Expression-based, consistent biomarkers for prognosis and diagnosis in lung cancer.

OVERVIEW: Lung cancer is one of the deadliest cancers in the world. Its histological classification depends on early diagnosis and successful treatment. Therefore, having specific biomarkers for a quick sorting widens the successful output of lung cancer treatment. MATERIAL AND METHODS: High-throughput sequencing (RNA-seq) was performed of small cohorts of BioBanco samples from healthy and tumour cells from lung adenocarcinoma (LUAD) and squamous cell carcinoma of the lung (lSCC). RNA-seq samples from small cell lung cancer (SCLC) were downloaded from databases. A bioinformatic workflow has been programmed for the identification of differentially expressed genes (DEGs). RESULTS: A total of 4777 DEGs were differentially expressed in SCLC, 3676 DEGs were in lSCC, while the lowest number of DEGs, 2819, appeared in LUAD. Among them, 945 DEGs were common to the three histological types. Once validated their expression profile and their survival predictive capacity in large, public cohorts, three DEGs can be exclusively considered as diagnostic biomarkers, three as prognosis biomarkers, and other three exhibit both diagnosis and prognosis capabilities. CONCLUSIONS: This prospective study presents evidences for the diagnostic and prognostic capabilities of expression changes in CAPN8-2, TMC5 and MUC1 in LUAD, while they are non-significant in SCLC and lSCC. Their translation to clinical practice is proposed.

Current diagnosis and treatment of Castleman's disease.

Castleman's disease is not just a single disease but rather an uncommon, heterogeneous group of nonclonal lymphoproliferative disorders, which have a broad spectrum of clinical expression. Three histological types have been reported, along with several clinical forms according to clinical presentation, histological substrate and associated diseases. Interleukin-6, its receptor polymorphisms, the human immunodeficiency virus and the human herpes virus 8 are involved in the etiopathogenesis of Castleman's disease. The study of this disease has shed light on a syndrome whose incidence is unknown. Despite recent significant advances in our understanding of this disease and the increasing therapeutic experience with rituximab, tocilizumab and siltuximab, there are still difficult questions concerning its aetiology, prognosis and optimal treatment.

[Nutrients and energy intake assessment in the critically ill patient on enteral nutritional therapy]. / Valoración de la ingesta de nutrientes y energía en paciente crítico bajo terapia nutricional enteral.

INTRODUCTION AND OBJECTIVES: The critically ill patient is especially susceptible to malnutrition due to his/her hypermetabolic state that leads to an increase in the nutritional requirementes, which many times are not compensated with the administered enteral formulas. The assessment of nutritional intake is essential in this kind of patients to know to what level their energetic and nutritional requirements are fulfilled, improving and monitoring in the most individualized possible way to indicated clinical and nutritional therapu. METHODOLOGY: This is a retrospective study in which all patients admitted to the Intensive Care Unit of Virgen de las Nieves Hospital were studied from January to December of 2003, aged more than 18 years, and on enteral nutrition. A total of 90 patients (52 men and 38 women) were studied, 81% of which were older than 50 years, and 57% had hospital stays longer than 8 days, with a 21% mortality rate. Intake was assessed from time of admission and throughout the whole hospitalization period. Energetic requirements were calculated according to the modified Long's formula and micronutrients intakes were compared to existing general recommendations for the Spanish, European and American populations, and to vitaminic requirements in critically ill patients. RESULTS: Percentages of mean energy and nutrients intakes in relation to theoretical calculated requirements for both genders are presented in figure 1. Mean energy intake was 1,326 cal in men and 917 cal in women. With regards to micronutrients intake, the values found for proteins, falts, and carbohydrates were lower than 50% of the requirements for both genders. The percentage of adequacy as referred to requirements for vitamins and minerals intake is shown in figure 2. Reference recommendations used correspond to sufficient intakes to cover the healthy individual requirements, therefore, the values obtained in our study show and adequacy greater than 75%, with the exception of particular elements such as vitamin A and magnesium. However, by taking a look at figure 3, which shows the adequacy of vitamins intake at recommended does for sick patients, the intake is lower than 25% of the requirements in all cases, and these deficiencies significantly interfere with wound healing, the immune, cardiovascular and nervous systems, as well as with metabolism of the remaining macronutrients leading to an unbalanced situation of the antioxidant system, worsening the patient's clinical status. CONCLUSIONS: The present study confirms the need for monitoring individually the nutritional requirements in the critically ill patient and adapting recommendations to his/her metabolic changes, since currently these recommendations are not clearly defined for these situations. It is necessary to provide micronutrients doses closer to the patient's demands, so that the nutritional status and the balance of the antioxidant system may be preserved or improved, making the adopted clinical treatment more effective.

Role of apolipoprotein E epsilon 4 allele on chronic allograft nephropathy after renal transplantation.

Lipid abnormalities may contribute to chronic allograft nephropathy (CAN). Apolipoprotein E (ApoE) gene polymorphism regulates lipoprotein metabolism, but little is known about an association between CAN and this polymorphism. The ApoE gene (E3/E4) polymorphism was typed by PCR assay (99 E3/E3, 28 E3/E4, 1 E4/E4) on 128 consecutive renal transplant patients with functioning grafts for more than 3 years (6.7 +/- 2.8 years). Twenty-eight patients with histological CAN were compared with 100 patients who had no clinical evidence of chronic rejection (no proteinuria and sCr < 2.5 mg%). As expected, univariate analysis revealed that patients with CAN experienced a greater acute rejection rate (78% vs 21%; P=.001), a higher serum creatinine (3.6 +/- 1.7 vs 1.4 +/- 0.5 mg%; P=.0001), and an older organ donor (43 +/- 20 vs 29 +/- 13 years; P=.0001). The lipid profiles (total cholesterol and triglycerides levels) were similar in both groups with 60% in each group receiving anti-lipemic drugs. Interestingly, the ApoE epsilon 4 allele was overrepresented in the group with CAN (39% vs 17%, P=.019). Logistic regression analysis showed that the epsilon 4 allele was an independent predictor of CAN (OR: 3.4; CI 95%: 1.07 to 11; P=.040) as were donor age and acute rejection episodes. In conclusion, an interaction between risk factors and genetic factors may determine CAN in this population. This finding may help to target prophylactic interventions in these recipients.

Effect of serum phosphate on parathyroid hormone secretion during hemodialysis.

BACKGROUND: Recent studies have demonstrated that a high concentration of phosphate directly stimulates parathyroid hormone (PTH) secretion. High serum levels of phosphate are usually observed in patients with end-stage renal disease. The aim of the present study was to evaluate whether serum phosphate concentration had an acute effect on PTH secretion in hemodialysis patients. The levels of serum phosphate were manipulated during the hemodialysis session by using a phosphate free dialysate or a dialysate with a high content of phosphate. METHODS: Ten stable hemodialysis patients with PTH values above 300 pg/ml were included in the study. A PTH-calcium curve was obtained during both high phosphate and phosphate free hemodialysis. RESULTS: The serum phosphate concentration remained high (2.17 +/- 0.18 mM) throughout the high phosphate hemodialysis and decreased progressively to normal levels (1.02 +/- 0.06 mM) during the phosphate free hemodialysis. The serum PTH levels at maximal inhibition by hypercalcemia (minimal PTH) were greater during the high phosphate than the phosphate free hemodialysis (413 +/- 79 vs. 318 +/- 76 pg/ml, P < 0.003). In all patients the values of minimum PTH were greater during the high phosphorus than the phosphorus free hemodialysis. The values of maximally stimulated PTH during hypocalcemia and the set point of the PTH-calcium curve were similar during the high phosphate and the phosphate free hemodialysis. CONCLUSION: The maintenance of high serum phosphorus levels during hemodialysis prevented, in part, the inhibition of PTH secretion by calcium, which strongly suggests that in hemodialysis patients high serum phosphate contributes directly to the elevation of PTH levels despite normal or high serum calcium concentration.