Prognostic factors in patients with non resectable metastatic colorectal cancer in the era of targeted biotherapies: Relevance of Köhne's risk classification

BackgroundKöhne's prognostic classification has been previously proposed, based on performance status, alkaline phosphatase level, number of metastatic sites and white blood cells count.AimsTo identify prognostic factors for survival and to assess the validity of Köhne's classification, in the era of targeted biotherapies, in patients treated with chemotherapy for non resectable metastatic colorectal cancer.MethodsA total of 290 consecutive patients were retrospectively identified in all gastroenterology units of one French county, between 2004 and 2008. Univariate and multivariate analysis for overall survival were performed using pre-treatment patient characteristics.ResultsAll data were available for prognostic categorization in 133 patients. Median survival was 22.1 months. The distribution and median survival for Köhne's prognostic groups were as following: good (n = 73; 24.8 months), intermediate (n = 35; 24.2 months), and poor (n = 25; 7.0 months). The survival difference was significant between good and poor prognostic groups (p < 0.01) and between intermediate and poor prognostic groups (p < 0.01), but not between good and intermediate prognostic groups (p = 0.5). The two independent prognostic factors of survival in multivariate analysis were performance status 0/1 (p < 0.01) and white blood cells count < 10 × 10⁹/L (p < 0.01).ConclusionsThe relevance of Köhne's classification is questioned. A simplified score could be validated by largest studies, based on white blood cells count and performance status.     

Inhibition of fatty acid synthase (FASN) affects the proliferation and apoptosis of HepG2 hepatoma carcinoma cells via the β-catenin/C-myc signaling pathway

Introduction and objectivesResearch in the last few years has proven that inhibition of fatty acid synthase (FASN) suppresses the migration and invasion of hepatoma carcinoma cells. This study aims to explore the effect of fatty acid synthase knockdown on the apoptosis and proliferation of HepG2 cells.Materials and methodsThe human liver cancer cell line HepG2 was cultured and then transfected with FASN-specific siRNA and negative control RNAi. After 48 h, cells and protein lysates were used for western blotting, CCK-8 (cell counting kit-8) assays, flow cytometry and other tests. To assess cell apoptosis, Bax, Bcl-2 and caspase-3 were detected; to assess proliferation, CDK4 (cyclin-dependent kinases 4) and P21 were detected; and to determine the signaling pathway involved, β-catenin and C-myc were also detected.ResultsInhibition of FASN in HepG2 cells can decrease proliferation and promote apoptosis. Flow cytometry and CCK-8 assays demonstrated that the apoptosis rate of FASN-specific siRNA-transfected cells was significantly increased compared to that of the control cells (p < 0.01). In addition, the cell cycle analysis revealed that FASN-specific siRNA-transfected cells induced G1 phase arrest (p < 0.05), but an increasing trend in G2 (p < 0.05).Compared with expression in negative RNAi-transfected cells, the expression of Bcl-2 and CDK-4 was reduced and the expression of Bax, caspase-3 and P21 was increased in FASN-specific siRNA-transfected cells (p < 0.05). Regarding the signaling pathway, the expression of β-catenin and C-myc was significantly reduced when compared to that in negative control cells (p < 0.05).ConclusionsInhibition of FASN suppressed the cell survival of HepG2 cells by inhibiting the β-catenin/C-myc pathway. This result suggests the potential treatment value of FASN for hepatoma carcinoma (HCC).     

Liver transplantation for NASH cirrhosis is not performed at the expense of major post-operative morbidity

BackgroundNon-alcoholic steatohepatitis (NASH) is an emerging indication for liver transplantation (LT) and coexists with multiple comorbidities. Obese and cirrhotic patients experience more perioperative complications. Limited data exist about short-term complications after LT for NASH cirrhosis.AimInvestigate short-term complications in patients transplanted for NASH cirrhosis.MethodsSingle center retrospective cohort study including patients >18 years who underwent LT between 2009–2015. Exclusion criteria were LT for acute liver failure and non-cirrhotic disease. Post-operative complications and severity within 90-days were classified using the Clavien–Dindo classification of surgical complications and comprehensive complication index (CCI). P < 0.05 was significant.ResultsOut of 169 eligible patients, 34 patients (20.1%) were transplanted for NASH cirrhosis. These patients were significantly older (59.2 vs. 54.8 years, P = 0.01), more obese (61.8% vs. 8.1%, P < 0.01), had more diabetes mellitus (73.5% vs. 20%, P < 0.01), metabolic syndrome (83.3% vs. 37.8%, P < 0.01) and cardiovascular disease (29.4% vs. 11.1%, P < 0.01). More grade 1 complications (OR 1.64, 95%CI 1.03–2.63, P = 0.04) and more grade 2 urogenital infections (OR 3.4, 95%CI 1.1–10.6, P = 0.03) were found. Major complications, CCI, 90-day mortality and graft survival were similar.ConclusionDespite significantly increased comorbidities in patients transplanted for NASH cirrhosis, major morbidity, mortality and graft survival after 90 days were comparable to patients transplanted for other indications.     

Serum sex steroids and steroidogenesis-related enzyme expression in skeletal muscle during experimental weight gain in men

ObjectivesLow-circulating testosterone is associated with development of type 2 diabetes in obese men. In this study, we examined the effects of experimental overfeeding and weight gain on serum levels of sex hormones and skeletal muscle expression of steroidogenic enzymes in healthy men with (FH+) and without (FH–) a family history of type 2 diabetes.MethodsFollowing a 3-day lead in energy balanced diet, FH+ (n = 9) and FH– men (n = 11) were overfed by 5200 kJ/day (45% fat) for 28 days. Body weight, fasting glucose, insulin, sex steroid, sex hormone binding globulin (SHBG) levels, insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) and body fat (DXA) were assessed in all individuals at baseline and day 28, and sex steroidogenesis-related enzyme expression in vastus lateralis biopsies was examined in a subset (n = 11).ResultsBody weight, fat mass and fasting insulin levels were increased by overfeeding (P < 0.01) and insulin was increased significantly more in FH+ men (P < 0.01). Serum sex hormone binding globulin (SHBG) and 5α-dihydrotestosterone (DHT) were reduced with overfeeding (P < 0.05), and serum testosterone and DHT were reduced to a greater extent in FH+ men (P < 0.05). Overfeeding reduced mRNA expression of 3β-hydroxysteroid dehydrogenase (HSD) and 17βHSD (P ≤ 0.007), independently of group. 5α-Reductase (SRD5A1) mRNA expression was not changed overall, but a time by group interaction was observed (P = 0.04).ConclusionOverfeeding reduced SHBG and muscle expression of enzymes involved in the formation of testosterone in skeletal muscle. Men with a family history of T2DM were more susceptible to deleterious outcomes of overfeeding with greater reductions in serum testosterone and DHT and greater increases in markers of insulin resistance, which may contribute to increased risk of developing type 2 diabetes.     

Hepatocellular carcinoma in patients without cirrhosis in Italy

BackgroundIn the Western world, hepatocellular carcinoma seldom develops in patients without cirrhosis, and reports describing the characteristics of non-cirrhotic patients with hepatocellular carcinoma are rather infrequent.MethodsWe evaluated the main clinical characteristics, treatment options, and survival of patients with hepatocellular carcinoma developed in non-cirrhotic liver among the 3027 consecutive cases of hepatocellular carcinoma accrued in the Italian Liver Cancer database during the last 20 years.ResultsWe identified 52 patients with hepatocellular carcinoma in non-cirrhotic livers (1.7% of all hepatocellular carcinomas), 42 with (80.8%) and 10 without (19.2%) chronic liver disease. In patients without chronic liver disease, median tumour diameter was greater compared to patients with chronic liver disease (7.8 versus 4.0 cm, P = 0.046). Curative treatment was feasible in 20 patients (38.5%). Median overall survival was 26 months and 5-year survival rate was 23.7%. Detection of hepatocellular carcinoma outside surveillance (P = 0.036), advanced hepatocellular carcinoma stage (P < 0.0001), and non-curative treatment (P = 0.007) were associated with worse prognosis, but tumour stage was the only independent predictor of survival.ConclusionsIn Italy, less than 2% of hepatocellular carcinomas develop in a non-cirrhotic liver, and almost never in a normal liver. These patients frequently present with advanced tumours, have low eligibility rates for curative treatment, and have a dismal prognosis despite their preserved liver function.     

Residual SYNTAX score can predict short- and long-term outcomes in patients with STEMI

ObjectivesThe prognostic value of residual SYNTAX score (rSS) has been observed in different patient groups. However, its prognostic value has not been compared in patients with ST segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI).MethodsA total of 208 patients meeting the eligibility criteria were included in the study. Complete revascularisation (CR) was defined as rSS = 0 and incomplete revascularisation (IR) was defined as rSS ≥ 1.ResultsAmong the sample, 78 patients (33.3%) were included in the CR group and 130 patients (67.7%) in the IR group. One patient (1.3%) in the CR group and 8 patients (6.2%) in the IR group died by day 30 (P < 0.01). The incidence of stent thrombosis, recurrent myocardial infarction (MI) and target lesion revascularisation (TLR) was similar between the two groups. During follow-up (mean 28.8 ± 7.1 months), 2 patients (2.6%) from the CR group and 10 (7.7%) patients from the IR group died (P > 0.05). The incidence of recurrent MI (18.5% vs. 7.7%; P < 0.01) and major adverse cardiovascular events (MACE) (24.6% vs. 7.7%; P < 0.01) were significantly higher in the IR group.ConclusionrSS, which is an indirect marker of incomplete revascularisation, was independently correlated with recurrent MI and MACE after STEMI.     

Optimal strategy of coronary revascularization in chronic kidney disease patients: A meta-analysis

BackgroundPatients with chronic kidney disease (CKD) have high risks of coronary artery disease (CAD). Coronary revascularization is beneficial for long-term survival, but the optimal strategy remains still controversial.MethodsWe searched studies that have compared percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) for revascularization of the coronary arteries in CKD patients. Short-term (30 days or in-hospital) mortality, long-term (at least 12 months) all-cause mortality, cardiac mortality and the incidence of late myocardial infarction and recurrence of revascularization were estimated.Results28 studies with 38,740 patients were included. All were retrospective studies from 1977 to 2012. Meta-analysis showed that PCI group had lower short-term mortality (OR 0.55, 95% CI 0.41 to 0.73, P < 0.01), but had higher long-term all-cause mortality (OR 1.29, 95% CI 1.23 to 1.35, P < 0.01). Higher cardiac mortality (OR 1.08, 95% CI 1.01 to 1.15, P < 0.05), higher incidence of late myocardial infarction (OR 1.78, 95% CI 1.65 to 1.91, P < 0.01) and recurring revascularization rate (OR 2.94, 95%CI 2.15 to 4.01, P < 0.01) is found amongst PCI treated patients compared to CABG group.ConclusionsCKD patients with CAD received CABG had higher risk of short-term mortality but lower risks of long-term all-cause mortality, cardiac mortality and late myocardial infarction compared to PCI. This could be due to less probable repeated revascularization.     

Voluntary post weaning exercise restores metabolic homeostasis in offspring of obese rats

AimPhysical exercise reduces obesity, insulin resistance and dyslipidemia. We previously found that maternal obesity alters central appetite circuits and contributes to increased adiposity, glucose intolerance and metabolic disease in offspring. Here we hypothesized that voluntary exercise would ameliorate the adverse metabolic effects of maternal obesity on offspring.Methods and ResultsSprague–Dawley females fed chow (C) or high-fat diet HFD (H) were mated. Female offspring from C dams were weaned onto chow (CC); those from H dams recieved chow (HC) or HFD (HH). Half of each group was provided with running wheels (CC_EX, HC_EX, HH_EX; n = 10–12).Maternal obesity increased body weight (12%), adiposity, plasma lipids and induced glucose intolerance (HC vs CC; P < 0.05). These were exaggerated by postweaning HFD (HH vs HC; P < 0.01), showed doubled energy intake, a 37% increase in body weight, insulin resistance and glucose intolerance (HH vs HC; P < 0.01). Exercise reduced fat mass, plasma lipids, HOMA and fasting glucose in HC_EX (vs HC; P < 0.05) and HH_EX (vs HH; P < 0.01). Values in HC_EX were indistinguishable from CC, however in HH_EX these metabolic parameters remained higher than the sedentary HC and CC rats (P < 0.01). mRNA expression of hypothalamic pro-opiomelanocortin, and adipose tumour necrosis factor α and 11β-hydroxysteroid dehydrogenase type 1 were reduced by exercise in HH_EX (vs HH; P < 0.05).ConclusionWhile voluntary exercise almost completely reversed the metabolic effects of maternal obesity in chow fed offspring, it did not fully attenuate the increased adiposity, glucose intolerance and insulin resistance in offspring weaned onto HFD.     

Correlation between three-dimensional echocardiography and cardiopulmonary fitness in patients with univentricular heart: A cross-sectional multicentre prospective study

BackgroundThe prognosis of patients with a functional single ventricle has improved, with better cardiopulmonary fitness, health-related quality of life and survival. Conventional echocardiography remains the first-line technique in single ventricle follow-up. Three-dimensional (3D) echocardiography has shown recent value in congenital cardiology, but its ability to predict functional status in patients with a single ventricle remains unknown.AimTo evaluate, in patients with a single ventricle, the association between 3D echocardiography variables and functional status determined by cardiopulmonary fitness.MethodsChildren and adults with a functional single ventricle were prospectively enrolled in this multicentre study. Cardiopulmonary fitness was assessed by cardiopulmonary exercise test, with measures of maximum oxygen uptake (VO_2max) and ventilatory efficiency (VE/VCO₂ slope). 3D echocardiography was performed with off-line reproducibility analyses, using TomTec Arena™ software. Health-related quality of life was assessed using the SF-36 questionnaire.ResultsA total of 33 patients were screened, and 3D echocardiography analyses were feasible in 22 subjects (mean age 28 ± 9 years). 3D echocardiography ejection fraction correlated with percent-predicted VO_2max (r = 0.64, P < 0.01), VE/VCO₂ slope (r = –0.41, P = 0.05), two-dimensional echocardiography ejection fraction (r = 0.55, P < 0.01) and health-related quality of life physical functioning dimension (r = 0.56, P = 0.04). 3D echocardiography indexed end-systolic volume correlated with percent-predicted VO_2max (r = –0.45, P = 0.03) and VE/VCO₂ slope (r = 0.65, P < 0.01). 3D echocardiography reproducibility was good.ConclusionsSingle ventricle ejection fraction and volumes measured by 3D echocardiography correlated with cardiopulmonary fitness, as determined by two main prognostic cardiopulmonary exercise test variables: VO_2max and VE/VCO₂ slope. Despite good reproducibility, 3D echocardiography feasibility remained limited. 3D echocardiography may be of value in single ventricle follow-up, provided that the technique and analysis software are improved.     

Prognostic Utility of Anemia and Pro-B-Type Natriuretic Peptide in Patients With Nonischemic Dilated Cardiomyopathy and Normal Renal Function

BackgroundIdiopathic dilated cardiomyopathy frequently coexists with anemia and high plasma NT proBNP levels. However, the prognostic impact of these features on the disease course is uncertain, especially in patients with normal renal function.MethodsForty-seven patients with idiopathic dilated cardiomyopathy with sinus rhythm and normal renal function were prospectively followed for a mean 25 ± 18 months period. Clinical end points were death (sudden cardiac death and deaths because of worsening heart failure) and cardiac transplantation. Prognostic impact of NT proBNP levels, anemia, echocardiographic and clinical parameters on the clinical end points was evaluated with Kaplan-Meier survival analysis. Cut-off values of hemoglobin and plasma NT proBNP levels for predicting end points were determined by receiver operating curve analysis.ResultsTwenty-eight patients (59.6%) suffered clinical end points. The patients who suffered clinical end points were anemic (P = 0.002), had lower systolic (P < 0.003) and diastolic (P < 0.0001) blood pressures, and higher NYHA functional classes (P = 0.005), lower left ventricle ejection fractions (P = 0.003), higher E/A ratios (P = 0.001), shorter E-wave deceleration times (P = 0.001), isovolumetric relaxation times (P = 0.05) and pulmonary acceleration times (P = 0.004), and higher plasma NT proBNP levels (P < 0.0001). Anemic patients had more clinical end points (P = 0.002). In univariate analysis the prognostic predictors of life expectancy were log NT proBNP, anemia, NYHA functional class, systolic blood pressure, left ventricle ejection fraction, and E-wave deceleration time. However, multivariate analysis revealed only plasma NT proBNP as independent predictor of clinical end points.ConclusionTracking plasma NT proBNP levels is a useful strategy during routine follow-ups of patients with nonischemic dilated cardiomyopathy. Its predictive value for prognosis needs more evaluation in larger controlled studies. In addition, the importance of anemia in those patients needs more study.     

Association entre tissu adipeux epicardique et dysfonction systolique infraclinique détectée par strain longitudinal chez les diabétiques mal équilibrés

ObjectiveThe aim of this study is to assess the association between epicardial adipose tissue (EAT) and infraclinical myocardial dysfunction detected by strain imaging in diabetic patients (T2DM) with poor glycemic control.Methods22 patients with T2DM and 22 healthy control subjects of similar age and sex were prospectively recruited. Echocardiographic parameters were investigated.ResultsIn comparison to controls, diabetic patients had significantly higher body mass index (27.7 vs. 24.6; P < 0.01), waist perimeter (103 vs. 84; P < 0.001) and usCRP level (5.4 vs. 1.5; P < 0.01). On echocardiography; no differences were found in terms of ejection fraction or ventricular mass; however, patients with T2DM had significantly thicker EAT (8.7 ± 0.7 vs. 3.0 ± 1.0; P < 0.001) and altered systolic longitudinal strain (−18.8 ± 3.2 vs. 22.3 ± 1.6; P < 0.001). On multivariate analysis, EAT was identified as an independent contributor (β=0,46, P = 0.001) to systolic longitudinal strain.ConclusionIn patients with T2DM and poor glycemic control; EAT was associated with infraclinical systolic dysfunction evaluated by global longitudinal strain despite normal at rest ejection fraction and no coronary artery disease.     

Diet,lifestyle and cognitive function in old Chinese adults

BackgroundThe relationship between diet, lifestyle and cognition of old adults has been indicated in several population-based studies. However, the conclusions derived from these studies are inconsistent.MethodsA cross-sectional study was carried out in 894 old Chinese adults aged 50 and above. Cognitive function of the participants was measured by using Montreal Cognitive Assessment (MoCA) test. Demographic characteristics and lifestyle was collected with a questionnaire. A semi-quantified FFQ method was used for dietary intake survey.ResultsComparing with normal subjects, mild cognition impairment (MCI) patients were characterized as old age and lower education (P < 0.01). The nuts and cooking oil intake of MCI patients was less than the normal subjects (P < 0.05). Fruit and vegetable intake will benefit orientation, name and attention ability in the elderly (P < 0.05). Fruit and vegetable juice drinking will benefit abstraction ability (P < 0.01).Subjects with regular reading and housekeeping habit had better cognition (P < 0.01).ConclusionsNuts, vegetables and fruit-rich diet might decrease the risk of cognition impairment. Reading and housekeeping help to maintain healthy cognition in the elderly.     

Effects of pioglitazone on beta-cell function in metabolic syndrome patients with impaired glucose tolerance

ObjectiveTo determine the potential effects of pioglitazone on beta-cell function in metabolic syndrome patients with impaired glucose tolerance and probe into the possible mechanisms.Research design and methodsTwenty-two subjects were treated with pioglitazone 30 mg/day for 4 months. At baseline and after treatment, each subject underwent an IVGTT. The acute insulin response (AIRg), the glucose disappearance rates (coefficients K) and the ratio of Δinsulin/Δglucose (ΔI/ΔG) were calculated according to IVGTT results. Hyperglycemic clamp study was conducted to determine the second-phase insulin response, insulin sensitivity index (ISI) and glucose infusion rate (GIR). Euglycemic–hyperinsulinemic clamp study was made to measure the glucose disposal rate (GDR). Plasma glucose, free fatty acids (FFAs), serum insulin and proinsulin levels were measured.ResultsAIRg unchanged (P = 0.25) after treatment, whereas the values of coefficients K (P < 0.01) and ΔI/ΔG increased (P < 0.05). The second-phase insulin response and GIR were both demonstrated marked increments (P < 0.01 and P < 0.01, respectively). Pioglitazone therapy also resulted in improvement of ISI value (P < 0.05). And the increment of GDR during the euglycemic–hyperinsulinemic clamp was also significant (P < 0.01). Furthermore, a decrease in fasting proinsulin level was observed (P < 0.001). And plasma glucose, FFAs and serum insulin levels all declined. The increase of ΔI₁/ΔG₁ was positively correlated with the improvement of GDR (r = 0.536, P = 0.089). And a positive relationship was observed between the change in the second-phase insulin response and change in K value (r = 0.682, P = 0.021).ConclusionsShort-term pioglitazone therapy improved beta-cell dysfunction, the mechanism might involve the attenuation of insulin resistance.     

Impacto de la edad del donante-receptor en la supervivencia al trasplante cardiaco. Subanálisis del Registro Español de Trasplante Cardiaco

Introduction and objectivesThe age of heart transplant recipients and donors is progressively increasing. It is likely that not all donor-recipient age combinations have the same impact on mortality. The objective of this work was to compare survival in transplant recipients according to donor-recipient age combinations.MethodsWe performed a retrospective analysis of transplants performed between 1 January 1993 and 31 December 2017 in the Spanish Heart Transplant Registry. Pediatric transplants, retransplants and combined transplants were excluded (6505 transplants included). Four groups were considered: a) donor < 50 years for recipient < 65 years; b) donor < 50 years for recipient ≥ 65 years; c) donor ≥ 50 years for recipient ≥ 65 years, and d) donor ≥ 50 years for recipient < 65 years.ResultsThe most frequent group was young donor for young recipient (73%). There were differences in the median survival between the groups (P < .001): a) younger-younger: 12.1 years, 95%CI, 11.5-12.6; b) younger-older: 9.1 years, 95%CI, 8.0-10.5; c) older-older: 7.5 years, 95%CI, 2.8-11.0; d) older-younger: 10.5 years, 95%CI, 9.6-12.1. On multivariate analysis, independent predictors of mortality were the age of the donor and the recipient (0.008 and 0.001, respectively). The worst combinations were older-older vs younger-younger (HR, 1.57; 95%CI, 1.22-2.01; P < .001) and younger-older vs younger-younger (HR, 1.33; 95%CI, 1.12-1.58; P = .001).ConclusionsAge (of the donor and recipient) is a relevant prognostic factor in heart transplant. The donor-recipient age combination has prognostic implications that should be identified when accepting an organ for transplant.Full English text available from: www.revespcardiol.org/en     

Geoepidemiology,clinical manifestations and outcome of primary biliary cholangitis in Greece

Background & aimsPrimary biliary cholangitis (PBC) is a disease with rising prevalence and considerable geographical variation. To describe the prevalence, spatial and time distribution, baseline characteristics, response to treatment, outcome and the validity of GLOBE score in a large cohort of Greek PBC patients as an independent validation of this score has not been done so far.MethodsThe last 16 years, 482 PBC patients (86.5% females) were evaluated and analysed retrospectively, using a prospectively collected database. Special attention was paid to the assessment of treatment response according to GLOBE score.ResultsAge at initial evaluation was 56.3 ± 13.7 years. Among 432 Thessaly residents, prevalence was 582/million (non-homogeneous distribution). Nineteen districts showed a prevalence > 800/million. Symptomatic disease onset could be identified in 91 patients, with a significant peak during spring (P = 0.03). At diagnosis, 43.6% were asymptomatic and 16.2% cirrhotic. Male sex (P = 0.02), older age (P < 0.001), alcohol consumption (P < 0.01) and concomitant liver disease (P < 0.001) were negative prognostic factors for cirrhosis. During a median [interquartile range, range] follow-up of 5.1 (7.8, 15.7) years, 62 patients died or underwent liver transplantation. Patients with GLOBE score > 0.30 had significantly worse prognosis (P < 0.001) with 5-, 10-, and 15-year survival rates of 84%, 50% and 42%.ConclusionsThere is increased PBC prevalence in Thessaly with remarkable geographic clustering and seasonal variability. PBC is diagnosed at early stages although males had a more advanced disease. GLOBE score applies perfectly in Greek patients and this will likely help detecting patients that may benefit from new therapies.     

Anemia in diabetic patients at an internal medicine ward: Clinical correlates and prognostic significance

BackgroundCharacteristics and prognostic significance of anemia in hospitalized diabetic patients are unknown.MethodsWe studied 3145 unselected patients admitted to two Internal Medicine Departments, 872 (27.7%) of whom were diabetic. Forty diabetic patients died during the first hospitalization period. Out of the remaining 832 patients, 334 (40.2%) were anemic and evaluated for survival. In 87 diabetic patients, the cause of anemia was evident on admission, whereas the other 247 had to be further investigated for etiology of anemia.ResultsCompared to non-anemic diabetic patients, the diabetic anemic patients were older (mean age 71.4 vs. 64.4 years, P < .001) and predominantly females (52.4% vs. 44.4%, P < .02). Of the 247 evaluated patients, 38% were deficient in iron, 12% in vitamin B₁₂ and/or folate, 54% had anemia of chronic disease, 47% suffered from heart failure, 39% had renal dysfunction and 22% were complex nursing care patients and/or had diabetic foot. On median follow-up of 19.2 months, mortality rate was higher in anemic compared to non-anemic diabetic patients (17.3% vs. 4%, P < .001), the main cause of death being infection. Male sex (P = .03), albuminuria (P = .01) and heart failure (P = .06) were associated with shorter survival, male sex being the most significant (OR 2.02, 95% CI 1.04 ? 4.00).ConclusionFrequency of anemia was increased in diabetic patients admitted to the Internal Medicine Departments, compared to the studies performed on ambulatory patient populations. Anemia was multifactorial and associated with higher mortality, predominantly from infections. Males with albuminuria and heart failure were at higher risk of death.     

Enteropathy associated T cell lymphoma in celiac disease: A large retrospective study

IntroductionPrognosis of enteropathy-associated T cell lymphoma is poor but predictors of survival remain ill-defined. How clinical presentation, pathological features and therapies influence outcome was evaluated in 37 thoroughly characterized patients with celiac disease and T-cell lymphoma.Patients and methodsMedical files were studied retrospectively. Lymphoma and intestinal mucosa were analysed by histopathology, multiplex PCR and intestinal intraepithelial lymphocytes phenotyping. Survival and prognostic factors were analysed using Kaplan–Meier curves with Logrank test and Cox Model.ResultsLymphoma complicated non clonal enteropathy, celiac disease (n = 15) and type I refractory celiac disease (n = 2) in 17 patients and clonal type II refractory celiac disease in 20 patients. Twenty-five patients underwent surgery with resection of the main tumour mass in 22 cases. In univariate analysis, non clonal celiac disease, serum albumin level > 21.6 g/L at diagnosis, chemotherapy and surgical resection predicted good survival (p = 0.0007, p < 0.0001, p < 0.0001, p < 0.0001, respectively). In multivariate analysis, serum albumin level > 21.6 g/L, chemotherapy and reductive surgery were all significantly associated with increased survival (p < 0.002, p < 0.03, p < 0.03, respectively).ConclusionsOur study underlines the prognostic value of celiac disease type in patients with T-cell lymphoma, and suggests that a combination of nutritional, chemotherapy and reductive surgery may improve survival.     

L’hypo-albuminémie contribue-t-elle à l’aggravation de l’insuffisance cardiaque ?

BackgroundHypoalbuminemia has now emerged as a powerful prognosticator in heart failure regardless of age, clinical presentation, left ventricular ejection fraction and usual prognostic markers. Growing evidence is that this prognostic value persists after adjusting for causative factors for hypoalbuminemia such as malnutrition, inflammation and liver dysfunction.ObjectiveTo address the prognostic relevance of hypoalbuminemia in frail elderly patients with well-characterized cardiogenic pulmonary edema at high risk for adverse outcome, beyond causative factors for low serum albumin levels. Serum albumin was measured after clinical stabilization to avoid hypervolemia.ResultsIn all, 67 patients with a mean age of 86 years were included. Hospital mortality was 30%. Patients who died and who survived were similar in age, ejection fraction, BNP concentration, serum creatinine, serum hemoglobin, total bilirubin and prealbumin. Patients who died had lower serum albumin levels (P < 0.001), higher blood urea nitrogen (P = 0.03) and higher C-reactive protein (P = 0.02). In multivariate analysis, serum albumin was the sole independent predictor of hospital death (P < 0.01), after adjusting for malnutrition (prealbumin P = ns), inflammation (C-reactive protein P = ns) and liver dysfunction (total bilirubin P = ns).ConclusionSerum albumin is a powerful prognosticator in frail elderly patients with acute cardiogenic pulmonary edema even after adjusting for main causative factors. These results suggest that hypoalbuminemia may contribute to the worsening of heart failure given the physiological properties of serum albumin that includes antioxidant activity and plasma colloid osmotic pressure action. Further studies are critically needed to address the relevance of prevention and correction of hypoalbuminemia in heart failure.     

Long Non-Coding RNA NANCI/NKX2-1 Duplex Impacts Prognosis in Stage I Non-Small-Cell Lung Cancer

BackgroundNANCI, an intergenic long non-coding RNA (lncRNA) is essential for buffering NKX2-1 expression during embryonic development and in adult tissue. We analyzed NANCI and NKX2-1 in human lung embryonic samples and adult lung tissues and evaluated their potential as prognostic markers in stage I non-small cell lung cancer (NSCLC).Methods and resultsNANCI and NKX2-1 expression was assessed by TaqMan assays in 18 human embryonic samples from 8 to 13 weeks, 59 non-tumoral (NT) lung tissue samples, and 98 stage I NSCLC tumor samples. NANCI and NKX2-1 expression in embryonic and NSCLC samples were downregulated in comparison to adult NT tissue. Patients with low expression of NANCI had shorter disease-free survival (DFS) and overall survival (OS) than those with high levels (47.6 vs 69.3 months, P = 0.032 and 57.7 vs 77.6 months, P = 0.021, respectively). When the expression levels of NANCI and NKX2-1 were evaluated in combination, four groups were identified (high NANCI/high NKX2-1, low NANCI/high NKX2-1, high NANCI/low NKX2-1 and low NANCI/low NKX2-1) with differential impact on DFS (P = 0.042) and OS (P = 0.024). Interestingly, the high NANCI/high NKX2-1 duplex group had longer DFS and OS than the other three groups (71.25 vs 46.3 months, P = 0.009 and 81.3 vs 56.1 months, P = 0.004, respectively). In the multivariate analysis, the high NANCI/high NKX2-1 duplex was identified as an independent prognostic factor for longer DFS (HR 0.346, 95% CI, 0.169–0.709; P = 0.004) and OS (HR 0.309, 95% CI, 0.121–0.786; P = 0.014).ConclusionsNANCI and the NANCI-NKX2-1 duplex impacts prognosis in stage I NSCLC patients.     

Lactate and other clinicolaboratory predictors for subtle myocardial dysfunction in pediatric intensive care unit

IntroductionThis study aimed to determine the incidence of admission subtle myocardial dysfunction (SMD) in critically ill children by measuring cardiac troponin I (cTnI) and to identify clinicolaboratory risk factors.MethodsAdmission systolic blood pressure (SBP) registration. Categorizing patients into 2 groups: sepsis and nonsepsis. Laboratory investigations including: Hemoglobin, urea, creatinine, alanine aminotransferase (ALT); aspartate transaminase (AST) and serum troponin I (cTnI) and lactate.ResultsSixty-three patients were enrolled. Eleven (17.5%) patients had SMD. All SMD patients were in severe sepsis or septic shock having significant characteristics: (1) cTnI (median 0.7 ng/mL, P < 0.000), lactate (median 5.5 mmol/L. P < 0.000). (2) Age (median 6mo, P < 0.04) (3) SBP (median 73 mm Hg. P < 0.001) (4) ALT and AST (median 259 IU/dl and 586 IU/dl, P < 0.000 for each). (5) BUN and Creatinine (median 29 mg/dl, P < 0.002, median 1.4 mg/dl, P < 0.01, respectively). (6) Hemoglobin (median 7.2 g/dl, P < 0.003). Lactate Level > 3.3 mmol/L(95% CI −.9 to −.25, P < 0.001) and high ALT (95% CI −.002 to .000, P < 0.001) are predictors of SMD. High Lactate had a sensitivity of 90.9%, specificity of 89.9% with positive predictive value of 83.3%, negative predictive value of 94.1% and accuracy of 90%. for SMD. Patients with SMD had significant mortality.ConclusionSubtle myocardial dysfunction is detected in infants with severe sepsis and septic shock. SMD should be suspected in those patients showing high ALT and Lactate level > 3.3 mmol/L.