AIM:To evaluates the effectiveness and safety of the first generation,NS3/4A protease inhibitors(PIs) in clinical practice against chronic C virus,especially in patients with advanced fibrosis. METHODS:Prospective stu...AIM:To evaluates the effectiveness and safety of the first generation,NS3/4A protease inhibitors(PIs) in clinical practice against chronic C virus,especially in patients with advanced fibrosis. METHODS:Prospective study and non-experimental analysis of a multicentre cohort of 38 Spanish hospitals that includes patients with chronic hepatitis C genotype 1,treatment-na?ve(TN) or treatment-experienced(TE),who underwent triple therapy with the first generation NS3/4A protease inhibitors,boceprevir(BOC) and telaprevir(TVR),in combination with pegylated interferon and ribavirin. The patients were treatment in routine practice settings. Data on the study population and on adverse clinical and virologic effects were compiled during the treatment period and during follow up.RESULTS:One thousand and fifty seven patients were included,405(38%) were treated with BOC and 652(62%) with TVR. Of this total,30%(n = 319) were TN and the remaining were TE:28%(n = 298) relapsers,12%(n = 123) partial responders(PR),25%(n = 260) null-responders(NR) and for 5%(n = 57) with prior response unknown. The rate of sustained virologic response(SVR) by intention-to-treatment(ITT) was greater in those treated with TVR(65%) than in those treated with BOC(52%)(P < 0.0001),whereas by modified intention-to-treatment(m ITT) no were found significant differences. By degree of fibrosis,56% of patients were F4 and the highest SVR rates were recorded in the non-F4 patients,both TN and TE. In the analysis by groups,the TN patients treated with TVR by ITT showed a higher SVR(P = 0.005). However,by m ITT there were no significant differences between BOC and TVR. In the multivariate analysis by m ITT,the significant SVR factors were relapsers,IL28 B CC and non-F4; the type of treatment(BOC or TVR) was not significant. The lowest SVR values were presented by the F4-NR patients,treated with BOC(46%) or with TVR(45%). 28% of the patients interrupted the treatment,mainly by non-viral response(51%):this outcome was more frequent in the TE than in the TN patients(57% vs 40%,P = 0.01). With respect to severe haematological disorders,neutropaenia was more likely to affect the patients treated with BOC(33% vs 20%,P ≤ 0.0001),and thrombocytopaenia and anaemia,the F4 patients(P = 0.000,P = 0.025,respectively). CONCLUSION:In a real clinical practice setting with a high proportion of patients with advanced fibrosis,effectiveness of first-generation PIs was high except for NR patients,with similar SVR rates being achieved by BOC and TVR.展开更多
In the current socio-economic scenario characterized by a growing shortage of resources and progressive budget constraints, the need to better coordinate processes in health institutions appears as a relevant aspect t...In the current socio-economic scenario characterized by a growing shortage of resources and progressive budget constraints, the need to better coordinate processes in health institutions appears as a relevant aspect to ensure the future sustainability of system. In this sense, Relational Coordination(RC) provides a valuable opportunity for the reconfiguration of clinical guidelines concerning isolated single-level considerations. In this research the RC model has been applied to explain best results in the process of diagnosing and offering clinical treatments for lung cancer. Lung cancer presents the higher rates of tumor's mortality worldwide. Through unstructured and informal interviews with clinicians at both levels(Primary/Specialist Care), a diagnosis of the situation in relation to joint management of lung cancer is provided. Solutions of continuity in terms of coordination are explained due to the observation of lack of effective knowledge transfer between the two levels. It is this disconnection which justifies the introduction of a modified model of RC for the study and implementation of transfer relations between the knowledge holders, in order to structure consolidated and cooperative evidence-based models that lead to a substantial shortening in the response times with a marked outcomes improvement. To our knowledge, the application of this model to a Public Health problem bringing together both levels of care, hasn't been made till now.展开更多
Objective To discuss the problems existing in the compensation of Chinese clinical trial participants and propose some suggestions for improving their rights.Methods The literature related to the participants’right t...Objective To discuss the problems existing in the compensation of Chinese clinical trial participants and propose some suggestions for improving their rights.Methods The literature related to the participants’right to compensation at home and abroad was searched to study the inadequacy of the compensation right for clinical trial participants in China from four aspects:insurance system,principle of attribution,legal relationship and compensation regulations.Then,some suggestions to improve the participants’right to compensation were proposed.Results and Conclusion China lacks clear legal norms for participants’right to compensation.There are problems such as unclear insurance rules and compensation rules,unclear contractual relationships between parties to clinical trials,and no laws and regulations to rely on for attribution and compensation.China should issue regulatory guidelines related to the right to compensation of participants in clinical trials,so that all parties in clinical trials can have rules to follow if there is the occurrence of injury,which can better protect the rights and interests of the participants.展开更多
Insulin resistance is the major feature of the metabolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resistance and type 2 diabetes mellitus are more often seen t...Insulin resistance is the major feature of the metabolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resistance and type 2 diabetes mellitus are more often seen than in healthy controls or chronic hepatitis B patients. Hepatitis C virus （HCV） infection promotes insulin resistance, mainly by increased TNF production together with enhancement of suppressor of cytokine （SOC-3）; both events block PI3K and Akt phosphorylation. Two types of insulin resistance could be found in chronic hepatitis C patients＇. ＂viral＂ and ＂metabolic＂ insulin resistance. Insulin resistance in chronic hepatitis C is relevant because it promotes steatosis and fibrosis. The mechanisms by which insulin resistance promotes fibrosis progression include： （1） steatosis, （2） hyperleptinemia, （3） increased TNF production, （4） impaired expression of PPARy receptors. Lastly, insulin resistance has been found as a common denominator in patients difficult-to-treat like cirrhotics, overweight, HIV coinfected and Afro-American. Insulin resistance together with fibrosis and genotype has been found to be independently associated with impaired response rate to peginterferon plus ribavirin. Indeed, in genotype 1, the sustained response rate was twice （60%） in patients with HOMA ≤ 2 than patients with HOMA 〉 2. In experiments carried out on Huh-7 cells transfected by full length HCVRNA, interferon alpha blocks HCV replication. However, when insulin （at doses of 128 μU/mL, similar that seen in the hyperinsulinemic state） was added to interferon, the ability to block HCV replication disappeared, and the PKR synthesis was abolished. In summary, hepatitis C promotes insulin resistance and insulin resistance induces interferon resistance, steatosis and fibrosis progression.展开更多
Hepatopulmonary syndrome (HPS) is characterized by abnormalities in blood oxygenation caused by the presence of intrapulmonary vascular dilations (IPVD) in the context of liver disease, generally at a cirrhotic stage....Hepatopulmonary syndrome (HPS) is characterized by abnormalities in blood oxygenation caused by the presence of intrapulmonary vascular dilations (IPVD) in the context of liver disease, generally at a cirrhotic stage. Knowledge about the subject is still only partial. The majority of the information about the etiopathogenesis of HPS has been obtained through experiments on animals. Reported prevalence in patients who are candidates for a liver transplantation (LT) varies between 4% and 32%, with a predominance of mild or moderate cases. Although it is generally asymptomatic it does have an impact on their quality of life and survival. The diagnosis requires taking an arterial blood gas sample of a seated patient with alveolar-arterial oxygen gradient (AaO<sub>2</sub>) ≥ 15 mm Hg, or ≥ 20 mm Hg in those over 64 years of age. The IPVD are identified through a transthoracic contrast echocardiography or a macroaggregated albumin lung perfusion scan (<sup>99m</sup>Tc-MAA). There is currently no effective medical treatment. LT has been shown to reverse the syndrome and improve survival rates, even in severe cases. Therefore the policy of prioritizing LT would appear to increase survival rates. This paper takes a critical and clinical look at the current understanding of HPS, as well as the controversies surrounding it and possible future research.展开更多
AIM:To evaluate the association between 25-hydroxyvitamin D[25(OH)D]and sustained virological response(SVR)in hepatitis C virus(HCV)infected individuals.METHODS:Relevant studies were identified by systematically searc...AIM:To evaluate the association between 25-hydroxyvitamin D[25(OH)D]and sustained virological response(SVR)in hepatitis C virus(HCV)infected individuals.METHODS:Relevant studies were identified by systematically searching MEDLINE databases up to March2012 and abstracts of the European and American Congress of Hepatology conducted in 2011.Studies must provide information on SVR and the levels of 25(OH)D3and/or 25(OH)D2[henceforth referred to as 25(OH)D]in sera samples from HCV infected individuals.The inclusion criteria were:clinical studies that included HCV infected patients aged older than 18 years regardless of HCV genotype or ethnic group;provided information on SVR rates;and were reported in the English languageas full papers.Due to the heterogeneity of studies in categorizing serum vitamin D levels,a cut-off value of30 ng/mL of serum 25(OH)D was used.Heterogeneity was assessed using I2statistics.The summary odds ratios with their corresponding 95%CI were calculated based on a random-effects model.RESULTS:Overall,11 studies(8 observational and 3interventional)involving 1575 individuals were included and 1117 HCV infected individuals(71%)showed low vitamin D levels.Most of the studies included monoinfected HCV individuals with the mean age ranging from 38 to 56 years.Four studies were conducted in human immunodeficiency virus/HCV infected individuals.Regarding vitamin D measurement,most of the studies employed radioimmunoassays(n=5)followed by chemiluminescence(n=4)and just one study employed high performance/pressure liquid chromatography(HPLC).Basal vitamin D levels varied from 17 to43 ng/mL in the studies selected,and most of the HCV infected individuals had genotype 1(1068/1575)with mean viral load varying from log 4.5-5.9 UI/mL.With regard to HCV treatment,most of the studies(n=8)included HCV individuals without previous treatment,where the pooled SVR rate was 46.4%.High rates of SVR were observed in HCV individuals with vitamin D levels above 30 ng/mL(OR=1.57;95%CI:1.12-2.2)and those supplemented with vitamin D(OR=4.59;95%CI:1.67-12.63)regardless of genotype.CONCLUSION:Our results demonstrated high prevalence of vitamin D deficiency and high SVR in individuals with higher serum vitamin D levels or receiving vitamin D supplementation.展开更多
The hepatitis C virus (HCV) induces lipid accumulation in vitro and in vivo. The pathogenesis of steatosis is due to both viral and host factors. Viral steatosis is mostly reported in patients with genotype 3a, wherea...The hepatitis C virus (HCV) induces lipid accumulation in vitro and in vivo. The pathogenesis of steatosis is due to both viral and host factors. Viral steatosis is mostly reported in patients with genotype 3a, whereas meta-bolic steatosis is often associated with genotype 1 and metabolic syndrome. Several molecular mechanisms responsible for steatosis have been associated with the HCV core protein, which is able to induce gene expres-sion and activity of sterol regulatory element binding protein 1 (SREBP1) and peroxisome proliferator-activat-ed receptor γ (PPARγ), increasing the transcription of genes involved in hepatic fatty acid synthesis. Steatosis has been also implicated in viral replication. In infected cells, HCV core protein is targeted to lipid droplets which serve as intracellular storage organelles. These studies have shown that lipid droplets are essential for virus assembly. Thus, HCV promotes steatosis as an eff icient mechanism for stable viral replication. Chronic HCV in-fection can also induce insulin resistance. In patients with HCV, insulin resistance is more strongly associated with viral load than visceral obesity. HCV seems to lead to insulin resistance through interference of intracellular insulin signalling by HCV proteins, mainly, the serine phosphorylation of insulin receptor-1 (IRS-1) and im-pairment of the downstream Akt signalling pathway. The HCV core protein interferes with in vitro insulin signal-ling by genotype-specif ic mechanisms, where the role of suppressor of cytokine signal 7 (SOCS-7) in genotype 3aand mammalian target of rapamycin (mTOR) in geno-type 1 in IRS-1 downregulation play key roles. Steatosis and insulin resistance have been associated with f ibrosis progression and a reduced rate of sustained response to peginterferon plus ribavirin.展开更多
Hepatocellular carcinoma is the third leading cause of cancer-related deaths in the world. It is associated with an important mortality rate and the incidence is increasing. Patients showing metabolic syndrome seem to...Hepatocellular carcinoma is the third leading cause of cancer-related deaths in the world. It is associated with an important mortality rate and the incidence is increasing. Patients showing metabolic syndrome seem to have higher incidence and mortality rates from hepatocellular carcinoma than healthy subjects, especially those with type 2 diabetes mellitus and obesity. Thus, metformin and statins, both to treat features of metabolic syndrome, have been proposed to decrease the risk of hepatocellular carcinoma. Otherwise, liver cancer is the result of a complex process which impairs several signaling cascades, such as RAS/RAF/mitogen-activated protein kinase kinase(MEK)/extracellularsignal-regulated kinase(ERK), phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)/AKT/mammalian target of rapamycin(m TOR) and Wnt/β-catenin signaling. Metformin(through 5′-adenosine monophosphateactivated protein kinase pathway activation) and statins(through 3-hydroxy-3-methylglutaryl coenzyme A inhibition) show anti-tumoral properties modifying several steps of RAS/RAF/MEK/ERK, PI3K/AKT/m TOR and Wnt/β-catenin signaling cascades. On the other hand, metformin and statins have been found to reduce the risk of hepatocellular carcinoma up to 50% and 60%, respectively. Furthermore, both drugs have shown a dose-dependent protective effect. However, information about chemopreventive role of metformin and statins is mainly obtained of observational studies,which could not take into account some bias. In conclusion, given the rising of incidence of hepatocellular carcinoma and the important morbidity and mortality rates associated with this cancer, looking for chemopreventive strategies is an essential task. Randomized controlled trials are needed to determine the definite role of metformin and statins on the prevention of hepatocellular carcinoma.展开更多
Cystic echinococcosis(CE) is a complex, chronic and neglected disease with a worldwide distribution. The liver is the most frequent location of parasitic cysts. In humans, its clinical spectrum ranges from asymptom-at...Cystic echinococcosis(CE) is a complex, chronic and neglected disease with a worldwide distribution. The liver is the most frequent location of parasitic cysts. In humans, its clinical spectrum ranges from asymptom-atic infection to severe, potentially fatal disease. Four approaches exist in the clinical management of CE: surgery, percutaneous techniques and drug treatment for active cysts, and the "watch and wait" approach for inactive cysts. Allocation of patients to these treat-ments should be based on cyst stage, size and location, available clinical expertise, and comorbidities. However, clinical decision algorithms, efficacy, relapse rates, and costs have never been properly evaluated. This paper reviews recent advances in classification and diagnosisand the currently available evidence for clinical deci-sion-making in cystic echinococcosis of the liver.展开更多
AIM: To evaluate the short and intermediate term out-come of percutaneous transluminal renal artery angioplasty (PTRA) and stenting particularly on blood pressure (BP) control and renal function and to evaluate predic...AIM: To evaluate the short and intermediate term out-come of percutaneous transluminal renal artery angioplasty (PTRA) and stenting particularly on blood pressure (BP) control and renal function and to evaluate predictors of poor BP response after successful PTRA and stenting. METHODS: We conducted a prospective analysis of all patients who underwent PTRA and stenting in our institute between August 2010 to September 2012. A total number of 86 patients were underwent PTRA and renal stenting. Selective angiography was done to confirm at least 70% angiographic stenosis. The predilatation done except few cases with critical stenosis, direct stenting was done in the rest of cases. All patients received aspirin 325 mg orally, and clopidogrel 300 mg orally within 24 h before the procedure. Heparin was used as the procedural anticoagulant agent. Optimal results with TIMI-Ⅲ flow obtained in all cases. Following stent placement, aspirin 150 mg orally once daily was continued for a minimum of 12 mo and clopidogrel 75 mg orally once daily for at least 4 wk. The clinical, radiological, electrocardiography, echocardiography and treatment data of all patients were recorded. The BP measurement, serum creatinine and glomerular filtration rate (GFR) were recorded before the procedure and 1 and 6 mo after PTRA. RESULTS: A total of 86 patients were included in the study. The mean age of study population was 55.87±11.85 years old and 67 (77.9%) of patients were male. There was a significant reduction in both systolic and diastolic BP at 1 mo after the procedure: 170.15±20.10 mmHg vs 146.60±17.32 mmHg and 98.38±10.55 mmHg vs 89.88±9.22 mmHg respectively (P=0.0000). The reduction in BP was constant throughout the follow-up period and was evident 6 mo after the procedure: 144.23±18.19 and 88.26±9.79 mmHg respectively (P=0.0000). However, no improvement in renal function was observed at any time during the follow-up period. After multivariate analysis, we found male sex, low GFR (<60 mL/min) and higher baseline mean BP as a poor predictors of successful outcome on BP response after PTRA and stenting. CONCLUSION: The PTRA and stenting can be considered as an effective therapeutic intervention for improving BP control with minimal effect on renal function. The male sex, higher baseline BP and low GFR are associated with poor BP response after successful PTRA and stenting.展开更多
AIM Evaluate the association between phase angle and the development of hepatic encephalopathy in the longterm follow-up of cirrhotic patients.METHODS This was a prospective cohort study. Clinical, nutritional and bio...AIM Evaluate the association between phase angle and the development of hepatic encephalopathy in the longterm follow-up of cirrhotic patients.METHODS This was a prospective cohort study. Clinical, nutritional and biochemical evaluations were performed. MannWhitney's U and χ2 tests were used as appropriate. Kaplan-Meier curves and Cox proportional Hazards analysis were used to evaluate the prediction and incidence of hepatic encephalopathy.RESULTS Two hundred and twenty were included; the most frequent etiology of cirrhosis was hepatitis C infection, 52% of the patients developed hepatic encephalopathy(18.6% covert and 33.3% overt); the main precipitating factors were infections and variceal bleeding. KaplanMeier curves showed a higher proportion of HE in the group with low phase angle(39%) compared to the normal phase angle group(13%)(P = 0.012). Furthermore, creatinine and phase angle remained independently associated to hepatic encephalopathy in the Cox regression multivariate analysis [hazard ratio = 1.80(1.07-3.03)]. CONCLUSION In our cohort of patients low phase angle was associated with an increased incidence of hepatic encephalopathy. Phase angle is a useful nutritional marker that evaluates cachexia and could be used as a part of the integral assessment in patients with cirrhosis.展开更多
This article is an extensive review that provides an update on the pathophysiology,symptoms,diagnosis,and treatment of diabetic gastroenteropathy.There is no reported prevalence,but it has been described that patients...This article is an extensive review that provides an update on the pathophysiology,symptoms,diagnosis,and treatment of diabetic gastroenteropathy.There is no reported prevalence,but it has been described that patients with type 1 diabetes have a cumulative incidence at 10 years of 5.2%,and type 2 patients,1%.Also,in the group of type 1 diabetes,it has been observed that women are more likely to present this condition(5.8%vs 3.5%).Many factors are associate with its development(e.g.,hyperglycemia,vagal dysfunction,loss of expression of neural nitric oxide synthase in the myenteric plexus,alterations in the Cajal interstitial cell network,and oxidative stress).Gastrointestinal discomfort could be perceived 70% higher in diabetic patients,describing that 25%of diabetic patients experience gastrointestinal symptoms.Diabetic enteropathy could affect any portion of the gastrointestinal tract,but esophageal alterations were described in more than 60% of diabetic patients,also 60% of them present constipation,and 20%,diarrhea.Gastric emptying scintigraphy is useful to evaluate gastroparesis,therefore,gastric retention of more than 60%at 2 h has a sensitivity of 100% and specificity of 20% for diagnosis;however,other studies such as breath tests,with a sensitivity of 89% and a specificity of 80%,or the endoscopic capsule contribute to the diagnosis.There is no cure;however,management must be multidisciplinary,focused on slowing the progression of diabetic gastroenteropathy,reducing symptoms,and restoring function;that includes nutritional recommendation,maintain glucose levels kept below 180 mg/dL,use of prokinetics,anti-emetics;nowadays,it has been special interest in surgical treatment,such as pyloroplasty,also gastric electrical stimulation appears to be another alternative.展开更多
Objective:To illustrate the clinical features and investigate the indicators associated with a fatal outcome in adult patients with severe Plasmodium falciparum malaria admitted to the Hospital for Tropical Diseases,B...Objective:To illustrate the clinical features and investigate the indicators associated with a fatal outcome in adult patients with severe Plasmodium falciparum malaria admitted to the Hospital for Tropical Diseases,Bangkok,Thailand.Methods:We studied 202 adult malaria patients admitted to the Intensive Care Unit.A total of 43 clinical variables were identified by univariate and logistic regression analyses,to eliminate confounding factors.Results:Regarding the statistical methods,only 6 variables-jaundice,cerebral malaria,metabolic acidosis,body mass index,initial respiratory rate,and white blood cell count-were significant indicators of death, with adjusted odds ratios(95%CI) of 15.2(2.1-32.3).4.3(2.3-12.6),3.3(2.3-5.7),2.4(1.9-3.5),2.2 (1.5-2.6),and 1.7(1.2-3.1),respectively.Conclusions:Our study found that jaundice,cerebral malaria,metabolic acidosis,body mass index,initial respiratory rate and white blood cell count were indicators of fatal outcome in severe Plasmodium falciparum malaria.Further studies on the fatal indicators in severe malaria need to be compared with data from different geographical areas,to construct practical measures to address potentially fatal indicators in different settings.展开更多
Non-adherence is a priority public health concern. Non-adherence means not taking medications, missing medications, taking too much, not taking enough, wrongtiming, wrong dose and/or wrong pill, but may also refer to ...Non-adherence is a priority public health concern. Non-adherence means not taking medications, missing medications, taking too much, not taking enough, wrongtiming, wrong dose and/or wrong pill, but may also refer to missing appointments, not booking appointments, not doing blood work, not returning calls and/or refusal to follow the treatment regimen. In renal transplantation, adherence to immunosuppressive medication is a fundamental requisite in order to preserve graft function, since non-adherence is one of the main causes for late acute rejection, incomplete recovery after rejection treatment, chronic graft dysfunction, graft loss, and death. Transplantation failure due to treatment nonadherence is economically, socially, ethically and morally unjustifiable. This is a very prevalent issue: in some studies, its incidence is as high as 70% of patients. The self-reported nonadherence levels found in certain studies, including those performed immediately after transplantation show the need for early and continued intervention after kidney transplantation in order to maximise adherence and consequently clinical outcomes. There is not a single method to assess non adherence, thus combining several measures increases diagnostic accuracy. Electronic monitoring with a microdevice that records each time a pill bottle is opened is considered the "gold standard" for measuring adherence, but selfreport at a confidential interview was the best measure of adherence. Thus non-adherence risk can be effectively assessed using clinically available assessment tools. Medication Adherence Scale, Brief Medical Questionnaire, Immunosuppressant Therapy Adherence Scale, Immunosuppressant Therapy Barrier Scale, Long-Term Medication Behavior Self-Efficacy Scale and Simplified Medication Adherence Questionnaire are some of the self-reported questionnaires. There are multiple factors associated with non-adherence in immunosuppressant therapy: Younger patients(adolescent, especially), poor health coverage, poor social support, unmarried, no family, non-Caucasian, immigrant, lower income, lower socioeconomic class, greater parental distress and lower family cohesion; complex medical regimens, higher number of drugs, longer time after transplant, toxicity, side effects, poor tolerance to medication, higher number of physicians involved, poor provider-patient rapport; psychological(dependency, high levels of anxiety and hostility, poorer behavioral functioning and greater distress in children) and psychiatric(depression) illnesses, low self-efficacy with medicine intake, perception of immunosuppressive therapy as not been necessary to preserve kidney function, forgetfulness, rebelliousness, poor perception of health, poor satisfaction, low Health-related quality of life, addictions, lack of coping strategies and avoidance behavior; patient morbidity: comorbidity, receiving a transplant from a live donor, retransplantation, and noninsulin-dependent diabetes. The most frequent strategies to promote medication-taking must focus on modifiable risk factors. Reasons for non-adherence are complex and diverse and any successful intervention aimed at improving adherence must be multidimensional. Although effective intervention strategies are needed to improve immunosuppressant therapy adherence, few intervention studies have been conducted in the adult renal transplant population. In this study, we perform an exhaustive review of the different strategies reported in the literature. A number of key reasons for non-adherence are also provided.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
Triple negative breast cancer(TNBC) is an aggressive subtype of breast cancer that currently lacks effective biomarkers and therapeutic targets required to investigate the diagnosis and treatment of TNBC. Here we perf...Triple negative breast cancer(TNBC) is an aggressive subtype of breast cancer that currently lacks effective biomarkers and therapeutic targets required to investigate the diagnosis and treatment of TNBC. Here we performed a comprehensive differential analysis of 165 TNBC samples by integrating RNA-seq data of breast tumor tissues and adjacent normal tissues from both our cohort and The Cancer Genome Atlas(TCGA). Pathway enrichment analysis was conducted to evaluate the biological function of TNBC-specific expressed genes. Further multivariate Cox proportional hazard regression was performed to evaluate the effect of these genes on TNBC prognosis. In this report, we identified a total of 148 TNBC-specific expressed genes that were primarily enriched in mammary gland morphogenesis and hormone levels related pathways, suggesting that mammary gland morphogenesis might play a unique role in TNBC patients differing from other breast cancer types. Further survival analysis revealed that nine genes(FSIP1, ADCY5, FSD1, HMSD, CMTM5, AFF3, CYP2 A7, ATP1 A2,and C11 orf86) were significantly associated with the prognosis of TNBC patients, while three of them(ADCY5,CYP2 A7, and ATP1 A2) were involved in the hormone-related pathways. These findings indicated the vital role of the hormone-related genes in TNBC tumorigenesis and may provide some independent prognostic markers as well as novel therapeutic targets for TNBC.展开更多
Background:Multiparous women are at a higher risk of gestational diabetes mellitus(GDM) than primiparas.Physical activity during pregnancy has been shown to be beneficial for GDM,but there is little evidence on the as...Background:Multiparous women are at a higher risk of gestational diabetes mellitus(GDM) than primiparas.Physical activity during pregnancy has been shown to be beneficial for GDM,but there is little evidence on the association between physical activity and glycemic control among women with GDM,whether primiparas or multiparas.Thus,the objective of the present study was to examine the association between physical activity and glycemic control in women with GDM and to determine what,if any,effects result from number of parous events.Methods:A prospective cohort of 1162 women with GDM was recruited,with 604 multiparas(51.98%).The general linear model was used to calculate the risk difference and its 95% confidence interval(95%CI) to quantify the impact of parous events on glycemic control in pregnancy as well as the association between physical activity time and glycemic control.Results:Among 1162 women with GDM,the median daily activity time was 65 mm(interquartile range(IQR):45-90 min),and the abnormal plasma glucose(PG) percentage,calculated as number of abnormal PG tests divided by the total number of PG tests,was 40.00%(IQR:22.22%-66.67%).The percentage of abnormal PG was stabilized and statistically lower with daily physical activity time exceeding 60 min among primiparas(IQR:30.89%-44.43%) and exceeding 90 min among multiparas(ranged from 27.76% to 38.82%).After adjusting for potential confoumders,primiparas tended to have a lower percentage of abnormal PG than do multiparas(rate difference=-0.39,95%CI:-3.61 to2.84).The same amount of physical activity time was significantly less effective for multiparas than for primiparas(trend p-value <0.01).Conclusion:In women with GDM,being multiparous is associated with less effective glycemic control through physical activity,such that multiparas need more physical activity to achieve glycemic control at a similar level to primiparas.展开更多
To determine the number of mutations in the NS5A region of the hepatitis C virus(HCV)and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to ...To determine the number of mutations in the NS5A region of the hepatitis C virus(HCV)and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments.METHODSSequences within HCV NS5A[PKR binding domain(PKRBD)and the interferon-sensitivity-determining region(ISDR)]were analysed via direct sequencing in a selected cohort of 72 patients,with a total of 201 treatments[interferon-alpha(IFN-α),n=49;IFN-α+ribavirin(RBV),n=75;pegylated(peg)IFN-α+RBV,n=47;first-generation direct-acting antivirals(DAAs),n=13;and second-generation DAAs,n=17].Of these,48/201 achieved a sustained virological response(SVR)and 153/201 achieved no virological response(NVR).RESULTSFor both regions,treatments resulting in SVR were associated with more baseline mutations than were treatments resulting in NVR(SVR vs NVR;PKRBD:5.82±3 vs 4.86±2 mutations,P=0.045;ISDR:2.65±2 vs 1.51±1.7 mutations,P=0.005).A decrease or no change in the number of mutations over time between treatments in the PKRBD or ISDR,as shown by sequencing,was associated with patients who usually failed to respond to treatment(PKRBD,P=0.02;ISDR,P=0.001).Moreover,patients showing a post-treatment baseline viral load>600000 IU/mL and increased ISDR mutations with respect to the previous treatment were 9.21 times more likely to achieve SVR(P=0.001).CONCLUSIONThe obtained results show that among patients who have shown no response to two or more antiviral treatments,the likelihood of achieving SVR increases with the genetic variability in the ISDR region(≥2 mutations or number of substitutions from the HCV-J and HCV-1 prototype),especially when the viral load is greater than 600000 IU/mL.展开更多
Emerging evidence suggests that dietary fats may influence testicular function. However, most of the published literature on this field has used semen quality parameters as the only proxy for testicular function. We e...Emerging evidence suggests that dietary fats may influence testicular function. However, most of the published literature on this field has used semen quality parameters as the only proxy for testicular function. We examined the association of fat intake with circulating reproductive hormone levels and testicular volume among healthy young Spanish men. This is a cross-sectional study among 209 healthy male volunteers conducted between October 2010 and November 2011 in Murcia Region of Spain. Participants completed questionnaires on lifestyle, diet, and smoking, and each underwent a physical examination, and provided a blood sample. Linear regression was used to examine the association between each fatty acid type and reproductive hormone levels and testicular volumes. Monounsaturated fatty acids intake was inversely associated with serum blood levels of calculated free testosterone, total testosterone, and inhibin B. A positive association was observed between the intake of polyunsaturated fatty acids, particularly of omega-6 polyunsaturated fatty acids, and luteinizing hormone concentrations. In addition, the intake of trans fatty acids was associated with lower total testosterone and calculated free testosterone concentrations （Ptrend = 0.01 and 0.02, respectively）. The intake of omega-3 polyunsaturated fatty acids was positively related to testicular volume while the intake of omega-6 polyunsaturated fatty acids and trans fatty acids was inversely related to testicular volume. These data suggest that fat intake, and particularly intake of omega 3, omega 6, and trans fatty acids, may influence testicular function.展开更多
Infective endocarditis has a high morbimortality rate,and delay in diagnosis and treatment is associated with a higher prevalence of complications.The clinical presentation is often atypical in older adults,and even w...Infective endocarditis has a high morbimortality rate,and delay in diagnosis and treatment is associated with a higher prevalence of complications.The clinical presentation is often atypical in older adults,and even when the classic symptoms are present,they may overlap with those of other conditions,making management more difficult.We present the case of a nonagenarian in whom cardiac-centered point-of-care ultrasound facilitated real-time decision making and the diagnosis of mitral endocarditis.展开更多
文摘AIM:To evaluates the effectiveness and safety of the first generation,NS3/4A protease inhibitors(PIs) in clinical practice against chronic C virus,especially in patients with advanced fibrosis. METHODS:Prospective study and non-experimental analysis of a multicentre cohort of 38 Spanish hospitals that includes patients with chronic hepatitis C genotype 1,treatment-na?ve(TN) or treatment-experienced(TE),who underwent triple therapy with the first generation NS3/4A protease inhibitors,boceprevir(BOC) and telaprevir(TVR),in combination with pegylated interferon and ribavirin. The patients were treatment in routine practice settings. Data on the study population and on adverse clinical and virologic effects were compiled during the treatment period and during follow up.RESULTS:One thousand and fifty seven patients were included,405(38%) were treated with BOC and 652(62%) with TVR. Of this total,30%(n = 319) were TN and the remaining were TE:28%(n = 298) relapsers,12%(n = 123) partial responders(PR),25%(n = 260) null-responders(NR) and for 5%(n = 57) with prior response unknown. The rate of sustained virologic response(SVR) by intention-to-treatment(ITT) was greater in those treated with TVR(65%) than in those treated with BOC(52%)(P < 0.0001),whereas by modified intention-to-treatment(m ITT) no were found significant differences. By degree of fibrosis,56% of patients were F4 and the highest SVR rates were recorded in the non-F4 patients,both TN and TE. In the analysis by groups,the TN patients treated with TVR by ITT showed a higher SVR(P = 0.005). However,by m ITT there were no significant differences between BOC and TVR. In the multivariate analysis by m ITT,the significant SVR factors were relapsers,IL28 B CC and non-F4; the type of treatment(BOC or TVR) was not significant. The lowest SVR values were presented by the F4-NR patients,treated with BOC(46%) or with TVR(45%). 28% of the patients interrupted the treatment,mainly by non-viral response(51%):this outcome was more frequent in the TE than in the TN patients(57% vs 40%,P = 0.01). With respect to severe haematological disorders,neutropaenia was more likely to affect the patients treated with BOC(33% vs 20%,P ≤ 0.0001),and thrombocytopaenia and anaemia,the F4 patients(P = 0.000,P = 0.025,respectively). CONCLUSION:In a real clinical practice setting with a high proportion of patients with advanced fibrosis,effectiveness of first-generation PIs was high except for NR patients,with similar SVR rates being achieved by BOC and TVR.
文摘In the current socio-economic scenario characterized by a growing shortage of resources and progressive budget constraints, the need to better coordinate processes in health institutions appears as a relevant aspect to ensure the future sustainability of system. In this sense, Relational Coordination(RC) provides a valuable opportunity for the reconfiguration of clinical guidelines concerning isolated single-level considerations. In this research the RC model has been applied to explain best results in the process of diagnosing and offering clinical treatments for lung cancer. Lung cancer presents the higher rates of tumor's mortality worldwide. Through unstructured and informal interviews with clinicians at both levels(Primary/Specialist Care), a diagnosis of the situation in relation to joint management of lung cancer is provided. Solutions of continuity in terms of coordination are explained due to the observation of lack of effective knowledge transfer between the two levels. It is this disconnection which justifies the introduction of a modified model of RC for the study and implementation of transfer relations between the knowledge holders, in order to structure consolidated and cooperative evidence-based models that lead to a substantial shortening in the response times with a marked outcomes improvement. To our knowledge, the application of this model to a Public Health problem bringing together both levels of care, hasn't been made till now.
基金Liaoning Pharmaceutical Industry Innovation and Development Strategy Research and Funding Project(2020lslktyb-095)National Medical Products Administration-Special Fund of Drug Regulatory Research Institute of Shenyang Pharmaceutical University(2021jgkx004)+1 种基金Shenzhen Maternity&Child Healthcare Hospital Science Foundation(2022(73))Shenzhen Health Economics Society Research Fund Project(202333).
文摘Objective To discuss the problems existing in the compensation of Chinese clinical trial participants and propose some suggestions for improving their rights.Methods The literature related to the participants’right to compensation at home and abroad was searched to study the inadequacy of the compensation right for clinical trial participants in China from four aspects:insurance system,principle of attribution,legal relationship and compensation regulations.Then,some suggestions to improve the participants’right to compensation were proposed.Results and Conclusion China lacks clear legal norms for participants’right to compensation.There are problems such as unclear insurance rules and compensation rules,unclear contractual relationships between parties to clinical trials,and no laws and regulations to rely on for attribution and compensation.China should issue regulatory guidelines related to the right to compensation of participants in clinical trials,so that all parties in clinical trials can have rules to follow if there is the occurrence of injury,which can better protect the rights and interests of the participants.
基金Supported by a grant of PAI-CTS-532 from Junta de Andalucía, Andalucía, Spain
文摘Insulin resistance is the major feature of the metabolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resistance and type 2 diabetes mellitus are more often seen than in healthy controls or chronic hepatitis B patients. Hepatitis C virus （HCV） infection promotes insulin resistance, mainly by increased TNF production together with enhancement of suppressor of cytokine （SOC-3）; both events block PI3K and Akt phosphorylation. Two types of insulin resistance could be found in chronic hepatitis C patients＇. ＂viral＂ and ＂metabolic＂ insulin resistance. Insulin resistance in chronic hepatitis C is relevant because it promotes steatosis and fibrosis. The mechanisms by which insulin resistance promotes fibrosis progression include： （1） steatosis, （2） hyperleptinemia, （3） increased TNF production, （4） impaired expression of PPARy receptors. Lastly, insulin resistance has been found as a common denominator in patients difficult-to-treat like cirrhotics, overweight, HIV coinfected and Afro-American. Insulin resistance together with fibrosis and genotype has been found to be independently associated with impaired response rate to peginterferon plus ribavirin. Indeed, in genotype 1, the sustained response rate was twice （60%） in patients with HOMA ≤ 2 than patients with HOMA 〉 2. In experiments carried out on Huh-7 cells transfected by full length HCVRNA, interferon alpha blocks HCV replication. However, when insulin （at doses of 128 μU/mL, similar that seen in the hyperinsulinemic state） was added to interferon, the ability to block HCV replication disappeared, and the PKR synthesis was abolished. In summary, hepatitis C promotes insulin resistance and insulin resistance induces interferon resistance, steatosis and fibrosis progression.
文摘Hepatopulmonary syndrome (HPS) is characterized by abnormalities in blood oxygenation caused by the presence of intrapulmonary vascular dilations (IPVD) in the context of liver disease, generally at a cirrhotic stage. Knowledge about the subject is still only partial. The majority of the information about the etiopathogenesis of HPS has been obtained through experiments on animals. Reported prevalence in patients who are candidates for a liver transplantation (LT) varies between 4% and 32%, with a predominance of mild or moderate cases. Although it is generally asymptomatic it does have an impact on their quality of life and survival. The diagnosis requires taking an arterial blood gas sample of a seated patient with alveolar-arterial oxygen gradient (AaO<sub>2</sub>) ≥ 15 mm Hg, or ≥ 20 mm Hg in those over 64 years of age. The IPVD are identified through a transthoracic contrast echocardiography or a macroaggregated albumin lung perfusion scan (<sup>99m</sup>Tc-MAA). There is currently no effective medical treatment. LT has been shown to reverse the syndrome and improve survival rates, even in severe cases. Therefore the policy of prioritizing LT would appear to increase survival rates. This paper takes a critical and clinical look at the current understanding of HPS, as well as the controversies surrounding it and possible future research.
基金Supported by Coordination of Improvement of Higher Education Personnel in part
文摘AIM:To evaluate the association between 25-hydroxyvitamin D[25(OH)D]and sustained virological response(SVR)in hepatitis C virus(HCV)infected individuals.METHODS:Relevant studies were identified by systematically searching MEDLINE databases up to March2012 and abstracts of the European and American Congress of Hepatology conducted in 2011.Studies must provide information on SVR and the levels of 25(OH)D3and/or 25(OH)D2[henceforth referred to as 25(OH)D]in sera samples from HCV infected individuals.The inclusion criteria were:clinical studies that included HCV infected patients aged older than 18 years regardless of HCV genotype or ethnic group;provided information on SVR rates;and were reported in the English languageas full papers.Due to the heterogeneity of studies in categorizing serum vitamin D levels,a cut-off value of30 ng/mL of serum 25(OH)D was used.Heterogeneity was assessed using I2statistics.The summary odds ratios with their corresponding 95%CI were calculated based on a random-effects model.RESULTS:Overall,11 studies(8 observational and 3interventional)involving 1575 individuals were included and 1117 HCV infected individuals(71%)showed low vitamin D levels.Most of the studies included monoinfected HCV individuals with the mean age ranging from 38 to 56 years.Four studies were conducted in human immunodeficiency virus/HCV infected individuals.Regarding vitamin D measurement,most of the studies employed radioimmunoassays(n=5)followed by chemiluminescence(n=4)and just one study employed high performance/pressure liquid chromatography(HPLC).Basal vitamin D levels varied from 17 to43 ng/mL in the studies selected,and most of the HCV infected individuals had genotype 1(1068/1575)with mean viral load varying from log 4.5-5.9 UI/mL.With regard to HCV treatment,most of the studies(n=8)included HCV individuals without previous treatment,where the pooled SVR rate was 46.4%.High rates of SVR were observed in HCV individuals with vitamin D levels above 30 ng/mL(OR=1.57;95%CI:1.12-2.2)and those supplemented with vitamin D(OR=4.59;95%CI:1.67-12.63)regardless of genotype.CONCLUSION:Our results demonstrated high prevalence of vitamin D deficiency and high SVR in individuals with higher serum vitamin D levels or receiving vitamin D supplementation.
基金Supported by A Grant, PAI-CTS-532, from Junta de Andalucía, Andalucía, Spain. CIBEREHD was Funded by Instituto de Salud Carlos Ⅲ
文摘The hepatitis C virus (HCV) induces lipid accumulation in vitro and in vivo. The pathogenesis of steatosis is due to both viral and host factors. Viral steatosis is mostly reported in patients with genotype 3a, whereas meta-bolic steatosis is often associated with genotype 1 and metabolic syndrome. Several molecular mechanisms responsible for steatosis have been associated with the HCV core protein, which is able to induce gene expres-sion and activity of sterol regulatory element binding protein 1 (SREBP1) and peroxisome proliferator-activat-ed receptor γ (PPARγ), increasing the transcription of genes involved in hepatic fatty acid synthesis. Steatosis has been also implicated in viral replication. In infected cells, HCV core protein is targeted to lipid droplets which serve as intracellular storage organelles. These studies have shown that lipid droplets are essential for virus assembly. Thus, HCV promotes steatosis as an eff icient mechanism for stable viral replication. Chronic HCV in-fection can also induce insulin resistance. In patients with HCV, insulin resistance is more strongly associated with viral load than visceral obesity. HCV seems to lead to insulin resistance through interference of intracellular insulin signalling by HCV proteins, mainly, the serine phosphorylation of insulin receptor-1 (IRS-1) and im-pairment of the downstream Akt signalling pathway. The HCV core protein interferes with in vitro insulin signal-ling by genotype-specif ic mechanisms, where the role of suppressor of cytokine signal 7 (SOCS-7) in genotype 3aand mammalian target of rapamycin (mTOR) in geno-type 1 in IRS-1 downregulation play key roles. Steatosis and insulin resistance have been associated with f ibrosis progression and a reduced rate of sustained response to peginterferon plus ribavirin.
文摘Hepatocellular carcinoma is the third leading cause of cancer-related deaths in the world. It is associated with an important mortality rate and the incidence is increasing. Patients showing metabolic syndrome seem to have higher incidence and mortality rates from hepatocellular carcinoma than healthy subjects, especially those with type 2 diabetes mellitus and obesity. Thus, metformin and statins, both to treat features of metabolic syndrome, have been proposed to decrease the risk of hepatocellular carcinoma. Otherwise, liver cancer is the result of a complex process which impairs several signaling cascades, such as RAS/RAF/mitogen-activated protein kinase kinase(MEK)/extracellularsignal-regulated kinase(ERK), phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)/AKT/mammalian target of rapamycin(m TOR) and Wnt/β-catenin signaling. Metformin(through 5′-adenosine monophosphateactivated protein kinase pathway activation) and statins(through 3-hydroxy-3-methylglutaryl coenzyme A inhibition) show anti-tumoral properties modifying several steps of RAS/RAF/MEK/ERK, PI3K/AKT/m TOR and Wnt/β-catenin signaling cascades. On the other hand, metformin and statins have been found to reduce the risk of hepatocellular carcinoma up to 50% and 60%, respectively. Furthermore, both drugs have shown a dose-dependent protective effect. However, information about chemopreventive role of metformin and statins is mainly obtained of observational studies,which could not take into account some bias. In conclusion, given the rising of incidence of hepatocellular carcinoma and the important morbidity and mortality rates associated with this cancer, looking for chemopreventive strategies is an essential task. Randomized controlled trials are needed to determine the definite role of metformin and statins on the prevention of hepatocellular carcinoma.
基金Supported by The EU grant FP7/2007-2013,No.602051-HERACLES(to Brunetti E)
文摘Cystic echinococcosis(CE) is a complex, chronic and neglected disease with a worldwide distribution. The liver is the most frequent location of parasitic cysts. In humans, its clinical spectrum ranges from asymptom-atic infection to severe, potentially fatal disease. Four approaches exist in the clinical management of CE: surgery, percutaneous techniques and drug treatment for active cysts, and the "watch and wait" approach for inactive cysts. Allocation of patients to these treat-ments should be based on cyst stage, size and location, available clinical expertise, and comorbidities. However, clinical decision algorithms, efficacy, relapse rates, and costs have never been properly evaluated. This paper reviews recent advances in classification and diagnosisand the currently available evidence for clinical deci-sion-making in cystic echinococcosis of the liver.
文摘AIM: To evaluate the short and intermediate term out-come of percutaneous transluminal renal artery angioplasty (PTRA) and stenting particularly on blood pressure (BP) control and renal function and to evaluate predictors of poor BP response after successful PTRA and stenting. METHODS: We conducted a prospective analysis of all patients who underwent PTRA and stenting in our institute between August 2010 to September 2012. A total number of 86 patients were underwent PTRA and renal stenting. Selective angiography was done to confirm at least 70% angiographic stenosis. The predilatation done except few cases with critical stenosis, direct stenting was done in the rest of cases. All patients received aspirin 325 mg orally, and clopidogrel 300 mg orally within 24 h before the procedure. Heparin was used as the procedural anticoagulant agent. Optimal results with TIMI-Ⅲ flow obtained in all cases. Following stent placement, aspirin 150 mg orally once daily was continued for a minimum of 12 mo and clopidogrel 75 mg orally once daily for at least 4 wk. The clinical, radiological, electrocardiography, echocardiography and treatment data of all patients were recorded. The BP measurement, serum creatinine and glomerular filtration rate (GFR) were recorded before the procedure and 1 and 6 mo after PTRA. RESULTS: A total of 86 patients were included in the study. The mean age of study population was 55.87±11.85 years old and 67 (77.9%) of patients were male. There was a significant reduction in both systolic and diastolic BP at 1 mo after the procedure: 170.15±20.10 mmHg vs 146.60±17.32 mmHg and 98.38±10.55 mmHg vs 89.88±9.22 mmHg respectively (P=0.0000). The reduction in BP was constant throughout the follow-up period and was evident 6 mo after the procedure: 144.23±18.19 and 88.26±9.79 mmHg respectively (P=0.0000). However, no improvement in renal function was observed at any time during the follow-up period. After multivariate analysis, we found male sex, low GFR (<60 mL/min) and higher baseline mean BP as a poor predictors of successful outcome on BP response after PTRA and stenting. CONCLUSION: The PTRA and stenting can be considered as an effective therapeutic intervention for improving BP control with minimal effect on renal function. The male sex, higher baseline BP and low GFR are associated with poor BP response after successful PTRA and stenting.
基金supported by CONACYT/UNAMsupported by Fundación para la Salud y Educación "Salvador Zubirán". Francisco Javier Cubero is a Ramón y Cajal Researcher (RYC-2014-15242)
文摘AIM Evaluate the association between phase angle and the development of hepatic encephalopathy in the longterm follow-up of cirrhotic patients.METHODS This was a prospective cohort study. Clinical, nutritional and biochemical evaluations were performed. MannWhitney's U and χ2 tests were used as appropriate. Kaplan-Meier curves and Cox proportional Hazards analysis were used to evaluate the prediction and incidence of hepatic encephalopathy.RESULTS Two hundred and twenty were included; the most frequent etiology of cirrhosis was hepatitis C infection, 52% of the patients developed hepatic encephalopathy(18.6% covert and 33.3% overt); the main precipitating factors were infections and variceal bleeding. KaplanMeier curves showed a higher proportion of HE in the group with low phase angle(39%) compared to the normal phase angle group(13%)(P = 0.012). Furthermore, creatinine and phase angle remained independently associated to hepatic encephalopathy in the Cox regression multivariate analysis [hazard ratio = 1.80(1.07-3.03)]. CONCLUSION In our cohort of patients low phase angle was associated with an increased incidence of hepatic encephalopathy. Phase angle is a useful nutritional marker that evaluates cachexia and could be used as a part of the integral assessment in patients with cirrhosis.
文摘This article is an extensive review that provides an update on the pathophysiology,symptoms,diagnosis,and treatment of diabetic gastroenteropathy.There is no reported prevalence,but it has been described that patients with type 1 diabetes have a cumulative incidence at 10 years of 5.2%,and type 2 patients,1%.Also,in the group of type 1 diabetes,it has been observed that women are more likely to present this condition(5.8%vs 3.5%).Many factors are associate with its development(e.g.,hyperglycemia,vagal dysfunction,loss of expression of neural nitric oxide synthase in the myenteric plexus,alterations in the Cajal interstitial cell network,and oxidative stress).Gastrointestinal discomfort could be perceived 70% higher in diabetic patients,describing that 25%of diabetic patients experience gastrointestinal symptoms.Diabetic enteropathy could affect any portion of the gastrointestinal tract,but esophageal alterations were described in more than 60% of diabetic patients,also 60% of them present constipation,and 20%,diarrhea.Gastric emptying scintigraphy is useful to evaluate gastroparesis,therefore,gastric retention of more than 60%at 2 h has a sensitivity of 100% and specificity of 20% for diagnosis;however,other studies such as breath tests,with a sensitivity of 89% and a specificity of 80%,or the endoscopic capsule contribute to the diagnosis.There is no cure;however,management must be multidisciplinary,focused on slowing the progression of diabetic gastroenteropathy,reducing symptoms,and restoring function;that includes nutritional recommendation,maintain glucose levels kept below 180 mg/dL,use of prokinetics,anti-emetics;nowadays,it has been special interest in surgical treatment,such as pyloroplasty,also gastric electrical stimulation appears to be another alternative.
文摘Objective:To illustrate the clinical features and investigate the indicators associated with a fatal outcome in adult patients with severe Plasmodium falciparum malaria admitted to the Hospital for Tropical Diseases,Bangkok,Thailand.Methods:We studied 202 adult malaria patients admitted to the Intensive Care Unit.A total of 43 clinical variables were identified by univariate and logistic regression analyses,to eliminate confounding factors.Results:Regarding the statistical methods,only 6 variables-jaundice,cerebral malaria,metabolic acidosis,body mass index,initial respiratory rate,and white blood cell count-were significant indicators of death, with adjusted odds ratios(95%CI) of 15.2(2.1-32.3).4.3(2.3-12.6),3.3(2.3-5.7),2.4(1.9-3.5),2.2 (1.5-2.6),and 1.7(1.2-3.1),respectively.Conclusions:Our study found that jaundice,cerebral malaria,metabolic acidosis,body mass index,initial respiratory rate and white blood cell count were indicators of fatal outcome in severe Plasmodium falciparum malaria.Further studies on the fatal indicators in severe malaria need to be compared with data from different geographical areas,to construct practical measures to address potentially fatal indicators in different settings.
文摘Non-adherence is a priority public health concern. Non-adherence means not taking medications, missing medications, taking too much, not taking enough, wrongtiming, wrong dose and/or wrong pill, but may also refer to missing appointments, not booking appointments, not doing blood work, not returning calls and/or refusal to follow the treatment regimen. In renal transplantation, adherence to immunosuppressive medication is a fundamental requisite in order to preserve graft function, since non-adherence is one of the main causes for late acute rejection, incomplete recovery after rejection treatment, chronic graft dysfunction, graft loss, and death. Transplantation failure due to treatment nonadherence is economically, socially, ethically and morally unjustifiable. This is a very prevalent issue: in some studies, its incidence is as high as 70% of patients. The self-reported nonadherence levels found in certain studies, including those performed immediately after transplantation show the need for early and continued intervention after kidney transplantation in order to maximise adherence and consequently clinical outcomes. There is not a single method to assess non adherence, thus combining several measures increases diagnostic accuracy. Electronic monitoring with a microdevice that records each time a pill bottle is opened is considered the "gold standard" for measuring adherence, but selfreport at a confidential interview was the best measure of adherence. Thus non-adherence risk can be effectively assessed using clinically available assessment tools. Medication Adherence Scale, Brief Medical Questionnaire, Immunosuppressant Therapy Adherence Scale, Immunosuppressant Therapy Barrier Scale, Long-Term Medication Behavior Self-Efficacy Scale and Simplified Medication Adherence Questionnaire are some of the self-reported questionnaires. There are multiple factors associated with non-adherence in immunosuppressant therapy: Younger patients(adolescent, especially), poor health coverage, poor social support, unmarried, no family, non-Caucasian, immigrant, lower income, lower socioeconomic class, greater parental distress and lower family cohesion; complex medical regimens, higher number of drugs, longer time after transplant, toxicity, side effects, poor tolerance to medication, higher number of physicians involved, poor provider-patient rapport; psychological(dependency, high levels of anxiety and hostility, poorer behavioral functioning and greater distress in children) and psychiatric(depression) illnesses, low self-efficacy with medicine intake, perception of immunosuppressive therapy as not been necessary to preserve kidney function, forgetfulness, rebelliousness, poor perception of health, poor satisfaction, low Health-related quality of life, addictions, lack of coping strategies and avoidance behavior; patient morbidity: comorbidity, receiving a transplant from a live donor, retransplantation, and noninsulin-dependent diabetes. The most frequent strategies to promote medication-taking must focus on modifiable risk factors. Reasons for non-adherence are complex and diverse and any successful intervention aimed at improving adherence must be multidimensional. Although effective intervention strategies are needed to improve immunosuppressant therapy adherence, few intervention studies have been conducted in the adult renal transplant population. In this study, we perform an exhaustive review of the different strategies reported in the literature. A number of key reasons for non-adherence are also provided.
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 the Nanjing Medical Science and Technique Development Foundation(ZKX17041)the Natural Science Foundation of Jiangsu Province(BK20161120)+2 种基金the Maternal and child health research project of Jiangsu Province(F201628)the Priority Academic Program Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine)Top-notch Academic Programs Project of Jiangsu Higher Education Institutions(PPZY2015A067)。
文摘Triple negative breast cancer(TNBC) is an aggressive subtype of breast cancer that currently lacks effective biomarkers and therapeutic targets required to investigate the diagnosis and treatment of TNBC. Here we performed a comprehensive differential analysis of 165 TNBC samples by integrating RNA-seq data of breast tumor tissues and adjacent normal tissues from both our cohort and The Cancer Genome Atlas(TCGA). Pathway enrichment analysis was conducted to evaluate the biological function of TNBC-specific expressed genes. Further multivariate Cox proportional hazard regression was performed to evaluate the effect of these genes on TNBC prognosis. In this report, we identified a total of 148 TNBC-specific expressed genes that were primarily enriched in mammary gland morphogenesis and hormone levels related pathways, suggesting that mammary gland morphogenesis might play a unique role in TNBC patients differing from other breast cancer types. Further survival analysis revealed that nine genes(FSIP1, ADCY5, FSD1, HMSD, CMTM5, AFF3, CYP2 A7, ATP1 A2,and C11 orf86) were significantly associated with the prognosis of TNBC patients, while three of them(ADCY5,CYP2 A7, and ATP1 A2) were involved in the hormone-related pathways. These findings indicated the vital role of the hormone-related genes in TNBC tumorigenesis and may provide some independent prognostic markers as well as novel therapeutic targets for TNBC.
基金supported by grants from the Research Program of Shanghai Sports Bureau (20Q001)Shanghai Shenkang Hospital Development Center Management Research Program (2020SKMR-32)+1 种基金Intelligence Funds of Shanghai Skin Disease Hospital (2021KYQD01)the National Key R & D Program of China (2018YFC1705300)。
文摘Background:Multiparous women are at a higher risk of gestational diabetes mellitus(GDM) than primiparas.Physical activity during pregnancy has been shown to be beneficial for GDM,but there is little evidence on the association between physical activity and glycemic control among women with GDM,whether primiparas or multiparas.Thus,the objective of the present study was to examine the association between physical activity and glycemic control in women with GDM and to determine what,if any,effects result from number of parous events.Methods:A prospective cohort of 1162 women with GDM was recruited,with 604 multiparas(51.98%).The general linear model was used to calculate the risk difference and its 95% confidence interval(95%CI) to quantify the impact of parous events on glycemic control in pregnancy as well as the association between physical activity time and glycemic control.Results:Among 1162 women with GDM,the median daily activity time was 65 mm(interquartile range(IQR):45-90 min),and the abnormal plasma glucose(PG) percentage,calculated as number of abnormal PG tests divided by the total number of PG tests,was 40.00%(IQR:22.22%-66.67%).The percentage of abnormal PG was stabilized and statistically lower with daily physical activity time exceeding 60 min among primiparas(IQR:30.89%-44.43%) and exceeding 90 min among multiparas(ranged from 27.76% to 38.82%).After adjusting for potential confoumders,primiparas tended to have a lower percentage of abnormal PG than do multiparas(rate difference=-0.39,95%CI:-3.61 to2.84).The same amount of physical activity time was significantly less effective for multiparas than for primiparas(trend p-value <0.01).Conclusion:In women with GDM,being multiparous is associated with less effective glycemic control through physical activity,such that multiparas need more physical activity to achieve glycemic control at a similar level to primiparas.
基金Supported by“Consejería de Salud de la Junta de Andalucía”,No.PI0137/07“Instituto de Salud CarlosⅢ”,No.FISIntrasalud PI010/717
文摘To determine the number of mutations in the NS5A region of the hepatitis C virus(HCV)and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments.METHODSSequences within HCV NS5A[PKR binding domain(PKRBD)and the interferon-sensitivity-determining region(ISDR)]were analysed via direct sequencing in a selected cohort of 72 patients,with a total of 201 treatments[interferon-alpha(IFN-α),n=49;IFN-α+ribavirin(RBV),n=75;pegylated(peg)IFN-α+RBV,n=47;first-generation direct-acting antivirals(DAAs),n=13;and second-generation DAAs,n=17].Of these,48/201 achieved a sustained virological response(SVR)and 153/201 achieved no virological response(NVR).RESULTSFor both regions,treatments resulting in SVR were associated with more baseline mutations than were treatments resulting in NVR(SVR vs NVR;PKRBD:5.82±3 vs 4.86±2 mutations,P=0.045;ISDR:2.65±2 vs 1.51±1.7 mutations,P=0.005).A decrease or no change in the number of mutations over time between treatments in the PKRBD or ISDR,as shown by sequencing,was associated with patients who usually failed to respond to treatment(PKRBD,P=0.02;ISDR,P=0.001).Moreover,patients showing a post-treatment baseline viral load>600000 IU/mL and increased ISDR mutations with respect to the previous treatment were 9.21 times more likely to achieve SVR(P=0.001).CONCLUSIONThe obtained results show that among patients who have shown no response to two or more antiviral treatments,the likelihood of achieving SVR increases with the genetic variability in the ISDR region(≥2 mutations or number of substitutions from the HCV-J and HCV-1 prototype),especially when the viral load is greater than 600000 IU/mL.
文摘Emerging evidence suggests that dietary fats may influence testicular function. However, most of the published literature on this field has used semen quality parameters as the only proxy for testicular function. We examined the association of fat intake with circulating reproductive hormone levels and testicular volume among healthy young Spanish men. This is a cross-sectional study among 209 healthy male volunteers conducted between October 2010 and November 2011 in Murcia Region of Spain. Participants completed questionnaires on lifestyle, diet, and smoking, and each underwent a physical examination, and provided a blood sample. Linear regression was used to examine the association between each fatty acid type and reproductive hormone levels and testicular volumes. Monounsaturated fatty acids intake was inversely associated with serum blood levels of calculated free testosterone, total testosterone, and inhibin B. A positive association was observed between the intake of polyunsaturated fatty acids, particularly of omega-6 polyunsaturated fatty acids, and luteinizing hormone concentrations. In addition, the intake of trans fatty acids was associated with lower total testosterone and calculated free testosterone concentrations （Ptrend = 0.01 and 0.02, respectively）. The intake of omega-3 polyunsaturated fatty acids was positively related to testicular volume while the intake of omega-6 polyunsaturated fatty acids and trans fatty acids was inversely related to testicular volume. These data suggest that fat intake, and particularly intake of omega 3, omega 6, and trans fatty acids, may influence testicular function.
文摘Infective endocarditis has a high morbimortality rate,and delay in diagnosis and treatment is associated with a higher prevalence of complications.The clinical presentation is often atypical in older adults,and even when the classic symptoms are present,they may overlap with those of other conditions,making management more difficult.We present the case of a nonagenarian in whom cardiac-centered point-of-care ultrasound facilitated real-time decision making and the diagnosis of mitral endocarditis.
