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Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial

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World journal of Gastrointestinal Oncology 2024年第2期16卷 386-397页

作者： Vilma Pacheco-Barcia Sara Custodio-Cabello Fatima Carrasco-Valero Magda Palka-Kotlowska Axel Mariño-Mendez Alberto Carmona-Bayonas javier Gallego A j muñoz Martín Paula jimenez-Fonseca Luis Cabezon-Gutierrez Department of Medical Oncology Hospital Universitario de TorrejonMadrid 28850Spain Department of Internal Medicine Hospital Universitario de TorrejonMadrid 28850Spain Department of Medical Oncology Hospital Universitario Central de AsturiasOviedo 33011Spain Department of Medical Oncology Hospital Universitario Morales MeseguerUniversity of MurciaMurcia 30001Spain Department of Medical Oncology Hospital General Universitario de ElcheElche 03202Spain Department of Medical Oncology Hospital General Universitario Gregorio MarañónUniversidad Complutense MadridMadrid 28007Spain Universidad Francisco de Vitoria Madrid 28223Spain

BACKGROUND The prognostic value of the Systemic Inflammation Response Index(SIRI)in advanced pancreatic cancer is recognized,but its correlation with patients´nutritional status and outcomes remains unexplored.AIM To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer.METHODS The PANTHEIA-Spanish Society of Medical Oncology(SEOM)study is a multicentric(16 Spanish hospitals),observational,longitudinal,non-interventional initiative,promoted by the SEOM Real World-Evidence work group.This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI.The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers.Patients with pathologically confirmed metastatic pancreatic adenocarcinoma,treated from january 2020 to january 2023,were included.The index was calculated using the product of neutrophil and monocyte counts,divided by lymphocyte counts,obtained within 15 days before initiation chemotherapy.This study evaluated associations between overall survival(OS),SIRI and weight loss.RESULTS A total of 50 patients were included.66%of these patients were male and the median age was 66 years.Metastasis sites:36%liver,12%peritoneal carcinomatosis,10%lung,and 42%multiple locations.Regarding the first line palliative chemotherapy treatments:50%received gemcitabine plus nab-paclitaxel;28%,modified fluorouracil,leucovorin,irinotecan and oxaliplatin,and 16%were administered gemcitabine.42%had a weight loss>5%in the three months(mo)preceding diagnosis.21 patients with a SIRI≥2.3×10^(3)/L exhibited a trend towards a lower median OS compared to those with a SIRI5%weight loss before diagnosis,the median OS was 6 mo,in contrast to 19 mo for those who did not experience such weight loss(P=0.003).Patients with a weight loss>5%showed higher SIRI levels.This difference was statistically significant(P<0.000).For patients with a SIRI<2.3×10^(3)/L,those who did not

关键词： Pancreatic cancer Nutrition Prognostic factor Inflammation Advanced cancer Systemic inflammatory response index Weight loss

An update on iron physiology

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World journal of Gastroenterology 2009年第37期15卷 4617-4626页

作者： Manuel muoz Isabel Villar josé antonio garcía-Erce Transfusion Medicine School of Medicine University of Málaga Málaga 29071 Spain Department of Hospital Pharmacy University Hospital Miguel Servet Zaragoza 50009 Spain Hematology and Hemotherapy University Hospital Miguel Servet Zaragoza 50009 Spain

Iron is an essential micronutrient, as it is required for adequate erythropoietic function, oxidative metabolism and cellular immune responses. Although the absorption of dietary iron (1-2 mg/d) is regulated tightly, it is just balanced with losses. Therefore, internal turnover of iron is essential to meet the requirements for erythropoiesis (20-30 mg/d). Increased iron requirements, limited external supply, and increased blood loss may lead to iron deficiency (ID) and iron-deficiency anemia. Hepcidin, which is made primarily in hepatocytes in response to liver iron levels, inflammation, hypoxia and anemia, is the main iron regulatory hormone. Once secreted into the circulation, hepcidin binds ferroportin on enterocytes and macrophages, which triggers its internalization and lysosomal degradation. Thus, in chronic inflammation, the excess of hepcidin decreases iron absorption and prevents iron recycling, which results in hypoferremia and iron-restricted erythropoiesis, despite normal iron stores (functional ID), and anemia of chronic disease (ACD), which can evolve to ACD plus true ID (ACD + ID). In contrast, low hepcidin expression may lead to iron overload, and vice versa. Laboratory tests provide evidence of iron depletion in the body, or reflect iron-deficient red cell production. The appropriate combination of these laboratory tests help to establish a correct diagnosis of ID status and anemia.

关键词：缺铁性贫血红细胞生成抗菌多肽生理细胞免疫应答化验结果微量营养素氧化代谢

Blood transfusion for the treatment of acute anaemia in inflammatory bowel disease and other digestive diseases

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World journal of Gastroenterology 2009年第37期15卷 4686-4694页

作者： josé antonio garcía-Erce Fernando Gomollón Manuel muoz Transfusion Medicine and Apheresis Unit Haematology and Haemotherapy Regional Service "Miguel Servet" University Hospital Zaragoza 50009 Spain Gastroenterology Unit University Clinical Hospital and Biomedical Investigation Center at Digestive and Hepatic Disease Network c/San Juan Bosco 15 Zaragoza 50009 Spain Transfusion Medicine School of Medicine University of Málaga Málaga 29071 Spain

Allogeneic blood transfusion (ABT) is frequently used as the first therapeutic option for the treatment of acute anaemia in patients with inflammatory bowel disease (IBD), especially when it developed due to gastrointestinal or perioperative blood loss, but is not risk-free. Adverse effects of ABT include, but are not limited to, acute hemolytic reaction (wrong blood or wrong patient), febrile non-hemolytic transfusional reaction, bacterial contamination, transfusion-related acute lung injury, transfusion associated circulatory overload, transfusion-related immuno-modulation, and transmission of almost all infectious diseases (bacteria, virus, protozoa and prion), which might result in increased risk of morbidity and mortality. Unfortunately, the main physiological goal of ABT, i.e. to increase oxygen consumption by the hypoxic tissues, has not been well documented. In contrast, the ABT is usually misused only to increase the haemoglobin level within a f ixed protocol [mostly two by two packed red blood cell (PRC) units] independently of the patient' s tolerance to normovolemic anaemia or his clinical response to the transfusion of PRC units according to a "one-by-one" administration schedule. Evidencebased clinical guidelines may promote best transfusion practices by implementing restrictive transfusion protocols, thus reducing variability and minimizing the avoidable risks of transfusion, and the use of autologous blood and pharmacologic alternatives. In this regard, preoperative autologous blood donation (PABD) consistently diminished the frequency of ABT, although its contribution to ABT avoidance is reduced when performed under a transfusion protocol. In addition, interpretation of utility of PABD in surgical IBD patients is hampered by scarcity of published data. However, the role of autologous red blood cells as drug carriers is promising. Finally, it must be stressed that a combination of methods used within wellconstructed protocols will offer better prospects for blood conservation in selected IBD patie

关键词：肠疾病临床煽动性 ABT

Intravenous iron in inflammatory bowel disease

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World journal of Gastroenterology 2009年第37期15卷 4666-4674页

作者： Manuel muoz Susana Gómez-Ramírez josé antonio garcía-Erce Transfusion Medicine School of Medicine University of Málaga Málaga 29071 Spain Department of Internal Medicine University Hospital Virgen de la Victoria Málaga 29010 Spain Department of Hematology and Hemoterapy University Hospital Miguel Servet Zaragoza 50008 Spain

The prevalence of anemia across studies on patients with inflammatory bowel disease (IBD) is high (30%). Both iron defi ciency (ID) and anemia of chronic disease contribute most to the development of anemia in IBD. The prevalence of ID is even higher (45%). Anemia and ID negatively impact the patient's quality of life. Therefore, together with an adequate control of disease activity, iron replacement therapy should start as soon as anemia or ID is detected to attain a normal hemoglobin (Hb) and iron status. Many patients will respond to oral iron, but compliance may be poor, whereas intravenous (IV) compounds are safe, provide a faster Hb increase and iron store repletion, and presents a lower rate of treatment discontinuation. Absolute indications for IV iron treatment should include severe anemia, intolerance or inappropriate response to oral iron, severe intestinal disease activity, or use of an erythropoietic stimulating agent. Four different products are principally used in clinical practice, which differ in their pharmacokinetic properties and safety profi les: iron gluconate and iron sucrose (lower single doses), and iron dextran and ferric carboxymaltose (higher single doses). After the initial resolution of anemia and the repletion of iron stores, the patient's hematological and iron parameters should be carefully and periodically monitored, and maintenance iron treatment should be provided as required. New IV preparations that allow for giving 1000-1500 mg in a single session, thus facilitating patient management,provide an excellent tool to prevent or treat anemia and ID in this patient population, which in turn avoids allogeneic blood transfusion and improves their quality of life.

关键词：炎症静脉肠铁

Control-based Fault Current Limiter for Minimizing Impact of Distributed Generation Units on Protection Systems

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journal of Modern Power Systems and Clean Energy 2023年第2期11卷 643-650页

作者： Pablo E.muñoz Ricardo j.Mantz Sergio A.González Instituto LEICI UNLPCONICETLa Plata 1900La PlataArgentina Commission of Scientific Researches of the Buenos Aires Province(CICpBA) La PlataArgentina

Distributed generation units(DGUs)bring some problems to the existing protection system,such as those associated with protection blinding and sympathetic tripping.It is known that fault current limiters(FCLs)help minimize the negative impact of DGUs on the protection system.In this paper,a control-based FCL is proposed,i.e.,the FCL is integrated into the DGU control law.To this end,a predictive control strategy with fault current limitation is suggested.In this way,a DGU is controlled,not only for power exchange with the power grid but also to limit its fault current contribution.The proposal is posed as a constrained optimization problem allowing taking into account the current limit explicitly in the design process as a closed-loop solution.A linear approximation is proposed to cope with the inherent nonlinear constraints.The proposal does not require incorporating extra equipment or mechanisms in the control loop,making the design process simple.To evaluate the proposed control-based FCL,both protection blinding and sympathetic tripping scenarios are considered.The control confines the DGU currents within the constraints quickly,avoiding large transient peaks.Therefore,the impact on the protection system is reduced without the necessity that the DGU goes out of service.

关键词： Distributed generation distribution network protection power electronic converter fault current limiter model-based predictive controller

Growth plasticity of conifers did not avoid declining resilience to soil and atmospheric droughts during the 20th century

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Forest Ecosystems 2023年第2期10卷 238-251页

作者： Tong Zheng jordi Martínez-Vilalta Raúl garcía-Valdés antonio Gazol j.julio Camarero Changcheng mu Maurizio Mencuccini Northeast Forestry University Harbin150040China CREAF E08193 Bellaterra(Cerdanyola del Vallès)CataloniaSpain Universitat Autònoma de Barcelona E08193 Bellaterra(Cerdanyola del Vallès)CataloniaSpain Centre de Ciència i Tecnologia Forestal de Catalunya(CTFC) E-25280SolsonaSpain Department of Biology GeologyPhysics and Inorganic ChemistryRey Juan Carlos University28933MóstolesMadridSpain Instituto Pirenaico de Ecologia(IPE-CSIC) Zaragoza50059Spain ICREA 08010BarcelonaSpain

Background:Plasticity in response to environmental drivers can help trees cope with droughts.However,our understanding of the importance of plasticity and physiological adjustments in trees under global change is limited.Methods:We used the International Tree-Ring Data Bank(ITRDB)to examine 20th century growth responses in conifer trees during(resistance)and following(resilience)years of severe soil and atmospheric droughts occurring in isolation or as compound events.Growth resilience indices were calculated using observed growth divided by expected growth to avoid spurious correlations,in which the expected values were obtained by the autoregressive moving average(ARIMA)model.We used high atmospheric vapour pressure deficit(VPD)to select years of atmospheric drought and low annual values of the Standardized Precipitation-Evapotranspiration Index(SPEI)to select years with soil drought.We acquired the sensitivities(i.e.,the slopes of the relationships)by fitting the resilience indices as a function of environmental drivers,and assessed how these sensitivities changed over time for different types of drought events using linear mixed models.We also checked whether plasticity in growth responses was sufficient to prevent long-term trends of growth reductions during or after severe droughts.We acknowledge that by focusing on the response of surviving trees from the ITRDB we are potentially biasing our results towards higher resilience,as stand level responses(e.g.,mortality)may result in lowered competition after the disturbance event.Results:Sensitivities of resilience to VPD and SPEI changed throughout the 20th century,with the directions of these changes often reversing in the second half of the century.For the 1961–2010 period,changing sensitivities had positive effects on resilience,especially following years of high-VPD and compound events,avoiding growth losses that would have occurred if sensitivities had remained constant.Despite sensitivity changes,resilience was still lower at the end of the 20th century

关键词： Tree rings Growth Drought Vapor pressure deficit Plasticity Acclimation

Post-acute pancreatitis diabetes:A complication waiting for more recognition and understanding

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World journal of Gastroenterology 2023年第28期29卷 4405-4415页

作者： Diego garcía-Compeán Alan R jiménez-Rodríguez juan M muñoz-Ayala josé A González-González Héctor j Maldonado-Garza jesús Z Villarreal-Pérez Department of Gastroenterology Autonomous University of Nuevo LeónMonterrey 64700Nuevo LeónMexico Department of Endocrinology Autonomous University of Nuevo LeónMonterrey 64700Nuevo LeónMexico

Post-acute pancreatitis diabetes(PAPD)is the second most common type of diabetes below type 2 diabetes mellitus.Due to the boom in research on this entity carried out during the last decade,its recognition has increased.However,much of the medical community still does not recognize it as a medium and long-term complication of acute pancreatitis(AP).Recent prospective cohort studies show that its incidence is about 23%globally and 34.5%in patients with severe AP.With the overall increase in the incidence of AP this complication will be certainly seen more frequently.Due to its high morbidity,mortality and difficult control,early detection and treatment are essential.However,its risk factors and pathophysiological mechanisms are not clearly defined.Its diagnosis should be made excluding pre-existing diabetes and applying the criteria of the American Diabetes Association after 90 d of resolution of one or more AP episodes.This review will show the evidence published so far on the incidence and prevalence,risk factors,possible pathophysiological mechanisms,clinical outcomes,clinical characteristics and preventive and corrective management of PAPD.Some important gaps needing to be clarified in forthcoming studies will also be discussed.

关键词： Acute pancreatitis Diabetes mellitus Chronic pancreatitis Post-pancreatitis diabetes Pancreatogenic diabetes

Comorbidity in inflammatory bowel disease

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World journal of Gastroenterology 2011年第22期17卷 2723-2733页

作者： antonio López San Román Fernando muoz Gastroenterology Ramón y Cajal Hospital E28034 Madrid Spain Digestive Diseases Complejo Hospitalario Hospital Altos de Nava 24080 León Spain

Patients with inflammatory bowel disease (IBD) can be affected by other unrelated diseases. These are called comorbid conditions, and can include any secondary health problem that affects a person suffering from a primary or main disease, and which is neither linked physiopathologically to the primary condition, nor is it due to the treatments used for the primary condition or to its long-term anatomical or physiological consequences. Different comorbid conditions, as well as their influence on IBD, are discussed.

关键词：肠道疾病合并症炎症鸡传染性法氏囊病健康问题 IBD 生理

Microphysiological systems for solid tumor immunotherapy:opportunities and challenges

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Microsystems & Nanoengineering 2023年第6期9卷 77-106页

作者： Sara Abizanda-Campo María Virumbrales-muñoz Mouhita Humayun Ines Marmol David j.Beebe Ignacio Ochoa Sara Oliván jose M.Ayuso Department of Dermatology University of Wisconsin-MadisonMadisonWIUSA University of Wisconsin Carbone Cancer Center MadisonWIUSA Department of Biomedical Engineering University of WisconsinMadisonWIUSA Tissue Microenvironment Lab(TME lab) Aragón Institute of Engineering Research(I3A)University of ZaragozaZaragozaSpain Instituto de Investigación Sanitaria Aragón(IISA) ZaragozaSpain Centro Investigación Biomédica en Red.Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN)ZaragozaSpain Department of Obstetrics and Gynecology University of Wisconsin-MadisonMadisonWIUSA Department of Biological Engineering Massachusetts Institute of Technology CambridgeCambridgeMAUSA Department of Pathology&Laboratory Medicine University of WisconsinMadisonWIUSA

Immunotherapy remains more effective for hematologic tumors than for solid tumors.One of the main challenges to immunotherapy of solid tumors is the immunosuppressive microenvironment these tumors generate,which limits the cytotoxic capabilities of immune effector cells(e.g.,cytotoxic T and natural killer cells).This microenvironment is characterized by hypoxia,nutrient starvation,accumulated waste products,and acidic pH.Tumor-hijacked cells,such as fibroblasts,macrophages,and T regulatory cells,also contribute to this inhospitable microenvironment for immune cells by secreting immunosuppressive cytokines that suppress the antitumor immune response and lead to immune evasion.Thus,there is a strong interest in developing new drugs and cell formulations that modulate the tumor microenvironment and reduce tumor cell immune evasion.Microphysiological systems(MPSs)are versatile tools that may accelerate the development and evaluation of these therapies,although specific examples showcasing the potential of MPSs remain rare.Advances in microtechnologies have led to the development of sophisticated microfluidic devices used to recapitulate tumor complexity.The resulting models,also known as microphysiological systems(MPSs),are versatile tools with which to decipher the molecular mechanisms driving immune cell antitumor cytotoxicity,immune cell exhaustion,and immune cell exclusion and to evaluate new targeted immunotherapies.Here,we review existing microphysiological platforms to study immuno-oncological applications and discuss challenges and opportunities in the field.

关键词： immunotherapy versatile solid