Diabetes mellitus and its complications are becoming one of the most important health problems in the world. Diabetic nephropathy is now the main cause of end-stage renal disease. The mechanisms leading tothe developm...Diabetes mellitus and its complications are becoming one of the most important health problems in the world. Diabetic nephropathy is now the main cause of end-stage renal disease. The mechanisms leading tothe development and progression of renal injury are not well known. Therefore, it is very important to f ind new pathogenic pathways to provide opportunities for early diagnosis and targets for novel treatments. At the present time, we know that activation of innate immunity with development of a chronic low grade inflammatory response is a recognized factor in the pathogenesis of diabetic nephropathy. Numerous experimental and clinical studies have shown the participation of different inflammatory molecules and pathways in the pathophysiology of this complication.展开更多
Nowadays, fracture surgery represents a big part of the orthopedic surgeon workload, and usually has associated major clinical and social cost implications. These fractures have several complications. Some of these ar...Nowadays, fracture surgery represents a big part of the orthopedic surgeon workload, and usually has associated major clinical and social cost implications. These fractures have several complications. Some of these are medical, and other related to the surgical treatment itself. Medical complications may affect around 20% of patients with hip fracture. Cognitive and neurological alterations, cardiopulmonary affections(alone or combined), venous thromboembolism, gastrointestinal tract bleeding, urinary tract complications, perioperative anemia, electrolytic and metabolic disorders, and pressure scars are the most important medical complications after hip surgery in terms of frequency, increase of length of stay and perioperative mortality. Complications arising from hip fracture surgery are fairly common, and vary depending on whether the fracture is intracapsular or extracapsular. The main problems in intracapsular fractures are biological: vascularization of the femoral head, and lack of periosteum-a major contributor to fracture healing- in the femoral neck. In extracapsularfractures, by contrast, the problem is mechanical, and relates to load-bearing. Early surgical fixation, the role of anti-thromboembolic and anti-infective prophylaxis, good pain control at the perioperative, detection and management of delirium, correct urinary tract management, avoidance of malnutrition, vitamin D supplementation, osteoporosis treatment and advancement of early mobilization to improve functional recovery and falls prevention are basic recommendations for an optimal maintenance of hip fractured patients.展开更多
Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors located in the alimentary tract. Its usual manifestation is gastrointestinal bleeding. However, small asymptomatic lesions are frequently d...Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors located in the alimentary tract. Its usual manifestation is gastrointestinal bleeding. However, small asymptomatic lesions are frequently detected as incidental finding. Characteristically, most GISTs(> 95%) are positive for the KIT protein(CD117) by IHC staining and approximately 80%-90% of GISTs carry a mutation in the c-KIT or PDGFRA genes. Mutational analysis should be performed when planning adjuvant and neoadjuvant therapy, due to its possible resistance to conventional treatment. The arise of tyrosine kinase inhibitor has supposed a revolution in GISTs treatment being useful as adjuvant, neoadjuvant or recurrence disease treatment. That is why a multidisciplinary approach to this disease is required. The correct characterization of the tumor at diagnosis(the diagnosis of recurrences and the evaluation of the response to treatment with tyrosine kinase inhibitors) is fundamental for facing these tumors and requires specialized Endoscopist, Radiologists and Nuclear Medicine Physician. Surgery is the only potentially curative treatment for suspected resectable GIST. In the case of high risk GISTs, surgery plus adjuvantImatinib-Mesylate for 3 years is the standard treatment. Neoadjuvant imatinib-mesylate should be considered to shrink the tumor in case of locally advanced primary or recurrence disease, unresectable or potentially resectable metastasic tumors, and potentially resectable disease in complex anatomic locations to decrease the related morbidity. In the case of Metastatic GIST under Neoadjuvant treatment, when there are complete response, stable disease or limited disease progression, complete cytoreductive surgery could be a therapeutic option if feasible.展开更多
BACKGROUND Helicobacter pylori(H.pylori)is a widespread microorganism related to gastric adenocarcinoma(AC).In contrast,it has been reported that an inverse association exists between H.pylori infection and esophageal...BACKGROUND Helicobacter pylori(H.pylori)is a widespread microorganism related to gastric adenocarcinoma(AC).In contrast,it has been reported that an inverse association exists between H.pylori infection and esophageal carcinoma.The mechanisms underlying this supposedly protective effect remain controversial.AIM To determine the prevalence of H.pylori infection in esophageal carcinoma patients,we performed a retrospective observational study of esophageal tumors diagnosed in our hospital.METHODS We retrospectively reviewed the prevalence of H.pylori infection in a cohort of patients diagnosed with esophageal carcinoma.Concomitant or previous proton pump inhibitor(PPI)usage was also recorded.RESULTS A total of 89 patients with esophageal carcinoma(69 males,77.5%),with a mean age of 66 years(range,26-93 years)were included.AC was the most frequent pathological variant(n=47,52.8%),followed by squamous cell carcinoma(n=37,41.6%).Fourteen ACs(29.8%)originated in the gastroesophageal junction and 33(70.2%)in the esophageal body.Overall,54 patients(60.7%)presented at stages III and IV.Previous H.pylori infection occurred only in 4 patients(4.5%),3 with AC(6.3%of all ACs)and 1 with squamous cell carcinoma(2.7%of all squamous cell tumors).All patients with previous H.pylori infection had stage III-IV.Only one patient had received prior H.pylori eradication therapy,whereas 86(96.6%)had received previous or concomitant PPI treatment.CONCLUSION In our cohort of patients,and after histologic evaluation of paraffin-embedded primary tumors,we found a very low prevalence of previous H.pylori infection.We also reviewed the medical history of the patients,concluding that the majority had received or were on PPI treatment.The minimal prevalence of H.pylori infection found in this cohort of patients with esophageal carcinoma suggests a protective role.展开更多
The current management therapies for hepatocellular carcinoma(HCC) patients are discussed in this review. Despite the development of new therapies, HCC remains a 'difficult to treat' cancer because HCC typical...The current management therapies for hepatocellular carcinoma(HCC) patients are discussed in this review. Despite the development of new therapies, HCC remains a 'difficult to treat' cancer because HCC typically occurs in advanced liver disease or hepatic cirrhosis. The progression of multistep and multicentric HCC hampers the prevention of the recurrence of HCC. Many HCC patients are treated with surgical resection and radiofrequency ablation(RFA), although these modalities should be considered in only selected cases with a certain HCC number and size. Although there is a shortage of grafts, liver transplantation has the highest survival rates for HCC. Several modalities are salvage treatments; however, intensive care in combination with other modalities or in combination with surgical resection or RFA might offer a better prognosis. Sorafenib is useful for patients with advanced HCC. In the near future, HCC treatment will include stronger molecular targeted drugs, which will have greater potency and fewer adverse events. Further studies will be ongoing.展开更多
Decision-making based on artificial intelligence(AI)methodology is increasingly present in all areas of modern medicine.In recent years,models based on deep-learning have begun to be used in organ transplantation.Taki...Decision-making based on artificial intelligence(AI)methodology is increasingly present in all areas of modern medicine.In recent years,models based on deep-learning have begun to be used in organ transplantation.Taking into account the huge number of factors and variables involved in donor-recipient(DR)matching,AI models may be well suited to improve organ allocation.AI-based models should provide two solutions:complement decision-making with current metrics based on logistic regression and improve their predictability.Hundreds of classifiers could be used to address this problem.However,not all of them are really useful for D-R pairing.Basically,in the decision to assign a given donor to a candidate in waiting list,a multitude of variables are handled,including donor,recipient,logistic and perioperative variables.Of these last two,some of them can be inferred indirectly from the team’s previous experience.Two groups of AI models have been used in the D-R matching:artificial neural networks(ANN)and random forest(RF).The former mimics the functional architecture of neurons,with input layers and output layers.The algorithms can be uni-or multi-objective.In general,ANNs can be used with large databases,where their generalizability is improved.However,they are models that are very sensitive to the quality of the databases and,in essence,they are black-box models in which all variables are important.Unfortunately,these models do not allow to know safely the weight of each variable.On the other hand,RF builds decision trees and works well with small cohorts.In addition,they can select top variables as with logistic regression.However,they are not useful with large databases,due to the extreme number of decision trees that they would generate,making them impractical.Both ANN and RF allow a successful donor allocation in over 80%of D-R pairing,a number much higher than that obtained with the best statistical metrics such as model for end-stage liver disease,balance of risk score,and survival outcomes following liver transplantation scores.Many barriers need to be overcome before these deeplearning-based models can be included for D-R matching.The main one of them is the resistance of the clinicians to leave their own decision to autonomous computational models.展开更多
The concept of oligometastatic disease was first described by Hellman and Weichselbaum in 1995. The mere insight of this concept led to the hypothesis that this disease may be cured using local ablative weapons. Surge...The concept of oligometastatic disease was first described by Hellman and Weichselbaum in 1995. The mere insight of this concept led to the hypothesis that this disease may be cured using local ablative weapons. Surgery has already demonstrated this hypothesis. Surgery limitations, either technical or due to refusalor associated comorbidity, have led to implement alternative ablative options such as stereotactic body radiation therapy(SBRT). SBRT evolved from(stereotactic radiosurgery) because of the need to irradiate extracranial lesions and has been shown to be safe and effective. SBRT achieves local control rates ranging from 70%-90%, but highly variable survival rates depending on the group analyzed. Series with heterogeneous metastatic sites and tumor origin have reported 20% survival rates at 2-3 years, similar to those achieved with surgery. Despite its excellent results, SBRT still faces significant clinical challenges. Its optimal integration with systemic treatment is unknown, and response assessment is very difficult. However, the greatest challenge lies in selection of patients most likely to remain oligometastatic, those who will most benefit from the technique. Biomarkers, molecular signatures, that accurately predict the biological behavior of malignancy are needed. The expression profile of specific mi RNAs has been shown to have a potential in this regard.展开更多
In the new era of functional magnetic resonance imaging(MRI), the utility of chest MRI is increasing exponentially due to several advances, including absence of ionizing radiation, excellent tissue contrast and high c...In the new era of functional magnetic resonance imaging(MRI), the utility of chest MRI is increasing exponentially due to several advances, including absence of ionizing radiation, excellent tissue contrast and high capability for lesion characterization and treatment monitoring. The application of several of these diagnostic weapons in a multiparametric fashion enables to better characterize thymic epithelial tumors and other mediastinal tumoral lesions, accurate assessment of the invasion of adjacent structures and detection of pathologic lymph nodes and metastasis. Also, "do not touch lesions" could be identified with the associated impact in the management of those patients. One of the hotspots of the multiparametric chest MR is its ability to detect with acuity early response to treatment in patients with mediastinal malignant neoplasms. This has been related with higher rates of overall survival and progression free survival.Therefore, in this review we will analyze the current functional imaging techniques available(18 F-Fluorodeoxiglucose positron emission tomography/computed tomography, diffusion-weighted imaging, dynamic contrast-enhanced MRI, diffusion tensor imaging and MR spectroscopy) for the evaluation of mediastinal lesions, with a focus in their correct acquisition and post-processing. Also, to review the clinical applications of these techniques in the diagnostic approach of benign and malignant conditions of the mediastinum.展开更多
We report an unusual pathological entity of a pseudoaneurysm of the right hepatic artery, which developed two years after the resection of a type 11 hilar cholangiocarcinoma and secondary to an excessive skeletonizati...We report an unusual pathological entity of a pseudoaneurysm of the right hepatic artery, which developed two years after the resection of a type 11 hilar cholangiocarcinoma and secondary to an excessive skeletonization for regional lymphadenectomy and neoadjuvant external-beam radiotherapy. After a sudden and massive hematemesis, a multidetector computed tomographic angiography （MDCTA） showed a hepatic artery pseudoaneurysm. Angiography with embolization of the pseudoaneurysm was attempted using microcoils with adequate patency of the hepatic artery and the occlusion of the pseudoaneurysm. A new episode of hematemesis 3 wk later revealed a partial revascularization of the pseudoaneurysm. A definitive interventional radiological treatment consisting of transarterial embolization （TAE） of the right hepatic artery with stainless steel coils and polyvinyl alcohol particles was effective and welltolerated with normal liver function tests and without signs of liver infarction.展开更多
The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or earl...The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage.This problem continues to trouble clinicians,and may have catastrophic consequences for the graft and patient.Ischemic injury,as a result of compromised hepatic artery flow,is a well-known cause of biliary strictures,sepsis,and graft failure.However,very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions(ITBL)that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise.Both the warm and cold ischemic period duration appear to influence the onset of ITBL.All of the commonly used MP techniques deliver oxygen to the graft cells,and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL.As clinical experience and published evidence grows for these modalities,the impact they have on ITBL rates is important to consider.In this review,the evidence for the three commonly used MP strategies(abdominal normothermic regional perfusion[A-NRP],hypothermic oxygenated perfusion[HOPE],and normothermic machine perfusion[NMP])for ITBL prevention has been critically reviewed.Inconsistencies with ITBL definitions used in trials,coupled with variations in techniques of MP,make interpretation challenging.Overall,the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage.The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.展开更多
Hepatitis C virus (HCV) is a major health problem that leads to chronic hepatitis, cirrhosis and hepatocellular carcinoma, being the most frequent indication for liver transplantation in several countries. Unfortunate...Hepatitis C virus (HCV) is a major health problem that leads to chronic hepatitis, cirrhosis and hepatocellular carcinoma, being the most frequent indication for liver transplantation in several countries. Unfortunately, HCV re-infects the liver graft almost invariably following reperfusion, with an accelerated history of recurrence, leading to 10%-30% of patients progressing to cirrhosis within 5 years of transplantation. In this sense, some groups have even advocated for not retransplanting this patients, as lower patient and graftoutcomes have been reported. However, the management of HCV recurrence is being optimized and several strategies to reduce post-transplant recurrence could improve outcomes, decrease the rate of re-transplantation and optimize the use of available grafts. Three moments may be the focus of potential actions in order to decrease the impact of viral recurrence: the pretransplant moment, the transplant environment and the post-transplant management. In the pre-transplant setting, it is not well established if reducing the pre transplant viral load affects the risk for HCV progression after transplant. Obviously, antiviral treatment can render the patient HCV RNA negative post transplant but the long-term benefit has not yet been fully established to justify the cost and clinical risk. In the transplant moment, factors as donor age, cold ischemia time, graft steatosis and ischemia/reperfusion injury may lead to a higher and more aggressive viral recurrence. After the transplant, discussion about immunosuppression and the moment to start the treatment (prophylactic, pre-emptive or once-confirmed) together with new antiviral drugs are of interest. This review aims to help clinicians have a global overview of posttransplant HCV recurrence and strategies to reduce its impact on our patients.展开更多
AIM To demonstrate the non-inferiority(15% non-inferiority limit) of monotherapy with tenofovir disoproxil fumarate(TDF) vs the combination of lamivudine(LAM) plus adefovir dipivoxil(ADV) in the maintenance of virolog...AIM To demonstrate the non-inferiority(15% non-inferiority limit) of monotherapy with tenofovir disoproxil fumarate(TDF) vs the combination of lamivudine(LAM) plus adefovir dipivoxil(ADV) in the maintenance of virologic response in patients with chronic hepatitis B(CHB) and prior failure with LAM.METHODS This study was a Phase IV prospective, randomized, open, controlled study with 2 parallel groups(TDF and LAM+ADV) of adult patients with hepatitis B e antigen(HBe Ag)-negative CHB, prior failure with LAM, on treatment with LAM+ADV for at least 6 mo, without prior resistance to ADV and with an undetectable viral load at the start of the study, in 14 Spanish hospitals. The follow-up time for each patient was 48 wk after randomization, with quarterly visits in which the viral load, biochemical and serological parameters, adverse effects, adherence to treatment and consumption of hospital resources were analysed.RESULTS Forty-six patients were evaluated [median age: 55.4 years(30.2-75.2); 84.8% male], including 22 patients with TDF and 24 with LAM+ADV. During study development, hepatitis B virus DNA(HBV-DNA) remained undetectable, all patients remained HBe Ag negative, and hepatitis B surface antigen(HBs Ag) positive. Alanine aminotransferase(ALT) values at the end of the study were similar in the 2 groups(25.1± 7.65, TDF vs 24.22 ± 8.38, LAM+ADV, P = 0.646). No significant changes were observed in creatinine or serum phosphorus values in either group. No significant differences between the 2 groups were noted in the identification of adverse effects(AEs)(53.8%, TDF vs 37.5%, LAM+ADV, P = 0.170), and none of the AEs which occurred were serious. Treatment adherence was 95.5% and 83.3% in the TDF and the LAM+ADV groups, respectively(P = 0.488). The costs associated with hospital resource consumption were significantly lower with the TDF treatment than the LAM+ADV treatment(€4943 ± 1059 vs €5811 ± 1538, respectively, P < 0.001).CONCLUSION TDF monotherapy proved to be safe and not inferior to the LAM+ADV combination therapy in maintaining virologic response in patients with CHB and previous LAM failure. In addition, the use of TDF generated a significant savings in hospital costs.展开更多
The use of mesenchymal stem-cells(MSC)in cell therapy has received considerable attention because of their properties.These properties include high expansion and differentiation in vitro,low immunogenicity,and modulat...The use of mesenchymal stem-cells(MSC)in cell therapy has received considerable attention because of their properties.These properties include high expansion and differentiation in vitro,low immunogenicity,and modulation of biological processes,such as inflammation,angiogenesis and hematopoiesis.Curiously,the regenerative effect of MSC is partly due to their paracrine activity.This has prompted numerous studies,to investigate the therapeutic potential of their secretome in general,and specifically their extracellular vesicles(EV).The latter contain proteins,lipids,nucleic acids,and other metabolites,which can cause physiological changes when released into recipient cells.Interestingly,contents of EV can be modulated by preconditioning MSC under different culture conditions.Among them,exposure to hypoxia stands out;these cells respond by activating hypoxia-inducible factor(HIF)at low O_(2) concentrations.HIF has direct and indirect pleiotropic effects,modulating expression of hundreds of genes involved in processes such as inflammation,migration,proliferation,differentiation,angiogenesis,metabolism,and cell apoptosis.Expression of these genes is reflected in the contents of secreted EV.Interestingly,numerous studies show that MSC-derived EV conditioned under hypoxia have a higher regenerative capacity than those obtained under normoxia.In this review,we show the implications of hypoxia responses in relation to tissue regeneration.In addition,hypoxia preconditioning of MSC is being evaluated as a very attractive strategy for isolation of EV,with a high potential for clinical use in regenerative medicine that can be applied to different pathologies.展开更多
AIM: To investigate the prognostic significance of resting heart rate in patients with acute coronary syndrome (ACS), independent of other known factors. METHODS: Patients 40 years of age or older who had been admitte...AIM: To investigate the prognostic significance of resting heart rate in patients with acute coronary syndrome (ACS), independent of other known factors. METHODS: Patients 40 years of age or older who had been admitted with acute coronary syndrome (ACS) to one of the 94 hospitals participating in the Prevalence of Peripheral Arterial Disease in Patients with Acute Coronary Syndrome (PAMISCA) study were included. Patients were divided into two groups based on their resting heart rate (HR ≥ or < 70 bpm). Complications were recording during a follow-up period of 1 year. RESULTS: There were 1054 ACS patients analyzed (43.5% with ST segment elevation and 56.5% without elevation). Mean age was 66.6 ± 11.7 years, 70.6% were male and 29.4% of subjects were female. During follow-up, more patients in the HR ≥ 70 bpm group were hospitalized for heart failure and they also had a higher mortality rate. In the multivariate analysis, a heart rate of ≥ 70 bpm was independently related to overall mortality during the follow-up period (hazard ratio 2.5; 95% confidence interval, 1.26-4.97, P = 0.009). CONCLUSION: A resting heart rate ≥ 70 bpm in patients who survive an ACS is an indicator of a high risk of suffering cardiovascular events during follow-up.展开更多
Nitric oxide (NO) is a lipophilic,highly diffusible and short-lived physiological messenger which regulates a variety of important physiological responses including va sodilation,respiration,cell migration,immune resp...Nitric oxide (NO) is a lipophilic,highly diffusible and short-lived physiological messenger which regulates a variety of important physiological responses including va sodilation,respiration,cell migration,immune resp onse and apoptosis.NO is synthesized by three differ entially gene-encoded NO synthase (NOS) in mammals: neuronal NOS (nNOS or NOS-1),inducible NOS (iNOS or NOS-2) and endothelial NOS (eNOS or NOS-3).All isof or ms of NOS catalyze the reaction of L-arginine,NA DPH and oxygen to NO,L-citrulline and NADP.NO may exert its cellular action by cGMP-dependent as well as by cGMP-independent pathways including postranslational modifications in cysteine (S-nitrosylation or S-nit rosation) and tyrosine (nitration) residues,mixed disulf ide formation (S-nitrosoglutathione or GSNO) or prom ot ing further oxidation protein stages which have been related to altered protein function and gene transcription,genotoxic lesions,alteration of cell-cycle check points,apoptosis and DNA repair.NO sensitizes tumor cells to chemotherapeutic compounds.The expression of NOS-2 and NOS-3 has been found to be increased ina variety of human cancers.The multiple actions of NO in the tumor environment is related to heterogeneous cell responses with particular attention in the regulation of the stress response mediated by the hypoxia inducible factor-1 and p53 generally leading to growth arrest,apoptosis or adaptation.展开更多
AIM To evaluate the rate of adverse events(AEs)during consecutive gastric and duodenal polypectomies in several Spanish centers.METHODS Polypectomies of protruded gastric or duodenal polyps≥5 mm using hot snare were ...AIM To evaluate the rate of adverse events(AEs)during consecutive gastric and duodenal polypectomies in several Spanish centers.METHODS Polypectomies of protruded gastric or duodenal polyps≥5 mm using hot snare were prospectively included.Prophylactic measures of hemorrhage were allowed in predefined cases.AEs were defined and graded according to the lexicon recommended by the American Society for Gastrointestinal Endoscopy.Patients were followed for 48 h,one week and 1 mo after theprocedure.RESULTS308 patients were included and a single polypectomy was performed in 205.Only 36(11.7%)were on prior anticoagulant therapy.Mean polyp size was 15±8.9 mm(5-60)and in 294 cases(95.4%)were located in the stomach.Hemorrhage prophylaxis was performed in 219(71.1%)patients.Nine patients presented AEs(2.9%),and 6 of them were bleeding(n=6,1.9%)(in 5 out of 6 AE,different types of endoscopic treatment were performed).Other 24 hemorrhagic episodes could be managed without any change in the outcome of the endoscopy and,consequently,were considered incidents.We did not find any independent risk factor of bleeding.CONCLUSION Gastroduodenal polypectomy using prophylactic measures has a rate of AEs small enough to consider this procedure a safe and effective method for polyp resection independently of the polyp size and location.展开更多
Extra virgin olive oil is characterized by its high content of unsaturated fatty acid residues in triglycerides,mainly oleic acid,and the presence of bioactive and antioxidant compounds.Its consumption is associated w...Extra virgin olive oil is characterized by its high content of unsaturated fatty acid residues in triglycerides,mainly oleic acid,and the presence of bioactive and antioxidant compounds.Its consumption is associated with lower risk of suffering chronic diseases and unwanted processes linked to aging,due to the antioxidant capacity and capability of its components to modulate cellular signaling pathways.Consumption of olive oil can alter the physiology of mesenchymal stem cells(MSCs).This may explain part of the healthy effects of olive oil consumption,such as prevention of unwanted aging processes.To date,there are no specific studies on the action of olive oil on MSCs,but effects of many components of such food on cell viability and differentiation have been evaluated.The objective of this article is to review existing literature on how different compounds of extra virgin olive oil,including residues of fatty acids,vitamins,squalene,triterpenes,pigments and phenols,affect MSC maintenance and differentiation,in order to provide a better understanding of the healthy effects of this food.Interestingly,most studies have shown a positive effect of these compounds on MSCs.The collective findings support the hypothesis that at least part of the beneficial effects of extra virgin olive oil consumption on health may be mediated by its effects on MSCs.展开更多
BACKGROUND The prevalence of heart failure(HF)increases with age,and it is one of the leading causes of hospitalization and death in older patients.However,there are little data on in-hospital mortality in patients wi...BACKGROUND The prevalence of heart failure(HF)increases with age,and it is one of the leading causes of hospitalization and death in older patients.However,there are little data on in-hospital mortality in patients with HF≥75 years in Spain.METHODS A retrospective analysis of the Spanish Minimum Basic Data Set was performed,including all HF episodes discharged from public hospitals in Spain between 2016 and 2019.Coding was performed using the International Classification of Diseases,10th Revision.Patients≥75 years with HF as the principal diagnosis were selected.We calculated:(1)the crude in-hospital mortality rate and its distribution according to age and sex;(2)the risk-standardized in-hospital mortality ratio;and(3)the association between in-hospital mortality and the availability of an intensive cardiac care unit(ICCU)in the hospital.RESULTS We included 354,792 HF episodes of patients over 75 years.The mean age was 85.2±5.5 years,and 59.2%of patients were women.The most frequent comorbidities were renal failure(46.1%),diabetes mellitus(35.5%),valvular disease(33.9%),cardiorespiratory failure(29.8%),and hypertension(26.9%).In-hospital mortality was 12.7%,and increased with age[odds ratio(OR)=1.07,95%CI:1.07–1.07,P<0.001]and was lower in women(OR=0.96,95%CI:0.92–0.97,P<0.001).The main predictors of mortality were the presence of cardiogenic shock(OR=19.5,95%CI:16.8–22.7,P<0.001),stroke(OR=3.5,95%CI:3.0–4.0,P<0.001)and advanced cancer(OR=2.6,95%CI:2.5–2.8,P<0.001).In hospitals with ICCU,the in-hospital risk-adjusted mortality tended to be lower(OR=0.85,95%CI:0.72–1.00,P=0.053).CONCLUSIONS In-hospital mortality in patients with HF≥75 years between 2016 and 2019 was 12.7%,higher in males and elderly patients.The main predictors of mortality were cardiogenic shock,stroke,and advanced cancer.There was a trend toward lower mortality in centers with an ICCU.展开更多
BACKGROUND Surgical resection and radiofrequency ablation(RFA)represent two possible strategy in treatment of hepatocellular carcinoma(HCC)in Milan criteria.AIM To evaluate short-and long-term outcome in elderly patie...BACKGROUND Surgical resection and radiofrequency ablation(RFA)represent two possible strategy in treatment of hepatocellular carcinoma(HCC)in Milan criteria.AIM To evaluate short-and long-term outcome in elderly patients(>70 years)with HCC in Milan criteria,which underwent liver resection(LR)or RFA.METHODS The study included 594 patients with HCC in Milan criteria(429 in LR group and 165 in RFA group)managed in 10 European centers.Statistical analysis was performed using the Kaplan-Meier method before and after propensity score matching(PSM)and Cox regression.RESULTS After PSM,we compared 136 patients in the LR group with 136 patients in the RFA group.Overall survival at 1,3,and 5 years was 91%,80%,and 76%in the LR group and 97%,67%,and 41%in the RFA group respectively(P=0.001).Diseasefree survival at 1,3,and 5 years was 84%,60%and 44%for the LR group,and 63%,36%,and 25%for the RFA group(P=0.001).Postoperative Clavien-Dindo IIIIV complications were lower in the RFA group(1%vs 11%,P=0.001)in association with a shorter length of stay(2 d vs 7 d,P=0.001).In multivariate analysis,Model for End-stage Liver Disease(MELD)score(>10)[odds ratio(OR)=1.89],increased value of international normalized ratio(>1.3)(OR=1.60),treatment with radiofrequency(OR=1.46),and multiple nodules(OR=1.19)were independent predictors of a poor overall survival while a high MELD score(>10)(OR=1.51)and radiofrequency(OR=1.37)were independent factors associated with a higher recurrence rate.CONCLUSION Despite a longer length of stay and a higher rate of severe postoperative complications,surgery provided better results in long-term oncological outcomes as compared to ablation in elderly patients(>70 years)with HCC in Milan criteria.展开更多
Lung transplantation(LT)is a life-saving therapeutic procedure that prolongs survival in patients with end-stage lung disease.Furthermore,as a therapeutic option for high-risk candidates,single LT(SLT)can be feasible ...Lung transplantation(LT)is a life-saving therapeutic procedure that prolongs survival in patients with end-stage lung disease.Furthermore,as a therapeutic option for high-risk candidates,single LT(SLT)can be feasible because the immediate morbidity and mortality after transplantation are lower compared to sequential single(double)LT(SSLTx).Still,the long-term overall survival is,in general,better for SSLTx.Despite the great success over the years,the early post-SLT period remains a perilous time for these patients.Patients who undergo SLT are predisposed to evolving early or late postoperative complications.This review emphasizes factors leading to post-SLT complications in the early and late periods including primary graft dysfunction and chronic lung allograft dysfunction,native lung complications,anastomosis complications,infections,cardiovascular,gastrointestinal,renal,and metabolite complications,and their association with morbidity and mortality in these patients.Furthermore,we discuss the incidence of malignancy after SLT and their correlation with immunosuppression therapy.展开更多
基金Supported by Ministerio de Ciencia e Innovación(Instituto de Salud Carlos Ⅲ-Fondo de Investigación Sanitaria:PI07/0870and PI10/576)Ministerio de Sanidad y Política Social(Dirección General de Terapias Avanzadas y Trasplante:TRA-182)Sociedad Espaola de Nefrología y ACINEF
文摘Diabetes mellitus and its complications are becoming one of the most important health problems in the world. Diabetic nephropathy is now the main cause of end-stage renal disease. The mechanisms leading tothe development and progression of renal injury are not well known. Therefore, it is very important to f ind new pathogenic pathways to provide opportunities for early diagnosis and targets for novel treatments. At the present time, we know that activation of innate immunity with development of a chronic low grade inflammatory response is a recognized factor in the pathogenesis of diabetic nephropathy. Numerous experimental and clinical studies have shown the participation of different inflammatory molecules and pathways in the pathophysiology of this complication.
文摘Nowadays, fracture surgery represents a big part of the orthopedic surgeon workload, and usually has associated major clinical and social cost implications. These fractures have several complications. Some of these are medical, and other related to the surgical treatment itself. Medical complications may affect around 20% of patients with hip fracture. Cognitive and neurological alterations, cardiopulmonary affections(alone or combined), venous thromboembolism, gastrointestinal tract bleeding, urinary tract complications, perioperative anemia, electrolytic and metabolic disorders, and pressure scars are the most important medical complications after hip surgery in terms of frequency, increase of length of stay and perioperative mortality. Complications arising from hip fracture surgery are fairly common, and vary depending on whether the fracture is intracapsular or extracapsular. The main problems in intracapsular fractures are biological: vascularization of the femoral head, and lack of periosteum-a major contributor to fracture healing- in the femoral neck. In extracapsularfractures, by contrast, the problem is mechanical, and relates to load-bearing. Early surgical fixation, the role of anti-thromboembolic and anti-infective prophylaxis, good pain control at the perioperative, detection and management of delirium, correct urinary tract management, avoidance of malnutrition, vitamin D supplementation, osteoporosis treatment and advancement of early mobilization to improve functional recovery and falls prevention are basic recommendations for an optimal maintenance of hip fractured patients.
文摘Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors located in the alimentary tract. Its usual manifestation is gastrointestinal bleeding. However, small asymptomatic lesions are frequently detected as incidental finding. Characteristically, most GISTs(> 95%) are positive for the KIT protein(CD117) by IHC staining and approximately 80%-90% of GISTs carry a mutation in the c-KIT or PDGFRA genes. Mutational analysis should be performed when planning adjuvant and neoadjuvant therapy, due to its possible resistance to conventional treatment. The arise of tyrosine kinase inhibitor has supposed a revolution in GISTs treatment being useful as adjuvant, neoadjuvant or recurrence disease treatment. That is why a multidisciplinary approach to this disease is required. The correct characterization of the tumor at diagnosis(the diagnosis of recurrences and the evaluation of the response to treatment with tyrosine kinase inhibitors) is fundamental for facing these tumors and requires specialized Endoscopist, Radiologists and Nuclear Medicine Physician. Surgery is the only potentially curative treatment for suspected resectable GIST. In the case of high risk GISTs, surgery plus adjuvantImatinib-Mesylate for 3 years is the standard treatment. Neoadjuvant imatinib-mesylate should be considered to shrink the tumor in case of locally advanced primary or recurrence disease, unresectable or potentially resectable metastasic tumors, and potentially resectable disease in complex anatomic locations to decrease the related morbidity. In the case of Metastatic GIST under Neoadjuvant treatment, when there are complete response, stable disease or limited disease progression, complete cytoreductive surgery could be a therapeutic option if feasible.
文摘BACKGROUND Helicobacter pylori(H.pylori)is a widespread microorganism related to gastric adenocarcinoma(AC).In contrast,it has been reported that an inverse association exists between H.pylori infection and esophageal carcinoma.The mechanisms underlying this supposedly protective effect remain controversial.AIM To determine the prevalence of H.pylori infection in esophageal carcinoma patients,we performed a retrospective observational study of esophageal tumors diagnosed in our hospital.METHODS We retrospectively reviewed the prevalence of H.pylori infection in a cohort of patients diagnosed with esophageal carcinoma.Concomitant or previous proton pump inhibitor(PPI)usage was also recorded.RESULTS A total of 89 patients with esophageal carcinoma(69 males,77.5%),with a mean age of 66 years(range,26-93 years)were included.AC was the most frequent pathological variant(n=47,52.8%),followed by squamous cell carcinoma(n=37,41.6%).Fourteen ACs(29.8%)originated in the gastroesophageal junction and 33(70.2%)in the esophageal body.Overall,54 patients(60.7%)presented at stages III and IV.Previous H.pylori infection occurred only in 4 patients(4.5%),3 with AC(6.3%of all ACs)and 1 with squamous cell carcinoma(2.7%of all squamous cell tumors).All patients with previous H.pylori infection had stage III-IV.Only one patient had received prior H.pylori eradication therapy,whereas 86(96.6%)had received previous or concomitant PPI treatment.CONCLUSION In our cohort of patients,and after histologic evaluation of paraffin-embedded primary tumors,we found a very low prevalence of previous H.pylori infection.We also reviewed the medical history of the patients,concluding that the majority had received or were on PPI treatment.The minimal prevalence of H.pylori infection found in this cohort of patients with esophageal carcinoma suggests a protective role.
文摘The current management therapies for hepatocellular carcinoma(HCC) patients are discussed in this review. Despite the development of new therapies, HCC remains a 'difficult to treat' cancer because HCC typically occurs in advanced liver disease or hepatic cirrhosis. The progression of multistep and multicentric HCC hampers the prevention of the recurrence of HCC. Many HCC patients are treated with surgical resection and radiofrequency ablation(RFA), although these modalities should be considered in only selected cases with a certain HCC number and size. Although there is a shortage of grafts, liver transplantation has the highest survival rates for HCC. Several modalities are salvage treatments; however, intensive care in combination with other modalities or in combination with surgical resection or RFA might offer a better prognosis. Sorafenib is useful for patients with advanced HCC. In the near future, HCC treatment will include stronger molecular targeted drugs, which will have greater potency and fewer adverse events. Further studies will be ongoing.
基金supported by a grant from Mutua Madrile?a XVIII Convovatoria de ayudas a la investigación。
文摘Decision-making based on artificial intelligence(AI)methodology is increasingly present in all areas of modern medicine.In recent years,models based on deep-learning have begun to be used in organ transplantation.Taking into account the huge number of factors and variables involved in donor-recipient(DR)matching,AI models may be well suited to improve organ allocation.AI-based models should provide two solutions:complement decision-making with current metrics based on logistic regression and improve their predictability.Hundreds of classifiers could be used to address this problem.However,not all of them are really useful for D-R pairing.Basically,in the decision to assign a given donor to a candidate in waiting list,a multitude of variables are handled,including donor,recipient,logistic and perioperative variables.Of these last two,some of them can be inferred indirectly from the team’s previous experience.Two groups of AI models have been used in the D-R matching:artificial neural networks(ANN)and random forest(RF).The former mimics the functional architecture of neurons,with input layers and output layers.The algorithms can be uni-or multi-objective.In general,ANNs can be used with large databases,where their generalizability is improved.However,they are models that are very sensitive to the quality of the databases and,in essence,they are black-box models in which all variables are important.Unfortunately,these models do not allow to know safely the weight of each variable.On the other hand,RF builds decision trees and works well with small cohorts.In addition,they can select top variables as with logistic regression.However,they are not useful with large databases,due to the extreme number of decision trees that they would generate,making them impractical.Both ANN and RF allow a successful donor allocation in over 80%of D-R pairing,a number much higher than that obtained with the best statistical metrics such as model for end-stage liver disease,balance of risk score,and survival outcomes following liver transplantation scores.Many barriers need to be overcome before these deeplearning-based models can be included for D-R matching.The main one of them is the resistance of the clinicians to leave their own decision to autonomous computational models.
文摘The concept of oligometastatic disease was first described by Hellman and Weichselbaum in 1995. The mere insight of this concept led to the hypothesis that this disease may be cured using local ablative weapons. Surgery has already demonstrated this hypothesis. Surgery limitations, either technical or due to refusalor associated comorbidity, have led to implement alternative ablative options such as stereotactic body radiation therapy(SBRT). SBRT evolved from(stereotactic radiosurgery) because of the need to irradiate extracranial lesions and has been shown to be safe and effective. SBRT achieves local control rates ranging from 70%-90%, but highly variable survival rates depending on the group analyzed. Series with heterogeneous metastatic sites and tumor origin have reported 20% survival rates at 2-3 years, similar to those achieved with surgery. Despite its excellent results, SBRT still faces significant clinical challenges. Its optimal integration with systemic treatment is unknown, and response assessment is very difficult. However, the greatest challenge lies in selection of patients most likely to remain oligometastatic, those who will most benefit from the technique. Biomarkers, molecular signatures, that accurately predict the biological behavior of malignancy are needed. The expression profile of specific mi RNAs has been shown to have a potential in this regard.
文摘In the new era of functional magnetic resonance imaging(MRI), the utility of chest MRI is increasing exponentially due to several advances, including absence of ionizing radiation, excellent tissue contrast and high capability for lesion characterization and treatment monitoring. The application of several of these diagnostic weapons in a multiparametric fashion enables to better characterize thymic epithelial tumors and other mediastinal tumoral lesions, accurate assessment of the invasion of adjacent structures and detection of pathologic lymph nodes and metastasis. Also, "do not touch lesions" could be identified with the associated impact in the management of those patients. One of the hotspots of the multiparametric chest MR is its ability to detect with acuity early response to treatment in patients with mediastinal malignant neoplasms. This has been related with higher rates of overall survival and progression free survival.Therefore, in this review we will analyze the current functional imaging techniques available(18 F-Fluorodeoxiglucose positron emission tomography/computed tomography, diffusion-weighted imaging, dynamic contrast-enhanced MRI, diffusion tensor imaging and MR spectroscopy) for the evaluation of mediastinal lesions, with a focus in their correct acquisition and post-processing. Also, to review the clinical applications of these techniques in the diagnostic approach of benign and malignant conditions of the mediastinum.
基金Ciberehd (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)Ciberehed is funded by the Instituto de Salud Carlos Ⅲ
文摘We report an unusual pathological entity of a pseudoaneurysm of the right hepatic artery, which developed two years after the resection of a type 11 hilar cholangiocarcinoma and secondary to an excessive skeletonization for regional lymphadenectomy and neoadjuvant external-beam radiotherapy. After a sudden and massive hematemesis, a multidetector computed tomographic angiography （MDCTA） showed a hepatic artery pseudoaneurysm. Angiography with embolization of the pseudoaneurysm was attempted using microcoils with adequate patency of the hepatic artery and the occlusion of the pseudoaneurysm. A new episode of hematemesis 3 wk later revealed a partial revascularization of the pseudoaneurysm. A definitive interventional radiological treatment consisting of transarterial embolization （TAE） of the right hepatic artery with stainless steel coils and polyvinyl alcohol particles was effective and welltolerated with normal liver function tests and without signs of liver infarction.
基金funding received in the form of the Catherine Marie Enright research scholarship from the Royal Australasian College of Surgeons to support his program of research
文摘The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage.This problem continues to trouble clinicians,and may have catastrophic consequences for the graft and patient.Ischemic injury,as a result of compromised hepatic artery flow,is a well-known cause of biliary strictures,sepsis,and graft failure.However,very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions(ITBL)that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise.Both the warm and cold ischemic period duration appear to influence the onset of ITBL.All of the commonly used MP techniques deliver oxygen to the graft cells,and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL.As clinical experience and published evidence grows for these modalities,the impact they have on ITBL rates is important to consider.In this review,the evidence for the three commonly used MP strategies(abdominal normothermic regional perfusion[A-NRP],hypothermic oxygenated perfusion[HOPE],and normothermic machine perfusion[NMP])for ITBL prevention has been critically reviewed.Inconsistencies with ITBL definitions used in trials,coupled with variations in techniques of MP,make interpretation challenging.Overall,the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage.The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.
基金Supported by The contribution of Ruben Ciria has been possible thanks to the support of a scholarship from the Sociedad Espa ola de Trasplante Hepático (SETH-2009)
文摘Hepatitis C virus (HCV) is a major health problem that leads to chronic hepatitis, cirrhosis and hepatocellular carcinoma, being the most frequent indication for liver transplantation in several countries. Unfortunately, HCV re-infects the liver graft almost invariably following reperfusion, with an accelerated history of recurrence, leading to 10%-30% of patients progressing to cirrhosis within 5 years of transplantation. In this sense, some groups have even advocated for not retransplanting this patients, as lower patient and graftoutcomes have been reported. However, the management of HCV recurrence is being optimized and several strategies to reduce post-transplant recurrence could improve outcomes, decrease the rate of re-transplantation and optimize the use of available grafts. Three moments may be the focus of potential actions in order to decrease the impact of viral recurrence: the pretransplant moment, the transplant environment and the post-transplant management. In the pre-transplant setting, it is not well established if reducing the pre transplant viral load affects the risk for HCV progression after transplant. Obviously, antiviral treatment can render the patient HCV RNA negative post transplant but the long-term benefit has not yet been fully established to justify the cost and clinical risk. In the transplant moment, factors as donor age, cold ischemia time, graft steatosis and ischemia/reperfusion injury may lead to a higher and more aggressive viral recurrence. After the transplant, discussion about immunosuppression and the moment to start the treatment (prophylactic, pre-emptive or once-confirmed) together with new antiviral drugs are of interest. This review aims to help clinicians have a global overview of posttransplant HCV recurrence and strategies to reduce its impact on our patients.
文摘AIM To demonstrate the non-inferiority(15% non-inferiority limit) of monotherapy with tenofovir disoproxil fumarate(TDF) vs the combination of lamivudine(LAM) plus adefovir dipivoxil(ADV) in the maintenance of virologic response in patients with chronic hepatitis B(CHB) and prior failure with LAM.METHODS This study was a Phase IV prospective, randomized, open, controlled study with 2 parallel groups(TDF and LAM+ADV) of adult patients with hepatitis B e antigen(HBe Ag)-negative CHB, prior failure with LAM, on treatment with LAM+ADV for at least 6 mo, without prior resistance to ADV and with an undetectable viral load at the start of the study, in 14 Spanish hospitals. The follow-up time for each patient was 48 wk after randomization, with quarterly visits in which the viral load, biochemical and serological parameters, adverse effects, adherence to treatment and consumption of hospital resources were analysed.RESULTS Forty-six patients were evaluated [median age: 55.4 years(30.2-75.2); 84.8% male], including 22 patients with TDF and 24 with LAM+ADV. During study development, hepatitis B virus DNA(HBV-DNA) remained undetectable, all patients remained HBe Ag negative, and hepatitis B surface antigen(HBs Ag) positive. Alanine aminotransferase(ALT) values at the end of the study were similar in the 2 groups(25.1± 7.65, TDF vs 24.22 ± 8.38, LAM+ADV, P = 0.646). No significant changes were observed in creatinine or serum phosphorus values in either group. No significant differences between the 2 groups were noted in the identification of adverse effects(AEs)(53.8%, TDF vs 37.5%, LAM+ADV, P = 0.170), and none of the AEs which occurred were serious. Treatment adherence was 95.5% and 83.3% in the TDF and the LAM+ADV groups, respectively(P = 0.488). The costs associated with hospital resource consumption were significantly lower with the TDF treatment than the LAM+ADV treatment(€4943 ± 1059 vs €5811 ± 1538, respectively, P < 0.001).CONCLUSION TDF monotherapy proved to be safe and not inferior to the LAM+ADV combination therapy in maintaining virologic response in patients with CHB and previous LAM failure. In addition, the use of TDF generated a significant savings in hospital costs.
基金Supported by “Instituto de Salud Carlos III”(ISCIII)“Ministerio de Economía y Competitividad”(MINECO) and European Union (EU),No. PI18/01659 and No. PI21/01935
文摘The use of mesenchymal stem-cells(MSC)in cell therapy has received considerable attention because of their properties.These properties include high expansion and differentiation in vitro,low immunogenicity,and modulation of biological processes,such as inflammation,angiogenesis and hematopoiesis.Curiously,the regenerative effect of MSC is partly due to their paracrine activity.This has prompted numerous studies,to investigate the therapeutic potential of their secretome in general,and specifically their extracellular vesicles(EV).The latter contain proteins,lipids,nucleic acids,and other metabolites,which can cause physiological changes when released into recipient cells.Interestingly,contents of EV can be modulated by preconditioning MSC under different culture conditions.Among them,exposure to hypoxia stands out;these cells respond by activating hypoxia-inducible factor(HIF)at low O_(2) concentrations.HIF has direct and indirect pleiotropic effects,modulating expression of hundreds of genes involved in processes such as inflammation,migration,proliferation,differentiation,angiogenesis,metabolism,and cell apoptosis.Expression of these genes is reflected in the contents of secreted EV.Interestingly,numerous studies show that MSC-derived EV conditioned under hypoxia have a higher regenerative capacity than those obtained under normoxia.In this review,we show the implications of hypoxia responses in relation to tissue regeneration.In addition,hypoxia preconditioning of MSC is being evaluated as a very attractive strategy for isolation of EV,with a high potential for clinical use in regenerative medicine that can be applied to different pathologies.
文摘AIM: To investigate the prognostic significance of resting heart rate in patients with acute coronary syndrome (ACS), independent of other known factors. METHODS: Patients 40 years of age or older who had been admitted with acute coronary syndrome (ACS) to one of the 94 hospitals participating in the Prevalence of Peripheral Arterial Disease in Patients with Acute Coronary Syndrome (PAMISCA) study were included. Patients were divided into two groups based on their resting heart rate (HR ≥ or < 70 bpm). Complications were recording during a follow-up period of 1 year. RESULTS: There were 1054 ACS patients analyzed (43.5% with ST segment elevation and 56.5% without elevation). Mean age was 66.6 ± 11.7 years, 70.6% were male and 29.4% of subjects were female. During follow-up, more patients in the HR ≥ 70 bpm group were hospitalized for heart failure and they also had a higher mortality rate. In the multivariate analysis, a heart rate of ≥ 70 bpm was independently related to overall mortality during the follow-up period (hazard ratio 2.5; 95% confidence interval, 1.26-4.97, P = 0.009). CONCLUSION: A resting heart rate ≥ 70 bpm in patients who survive an ACS is an indicator of a high risk of suffering cardiovascular events during follow-up.
文摘Nitric oxide (NO) is a lipophilic,highly diffusible and short-lived physiological messenger which regulates a variety of important physiological responses including va sodilation,respiration,cell migration,immune resp onse and apoptosis.NO is synthesized by three differ entially gene-encoded NO synthase (NOS) in mammals: neuronal NOS (nNOS or NOS-1),inducible NOS (iNOS or NOS-2) and endothelial NOS (eNOS or NOS-3).All isof or ms of NOS catalyze the reaction of L-arginine,NA DPH and oxygen to NO,L-citrulline and NADP.NO may exert its cellular action by cGMP-dependent as well as by cGMP-independent pathways including postranslational modifications in cysteine (S-nitrosylation or S-nit rosation) and tyrosine (nitration) residues,mixed disulf ide formation (S-nitrosoglutathione or GSNO) or prom ot ing further oxidation protein stages which have been related to altered protein function and gene transcription,genotoxic lesions,alteration of cell-cycle check points,apoptosis and DNA repair.NO sensitizes tumor cells to chemotherapeutic compounds.The expression of NOS-2 and NOS-3 has been found to be increased ina variety of human cancers.The multiple actions of NO in the tumor environment is related to heterogeneous cell responses with particular attention in the regulation of the stress response mediated by the hypoxia inducible factor-1 and p53 generally leading to growth arrest,apoptosis or adaptation.
文摘AIM To evaluate the rate of adverse events(AEs)during consecutive gastric and duodenal polypectomies in several Spanish centers.METHODS Polypectomies of protruded gastric or duodenal polyps≥5 mm using hot snare were prospectively included.Prophylactic measures of hemorrhage were allowed in predefined cases.AEs were defined and graded according to the lexicon recommended by the American Society for Gastrointestinal Endoscopy.Patients were followed for 48 h,one week and 1 mo after theprocedure.RESULTS308 patients were included and a single polypectomy was performed in 205.Only 36(11.7%)were on prior anticoagulant therapy.Mean polyp size was 15±8.9 mm(5-60)and in 294 cases(95.4%)were located in the stomach.Hemorrhage prophylaxis was performed in 219(71.1%)patients.Nine patients presented AEs(2.9%),and 6 of them were bleeding(n=6,1.9%)(in 5 out of 6 AE,different types of endoscopic treatment were performed).Other 24 hemorrhagic episodes could be managed without any change in the outcome of the endoscopy and,consequently,were considered incidents.We did not find any independent risk factor of bleeding.CONCLUSION Gastroduodenal polypectomy using prophylactic measures has a rate of AEs small enough to consider this procedure a safe and effective method for polyp resection independently of the polyp size and location.
基金Supported by grants "Fragilidad y Envejecimiento Saludable"(CIBERFES)of "Instituto de Salud Carlos Ⅲ"(ISCⅢ)No.PI15/01857,PI18/01659 and CIBER
文摘Extra virgin olive oil is characterized by its high content of unsaturated fatty acid residues in triglycerides,mainly oleic acid,and the presence of bioactive and antioxidant compounds.Its consumption is associated with lower risk of suffering chronic diseases and unwanted processes linked to aging,due to the antioxidant capacity and capability of its components to modulate cellular signaling pathways.Consumption of olive oil can alter the physiology of mesenchymal stem cells(MSCs).This may explain part of the healthy effects of olive oil consumption,such as prevention of unwanted aging processes.To date,there are no specific studies on the action of olive oil on MSCs,but effects of many components of such food on cell viability and differentiation have been evaluated.The objective of this article is to review existing literature on how different compounds of extra virgin olive oil,including residues of fatty acids,vitamins,squalene,triterpenes,pigments and phenols,affect MSC maintenance and differentiation,in order to provide a better understanding of the healthy effects of this food.Interestingly,most studies have shown a positive effect of these compounds on MSCs.The collective findings support the hypothesis that at least part of the beneficial effects of extra virgin olive oil consumption on health may be mediated by its effects on MSCs.
文摘BACKGROUND The prevalence of heart failure(HF)increases with age,and it is one of the leading causes of hospitalization and death in older patients.However,there are little data on in-hospital mortality in patients with HF≥75 years in Spain.METHODS A retrospective analysis of the Spanish Minimum Basic Data Set was performed,including all HF episodes discharged from public hospitals in Spain between 2016 and 2019.Coding was performed using the International Classification of Diseases,10th Revision.Patients≥75 years with HF as the principal diagnosis were selected.We calculated:(1)the crude in-hospital mortality rate and its distribution according to age and sex;(2)the risk-standardized in-hospital mortality ratio;and(3)the association between in-hospital mortality and the availability of an intensive cardiac care unit(ICCU)in the hospital.RESULTS We included 354,792 HF episodes of patients over 75 years.The mean age was 85.2±5.5 years,and 59.2%of patients were women.The most frequent comorbidities were renal failure(46.1%),diabetes mellitus(35.5%),valvular disease(33.9%),cardiorespiratory failure(29.8%),and hypertension(26.9%).In-hospital mortality was 12.7%,and increased with age[odds ratio(OR)=1.07,95%CI:1.07–1.07,P<0.001]and was lower in women(OR=0.96,95%CI:0.92–0.97,P<0.001).The main predictors of mortality were the presence of cardiogenic shock(OR=19.5,95%CI:16.8–22.7,P<0.001),stroke(OR=3.5,95%CI:3.0–4.0,P<0.001)and advanced cancer(OR=2.6,95%CI:2.5–2.8,P<0.001).In hospitals with ICCU,the in-hospital risk-adjusted mortality tended to be lower(OR=0.85,95%CI:0.72–1.00,P=0.053).CONCLUSIONS In-hospital mortality in patients with HF≥75 years between 2016 and 2019 was 12.7%,higher in males and elderly patients.The main predictors of mortality were cardiogenic shock,stroke,and advanced cancer.There was a trend toward lower mortality in centers with an ICCU.
文摘BACKGROUND Surgical resection and radiofrequency ablation(RFA)represent two possible strategy in treatment of hepatocellular carcinoma(HCC)in Milan criteria.AIM To evaluate short-and long-term outcome in elderly patients(>70 years)with HCC in Milan criteria,which underwent liver resection(LR)or RFA.METHODS The study included 594 patients with HCC in Milan criteria(429 in LR group and 165 in RFA group)managed in 10 European centers.Statistical analysis was performed using the Kaplan-Meier method before and after propensity score matching(PSM)and Cox regression.RESULTS After PSM,we compared 136 patients in the LR group with 136 patients in the RFA group.Overall survival at 1,3,and 5 years was 91%,80%,and 76%in the LR group and 97%,67%,and 41%in the RFA group respectively(P=0.001).Diseasefree survival at 1,3,and 5 years was 84%,60%and 44%for the LR group,and 63%,36%,and 25%for the RFA group(P=0.001).Postoperative Clavien-Dindo IIIIV complications were lower in the RFA group(1%vs 11%,P=0.001)in association with a shorter length of stay(2 d vs 7 d,P=0.001).In multivariate analysis,Model for End-stage Liver Disease(MELD)score(>10)[odds ratio(OR)=1.89],increased value of international normalized ratio(>1.3)(OR=1.60),treatment with radiofrequency(OR=1.46),and multiple nodules(OR=1.19)were independent predictors of a poor overall survival while a high MELD score(>10)(OR=1.51)and radiofrequency(OR=1.37)were independent factors associated with a higher recurrence rate.CONCLUSION Despite a longer length of stay and a higher rate of severe postoperative complications,surgery provided better results in long-term oncological outcomes as compared to ablation in elderly patients(>70 years)with HCC in Milan criteria.
文摘Lung transplantation(LT)is a life-saving therapeutic procedure that prolongs survival in patients with end-stage lung disease.Furthermore,as a therapeutic option for high-risk candidates,single LT(SLT)can be feasible because the immediate morbidity and mortality after transplantation are lower compared to sequential single(double)LT(SSLTx).Still,the long-term overall survival is,in general,better for SSLTx.Despite the great success over the years,the early post-SLT period remains a perilous time for these patients.Patients who undergo SLT are predisposed to evolving early or late postoperative complications.This review emphasizes factors leading to post-SLT complications in the early and late periods including primary graft dysfunction and chronic lung allograft dysfunction,native lung complications,anastomosis complications,infections,cardiovascular,gastrointestinal,renal,and metabolite complications,and their association with morbidity and mortality in these patients.Furthermore,we discuss the incidence of malignancy after SLT and their correlation with immunosuppression therapy.
