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Multiresistant bacterial infections in liver cirrhosis: Clinical impact and new empirical antibiotic treatment policies

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World Journal of Hepatology 2015年第7期7卷 916-921页

作者： juan acevedo Department of Gastroenterology and Hepatology Queen Alexandra Hospital

Recently, important changes have been reported regarding the epidemiology of bacterial infections in liver cirrhosis. There is an emergence of multiresistant bacteria in many European countries and also worldwide, including the United States and South Korea. The classic empirical antibiotic treatment(third-generation cephalosporins, e.g., ceftriaxone, cefotaxime or amoxicillin-clavulanic acid) is still effective in infections acquired in the community, but its failure rate in hospital acquired infections and in some health-care associated infections is high enough to ban its use in these settings. The current editorial focuses on the different epidemiology of bacterial infections in cirrhosis across countries and on its therapeutic implications.

关键词： Bacterial infections Multiresistant bacteria Antibiotic Liver cirrhosis

Hepatopulmonary syndrome: What we know and what we would like to know

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World Journal of Gastroenterology 2016年第25期22卷 5728-5741页

作者： Israel Grilo-Bensusan juan Manuel Pascasio-acevedo Digestive Diseases Department HAR écija APS Bajo Guadalquivir Unit for the Clinical Management of Digestive Diseases IBIS CIBERehd Virgen del Rocío University Hospital

Hepatopulmonary syndrome (HPS) is characterized by abnormalities in blood oxygenation caused by the presence of intrapulmonary vascular dilations (IPVD) in the context of liver disease, generally at a cirrhotic stage. Knowledge about the subject is still only partial. The majority of the information about the etiopathogenesis of HPS has been obtained through experiments on animals. Reported prevalence in patients who are candidates for a liver transplantation (LT) varies between 4% and 32%, with a predominance of mild or moderate cases. Although it is generally asymptomatic it does have an impact on their quality of life and survival. The diagnosis requires taking an arterial blood gas sample of a seated patient with alveolar-arterial oxygen gradient (AaO2) ≥ 15 mm Hg, or ≥ 20 mm Hg in those over 64 years of age. The IPVD are identified through a transthoracic contrast echocardiography or a macroaggregated albumin lung perfusion scan (99mTc-MAA). There is currently no effective medical treatment. LT has been shown to reverse the syndrome and improve survival rates, even in severe cases. Therefore the policy of prioritizing LT would appear to increase survival rates. This paper takes a critical and clinical look at the current understanding of HPS, as well as the controversies surrounding it and possible future research.

关键词： Hepatopulmonary syndrome Liver cirrhosis Liver transplantation Contrast echocardiography Macroaggregated albumin lung perfusion scan

Update on management of gastric varices

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World Journal of Hepatology 2019年第3期11卷 250-260页

作者： Louisa J Vine Mohsan Subhani juan G acevedo South West Liver Unit University Hospitals Plymouth NHS Trust

Gastric varices(GV) have different physiology and clinical characteristics compared to oesophageal varices(OV). There is little information about the management of GV. Most part of the recommendations is extrapolated from studies where the majority of participants had OV. Thus, most recommendations lack of strong evidence. This is a comprehensive review on all aspects of management of GV, i.e., primary, secondary prophylaxis and management of acute bleeding. The papers on which international societies' recommendations are based are scrutinised in this review and areas of research are identified.

关键词： Gastric varices Oesophageal varices Portal hypertension Cirrhosis

Hepatorenal syndrome:Update on diagnosis and therapy

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World Journal of Hepatology 2017年第6期9卷 293-299页

作者： juan G acevedo Matthew E Cramp South West Liver Unit Plymouth Hospitals Trust Hepatology Research Group Plymouth University Peninsula Schools of Medicine and Dentistry

Hepatorenal syndrome(HRS) is a manifestation of extreme circulatory dysfunction and entails high morbidity and mortality.A new definition has been recently recommended by the International Club of Ascites,according to which HRS diagnosis relies in serum creatinine changes instead that on a fixed high ***,new data on urinary biomarkers has been recently *** this sense,the use of urinary neutrophil gelatinase-associated lipocalin seems useful to identify patients with acute tubular necrosis and should be employed in the diagnostic *** with terlipressin and albumin is the current standard of *** data show that terlipressin in intravenous continuous infusion is better tolerated than intravenous boluses and has the same *** is effective in reversing HRS in only 40%-50% of *** bilirubin and creatinine levels along with the increase in blood pressure and the presence of systemic inflammatory response syndrome have been identified as predictors of ***,there is a need for further research in novel *** treatments have been assessed such as noradrenaline,dopamine,transjugular intrahepatic portosystemic shunt,renal and liver replacement therapy,*** all of them,liver transplant is the only curative option and should be considered in all *** can be prevented with volume expansion with albumin during spontaneous bacterial peritonitis and after post large volume paracentesis,and with antibiotic prophylaxis in patients with advanced cirrhosis and low proteins in the ascitic *** manuscript reviews the recent advances in the diagnosis and management of this life-threatening condition.

关键词： Hepatorenal syndrome Acute-on-chronic liver failure Liver cirrhosis Terlipressin Acute kidney injury

Ion channels, phosphorylation and mammalian sperm apacitation

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Asian Journal of Andrology 2011年第3期13卷 395-405,511页

作者： Pablo E Visconti Dario Krapf Jose Luis de la Vega-Beltran juan Jose acevedo Alberto Darszon Department of Veterinary and Animal Science Paige Labs University of Massachusets Amherst MA 01003 USA Institute of Molecular and Cell Biology of Rosario （CONICETUNR） and Area Biologia Facultad de Ciencias Biologicas y Farmaceuticas UNR Rosario 2000 Argentina Departamento de Genetica del Desarrollo y Fisiologia Molecular Institute de Biotecnologia Universidad Nacional Autonoma de Mexico （UNAM） Cuemavaca Merelos C.P. 62510 Mexico Departamento de Fisiologia y Farmacologia Facultad de Medicina Universidad Autenoma del Estado de Morelas Cuernavaca C.P. 62510 Mexico

Sexually reproducing animals require an orchestrated communication between spermatozoa and the egg to generate a new individual. Capacitation, a maturational complex phenomenon that occurs in the female reproductive tract, renders spermatozoa capable of binding and fusing with the oocyte, and it is a requirement for mammalian fertilization. Capacitation encompasses plasma membrane reorganization, ion permeability regulation, cholesterol loss and changes in the phosphorylation state of many proteins. Novel tools to study sperm ion channels, image intracellular ionic changes and proteins with better spatial and temporal resolution, are unraveling how modifications in sperm ion transport and phosphorylation states lead to capacitation. Recent evidence indicates that two parallel pathways regulate phosphorylation events leading to capacitation, one of them requiring activation of protein kinase A and the second one involving inactivation of ser/thr phosphatases. This review examines the involvement of ion transporters and phosphorylation signaling processes needed for spermatozoa to achieve capacitation. Understanding the molecular mechanisms leading to fertilization is central for societies to deal with rising male infertility rates, to develop safe male gamete-based contraceptives and to preserve biodiversity through better assisted fertilization strategies.

关键词： capacitation ion channels lipids phosphorylation sperm

Sensitivity of diagnosis of spontaneous bacterial peritonitis is higher with the automated cell count method

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World Journal of Hepatology 2024年第11期16卷 1265-1281页

作者： juan G acevedo-Haro Waddah Mohamed Prebashan Moodley Oliver Bendall Kris Bennett Nigel Keelty Sally Chan Sam Waddy Joanne Hosking Wayne Thomas Robert Tilley South West Liver Unit University Hospitals Plymouth NHS TrustPlymouth PL68DHUnited Kingdom Medical School University of PlymouthPlymouth PL68DHUnited Kingdom Intensive Care Unit University Hospitals Plymouth NHS TrustPlymouth PL68DHUnited Kingdom Medical Statistics Group Peninsula Clinical Trials UnitUniversity of PlymouthPlymouth PL68DHUnited Kingdom Haematology Service University Hospitals Plymouth NHS TrustPlymouth PL68DHUnited Kingdom Microbiology Service University Hospitals Plymouth NHS TrustPlymouth PL68DHUnited Kingdom

BACKGROUND Spontaneous bacterial peritonitis(SBP)is one of the most important complications of patients with liver cirrhosis entailing high morbidity and *** an accurate early diagnosis of this infection is key in the outcome of these *** current definition of SBP is based on studies performed more than 40 years ago using a manual technique to count the number of polymorphs in ascitic fluid(AF).There is a lack of data comparing the traditional cell count method with a current automated cell ***,current international guidelines do not mention the type of cell count method to be employed and around half of the centers still rely on the traditional manual *** To compare the accuracy of polymorph count on AF to diagnose SBP between the traditional manual cell count method and a modern automated cell counter against SBP cases fulfilling gold standard criteria:Positive AF culture and signs/symptoms of *** Retrospective analysis including two cohorts:Cross-sectional(cohort 1)and case-control(cohort 2),of patients with decompensated cirrhosis and *** cell count methods were conducted *** SBP cases had a pathogenic bacteria isolated on AF and signs/symptoms of *** A total of 137 cases with 5 positive-SBP,and 85 cases with 33 positive-SBP were included in cohort 1 and 2,***-SBP cases had worse liver function in both *** automated method showed higher sensitivity than the manual cell count:80%vs 52%,P=0.02,in cohort *** methods showed very good specificity(>95%).The best cutoff using the automated cell counter was polymorph≥0.2 cells×10^(9)/L(equivalent to 200 cells/mm^(3))in AF as it has the higher sensitivity keeping a good *** The automated cell count method should be preferred over the manual method to diagnose SBP because of its higher *** definition,using the automated method,as polymorph cell count≥0.2 cells×1

关键词： Spontaneous bacterial peritonitis Diagnosis Cirrhosis Bacterial infection Automated cell count method Manual cell count method Ascitic fluid

Minimally Invasive Surgical Approach for Spinal Canal Tumors—Technique Description and Experience from a Reference Center

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Journal of Cancer Therapy 2017年第3期8卷 268-277页

作者： Miguel Berbeo Roberto Diaz juan Carlos Perez Manuel Giraldo-Grueso Santiago Gutierrez María Camila Villegas juan acevedo Oscar Feo Lee Oscar Zorro juan Gomez Carlos Lindado Pablo Harker juan Sardi Hospital Universitario San Ignacio Pontificia Universidad Javeriana Bogotá Colombia

Background: Spinal canal tumors are difficult to diagnose and treat. The traditional surgical approaches for attempting a complete excision of these lesions frequently involve big incisions and tissue dissection with high risk of postop instability and cerebrospinal fluid leakage. Also, there is a risk of neurological worsening, sometimes irreversible. Methods: We present our experience in a patient series with spinal canal tumors and describe the surgical approach with minimally invasive techniques (MIS). All of them were performed by the Neurosurgery team of the Hospital Universitario San Ignacio during the period of 2011-2016. Results: We reviewed forty patients with spinal canal tumors surgically treated with MIS techniques. 15 patients (37.5%) had Meningioma diagnosis (complete resection in 11 (73.3%), subtotal in 3 (20%) and biopsy in one patient), 10 patients (25%) with Schwannomas reached complete resection in 70% and subtotal in 30%. 5 patients had spinal cord metastasis, with complete resection in 4 patients (80%) and subtotal in 1 (20%). Other included ependymoma, astrocytoma, and miscellaneous. No patient has had cerebrospinal fluid leakage and no postoperative fusion has been required. Conclusions: The minimally invasive approach allowed complete tumors removal in a high number of patients and good postoperative results. These findings are similar and in some cases, better than the reported with traditional techniques. This MIS technique provides encouraging results. It requires a wide learning curve and a high degree of surgical experience.

关键词： Spinal Tumors Minimally Invasive Spine Surgery Surgical Technique

Stiffness-tunable biomaterials provide a good extracellular matrix environment for axon growth and regeneration

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Neural Regeneration Research 2025年第5期20卷 1364-1376页

作者： Ronglin Han Lanxin Luo Caiyan Wei Yaru Qiao Jiming Xie Xianchao Pan juan Xing Department of Pathophysiology School of Basic Medical SciencesSouthwest Medical UniversityLuzhouSichuan ProvinceChina Department of Medicinal Chemistry School of PharmacySouthwest Medical UniversityLuzhouSichuan ProvinceChina

Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.

关键词： alginate axon growth biomaterials extracellular matrix neural repair neurons neuroregeneration polyacrylamide polydimethylsiloxane stiffness

Anti-amyloid antibodies in Alzheimer’s disease: what did clinical trials teach us?

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Neural Regeneration Research 2025年第4期20卷 1092-1093页

作者： Danko Jeremic Lydia Jiménez-Díaz juan D.Navarro-López NeuroPhysiology&Behavior Lab University of Castilla-La ManchaBiomedical Research Center(CRIB)School of Medicine of Ciudad RealCiudad RealSpain

Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the ***,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in AD,being able to precede and influence one *** researchers argue that these proteins are mere executors rather than primary causes of ***,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early ***,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).

关键词： amyloid Alzheimer additive