute COVID-19 infection have been presented,although the risk factors and pathophysiological mechanisms leading to HRS in COVID-19 infection or following COVID-19 treatment remain largely unestablished due to the relative lack and novelty of published data.Evidence discussing the management of HRS in highdependency care and intensive care contexts is only emerging.In this article,we provide an overview on the speculative pathophysiological me-chanisms of COVID-19 induced HRS and propose strategies for clinical diagnosis and management to optimize outcomes in this scenario.

关键词： COVID-19 Hepatorenal syndrome Pathophysiology Clinical assessment Management Prognosis

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Mucin-like glycopolymer gels in electrosensory tissues generate cues which direct electrolocation in amphibians and neuronal activation in mammals

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Neural Regeneration Research 2019年第7期14卷 1191-1195页

作者： James Melrose Raymond Purves Bone and Joint Research Laboratory Kolling InstituteNorthern Sydney Local Health District Graduate School of Biomedical Engineering University of New South Wales Sydney Medical School NorthernThe University of Sydney Faculty of Medicine and Health University of SydneyRoyal North Shore Hospital

Mucin-like glycoproteins have established roles in epithelial boundary protection and lubricative roles in some tissues.This mini-review illustrates alternative functional roles which rely on keratan sulphate and sialic acid modifications to mucin glycopolymers which convey charge properties suggestive of novel electroconductive properties not previously ascribed to these polymers.Many tumour cells express mucin-like glycopolymers modified with highly sulphated keratan sulphate and sialic which can be detected using diagnostic biosensors.The mucin-like keratan sulphate glycopolymer present in the ampullae of lorenzini is a remarkable sensory polymer which elasmobranch fish(sharks,rays,skate) use to detect weak electrical fields emitted through muscular activity of prey fish.Information on the proton gradients is conveyed to neuromast cells located at the base of the ampullae and mechanotransduced to neural networks.This ampullae keratan sulphate sensory gel is the most sensitive proton gradient detection polymer known in nature.This process is known as electrolocation,and allows the visualization of prey fish under conditions of low visibility.The bony fish have similar electroreceptors located along their lateral lines which consist of neuromast cells containing sensory hairs located within a cupula which contains a sensory gel polymer which detects distortions in fluid flow in channels within the lateral lines and signals are sent back to neural networks providing information on the environment around these fish.One species of dolphin,the Guiana dolphin,has electrosensory pits in its bill with similar roles to the ampullae but which have evolved from its vibrissal system.Only two terrestrial animals can undertake electrolocation,these are the Duck-billed platypus and long and short nosed Echidna.In this case the electrosensor is a highly evolved innervated mucous gland.The platypus has 40,000 electroreceptors around its bill through which it electrolocates food species.The platypus has poor eyesight,is a noctur

关键词： mucin glycopolymers keratan sulfate electrolocation monosulphated keratan sulfate neuroregulation glycosaminoglycan neurosensory hair cells neurosensory proteoglycan

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Antihypertensive prescribing patterns in non-dialysis dependent chronic kidney disease:Findings from the Salford Kidney Study

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World Journal of Nephrology 2023年第5期12卷 168-181页

作者： Rajkumar Chinnadurai Henry H L Wu Jones Abuomar Sharmilee Rengarajan David I New Darren Green Philip A Kalra Donal O’Donoghue Renal Research Centre&Department of Renal Medicine Northern Care Alliance NHS Foundation TrustSalford M68HDUnited Kingdom Department of Renal Research Kolling Institute of Medical ResearchRoyal North Shore Hospital&The University of SydneySt.Leonards(Sydney)2065New South WalesAustralia Faculty of Biology Medicine&HealthThe University of ManchesterManchester M17HRUnited Kingdom

BACKGROUND Hypertension is commonly observed in patients living with chronic kidney disease(CKD).Finding an optimal treatment regime remains challenging due to the complex bidirectional cause-and-effect relationship between hypertension and CKD.There remains variability in antihypertensive treatment practices.AIM To analyze data from the Salford Kidney Study database in relation to antihypertensive prescribing patterns amongst CKD patients.METHODS The Salford Kidney Study is an ongoing prospective study that has been recruiting CKD patients since 2002.All patients are followed up annually,and their medical records including the list of medications are updated until they reach study endpoints[starting on renal replacement therapy or reaching estimated glomerular filtration rate(eGFR)expressed as mL/min/1.73 m2≤10 mL/min/1.73 m2,or the last follow-up date,or data lock on December 31,2021,or death].Data on antihypertensive prescription practices in correspondence to baseline eGFR,urine albumin-creatinine ratio,primary CKD aetiology,and cardiovascular disease were evaluated.Associations between patients who were prescribed three or more antihypertensive agents and their clinical outcomes were studied by Cox regression analysis.Kaplan-Meier analysis demonstrated differences in survival probabilities.RESULTS Three thousand two hundred and thirty non-dialysis-dependent CKD patients with data collected between October 2002 and December 2019 were included.The median age was 65 years.A greater proportion of patients were taking three or more antihypertensive agents with advancing CKD stages(53%of eGFR≤15 mL/min/1.73 m2 vs 26%of eGFR≥60 mL/min/1.73 m2,P<0.001).An increased number of patients receiving more classes of antihypertensive agents was observed as the urine albumin-creatinine ratio category increased(category A3:62%vs category A1:40%,P<0.001),with the upward trends particularly noticeable in the number of individuals prescribed renin angiotensin system blockers.The prescription of three or more antihypertensive age

关键词： Hypertension Chronic kidney disease Antihypertensive agents Prescribing patterns Cardiovascular complications Renin angiotensin system blockers

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Endoscopic Management of Pediatric Cholesteatoma

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Journal of Otology 2020年第1期15卷 17-26页

作者： Peter J.Ryan Nirmal P.Patel Department of Otolaryngology and Head and Neck Surgery Royal North Shore HospitalSt LeonardsNSWAustralia kolling Deafness Research Centre Macquarie University and University of SydneyNSWAustralia

Pediatric cholesteatoma occurs in one of two forms:congenital cholesteatoma,developing from embryonic epidermal cell rests or acquired cholesteatoma,associated with a focal defect in the tympanic membrane.This disease has been traditionally managed with the operating microscope,often requiring mastoidectomy for adequate visualization of and access to the middle ear and mastoid cavities.Recently,advances in endoscopic equipment have enabled otologists to manage most cases of pediatric cholesteatoma via a minimally-invasive,transcanal endoscopic approach.This review discusses the current literature relating to the etiopathogenesis,assessment and endoscopic management of pediatric cholesteatoma.Early outcomes of endoscopic treatment,emerging trends and technologies are also reviewed.

关键词： Cholesteatoma Pediatric Endoscopic Minimally-invasive Middle ear Mastoid

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Frailty and antineutrophil cytoplasmic antibody-associated vasculitis:What do we know?

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Rheumatology & Autoimmunity 2023年第4期3卷 250-252页

作者： Henry H.L.Wu Nina Brown Rajkumar Chinnadurai Renal Research Kolling Institute of Medical ResearchRoyal North Shore HospitalThe University of SydneySydneyAustralia Department of Renal Medicine Northern Care Alliance NHS Foundation TrustSalfordUK Faculty of Biology Medicine&HealthThe University of ManchesterManchesterUK

To the Editor,Anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV)is an autoimmune condition that mainly affects small vessels of the body.AAV is a condition that may have multisystem manifestations and has an increased prevalence among older individuals.1 AAV patients conventionally present with symptoms at 65 years of age or older.Previous studies have demonstrated worse clinical outcomes in the aging population.Many older patients live with various comorbidities in addition to potentially relapsing AAV.Dealing with the pathophysiological impact of AAV can be burdensome,as this multifaceted condition may lead to impairment of physical function and contribute to significant mental and emotional stress.The impact of aging on the pathophysiology of AAV is not fully known.Immune dysregulation induced by cell senescence is hypothesized to be a key factor,alongside a mixture of genetic and environmental factors2.

关键词： neutrophil clinical impairment

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