Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory enshea...Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.展开更多
BACKGROUND Data regarding complex Crohn’s perianal fistulas(CPF)epidemiology are limited,and optimal treatment strategies are elusive.An improved understanding of how CPF treatment options are used in the real-world ...BACKGROUND Data regarding complex Crohn’s perianal fistulas(CPF)epidemiology are limited,and optimal treatment strategies are elusive.An improved understanding of how CPF treatment options are used in the real-world setting and factors associated with CPF development,treatment failure,and reasons for undergoing multiple surgeries may help to inform optimal patient management strategies,reduce treatment burden,and improve outcomes in patients with CPF.AIM To describe the epidemiology,treatments,outcomes,and associated risk/protective factors for complex CPF.METHODS Electronic databases(MEDLINE,EMBASE,EBM Reviews,EconLit)were searched.Two reviewers independently used populations,interventions,comparators,outcomes,study designs,and time criteria to identify relevant studies.Observational studies published in English from January 1,2015 to February 17,2022 with>50 patients were included,even if complex CPF was not defined.Items of interest included complex CPF definitions,epidemiology,treatment patterns,morbidity,mortality,and risk factors associated with complex CPF development,treatment failure,and undergoing multiple surgeries.Data were reported using descriptive statistics.RESULTS Overall,140 studies were included.Complex CPF definitions were heterogeneous and rarely reported(24 studies).Hence,data mostly related to CPF in general.CPF prevalence was variable(range:1.5%-81.0%).Incidence was wide-ranging and mostly reported cumulatively at 1-year post-Crohn’s disease diagnosis(range:3.5%-50.1%).Overall healing and failure rates after treatment were in the range of 10.5%-80.2%and 3.6%-83.0%,respectively.Abscesses were the most frequently reported morbidity(n=18).No CPF-related deaths were reported.No consistent risk or protective factors were identified.CONCLUSION Epidemiology,treatment patterns,and risk factors for CPF vary,likely due to inconsistent CPF and clinical outcome definitions.Standardization would facilitate comparability,which may inform optimal complex CPF treatment strategies.展开更多
The search for reliable biomarkers to predict metabolic dysfunction-associated steatotic liver disease(MASLD)remains a key research focus.Traditional anthropometric parameters,such as triglycerides,glucose,and waist c...The search for reliable biomarkers to predict metabolic dysfunction-associated steatotic liver disease(MASLD)remains a key research focus.Traditional anthropometric parameters,such as triglycerides,glucose,and waist circumference(WC),have proven to be robust tools for diagnosing,stratifying,and predicting health outcomes.These measures facilitate early detection,personalized treatment strategies,and long-term risk assessment in metabolic health.The triglycerideglucose(TyG)index and related parameters,particularly the TyG-WC index,are gaining recognition as reliable biomarkers for MASLD,with consistently high diagnostic accuracy across diverse populations.The TyG-WC index is associated with MASLD and an increased likelihood of all-cause,cardiovascular,and diabetes-related mortality,highlighting its importance in stratification and patient management.This opinion review summarizes key findings on the TyG-WC index across different MASLD populations and provides nutritional recommendations aimed at reducing this index.The TyG-WC index stands out as a practical and scalable biomarker for identifying and stratifying the risk of MASLD,particularly in resource-limited environments where access to advanced diagnostic tools is restricted.However,before the TyG-WC index can be integrated into routine clinical practice,rigorous,longitudinal studies involving ethnically diverse cohorts must validate its prognostic performance.It should be viewed as a complementary tool within a comprehensive metabolic risk assessment framework,supporting preventive strategies while awaiting formal endorsement in clinical guidelines.展开更多
AIM:To analyze the prognostic factors involved in survival and cancer recurrence in patients undergoing surgical treatment for colorectal liver metastases(CLM) and to describe the effects of time-related changes on su...AIM:To analyze the prognostic factors involved in survival and cancer recurrence in patients undergoing surgical treatment for colorectal liver metastases(CLM) and to describe the effects of time-related changes on survival and recurrence in these patients.METHODS:From January 1994 to January 2006,236 patients with CLM underwent surgery with the aim of performing curative resection of neoplastic disease at our institution and 189(80%) of these patients underwent resection of CLM with curative intention.Preoperative,intraoperative and postoperative data,including primary tumor and CLM pathology results,were retrospectively reviewed.Patients were divided into two time periods:a first period from January 1994 to January 2000(n = 93),and a second period from February 2000 to January 2006(n = 143).RESULTS:Global survival at 1,3 and 5 years in patients undergoing hepatic resection was 91%,54% and 47%,respectively.Patients with preoperative extrahepatic disease,carcinoembryonic antigen(CEA) levels over 20 ng/dL,more than four nodules or extrahepatic invasion at pathological analysis had worse survival.Tumor recurrence rate at 1 year was 48.3%,being more frequent in patients with preoperative and pathological extrahepatic disease and CEA levels over 20 ng/dL.Although patients in the second time period had more adverse prognostic factors,no differences in overall survival and recurrence were observed between the two periods.CONCLUSION:Despite advances in surgical technique and better adjuvant treatments and preoperative imaging,careful patient staging and selection is crucial to continue offering a chance of cure to patients with CLM.展开更多
Animal models have allowed detailed study of hemodynamic alterations typical of portal hypertension and the molecular mechanisms involved in abnormalities in splanchnic and systemic circulation associated with this sy...Animal models have allowed detailed study of hemodynamic alterations typical of portal hypertension and the molecular mechanisms involved in abnormalities in splanchnic and systemic circulation associated with this syndrome. Models of prehepatic portal hypertension can be used to study alterations in the splanchnic circulation and the pathophysiology of the hyperdynamic circulation. Models of cirrhosis allow study of the alterations in intrahepatic microcirculation that lead to increased resistance to portal flow. This review summarizes the currently available literature on animal models of portal hypertension and analyzes their relative utility. The criteria for choosing a particular model, depending on the specific objectives of the study, are also discussed.展开更多
Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system whi...Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system which triggers an exaggerated immune response and subsequent bowel tissue damage. IBD has been more frequently found in families, an observation that could be due to either genetic, environmental or both types of factors present in these families. In addition to expanding our knowledge on IBD pathogenesis, defining the specific contribution to familial IBD of each one of these factors might have also clinical usefulness. We review the available evidence on familial IBD pathogenesis.展开更多
Milan criteria are currently the benchmark related to liver transplantation(LT) for hepatocellular carcinoma. However, several groups have proposed different expanded criteria with acceptable results. In this article,...Milan criteria are currently the benchmark related to liver transplantation(LT) for hepatocellular carcinoma. However, several groups have proposed different expanded criteria with acceptable results. In this article, we review the current status of LT beyond the Milan criteria in three different scenarios-expanded criteria with cadaveric LT, downstaging to Milan criteria before LT, and expansion in the context of adult living donor LT. The review focuses on three main questions: what would the impact of the expansion beyond Milan criteria be on the patients on the waiting list; whether the dichotomous criteria(yes/no) currently used are appropriate for LT or continuous survival estimations, such as the one of "Metroticket" and whether it should enter into the clinical practice; and, whether the use of living donor LT in the context of expansion beyond Milan criteria is justified.展开更多
Inflammatory bowel disease (IBD) includes two entities, Crohn’s disease and ulcerative colitis. Both are chronic conditions with frequent complications and surgical procedures and a great impact on patient’s quality...Inflammatory bowel disease (IBD) includes two entities, Crohn’s disease and ulcerative colitis. Both are chronic conditions with frequent complications and surgical procedures and a great impact on patient’s quality of life. The thiopurine antimetabolites azathioprine and 6-mercaptopurine are widely used in IBD patients. Current indications include maintenance therapy, steroid-dependant disease, fistula closure, prevention of infliximab immunogenicity and prevention of Crohn’s disease recurrence. Surprisingly, the wide use of immunosuppressants in the last decades has not decreased the need of surgery, probably because these treatments are introduced at too late stages in disease course. An earlier use of immunossupressants is now advocated by some authors. The rational includes: (1) failure to modify IBD natural history of present therapeutic approach, (2) demonstration that azathioprine can induce mucosal healing, a relevant prognostic factor for Crohn’s disease and ulcerative colitis, and (3) demonstration that early immunossupression has a very positive impact on pediatric, recently diagnosed Crohn’s disease patients. We are now awaiting the results of new studies, to clarify the contribution of azathioprine, as compared to infliximab (SONIC Study), and to demonstrate the usefulness of azathioprine in recently diagnosed adult Crohn’s disease patients (AZTEC study).展开更多
MicroRNAs （miRNAs） are essential for regulating cell differentiation and maintaining the pluripotent state of stem cells. Although dysregulation of specific miRNAs has been associated with certain types of cancer, t...MicroRNAs （miRNAs） are essential for regulating cell differentiation and maintaining the pluripotent state of stem cells. Although dysregulation of specific miRNAs has been associated with certain types of cancer, to date no evidence has linked miRNA expression in embryonic and tumor tissues. We assessed the expression of mature miRNAs in human embryonic colon tissue, and in colorectal cancer and paired normal colon tissue. Overlapping miRNA expression was detected between embryonic colonic mucosa and colorectal cancer. We have found that the miR-17-92 cluster and its target, E2F1, exhibit a similar pattern of expression in human colon development and colonic carcinogenesis, regulating cell proliferation in both cases. In situ hybridization confirmed the high level of expression of miR-17-5p in the crypt progenitor compartment. We conclude that miRNA pathways play a major role in both embryonic development and neoplastic transformation of the colonic epithelium.展开更多
Xanthogranulomatous cholecystitis(XGC)is an uncommon variant of chronic cholecystitis.The perioperative findings in aggressive cases may be indistinguishable from those of gallbladder or biliary tract carcinomas.Three...Xanthogranulomatous cholecystitis(XGC)is an uncommon variant of chronic cholecystitis.The perioperative findings in aggressive cases may be indistinguishable from those of gallbladder or biliary tract carcinomas.Three patients presented mass lesions that infiltrated the hepatic hilum,provoked biliary dilatation and jaundice,and were indicative of malignancy.Surgical excision was performed following oncological principles and included extirpation of the gallbladder,extrahepatic bile duct,and hilar lymph nodes,as well as partial hepatectomy.Postoperative morbidity was minimal.Surgical pathology demonstrated XGC and absence of malignancy in all three cases.All three patients are alive and well after years of follow-up.XGC may have such an aggressive presentation that carcinoma may only be ruled out on surgical pathology.In such cases,the best option may be radical resection following oncological principles performed by expert surgeons,in order that postoperative complications may be minimized if not avoided altogether.展开更多
Pancreatitis-associated protein (PAP) was discovered in the pancreatic juice of rats with acute pancreatitis. PAP is a 16 kDa secretory protein structurally related to the C-type lectins although classical lectin-rela...Pancreatitis-associated protein (PAP) was discovered in the pancreatic juice of rats with acute pancreatitis. PAP is a 16 kDa secretory protein structurally related to the C-type lectins although classical lectin-related function has not been reported yet. Then, it was demonstrated that PAP expression may be activated in some tissues in a constitutive or injury- and inflammation-induced manner. More recently, it has been found that PAP acts as an anti-inflammatory factor in vitro and in vivo. PAP expression can be induced by several pro- and anti-inflammatory cytokines and by itself through a JAK/STAT3-dependent pathway. PAP is able to activate the expression of the anti-inflammatory factor SOCS3 through the JAK/STAT3-dependent pathway. The JAK/STAT3/SOCS3 pathway seems to be a common point between PAP and several cytokines. Therefore, it is reasonable to propose that PAP is a new anti- inflammatory cytokine.展开更多
AIM： To determine the effects of prophylactic peroxisome proliferator-activated receptor （PPARy） agonist administration in an experimental model of post-endoscopic retrograde cholangiopancreatography （post-ERCP） ...AIM： To determine the effects of prophylactic peroxisome proliferator-activated receptor （PPARy） agonist administration in an experimental model of post-endoscopic retrograde cholangiopancreatography （post-ERCP） acute pancreatitis. METHODS： Post-ERCP pancreatitis was induced in male Wistar rats by infusion of contrast medium into the pancreatic duct. In additional group, rosiglitazone, a PPARγ agonist, was administered 1 h before infusion of contrast medium. Plasma and pancreas samples were obtained 6 h after the infusion. RESULTS： Infusion of contrast medium into the pancreatic duct resulted in an inflammatory process characterized by increased lipase levels in plasma, and edema and myeloperoxidase activity （MPO） in pancreas. This result correlated with the activation of nuclear factor κB （NFκB） and the inducible NO synthase （iNOS） expression in pancreatic cells. Rosiglitazone reduced the increase in lipase and the level of edema and the increase in myeloperoxidase as well as the activation of NFκB and iNOS expression. CONCLUSION： A single oral dose of rosiglitazone, given 1 h before post-ERCP pancreatitis induction is effective in reducing the severity of the subsequent inflammatory process. The protective effect of rosiglitazone was associated with NFκB inhibition and the blockage of leukocyte infiltration in pancreas.展开更多
AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy.
AIM:To study the activation of pancreatic and pulmonary mast cells and the effect of mast cell inhibition on the activation of peritoneal and alveolar macrophages during acute pancreatitis.METHODS:Pancreatitis was ind...AIM:To study the activation of pancreatic and pulmonary mast cells and the effect of mast cell inhibition on the activation of peritoneal and alveolar macrophages during acute pancreatitis.METHODS:Pancreatitis was induced by intraductal infusion of 5% sodium taurodeoxycholate in rats.The mast cell inhibitor cromolyn was administered intraperitoneally(i.p.) 30 min before pancreatitis induction.The pancreatic and pulmonary tissue damage was evaluated histologically and mast cells and their state of activation were evaluated.Peritoneal and alveolar macrophages were obtained and the expression of tumor necrosis factor α was determined.Myeloperoxidase activity was measured to evaluate the effect of mast cell inhibition on the progression of the inflammatory process.Finally,the effect of plasma on cultured mast cells or macrophages was evaluated in vitro.RESULTS:The mast cell stabilizer signif icantly reduced inflammation in the pancreas and lung and the activation of alveolar macrophages but had no effect on peritoneal macrophages.Mast cell degranulation was observed in the pancreas during pancreatitis but no changes were observed in the lung.Plasma from rats with pancreatitis could activate alveolar macrophages but did not induce degranulation of mast cells in vitro.CONCLUSION:Pancreatic mast cells play an important role in triggering the local and systemic inflammatory response in the early stages of acute pancreatitis.In contrast,lung mast cells are not directly involved in the inflammatory response related to pancreatic damage.展开更多
Metabolic syndrome is a cluster of several clinical conditions characterized by insulin-resistance and high cardiovascular risk. Non-alcoholic fatty liver disease is the liver expression of the metabolic syndrome, and...Metabolic syndrome is a cluster of several clinical conditions characterized by insulin-resistance and high cardiovascular risk. Non-alcoholic fatty liver disease is the liver expression of the metabolic syndrome, and insulin resistance can be a frequent comorbidity in several chronic liver diseases, in particular hepatitis C virus infection and/or cirrhosis. Several studies have demonstrated that insulin action is not only relevant for glucose control, but also for vascular homeostasis. Insulin regulates nitric oxide production, which mediates to a large degree the vasodilating, antiinflammatory and antithrombotic properties of a healthy endothelium, guaranteeing organ perfusion. The effects of insulin on the liver microvasculature and the effects of IR on sinusoidal endothelial cells have been studied in animal models of non-alcoholic fatty liver disease. The hypotheses derived from these studies and the potential translation of these results into humans are critically discussed in this review.展开更多
There have been major developments in endoscopic imaging techniques in recent years.Endoscopes with high definition and magnification can provide high quality images that allow for the histological estimation of lesio...There have been major developments in endoscopic imaging techniques in recent years.Endoscopes with high definition and magnification can provide high quality images that allow for the histological estimation of lesions in vivo and in situ when combined with ancillary enhancement techniques such as chromoendoscopy(CE)and virtual CE(narrow band imaging fujinon intelligent chromoendoscopy,or i-Scan).Despite the enormous potential for these advanced techniques,their value and feasibility in the clinic are still doubted,particularly in cases of colonic polyps that are slated for removal,where in vivo characterization may be deemed unnecessary.However,there are several advantages offered by such advanced endoscopic imaging.CE with or without magnification demonstrates highly accurate histology and invasion depth prediction,and virtual CE is a feasible and less cumbersome alternative to CE in terms of histological estimation,though not sufficiently accurate for depth invasion prediction.Furthermore,the supplementary information provided by advanced imaging systems can assist the endoscopist in the selection of a strategic approach,such as in deciding whether a colonic lesion should be resected,left in situ,or requires more intensive surgical treatment.Lastly,advanced high-resolution imaging techniques may be more cost effective,such that histopathology of lowrisk lesions following resection can be eliminated.The results of these evaluations and comparisons with traditional CE are presented and discussed.Taken together,the benefits provided by these advanced capabilities justify their development,and advocates their use for the treatment and management of colonic polyps.展开更多
AIM To systematically review the literature on epidemiology,disease burden, and treatment outcomes for Crohn's disease(CD) patients with complex perianal fistulas.METHODS PubMed, Embase, and Cochrane were searched...AIM To systematically review the literature on epidemiology,disease burden, and treatment outcomes for Crohn's disease(CD) patients with complex perianal fistulas.METHODS PubMed, Embase, and Cochrane were searched for relevant articles(published 2000-November 2016) and congress abstracts(published 2011-November 2016).RESULTS Of 535 records reviewed, 62 relevant sources were identified(mostly small observational studies). The cumulative incidence of complex perianal fistulas in CD from two referral-centre studies was 12%-14%(follow-up time, 12 years in one study; not reported in the second study). Complex perianal fistulas result in greatly diminished quality of life; up to 59% of patients are at risk of faecal incontinence. Treatments include combinations of medical and surgical interventions and expanded allogeneic adipose-derived stem cells. High proportions of patients experience lack of or inadequate response to treatment(failure and relapse rates,respectively: medical, 12%-73% and 0%-41%; surgical:0%-100% and 11%.20%; combined medical/surgical:0%-80% and 0%-50%; stem cells: 29%-47% and not reported). Few studies(1 of infliximab; 3 of surgical interventions)have been conducted in treatment-refractory patients, a population with high unmet needs. Limited data exist on the clinical value of anti-tumour necrosis factor-α dose escalation in patients with complex perianal fistulas in CD.CONCLUSION Complex perianal fistulas in CD pose substantial clinical and humanistic burden. There is a need for effective treatments, especially for patients refractory to antitumour necrosis factor-α agents, as evidenced by high failure and relapse rates.展开更多
Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is the most common form of hereditary colorectal cancer. Although great advances in the understanding of its molecular basis have taken...Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is the most common form of hereditary colorectal cancer. Although great advances in the understanding of its molecular basis have taken place in the last decade, optimal selection of individuals for HNPCC genetic testing remains controversial. This is especially relevant since colonoscopy has been proven effective for reducing colorectal cancer incidence and mortality in individuals at-risk for this disorder. In this manuscript, we summarize the most significant contributions to this important issue that have appearedin the last few years.展开更多
Telaprevir and Boceprevir are the first direct acting antivirals approved for chronic hepatitis C in combination with peg-interferon alfa and ribavirin.Pancytopenia due to myelotoxicity caused by these drugs may occur...Telaprevir and Boceprevir are the first direct acting antivirals approved for chronic hepatitis C in combination with peg-interferon alfa and ribavirin.Pancytopenia due to myelotoxicity caused by these drugs may occur,but severe hematological abnormalities or aplastic anemia(AA) have not been described.We collected all cases of severe pancytopenia observed during triple therapy with telaprevir in four Spanish centers since approval of the drug in 2011.Among 142 cirrhotic patients receiving treatment,7 cases of severe pancytopenia(5%) were identified and three were consistent with the diagnosis of AA.Mean age was 59 years,five patients had compensated cirrhosis and two patients had severe hepatitis C recurrence after liver transplantation.Severe pancytopenia was diagnosed a median of 10 wk after the initiation of therapy.Three patients had pre-treatment hematological abnormalities related to splenomegaly.In six patients,antiviral treatment was interrupted at the onset of hematological abnormalities.Two patients died due to septic complications and one patient due to acute alveolar hemorrhage.The remaining patients recovered.Severe pancytopenia and especially AA,are not rare during triple therapy with telaprevir in patients with advanced liver disease.Close monitoring is imperative in this setting to promptly detect serious hematological disorders and to prevent further complications.展开更多
基金supported by the Spanish Ministry of Economy and Competitiveness,No.PID2019-106498GB-I00(to MVS)the Instituto de Salud CarlosⅢ,Fondo Europeo de Desarrollo Regional“Una manera de hacer Europa”,No.PI19/00071(to MAB)+1 种基金Ministerio de Ciencia e Innovación Project,No.SAF2017-82736-C2-1-R(to MTMF)in Universidad Autónoma de MadridFundación Universidad Francisco de Vitoria(to JS)。
文摘Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.
基金Supported by Takeda Pharmaceuticals USA,Inc.Medical writing support was provided by Luke Humphreys,PhD,of Oxford PharmaGenesis,Oxford,UK and was funded by Takeda Development Center Americas,Inc.
文摘BACKGROUND Data regarding complex Crohn’s perianal fistulas(CPF)epidemiology are limited,and optimal treatment strategies are elusive.An improved understanding of how CPF treatment options are used in the real-world setting and factors associated with CPF development,treatment failure,and reasons for undergoing multiple surgeries may help to inform optimal patient management strategies,reduce treatment burden,and improve outcomes in patients with CPF.AIM To describe the epidemiology,treatments,outcomes,and associated risk/protective factors for complex CPF.METHODS Electronic databases(MEDLINE,EMBASE,EBM Reviews,EconLit)were searched.Two reviewers independently used populations,interventions,comparators,outcomes,study designs,and time criteria to identify relevant studies.Observational studies published in English from January 1,2015 to February 17,2022 with>50 patients were included,even if complex CPF was not defined.Items of interest included complex CPF definitions,epidemiology,treatment patterns,morbidity,mortality,and risk factors associated with complex CPF development,treatment failure,and undergoing multiple surgeries.Data were reported using descriptive statistics.RESULTS Overall,140 studies were included.Complex CPF definitions were heterogeneous and rarely reported(24 studies).Hence,data mostly related to CPF in general.CPF prevalence was variable(range:1.5%-81.0%).Incidence was wide-ranging and mostly reported cumulatively at 1-year post-Crohn’s disease diagnosis(range:3.5%-50.1%).Overall healing and failure rates after treatment were in the range of 10.5%-80.2%and 3.6%-83.0%,respectively.Abscesses were the most frequently reported morbidity(n=18).No CPF-related deaths were reported.No consistent risk or protective factors were identified.CONCLUSION Epidemiology,treatment patterns,and risk factors for CPF vary,likely due to inconsistent CPF and clinical outcome definitions.Standardization would facilitate comparability,which may inform optimal complex CPF treatment strategies.
文摘The search for reliable biomarkers to predict metabolic dysfunction-associated steatotic liver disease(MASLD)remains a key research focus.Traditional anthropometric parameters,such as triglycerides,glucose,and waist circumference(WC),have proven to be robust tools for diagnosing,stratifying,and predicting health outcomes.These measures facilitate early detection,personalized treatment strategies,and long-term risk assessment in metabolic health.The triglycerideglucose(TyG)index and related parameters,particularly the TyG-WC index,are gaining recognition as reliable biomarkers for MASLD,with consistently high diagnostic accuracy across diverse populations.The TyG-WC index is associated with MASLD and an increased likelihood of all-cause,cardiovascular,and diabetes-related mortality,highlighting its importance in stratification and patient management.This opinion review summarizes key findings on the TyG-WC index across different MASLD populations and provides nutritional recommendations aimed at reducing this index.The TyG-WC index stands out as a practical and scalable biomarker for identifying and stratifying the risk of MASLD,particularly in resource-limited environments where access to advanced diagnostic tools is restricted.However,before the TyG-WC index can be integrated into routine clinical practice,rigorous,longitudinal studies involving ethnically diverse cohorts must validate its prognostic performance.It should be viewed as a complementary tool within a comprehensive metabolic risk assessment framework,supporting preventive strategies while awaiting formal endorsement in clinical guidelines.
基金Supported by An investigation grant from Abertis Infraestructuras S.A
文摘AIM:To analyze the prognostic factors involved in survival and cancer recurrence in patients undergoing surgical treatment for colorectal liver metastases(CLM) and to describe the effects of time-related changes on survival and recurrence in these patients.METHODS:From January 1994 to January 2006,236 patients with CLM underwent surgery with the aim of performing curative resection of neoplastic disease at our institution and 189(80%) of these patients underwent resection of CLM with curative intention.Preoperative,intraoperative and postoperative data,including primary tumor and CLM pathology results,were retrospectively reviewed.Patients were divided into two time periods:a first period from January 1994 to January 2000(n = 93),and a second period from February 2000 to January 2006(n = 143).RESULTS:Global survival at 1,3 and 5 years in patients undergoing hepatic resection was 91%,54% and 47%,respectively.Patients with preoperative extrahepatic disease,carcinoembryonic antigen(CEA) levels over 20 ng/dL,more than four nodules or extrahepatic invasion at pathological analysis had worse survival.Tumor recurrence rate at 1 year was 48.3%,being more frequent in patients with preoperative and pathological extrahepatic disease and CEA levels over 20 ng/dL.Although patients in the second time period had more adverse prognostic factors,no differences in overall survival and recurrence were observed between the two periods.CONCLUSION:Despite advances in surgical technique and better adjuvant treatments and preoperative imaging,careful patient staging and selection is crucial to continue offering a chance of cure to patients with CLM.
基金Fondo de Investigación Sanitaria (CM04/00031and PI050519)Ministerio de Educación y Ciencia, No.SAF04/04783Instituto de Salud Carlos III, No. C03/02
文摘Animal models have allowed detailed study of hemodynamic alterations typical of portal hypertension and the molecular mechanisms involved in abnormalities in splanchnic and systemic circulation associated with this syndrome. Models of prehepatic portal hypertension can be used to study alterations in the splanchnic circulation and the pathophysiology of the hyperdynamic circulation. Models of cirrhosis allow study of the alterations in intrahepatic microcirculation that lead to increased resistance to portal flow. This review summarizes the currently available literature on animal models of portal hypertension and analyzes their relative utility. The criteria for choosing a particular model, depending on the specific objectives of the study, are also discussed.
基金Supported by Grants from Ministerio de Ciencia e Innovación(SAF2008/03676) and Fundació Miarnau to Sans M
文摘Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system which triggers an exaggerated immune response and subsequent bowel tissue damage. IBD has been more frequently found in families, an observation that could be due to either genetic, environmental or both types of factors present in these families. In addition to expanding our knowledge on IBD pathogenesis, defining the specific contribution to familial IBD of each one of these factors might have also clinical usefulness. We review the available evidence on familial IBD pathogenesis.
基金Supported by the Association Llavaneres contra el Cáncer,No.IP004500
文摘Milan criteria are currently the benchmark related to liver transplantation(LT) for hepatocellular carcinoma. However, several groups have proposed different expanded criteria with acceptable results. In this article, we review the current status of LT beyond the Milan criteria in three different scenarios-expanded criteria with cadaveric LT, downstaging to Milan criteria before LT, and expansion in the context of adult living donor LT. The review focuses on three main questions: what would the impact of the expansion beyond Milan criteria be on the patients on the waiting list; whether the dichotomous criteria(yes/no) currently used are appropriate for LT or continuous survival estimations, such as the one of "Metroticket" and whether it should enter into the clinical practice; and, whether the use of living donor LT in the context of expansion beyond Milan criteria is justified.
基金Grants from Ministerio de Educación y Ciencia(SAF2005-00280) to MS
文摘Inflammatory bowel disease (IBD) includes two entities, Crohn’s disease and ulcerative colitis. Both are chronic conditions with frequent complications and surgical procedures and a great impact on patient’s quality of life. The thiopurine antimetabolites azathioprine and 6-mercaptopurine are widely used in IBD patients. Current indications include maintenance therapy, steroid-dependant disease, fistula closure, prevention of infliximab immunogenicity and prevention of Crohn’s disease recurrence. Surprisingly, the wide use of immunosuppressants in the last decades has not decreased the need of surgery, probably because these treatments are introduced at too late stages in disease course. An earlier use of immunossupressants is now advocated by some authors. The rational includes: (1) failure to modify IBD natural history of present therapeutic approach, (2) demonstration that azathioprine can induce mucosal healing, a relevant prognostic factor for Crohn’s disease and ulcerative colitis, and (3) demonstration that early immunossupression has a very positive impact on pediatric, recently diagnosed Crohn’s disease patients. We are now awaiting the results of new studies, to clarify the contribution of azathioprine, as compared to infliximab (SONIC Study), and to demonstrate the usefulness of azathioprine in recently diagnosed adult Crohn’s disease patients (AZTEC study).
文摘MicroRNAs （miRNAs） are essential for regulating cell differentiation and maintaining the pluripotent state of stem cells. Although dysregulation of specific miRNAs has been associated with certain types of cancer, to date no evidence has linked miRNA expression in embryonic and tumor tissues. We assessed the expression of mature miRNAs in human embryonic colon tissue, and in colorectal cancer and paired normal colon tissue. Overlapping miRNA expression was detected between embryonic colonic mucosa and colorectal cancer. We have found that the miR-17-92 cluster and its target, E2F1, exhibit a similar pattern of expression in human colon development and colonic carcinogenesis, regulating cell proliferation in both cases. In situ hybridization confirmed the high level of expression of miR-17-5p in the crypt progenitor compartment. We conclude that miRNA pathways play a major role in both embryonic development and neoplastic transformation of the colonic epithelium.
基金Supported by Nacif LS was supported by an International Travel Scholar Award from the International Liver Transplantation Society(ILTS)
文摘Xanthogranulomatous cholecystitis(XGC)is an uncommon variant of chronic cholecystitis.The perioperative findings in aggressive cases may be indistinguishable from those of gallbladder or biliary tract carcinomas.Three patients presented mass lesions that infiltrated the hepatic hilum,provoked biliary dilatation and jaundice,and were indicative of malignancy.Surgical excision was performed following oncological principles and included extirpation of the gallbladder,extrahepatic bile duct,and hilar lymph nodes,as well as partial hepatectomy.Postoperative morbidity was minimal.Surgical pathology demonstrated XGC and absence of malignancy in all three cases.All three patients are alive and well after years of follow-up.XGC may have such an aggressive presentation that carcinoma may only be ruled out on surgical pathology.In such cases,the best option may be radical resection following oncological principles performed by expert surgeons,in order that postoperative complications may be minimized if not avoided altogether.
文摘Pancreatitis-associated protein (PAP) was discovered in the pancreatic juice of rats with acute pancreatitis. PAP is a 16 kDa secretory protein structurally related to the C-type lectins although classical lectin-related function has not been reported yet. Then, it was demonstrated that PAP expression may be activated in some tissues in a constitutive or injury- and inflammation-induced manner. More recently, it has been found that PAP acts as an anti-inflammatory factor in vitro and in vivo. PAP expression can be induced by several pro- and anti-inflammatory cytokines and by itself through a JAK/STAT3-dependent pathway. PAP is able to activate the expression of the anti-inflammatory factor SOCS3 through the JAK/STAT3-dependent pathway. The JAK/STAT3/SOCS3 pathway seems to be a common point between PAP and several cytokines. Therefore, it is reasonable to propose that PAP is a new anti- inflammatory cytokine.
基金Supported by FIS grant PI020286 and PI050599 and Ramón y Cajal contract to Emma Folch-Puy. Susana Granell was a recipient for an IDIBAPS grant
文摘AIM： To determine the effects of prophylactic peroxisome proliferator-activated receptor （PPARy） agonist administration in an experimental model of post-endoscopic retrograde cholangiopancreatography （post-ERCP） acute pancreatitis. METHODS： Post-ERCP pancreatitis was induced in male Wistar rats by infusion of contrast medium into the pancreatic duct. In additional group, rosiglitazone, a PPARγ agonist, was administered 1 h before infusion of contrast medium. Plasma and pancreas samples were obtained 6 h after the infusion. RESULTS： Infusion of contrast medium into the pancreatic duct resulted in an inflammatory process characterized by increased lipase levels in plasma, and edema and myeloperoxidase activity （MPO） in pancreas. This result correlated with the activation of nuclear factor κB （NFκB） and the inducible NO synthase （iNOS） expression in pancreatic cells. Rosiglitazone reduced the increase in lipase and the level of edema and the increase in myeloperoxidase as well as the activation of NFκB and iNOS expression. CONCLUSION： A single oral dose of rosiglitazone, given 1 h before post-ERCP pancreatitis induction is effective in reducing the severity of the subsequent inflammatory process. The protective effect of rosiglitazone was associated with NFκB inhibition and the blockage of leukocyte infiltration in pancreas.
基金Supported by"Ajut Josep Font"(Hospital Clinic,Barcelona)and an ASISA fellowship to Xabier García-Albéniz
文摘AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy.
基金Supported by The Project SAF2006-08449 and agrant from Fundación para la Investigación del Hospital General Universitario de AlicanteInmaculada Lopez-Font has a Juan de la Cierva contract supported by the Spanish Ministry of Science and Innovation
文摘AIM:To study the activation of pancreatic and pulmonary mast cells and the effect of mast cell inhibition on the activation of peritoneal and alveolar macrophages during acute pancreatitis.METHODS:Pancreatitis was induced by intraductal infusion of 5% sodium taurodeoxycholate in rats.The mast cell inhibitor cromolyn was administered intraperitoneally(i.p.) 30 min before pancreatitis induction.The pancreatic and pulmonary tissue damage was evaluated histologically and mast cells and their state of activation were evaluated.Peritoneal and alveolar macrophages were obtained and the expression of tumor necrosis factor α was determined.Myeloperoxidase activity was measured to evaluate the effect of mast cell inhibition on the progression of the inflammatory process.Finally,the effect of plasma on cultured mast cells or macrophages was evaluated in vitro.RESULTS:The mast cell stabilizer signif icantly reduced inflammation in the pancreas and lung and the activation of alveolar macrophages but had no effect on peritoneal macrophages.Mast cell degranulation was observed in the pancreas during pancreatitis but no changes were observed in the lung.Plasma from rats with pancreatitis could activate alveolar macrophages but did not induce degranulation of mast cells in vitro.CONCLUSION:Pancreatic mast cells play an important role in triggering the local and systemic inflammatory response in the early stages of acute pancreatitis.In contrast,lung mast cells are not directly involved in the inflammatory response related to pancreatic damage.
文摘Metabolic syndrome is a cluster of several clinical conditions characterized by insulin-resistance and high cardiovascular risk. Non-alcoholic fatty liver disease is the liver expression of the metabolic syndrome, and insulin resistance can be a frequent comorbidity in several chronic liver diseases, in particular hepatitis C virus infection and/or cirrhosis. Several studies have demonstrated that insulin action is not only relevant for glucose control, but also for vascular homeostasis. Insulin regulates nitric oxide production, which mediates to a large degree the vasodilating, antiinflammatory and antithrombotic properties of a healthy endothelium, guaranteeing organ perfusion. The effects of insulin on the liver microvasculature and the effects of IR on sinusoidal endothelial cells have been studied in animal models of non-alcoholic fatty liver disease. The hypotheses derived from these studies and the potential translation of these results into humans are critically discussed in this review.
基金Supported by The CIBERehd(Centro de Investigación Biomédica en Red,enfermedades hepaticas y digestivas)to Sanabria E
文摘There have been major developments in endoscopic imaging techniques in recent years.Endoscopes with high definition and magnification can provide high quality images that allow for the histological estimation of lesions in vivo and in situ when combined with ancillary enhancement techniques such as chromoendoscopy(CE)and virtual CE(narrow band imaging fujinon intelligent chromoendoscopy,or i-Scan).Despite the enormous potential for these advanced techniques,their value and feasibility in the clinic are still doubted,particularly in cases of colonic polyps that are slated for removal,where in vivo characterization may be deemed unnecessary.However,there are several advantages offered by such advanced endoscopic imaging.CE with or without magnification demonstrates highly accurate histology and invasion depth prediction,and virtual CE is a feasible and less cumbersome alternative to CE in terms of histological estimation,though not sufficiently accurate for depth invasion prediction.Furthermore,the supplementary information provided by advanced imaging systems can assist the endoscopist in the selection of a strategic approach,such as in deciding whether a colonic lesion should be resected,left in situ,or requires more intensive surgical treatment.Lastly,advanced high-resolution imaging techniques may be more cost effective,such that histopathology of lowrisk lesions following resection can be eliminated.The results of these evaluations and comparisons with traditional CE are presented and discussed.Taken together,the benefits provided by these advanced capabilities justify their development,and advocates their use for the treatment and management of colonic polyps.
基金Kate Lothman of RTI Health Solutions provided medical writing services,which were funded by Takeda
文摘AIM To systematically review the literature on epidemiology,disease burden, and treatment outcomes for Crohn's disease(CD) patients with complex perianal fistulas.METHODS PubMed, Embase, and Cochrane were searched for relevant articles(published 2000-November 2016) and congress abstracts(published 2011-November 2016).RESULTS Of 535 records reviewed, 62 relevant sources were identified(mostly small observational studies). The cumulative incidence of complex perianal fistulas in CD from two referral-centre studies was 12%-14%(follow-up time, 12 years in one study; not reported in the second study). Complex perianal fistulas result in greatly diminished quality of life; up to 59% of patients are at risk of faecal incontinence. Treatments include combinations of medical and surgical interventions and expanded allogeneic adipose-derived stem cells. High proportions of patients experience lack of or inadequate response to treatment(failure and relapse rates,respectively: medical, 12%-73% and 0%-41%; surgical:0%-100% and 11%.20%; combined medical/surgical:0%-80% and 0%-50%; stem cells: 29%-47% and not reported). Few studies(1 of infliximab; 3 of surgical interventions)have been conducted in treatment-refractory patients, a population with high unmet needs. Limited data exist on the clinical value of anti-tumour necrosis factor-α dose escalation in patients with complex perianal fistulas in CD.CONCLUSION Complex perianal fistulas in CD pose substantial clinical and humanistic burden. There is a need for effective treatments, especially for patients refractory to antitumour necrosis factor-α agents, as evidenced by high failure and relapse rates.
基金Ministerio de Educación y Ciencia (SAF 04-07190 and 07/-64873) from the Asociación Espaola contra el Cáncer, the Hospital Clínic and Fondo de Investigación Sanitaria
文摘Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is the most common form of hereditary colorectal cancer. Although great advances in the understanding of its molecular basis have taken place in the last decade, optimal selection of individuals for HNPCC genetic testing remains controversial. This is especially relevant since colonoscopy has been proven effective for reducing colorectal cancer incidence and mortality in individuals at-risk for this disorder. In this manuscript, we summarize the most significant contributions to this important issue that have appearedin the last few years.
基金(in part)Instituto de Salud Carlos III(PI11/01907),Ministerio de Economia y Competitividad,co-funded by Fondo Europeo de Desarrollo Regional,Union Europea,Una manera de hacer EuropaRoche Organ Transplantation Research Foundation(ROTRF,CI:442035057)(all to Forns X)
文摘Telaprevir and Boceprevir are the first direct acting antivirals approved for chronic hepatitis C in combination with peg-interferon alfa and ribavirin.Pancytopenia due to myelotoxicity caused by these drugs may occur,but severe hematological abnormalities or aplastic anemia(AA) have not been described.We collected all cases of severe pancytopenia observed during triple therapy with telaprevir in four Spanish centers since approval of the drug in 2011.Among 142 cirrhotic patients receiving treatment,7 cases of severe pancytopenia(5%) were identified and three were consistent with the diagnosis of AA.Mean age was 59 years,five patients had compensated cirrhosis and two patients had severe hepatitis C recurrence after liver transplantation.Severe pancytopenia was diagnosed a median of 10 wk after the initiation of therapy.Three patients had pre-treatment hematological abnormalities related to splenomegaly.In six patients,antiviral treatment was interrupted at the onset of hematological abnormalities.Two patients died due to septic complications and one patient due to acute alveolar hemorrhage.The remaining patients recovered.Severe pancytopenia and especially AA,are not rare during triple therapy with telaprevir in patients with advanced liver disease.Close monitoring is imperative in this setting to promptly detect serious hematological disorders and to prevent further complications.
