Impact of diabetes on the predictive value of heart failure biomarkers.

BACKGROUND: Patients with diabetes mellitus (DM) have an increased risk of developing heart failure (HF). Further, DM is associated with poor prognosis in patients with HF. Our aim was to determine whether DM has any impact on the predictive value of a multi-biomarker panel in patients with HF. METHODS: We included 1069 consecutive ambulatory HF patients in the study: age 66.2 ± 12.8 years, 33.5 ± 13.3 left ventricular ejection fraction, 36% diabetic patients. We measured serum concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), ST2, galectin-3, high-sensitivity C reactive protein (hs-CRP), cystatin-C, soluble transferrin receptor (sTfR), and neprilysin and followed patients for 4.9 ± 2.8 years. Primary endpoints were all-cause and cardiovascular death. RESULTS: During follow-up, 534 patients died; 283 died of cardiovascular causes. Diabetic subjects had higher mortality (57.7 vs. 45.6%, p < 0.001). NTproBNP (p = 0.07), hs-TnT (p < 0.001), galectin-3 (p < 0.001), and cystatin-C (p = 0.001) concentrations were higher in diabetic patients, whereas sTfR levels were lower (p = 0.005). There were no interactions between DM and NTproBNP, hs-TnT, galectin-3, hs-CRP, cystatin-C, sTfR, and neprilysin relative to risk prediction for all-cause or cardiovascular death. By contrast, ST2 significantly interacted with DM for all-cause (p = 0.02) and cardiovascular (p = 0.03) death. In diabetic patients, HRs for ST2 were 1.27 (95% CI 1.16-1.40, p < 0.001) and 1.23 (95% CI 1.09-1.39, p = 0.001) for all-cause and cardiovascular death, respectively. In nondiabetic patients, HRs for ST2 were 1.53 (95% CI 1.35-1.73, p < 0.001) and 1.64 (95% CI 1.31-2.05, p < 0.001) for all-cause and cardiovascular death, respectively. The multivariable Cox regression analysis showed that hs-TnT and ST2 were the only markers that were independently associated with both all-cause and cardiovascular mortality in patients with HF and diabetes. Moreover, in these patients, the combination of these two markers significantly increased discrimination as assessed by the area under the curve. CONCLUSIONS: Biomarkers used in the general population to predict the clinical course of heart failure are also useful in patients with diabetes. In these patients, among all the biomarkers analysed only hs-TnT and ST2 were independently associated with both all-cause and cardiovascular mortality.

Pregnancy-associated plasma protein-A is related to gender and to adipocytokine levels: results of the Health Survey of Catalonia.

OBJECTIVE: Pregnancy-associated plasma protein-A (PAPP-A) is a protease promoting IGF1 tissue availability and considered as a new biomarker of cardiovascular disease. AIM: To evaluate the relationship between PAPP-A concentrations and anthropometric variables, physical activity, smoking status, glucose homoeostasis and adipocytokines in healthy adults. DESIGN AND METHODS: One hundred and forty-nine subjects (77 women; mean age 39·7 ± 14 years; mean BMI 23·7 ± 1·9 kg/m(2) ) were randomly selected from 8000 adults of The Health Survey of Catalonia. Possible effects of gender, age, body composition, smoking status, physical activity, glucose homoeostasis and adipocytokines on PAPP-A concentrations were assessed. RESULTS: Pregnancy-associated plasma protein-A was significantly higher in men than in women [1·04 (0·61-0·44) vs 0·61 (0·41-0·90) µIU/ml; P < 0·0001]; there were no differences in relation to physical activity or smoking status. PAPP-A showed a negative correlation with leptin in men (P = 0·01) and women (P = 0·05), and a positive correlation with adiponectin (P = 0·006) in women and a trend (P = 0·073) in men. Homoeostasis model assessment of insulin resistance (HOMA-IR) showed a negative correlation with PAPP-A only in women (P = 0·019). No association was found with blood pressure, IGF1, lipids or glucose in either gender. When a multiple regression analysis was performed including gender, age, BMI, waist-hip ratio, HOMA-IR, adiponectin and leptin as confounders, PAPP-A was independently correlated with adiponectin (ß = 0·23; P = 0·02) and leptin (ß = -0·33; P = 0·04). CONCLUSIONS: Our study shows a sexual dimorphism of PAPP-A, and a possible influence of leptin and adiponectin on its concentrations in healthy subjects. The mechanisms responsible for this relationship remain to be determined.

Bio-profiling and bio-prognostication of chronic heart failure with mid-range ejection fraction.

BACKGROUND: Recent ESC guidelines on heart failure (HF) have introduced a new phenotype based on left ventricular ejection fraction (LVEF), called the mid-range (HFmrEF). This phenotype falls between the classical reduced (HFrEF) and preserved (HFpEF) HF phenotypes. We aimed to characterize the HFmrEF biomarker profile and outcomes. METHODS: 1069 consecutive ambulatory patients were included in the study (age 66.2 ±â€¯12.8 years); 800 with HFrEF (74.8%), 134 with HFmrEF (12.5%), and 135 with HFpEF (12.5%). We measured serum concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), soluble suppression of tumorigenicity (ST2), galectin-3, high-sensitivity C-reactive protein, cystatin-C, neprilysin, and soluble transferrin receptor, during 4.9 ±â€¯2.8 years of follow-up. The primary end-point was the composite: cardiovascular death or HF-related hospitalization. We also examined all-cause, cardiovascular death, and the composite: all-cause death or HF-related hospitalization. RESULTS: NTproBNP levels in HFmrEF were similar to levels in HFpEF, but significantly lower than levels in HFrEF. No other studied biomarkers were different between HFmrEF and HFrEF. All biomarkers, except neprilysin, showed higher risk prediction capabilities in HFmrEF than in HFrEF or HFpEF. The largest difference between HFrEF and HFmrEF was the hs-TnT level (hazard ratio [HR]: 4.72, 95% CI: 2.81-7.94 vs. HR: 1.67, 95%CI: 1.74-1.89; all p < 0.001). CONCLUSIONS: Although HFmrEF is acknowledged as an intermediate phenotype between HFrEF and HFpEF, from a multi-biomarker point of view, HFmrEF was similar to HFrEF, except that NTproBNP levels were lower. Biomarkers commonly used for HFrEF risk prediction are more valuable for HFmrEF risk stratification.

[Early-onset Parkinsonism. A report on a Spanish series]. / Parkinson de inicio precoz. A proposito de una serie espanola.

INTRODUCTION: Early-onset Parkinsonism is a condition that has received little attention from researchers due to its low incidence and prevalence. We conducted a retrospective, cross-sectional, multi-centre study in order to obtain a representative sample of the Spanish population. PATIENTS AND METHODS: The study involved 92 Spanish patients who had been diagnosed with idiopathic Parkinson's disease that began before the age of 40 years and these patients were divided into two groups: group 1, which consisted of 86 patients, with an age at onset of between 21 and 40 years (early-onset Parkinsonism), and group 2, with an age at onset of below 21 years, which included a total of 6 patients (juvenile Parkinsonism). Our analysis involved demographic data, patient's personal and family history, age and symptoms of onset of the disease, complementary studies, drug therapy and pharmacological complications. RESULTS: In group 1 we found a high incidence of early-onset Parkinsonism in the family. In our series there was a clear predominance of patients from urban settings. The predominant form of onset was akinesia, followed by tremor at rest, rigidity and postural tremor. Since they began treatment with levodopa, some patients presented fluctuations and dyskinesias which progressively increased over the years. CONCLUSIONS: Our series of patients is not wholly similar to those reported in the literature; it is comparable, however, to those found in western countries and can be considered to be valid due to the number of cases analysed and owing to the fact that patients were selected from different areas around Spain. This provides an overall picture of this subtype of Parkinson's disease for the country as a whole.

Evaluation of Vitamin and Trace Element Requirements after Sleeve Gastrectomy at Long Term.

BACKGROUND: Nutritional deficiencies are common after bariatric surgery, but data are scarce after sleeve gastrectomy (SG) at long term. METHODS: We performed a prospective nutritional status evaluation before and at 2 and 5 years after SG in morbid obese patients receiving mulvitamin and mineral supplementation at a Spanish university hospital. One hundred seventy-six patients (49.3 ± 9.1 years and 46.7 ± 7.4 kg/m2) were evaluated; 51 of them were followed during 5 years. Anthropometric, compliance supplementation intake, and micronutrient evaluation were performed. RESULTS: Baseline concentrations were below normal values for 25(OH) vitamin D (73%), folic acid (16.5%), cobalamin (6.9%), pyridoxine (12%), thiamine (3.4%), and copper (0.5%). Anemia was found in 23%. In 49% of the subjects, at least one micronutrient deficiency was found at 2 years after SG. Vitamin D deficiency persisted at 2 and 5 years higher than 30% of patients. Frequencies of deficiencies for folic acid, B12, B6, and B1 vitamins decreased significantly after 2 years with normalization at 5 years. Copper deficiency increased between 1 and 2 years and it persisted at 5 years after SG. Vitamin supplementation compliance decreased progressively from the first year after surgery (94.8 to 81% at 2 years and to 53% 5 years after surgery). CONCLUSIONS: Vitamin D deficiency is the most prevalent long-term nutritional deficiency after SG. About half of patients show some micronutrient deficiency at medium long term, despite supplementation. A proactive follow-up is required to ensure a personalized and adequate supplementation in all surgically treated obese patients including those in which SG has been performed.

Absorption and transport of dietary long-chain fatty acids in cirrhosis: a stable-isotope-tracing study.

BACKGROUND: In rats, 30-70% of dietary fatty acids (FAs) are absorbed through the portal vein. Whether this occurs in humans is unknown, but it may occur in persons with cirrhosis, who show a blunted chylomicronemic response to dietary fat without significant steatorrhea. OBJECTIVE: The objective was to investigate whether portal FA absorption occurs in humans with cirrhosis. DESIGN: Six control subjects and 10 patients with (n = 5) and without (n = 5) cirrhotic ascites were fed [1-(13)C]palmitic and oleic acids in a test meal. Samples were drawn before and 30, 60, 90, 120, 240, 360, 480, and 720 min afterward for plasma [1-(13)C]-labeled FAs and breath (13)CO(2) assay. Fecal [1-(13)C]-labeled FAs were also measured. RESULTS: [1-(13)C]-Labeled FAs increased in chylomicrons in all groups, but less in ascitic cirrhotic patients, because their median area under the curve from 120 to 720 min was significantly lower than in the control subjects for labeled palmitate [520 (interquartile range: 192-1137) compared with 2862 (2674-4175) micromol . min/L] and oleate [829 (781-1263) compared with 3119 (2939-4986) micromol . min/L]. [1-(13)C]-Labeled FA enrichment of VLDL was also lower in cirrhotic patients. [1-(13)C]-Labeled FA in free FAs peaked earlier in ascitic than in nonascitic patients and control subjects, mainly for [1-(13)C]oleate, and the median area under the curve from 0 to 120 min was significantly higher in ascitic patients than in control subjects [301 (255-400) compared with 48 (34-185) micromol . min/L]. Fecal excretion of [1-(13)C]-labeled FA was negligible and not significantly different between groups. CONCLUSIONS: The low [1-(13)C]-labeled FA concentrations in chylomicrons and VLDL, without increased fecal losses, confirm previous data in cirrhotic patients with the use of an unlabeled fat load. The earlier [1-(13)C]-labeled FA appearance in free FAs supports the portal absorption of dietary fat in patients with advanced cirrhosis with spontaneous portal-systemic shunting.

Pretransplant pregnancy-associated plasma protein-a as a predictor of chronic allograft nephropathy and posttransplant cardiovascular events.

BACKGROUND: Cardiovascular disease and chronic allograft nephropathy (CAN) are two of the main complications observed in patients after renal transplantation. Both appear to be manifestations of the same process, in which inflammation plays a determinate role. Pregnancy-associated plasma protein A (PAPP-A) has been shown to be a marker of acute coronary syndrome and cardiovascular pathology. The objective of this study was to demonstrate whether or not serum concentration of pretransplant PAPP-A is a marker of CAN and a predictor of posttransplant cardiovascular events. METHODS: In all, 178 renal transplants (65% males; 53+/-12 years of age) followed up over the course of 49.3+/-33.6 months were used in this study. During the follow-up period, 19 patients developed CAN (diagnosed by renal biopsy) and 27 patients had a cardiovascular event. Previous to transplantation, the following were determined: ultrasensitive C-reactive protein (CRP) (nephelometry); interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) (immunofluorimetric automatized method), and ultrasensitive PAPP-A (ELISA). RESULTS: A positive correlation was found between PAPP-A and the inflammatory markers (PAPP-A vs. CRP, r=0.218; P=0.004; PAPP-A vs. IL-6, r=0.235; P<0.001; PAPP-A vs. TNF-alpha, r=0.372; P<0.001). The multiple regression analysis showed PAPP-A (relative risk [RR]: 6.4; 95% confidence interval [CI]:1.24-33.11; P=0.027) and CRP (RR: 6.05; 95% CI:1.21-29.74; P=0.028) to be predictors of posttransplant cardiovascular events and PAPP-A (RR: 4.27; 95% CI: 1.03-17.60; P=0.044) and TNF-alpha (RR: 5.6; 95% CI: 1.43-21.83; P=0.013) to be predictors of CAN. CONCLUSIONS: PAPP-A correlated with the inflammatory markers studied (CRP, IL-6 and TNF-alpha). Pretransplant serum concentration of PAPP-A is a predictor of posttransplant cardiovascular events and CAN.

Usefulness of tumor markers CA 125 and CA 15.3 at diagnosis and during follow-up in non-Hodgkin's lymphoma: study of 200 patients.

CA 125 and CA 15.3 serum levels were measured at diagnosis, after treatment and at the time of recurrence in 200 consecutive patients (114 males, median age 56 years) with non-Hodgkin's lymphoma (NHL) to explore its usefulness in the evaluation of response to treatment and survival in patients with NHL compared to lactate dehydrogense (LDH) and beta2-microglobulin (beta2-M). Their association with the clinical - biologic parameters at diagnosis, response to treatment, event-free survival (EFS) and overall survival (OS) was analysed. Eighty-six patients (43%) had elevated CA 125 levels and 35 (17.5%) had elevated CA 15.3 levels at diagnosis. CA 125 was associated with advanced stage, lung, pleural or gastrointestinal tract involvement and CA 15.3 was correlated with advanced stage, bone involvement, aggressive histology and bulky disease. LDH had the highest predictive value for failure to achieve complete remission (P = 0.001). A shorter OS was associated with increased LDH (P < 0.0001), beta2-M (P = 0.013) and CA 125 (P = 0.025) whereas CA 15.3 was associated with a shorter EFS (P = 0.027). When elevated at diagnosis, CA 125 and CA 15.3 should be monitored during follow-up of patients with NHL.

Improved method for gas chromatographic-mass spectrometric analysis of 1-(13)C-labeled long-chain fatty acids in plasma samples.

BACKGROUND: Gas chromatographic-mass spectrometric (GC/MS) tracking of stable-isotope-labeled substrates is useful in metabolic studies. However, GC/MS analysis of long-chain fatty acid methyl esters yields results that mostly depend on their concentration in the system. We describe a protocol aimed to obviate this and other drawbacks in plasma [1-(13)C]palmitic and [1-(13)C]oleic acid measurements. METHODS: Lipoproteins were separated by sequential ultracentrifugation. Free or esterified heptadecanoic acid was used as internal standard. Fatty acids were derivatized to trimethylsilyl (TMS) esters. GC separation was in isothermal mode at 210 degrees C for 27 min. For both TMS-palmitate and TMS-oleate, M and [M + 1] signals were simultaneously acquired with a dual acquisition program in single-ion monitoring mode. Calibration mixtures containing increasing amounts of labeled fatty acids were prepared gravimetrically to construct calibration curves for isotopic enrichment. Likewise, five calibration curves (for increasing concentrations) were constructed for each fatty acid; this allowed selection of the most appropriate curve for the concentration in a plasma sample. RESULTS: Oleic acid-TMS ester was clearly separated from that of its stereoisomer, elaidic acid. Within a 10-fold concentration range, the isotopic ratio was independent on the amount of the analyte in the sample, with a maximum uncertainty of 0.34% in terms of molar percent excess. In addition, the within- and between-day imprecision (CV) of the method was <1%. CONCLUSION: Results obtained with this method are independent of concentration and sufficiently precise for tracking 1-(13)C-labeled palmitic and oleic acids in biological samples

[Ectopic left ureter emptying into the ipsilateral seminal vesicle: diagnosis with nuclear magnetic resonance]. / Desembocadura ectópica ureteral izquierda en vesícula seminal ipsilateral: diagnóstico por resonancia magnética nuclear.

We report on a 35-year-old male patient with ectopic left ureter entering the seminal vesicle associated with ipsilateral renal dysplasia who consulted for pain in the left renal fossa, painful ejaculation and recurrent episodes of left epididymitis. Patient evaluation included cystoscopy, urography, CT and MRI. However, only MRI showed precise images of the trajectory of the ectopic ureter, thereby obviating the need for other invasive diagnostic techniques and permitting surgical correction of the anomaly.

[Fournier gangrene: our experience]. / Gangrena de Fournier: nuestra experiencia.

OBJECTIVE: Fournier's gangrene is a necrotizing fasciitis involving the genitoperineal region caused by the synergistic action of aerobic and anaerobic pathogens. It is a rapidly progressing disease and carries a high mortality. Our experience with Fournier's gangrene is presented. METHODS: Herein we describe 11 cases of Fournier's gangrene that were diagnosed and treated from 1991 to 1996. The most important predisposing factor was diabetes mellitus and the most common triggering factor was a perianal condition. RESULTS/CONCLUSIONS: The survival rate was high (81%) and can be ascribed to early diagnosis, aggressive and rapid surgical treatment with debridement, resection of the necrotic areas, drainage, simultaneous broad spectrum antibiotic therapy and frequent local treatment.

Parkinson de inicio precoz. A propósito de una serie española / Early-onset parkinsonism a report on a Spanish series

El Parkinson de inicio precoz es una entidad poco estudiada a causa de la baja incidencia y prevalencia.Hemos realizado un estudio retrospectivo transversal multicéntrico para tener una muestra representativa de la población española. Pacientes y métodos. Se incluyeron en el estudio 92 pacientes españoles diagnosticados de enfermedad de Parkinsonidiopática de inicio antes de los 40 años, que se dividieron en dos grupos: grupo 1, con 86 pacientes, con edad de inicio entre 21 y 40 años (Parkinson de inicio precoz), y grupo 2, con edad de inicio inferior a los 21 años, con un total de 6 pacientes (Parkinson juvenil). Analizamos: datos demográficos, antecedentes personales y familiares, edad y síntomas de comienzode la enfermedad, estudios complementarios, farmacoterapia y complicaciones farmacológicas. Resultados. En el grupo 1 encontramos una gran incidencia familiar de Parkinson de inicio precoz. En nuestra serie hubo un claro predominiode pacientes del medio urbano. La forma predominante de inicio fue la acinesia, seguida del temblor de reposo, rigidez y temblor de actitud. Algunos pacientes presentaron, desde el inicio del tratamiento con levodopa, fluctuaciones y discinesias queaumentaron progresivamente a lo largo de los años. Conclusiones. Nuestra serie de pacientes no es totalmente similar con lasdescritas en la literatura; sí es parecida a las encontradas en los países occidentales y tiene validez por el número de casosanalizados y por seleccionar pacientes de varios sitios del territorio español, dando una imagen general sobre este subtipo de enfermedad de Parkinson nacionalmente

Early-onset Parkinsonism is a condition that has received little attention from researchers due to itslow incidence and prevalence. We conducted a retrospective, cross-sectional, multi-centre study in order to obtain a representative sample of the Spanish population. Patients and methods. The study involved 92 Spanish patients who had been diagnosed with idiopathic Parkinson's disease that began before the age of 40 years and these patients were divided into twogroups: group 1, which consisted of 86 patients, with an age at onset of between 21 and 40 years (early-onset Parkinsonism), and group 2, with an age at onset of below 21 years, which included a total of 6 patients (juvenile Parkinsonism). Our analysisinvolved demographic data, patient’s personal and family history, age and symptoms of onset of the disease, complementary studies, drug therapy and pharmacological complications. Results. In group 1 we found a high incidence of early-onset Parkinsonism in the family. In our series there was a clear predominance of patients from urban settings. The predominant form of onset was akinesia, followed by tremor at rest, rigidity and postural tremor. Since they began treatment with levodopa, some patients presented fluctuations and dyskinesias which progressively increased over the years. Conclusions. Our series of patients is not wholly similar to those reported in the literature; it is comparable, however, to those found in western countries and can be considered to be valid due to the number of cases analysed and owing to the fact that patients were selected from different areas around Spain. This provides an overall picture of this subtype of Parkinson's disease for the country as a whole