Prognostic tools at hospital arrival in acute myocardial infarction: copeptin and hepatocyte growth factor.

BACKGROUND: Prompt evaluation and treatment of acute coronary syndrome has demonstrated to reduce mortality. Although several biomarkers have been studied for risk stratification and prognostic purposes, none is recommended to guide treatment based on its prognostic value. Copeptin and hepatocyte growth factor have been associated with poor outcome in patients with acute myocardial infarction. The aim of this study is to evaluate the early prognostic value of measurements of copeptin and hepatocyte growth factor for hospital mortality risk and 1-year-follow-up mortality, in patients with acute myocardial infarction. In our retrospective observational study, we measured hepatocyte growth factor and copeptin in blood samples collected at hospital arrival in patients with acute myocardial infarction; and follow-up them until 1-year. RESULTS: 84 patients with were included in the study, mainly male (65%) with a median age of 70.3 ± 13.56 years. Hospital mortality was 11.9%. Plasma levels of copeptin at hospital arrival were statistically significant higher in patients who died during hospital admission (145.60 pmol/L [52.21-588.50] vs. 24.79 pmol/L [10.90-84.82], p 0.01). However, we found no statistically significant association between plasma levels of hepatocyte growth factor and hospital mortality (381.05 pg/ml [189.95-736.65] vs. 355.24 pg/ml [175.55-521.76], p 0.73). 1-year follow-up mortality was 21.4%. Plasma levels of copeptin at hospital arrival were higher in those patients who died in the following year (112.28 pmol/L [25.10-418.27] vs. 23.82 pmol/L [10.96-77.30], p 0.02). In the case of HGF, we also find no association between hepatocyte growth factor plasma levels and 1 -year follow-up mortality (350.00 pg/ml [175.05-555.08] vs. 345.53 pg/ml [183.68-561.15], p 0.68). CONCLUSIONS: In patients with acute myocardial infarction measurement of copeptin at hospital arrival could be a useful tool to assess the prognosis of these patients, since their elevation is associated with a higher hospital mortality and higher 1-year follow-up mortality. We have not found this association in the case of hepatocyte growth factor measurement.

Factor de crecimiento de hepatocitos séricos como herramienta diagnóstica en pacientes con dolor torácico agudo / Serum hepatocyte growth factor as diagnostic tool in patients with acute chest pain

Resumen Objetivo Determinar si los niveles plasmáticos de factor de crecimiento de hepatocitos podrían ayudar a realizar el diagnóstico diferencial en pacientes con dolor torácico prolongado y elevación de la troponina cardiaca, y evaluar su valor pronóstico de mortalidad al año en estos pacientes. Método: Estudio prospectivo observacional. Se incluyeron pacientes mayores de 18 años que acudieron a urgencias con dolor torácico agudo de más de 20 minutos y elevación de la troponina cardiaca, con seguimiento al año. Resultados Se incluyeron 303 pacientes, 103 (34%) con infarto de miocardio y 200 (66%) con otras enfermedades. Los niveles plasmáticos del factor de crecimiento de hepatocitos fueron superiores en el grupo sin infarto de miocardio: 329 pg/ml (rango intercuartílico [IQR]: 66-558) vs. 476 pg/ml (IQR: 264-908; p < 0.001). La mortalidad al año fue del 30.7%, superior en el grupo sin infarto de miocardio (36.5% vs. 19.4%; p = 0.002). Se encontró una fuerte asociación entre la mortalidad y los niveles elevados de factor de crecimiento de hepatocitos (650 pg/ml [344-1159] vs. 339 pg/ml [205-607]; p < 0.001). En el análisis multivariado se halló que los niveles de factor de crecimiento de hepatocitos, la edad y la escala GRACE son factores independientes de mortalidad al año en estos pacientes. Conclusiones En los pacientes con dolor torácico agudo prolongado y elevación de la troponina cardiaca, la determinación de los niveles del factor de crecimiento de hepatocitos no permite confirmar ni descartar la presencia de infarto agudo de miocardio. No obstante, podría ser un marcador pronóstico de mortalidad en estos pacientes, junto con la edad y la escala GRACE.

Abstract Objective To determine if plasma levels of hepatocyte growth factor could help in the differential diagnosis of patients with prolonged chest pain and elevated cardiac troponin; and to evaluate its prognostic value for one-year mortality in these patients. Method A prospective observational study. Patients over the age of 18 who were seen in the emergency room for acute chest pain lasting longer than 20 minutes and elevated cardiac troponin were included, with follow up after one year. Results We included 303 patients, 103 (34%) with myocardial infarction and 200 (66%) with other diseases. Plasma levels of hepatocyte growth factor were higher in the group without myocardial infarction: 329 pg/ml (IQR: 166-558) vs. 476 pg/ml (IQR: 264-908; p < 0.001). One-year mortality was 30.7%, higher in the group without myocardial infarction (36.5% vs. 19.4%; p = 0.002). We found a strong association between mortality and elevated levels of hepatocyte growth factor (650 pg/ml [344-1,159] vs. 339 pg/ml [205-607]; p < 0.001). Multivariate analysis showed that levels of hepatocyte growth factor, age and the GRACE scale are independent factors for one-year mortality in these patients. Conclusions In patients with prolonged acute chest pain and elevated cardiac troponin, hepatocyte growth factor levels do not confirm or rule out acute myocardial infarction, although they may be a prognostic marker for mortality in these patients, along with age and the GRACE scale.

Validation of a novel and accurate ApoE4 assay for automated chemistry analyzers.

The allele ε4 of the apolipoprotein E gene (APOE ε4) is the major genetic risk factor for non-dominantly inherited Alzheimer's Disease (AD). Current techniques for APOE ε4 carriers identification show good accuracy but have several disadvantages that limit its implementation in a clinical laboratory. These include the need for sample preprocessing, poor automation, low throughput, requirement of additional equipment, and high cost. We followed ISO 13485 guidelines to validate the e4Risk test, a new latex-enhanced immunoturbidimetric blood assay for apolipoprotein E4 (ApoE4) determination in human plasma samples. The test showed high performance in terms of lot to lot variability, precision, interferences, reagents stability, prozone, and detectability. Furthermore, diagnostic accuracy is almost equal (99%) to the gold standard, APOE ε4 genotyping by polymerase chain reaction (PCR). Furthermore, we demonstrated that the e4Risk test can be adapted to any clinical chemistry analyzer, including the high throughput analyzers present in most hospitals and clinical laboratories. The e4Risk test versatility, low cost, and easiness provides an excellent solution for APOE ε4 carriers identification using the same blood sample drawn for biochemical diagnostic work-up of AD patients, which can have important advantages for patient stratification in clinical trials, preventative strategies for AD, and clinical assessment of risk for brain amyloidosis.

CYFRA 21-1 in patients with suspected cancer: evaluation of an optimal cutoff to assess the diagnostic efficacy and prognostic value.

Objectives: Chosen cutoff for cytokeratin 19 fragment antigen (CYFRA 21-1) as a tumor biomarker considerably influences its diagnostic and prognostic usefulness. The aim of the present study is to determine an optimal cutoff value for diagnostic validity of CYFRA 21-1 by Lumipulse ® technology in patients with suspected cancer and also to determine if CYFRA 21-1 levels provide prognostic value. Methods: A consecutive 284 patients suggestive of malignant disease from six hospitals of Madrid were enrolled in a retrospective design. Optimal CYFRA 21-1 cutoff value was obtained by receiver operating characteristic curve and Youden test. The diagnostic validity was evaluated according to sensitivity, specificity, predictive values and likelihood ratios. The prognostic value of CYFRA 21-1 was checked using multiple logistic regression. Thirty-two diagnostic cancers were confirmed. Results: The most optimal cutoff was 3.15 ng/mL. This cutoff showed a better specificity 93.63% (95% confidence interval [CI], 89.66-96.16), positive predictive value 60.98% (95% CI, 44.54-75.38) and positive likelihood ratio 12.65 (95% CI, 7.64-20.95) than the cutoff recommended by Fujirebio® (1.8 ng/mL) (specificity: 73.71% [95% CI, 67.72-78.95], positive predictive value: 29.79% [95% CI, 21.02-40.23] and positive likelihood ratio 3.43 [95% CI, 2.71-4.35]), improving the current diagnostic accuracy. In multivariate analysis, elevated levels of CYFRA 21-1 (>3.15 ng/mL) was confirmed as an unfavorable prognostic factor. Conclusions: The best cutoff for CYFRA 21-1 obtained was 3.15 ng/mL in patients with suspected cancer. This new cutoff decreases the false positive rate and improves the diagnostic efficacy of CYFRA 21-1 as a tumor marker as well as its association with death events.

A new goniopholidid crocodyliform, Hulkepholis rori sp. nov. from the Camarillas Formation (early Barremian) in Galve, Spain).

BACKGROUND: The neosuchian crocodyliform genus Hulkepholis constitutes the longirostral lineage of the European Goniopholididae. It comprises two species ranging from the Valanginian of southern England to the lower Albian of the northern Teruel (Spain). A new species of Hulkepholis is described based on a partially complete skull from the lower Barremian Camarillas Formation. We investigate its phylogenetic position and the palatal patterns among members of Goniopholididae and the closely related Thalattosuchia and Tethysuchia. METHODS: Phylogenetic relationships were investigated with two matrices using a previously published dataset as the basis: the first differed only by the addition of the new species, the second had newly discovered states for 11 characters, the new species plus several additional specimens of Hulkepholis and Anteophthalmosuchus. Both matrices were processed using TNT v. 1.1, in a heuristic analysis of maximum parsimony, with tree bisection and reconnection 1,000 random addition replicates and saving the 10 most parsimonious trees per replicate, and up to 10 suboptimal trees to calculate Bremer supports. The skull geometry of nine species from Thalattosuchia, Tethysuchia and Goniopholididae was explored to test shape variation between the rostral and postrostral modules, and to visualize the differences on the secondary palate. A set of 18 landmarks was used to delimit significant anatomical features, and the skulls were isotropically scaled using Adobe Illustrator, with the longest skull (Sarcosuchus imperator) as the baseline for comparison. RESULTS: The European lineages of goniopholidids are two clades (Nannosuchus + Goniopholis) plus (Hulkepholis + Anteophthalmosuchus). The new species, Hulkepholis rori sp. nov, shares with the latter clade the following apormorphies: a long anterolateral postorbital process, postorbital process almost reaching the anterior jugal ramus, and basioccipital tubera with lateral edges turned posteriorly. Anteophthalmosuchus was found to be monophyletic, and Hulkepholis paraphyletic due to the poor preservation of H. willetti. Hulkepholis rori is distinguished by having vascular fossae and a mid-protuberance on the ventral surface of the basioccipital, and wide internal fossae in the quadrate. Among Goniopholididae differences on the secondary palate are the presence of a palatal cleft, the narrowness of the secondary choana, and a wide foramen of the median pharyngeal tube. CONCLUSIONS: The new species is the earliest Hulkepholis from the Iberian Peninsula. New characters have been recognized in the organization of the palate and in the occipital region raising unexpected questions on the evolution of Goniopholididae. The set of palatal characters is discussed as part of a singular palatogenesis in Goniopholididae. The protruding occipital areas suggest that the longirostral Hulkepholis would have had an aquatic lifestyle with particular neck and skull movements.

Impact of a Barcode Medication Administration System on Patient Safety
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OBJECTIVES: To determine the impact of barcode medication administration (BCMA) on the incidence of medication administration errors among patients in an onco-hematology day hospital and to identify the characteristics of medication errors in that setting.
. SAMPLE & SETTING: 715 patients treated in the onco-hematology day unit at the Príncipe de Asturias University Hospital in Madrid, Spain.
. METHODS & VARIABLES: A between-groups, pre-/postintervention study was conducted. Administration errors observed in patients with solid tumors (intervention group) were compared with those in patients with hematologic cancer (control group) before and after the introduction of BCMA. Error incidence, type, and severity were assessed, as was length of stay for treatment.
. RESULTS: Use of a BCMA system reduced the incidence and severity of errors in medication administration in the onco-hematology day hospital.
. IMPLICATIONS FOR NURSING: BCMA is a useful technology to check the five rights of medication administration in the onco-hematology day hospital and could help nurses increase the time spent on direct patient care activities. 
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La farmacia del hospital Nuestra Señora de Gracia de Zaragoza: la importancia histórica de un legado / The pharmacy of the Nuestra Señora de Gracia Hospital in Zaragoza: the historical importance of a legacy

Las farmacias de hospital han tenido a lo largo de los siglos una importancia relevnate dentro del desarrollo global de la farmacia, tanto desde el aspecto profesional, como en el científico y el artístico. En España han sido destacables las aportaciones y la historial de la farmacia del Hospital de la Santa Creu de Barcelona, de la que se tienen datos desde la fundación del Hospital en 1404 y las de los hospitales General de Valencia y el de Madrid. En Aragón el Hospital de Nuestra Señora de Gracia de Zaragoza ha sido durante siglos su principal centro sanitario. De su botica tenemos conocimiento desde tiempos de Fernando el Católico y su importancia está avalada por documentos y estudios de distintas épocas. Trasladado el Hospital a su actual emplazamiento, tras la destrucción del primitivo en 1808, la farmacia sufrió varias remodelaciones, la más importante se realizó poco después de hacerse cargo la Diputación Provincial de Zaragoza del funcionamiento del centro en el último tercio del siglo XIX. En este trabajo pretendemos exponer el funcionamiento del Hospital Nuestra Señora de Gracia de Zaragoza y especialmente de su farmacia en el último tercio del siglo XIX describiendo sus funciones, la importancia de los farmacéuticos que trabajaron ella y la renovación de sus estructura en 1881 que se ha conservado en su esencia hasta el presente

Over centuries hospital pharmacies have played an important role in the global development of Pharmacy, as much from the professional as scientific and artistic aspects. In Spain, the contribution and history of the pharmacy of the Hospital de Santa Creu in Barcelona, with data from its foundation in 1404, and those of the General hospitals of both Valencia and Madrid, have been outstanding. In Aragon, Zaragoza's Nuestra Señora de Gracia Hospital has been the main health centre. We have knowledge from its pharmacy dating from the time of Fernando the Catholic and its importance is backed by documents and studies from different periods. The Hospital was moved to its current localtion after the original was destroyed in 1808, the pharmacy underwent several restructurings with the most important was done shortly after the Diputación Provincial de Zaragoza took over its running in the last third of the XIXth century. This work intends to show how Zaragoza's Nuestra Señora de Gracia hospital worked and, in particular, its pharmacy in the last third of the XIXth century, describing its functions, the importance of the pharmacists working there and the renewal of its structure in 1881, which have been maintained in essence until the present day

Development and validation of a short version of the Spanish pediatric voice handicap index (P-VHI-10).

OBJECTIVES: A child's voice is used both as a tool for communication and as a form of emotional expression. Thus, voice disorders suffered by children have negative effects on their quality of life, which can be assessed using the "Pediatric Voice Handicap Index" (P-VHI). This questionnaire is completed by the parents of dysphonic patients and it has been validated in different languages: Italian, Korean, Arabic, and Spanish. More recently, the "Children Voice Handicap Index-10" test (C-VHI-10) was developed and validated, an Italian version reduced into 10 items that is answered by children themselves. The objective of this study was to develop and validate a short Spanish version of the P-VHI (P-VHI-10) and to assess whether it is comparable to the Italian C-VHI-10. MATERIALS AND METHODS: We conducted a cross-sectional study on 27 patients between 6-15 years of age. We developed an abbreviated version of the P-VHI that consisted of 10 statements to be answered by parents of children with dysphonia (P-VHI-10). These statements were based on the 10 items with the highest score in the validated Spanish version of the P-VHI. In addition, the validated Italian version of C-VHI-10 was translated into Spanish and this translation was reviewed and modified by three specialists, resulting in an adapted version to be answered by parents (C*-VHI-10). The parents and children included in the study of this index were the same patients as those included in the study to validate the Spanish P-VHI. RESULTS: There were no significant differences in the results obtained with the extended version of the P-VHI (17.4) and with the P-VHI-10 (18.7: Pearson coefficient = 0.602, p < 0.36). A paired student's t-test identified significant differences (p < 0.0001) when comparing the P-VHI-10 and C*-VHI-10, both of which were answered by parents, with average scores of 18.7 and 9.48, respectively. Both these reduced versions have good internal consistency, with a satisfactory Cronbach's alpha coefficient (α = 0.75 to P-VHI-10 and α = 0.73 in C*-VHI-10). No statistically significant differences were found when the average total score between the C-VHI-10 and C*-VHI-10 were compared, with a Pearson's correlation coefficient of 0.559 (p < 0.9). CONCLUSION: The short version of the P-VHI10 questionnaire is a clinically valid tool that has good internal consistency.

Can the tandem measurement of age adjusted D-dimer and tissue plasminagen activator improve the clinical utility of a conventional D-dimer in the pulmonary embolism diagnosis?

BACKGROUND: The aim of this study was to evaluate if a sequential measurement of age adjust D-dimer (ADD) and tissue plasminogen activator (tPA) could increase the clinical utility in patients with suspected pulmonary embolism (PE) compared to a conventional D-dimer. METHODS: We measured a conventional D-dimer (CDD), an ADD alone and a sequential combination ADD and tPA (ADD/tPA combination) in a prospective sample of 127 outpatients with PE suspected. Diagnosis of PE was based on a strict protocol. Plasma sample to measure levels of tPA and D-dimer was obtained at enrollment, and CDD, ADD and tPA were assessed at the end of study. For CDD the cut-off value was 500 ng/mL and for ADD the cut-off value was defined as (patient's age x10) ng/mL in patients aged >50. We compared the sensitivity, specificity and clinical utility obtained for CDD, ADD alone, and ADD/tPA combination. RESULTS: PE was confirmed in 41 patients (32%). The sensitivity, specificity and clinical utility for CDD were 95%, 36% and 28%, respectively. The ADD/tPA combination and ADD alone demonstrated an increased in specificity of +29% and +12% respectively, and increased in clinical utility of +20% and +8%, respectively, compared to CDD, and this was obtained without loss of sensitivity. CONCLUSION: The ADD/tPA combination substantially increased the clinical utility in the PE diagnosis compared with conventional D-dimer, without reducing the security. The ADD/tPA combination could decrease the need for pulmonary vascular imaging for the PE diagnosis in nearly the half. These promising results should be validated prospectively.

Clinical usefulness and safety of an age-adjusted D-dimer cutoff levels to exclude pulmonary embolism: a retrospective analysis.

Age-adjusted D-dimer (AADD) appears to increase the proportion of patients in whom pulmonary embolism (PE) can safely be excluded compared with conventional D-dimer (CDD), according to a limited number of studies. The aim if this study was to assess whether the use of an AADD might safely increase the clinical usefulness of CDD for the diagnosis of PE in our setting. Three hundred and sixty two consecutive outpatients with clinically suspected PE in whom plasma samples were obtained to measure D-dimer were included in this post hoc analysis of a previous study. CDD cutoff value was 500 ng/mL and AADD was calculated as (patient's age × 10) ng/mL in patients aged >50. Sensitivity, specificity, clinical usefulness (i.e., proportion of true-negative tests among all patients with suspected PE), and the proportion of false negatives were calculated for both AADD and CDD among patients with low-to-moderate clinical probability of PE according to Well's criteria. PE was confirmed in 98 patients (27%). Among 331 patients with low-to-moderate clinical probability of PE, sensitivity and clinical usefulness were 100 and 27.8% for CDD, respectively, and 100 and 36.5% for AADD, respectively. In 29 patients aged >50 with CDD >500 ng/mL, AADD showed values under its normal cutoff point, without false negatives for the diagnosis of PE (0%, 95% CI 0-11%). AADD increases clinical usefulness notably with respect to that of CDD in patients with clinical suspected PE without losing sensitivity in our cohort. The use of AADD apparently does not reduce the safety of CDD for the exclusion of PE.

Adaptation and validation of Spanish version of the pediatric Voice Handicap Index (P-VHI).

OBJECTIVES: The voice in childhood is a communication tool and a form of emotional expression. It is estimated that 6 to 23% of children may have voice disorders. There is a test, the Pediatric Voice Handicap Index (P-VHI), validated in English to assess the specific impact on quality of life of children with speech pathology. Spanish is the second most widely used language in the world in terms of number of speakers, with over 500 million native speakers, so it is necessary to have tools that allow us to evaluate the effects of dysphonia in Spanish-speaking children. The aim of our study is the validation of the Spanish version of the P-VHI. MATERIAL AND METHODS: We performed a cross-sectional study including patients between 4 and 15 years of age. The English P-VHI validated version was translated into Spanish and this translation was reviewed and modified by three specialists in Otorhinolaryngology. There were two study groups, children who had dysphonia (n=44) and a control group of children without alterations in voice (n=44). The questionnaire was always answered by parents. RESULTS: Significant differences were found between the group of children with dysphonia and the control group in the overall P-VHI score and the different subscales (p<0.001). Optimal internal consistency with a good Cronbach's alpha (α=0.81) was found, with high test-retest reliability (Wilcoxon z: -0847, p>0.05). CONCLUSIONS: The Spanish version of the P-VHI is a validated tool that has good internal consistency. It is a reliable test that evaluates the Voice Handicap Index in the pediatric population, with easy application for daily clinical practice.

Tissue plasminogen activator as a novel diagnostic aid in acute pulmonary embolism.

BACKGROUND: We evaluated the diagnostic efficacy of tissue plasminogen activator (tPA), using an enzyme-linked immunosorbent assay (ELISA) and compared it with an ELISA D-dimer (VIDAS D-dimer) in acute pulmonary embolism (PE). PATIENTS AND METHODS: We studied 127 consecutive outpatients with clinically suspected PE. The diagnosis of PE was based on a clinical probability pretest for PE and a strict protocol of imaging studies. A plasma sample to measure the levels of tPA and D-dimer was obtained at enrollment. Diagnostic accuracy for tPA and D-dimer was determined by the area under the receiver operating characteristic (ROC) curve. Sensitivity, specificity, predictive values, and the diagnostic utility of tPA with a cutoff of 8.5 ng/mL and D-dimer with a cutoff of 500 ng/mL, were calculated for PE diagnosis. RESULTS: PE was confirmed in 41 patients (32 %). Areas under ROC curves were 0.86 for D-dimer and 0.71 for tPA. The sensitivity/negative predictive value for D-dimer using a cutoff of 500 ng/mL, and tPA using a cutoff of 8.5 ng/mL, were 95 % (95 % CI, 88-100 %)/95 % (95 % CI, 88-100 %) and 95 % (95 % CI, 88-100 %)/94 %), respectively. The diagnostic utility to exclude PE was 28.3 % (95 % CI, 21-37 %) for D-dimer and 24.4 % (95 % CI, 17-33 %) for tPA. CONCLUSIONS: The tPA with a cutoff of 8.5 ng/mL has a high sensitivity and negative predictive value for exclusion of PE, similar to those observed for the VIDAS D-dimer with a cutoff of 500 ng/mL, although the diagnostic utility was slightly higher for the D-dimer.

Bisphenol-A induces podocytopathy with proteinuria in mice.

Bisphenol-A, a chemical used in the production of the plastic lining of food and beverage containers, can be found in significant levels in human fluids. Recently, bisphenol-A has been associated with low-grade albuminuria in adults as well as in children. Since glomerular epithelial cells (podocytes) are commonly affected in proteinuric conditions, herein we explored the effects of bisphenol-A on podocytes in vitro and in vivo. On cultured podocytes we first observed that bisphenol-A-at low or high concentrations-(10 nM and 100 nM, respectively) was able to induce hypertrophy, diminish viability, and promote apoptosis. We also found an increase in the protein expression of TGF-ß1 and its receptor, the cyclin-dependent kinase inhibitor p27Kip1, as well as collagen-IV, while observing a diminished expression of the slit diaphragm proteins nephrin and podocin. Furthermore, mice intraperitoneally injected with bisphenol-A (50 mg/Kg for 5 weeks) displayed an increase in urinary albumin excretion and endogenous creatinine clearance. Renal histology showed mesangial expansion. At ultrastructural level, podocytes displayed an enlargement of both cytoplasm and foot processes as well as the presence of condensed chromatin, suggesting apoptosis. Furthermore, immunohistochemistry for WT-1 (specific podocyte marker) and the TUNEL technique showed podocytopenia as well as the presence of apoptosis, respectively. In conclusion, our data demonstrate that Bisphenol-A exposure promotes a podocytopathy with proteinuria, glomerular hyperfiltration and podocytopenia. Further studies are needed to clarify the potential role of bisphenol-A in the pathogenesis as well as in the progression of renal diseases.

Comparison of intra-articular injections of plasma rich in growth factors (PRGF-Endoret) versus Durolane hyaluronic acid in the treatment of patients with symptomatic osteoarthritis: a randomized controlled trial.

PURPOSE: The purpose of this study was to compare the efficacy and safety in a randomized, clinical trial of 3 injections of PRGF-Endoret (BTI Biotechnology Institute, Vitoria, Spain) versus one single intra-articular injection of Durolane hyaluronic acid (HA) (Q-MED AB, Uppsala, Sweden) as a treatment for reducing symptoms in patients with knee osteoarthritis (OA). METHODS: Ninety-six patients with symptomatic knee OA were randomly assigned to receive PRGF-Endoret (3 injections on a weekly basis) or one infiltration with Durolane HA. The primary outcome measures were a 30% decrease and a 50% decrease in the summed score for the pain, physical function, and stiffness subscales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Lequesne scores from baseline to weeks 24 and 48. The percentage of OMERACT-OARSI (Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative) responders was also documented. As secondary outcomes, pain, stiffness, and physical function by use of the WOMAC and the Lequesne score were considered and overall safety of the injection themselves. RESULTS: The mean age of the patients was 63.6 years. Treatment with PRGF-Endoret was significantly more efficient than treatment with Durolane HA in reducing knee pain and stiffness and improving physical function in patients with knee OA. The rate of response to PRGF-Endoret was significantly higher than the rate of response to HA for all the scores including pain, stiffness, and physical function on the WOMAC, Lequesne index, and OMERACT-OARSI responders at 24 and 48 weeks. Adverse events were mild and evenly distributed between the groups. CONCLUSIONS: Our findings show that PRGF-Endoret is safe and significantly superior to Durolane HA in primary and secondary efficacy analysis both at 24 and 48 weeks; provides a significant clinical improvement, reducing patients' pain and improving joint stiffness and physical function with respect to basal levels in patients with knee OA; and should be considered in the treatment of patients with knee OA.

Individualized PEEP setting in subjects with ARDS: a randomized controlled pilot study.

BACKGROUND: Low-tidal-volume ventilation may be associated with repetitive opening and closing of terminal airways. The use of PEEP is intended to keep the alveoli open. No method of adjusting the optimal PEEP has shown to be superior or to improve clinical outcomes. We conducted a pilot study to evaluate the effect of setting an individualized level of PEEP at the highest compliance on oxygenation, multiple-organ-dysfunction, and survival in subjects with ARDS. METHODS: Subjects with ARDS ventilated with low tidal volumes and limitation of airway pressure to 30 cm H2O were randomized to either a compliance-guided PEEP group or an FIO2-guided group. RESULTS: Of the 159 patients with ARDS admitted during the study period, 70 met the inclusion criteria. Subjects in the compliance-guided group showed nonsignificant improvements in PaO2/FIO2 during the first 14 days, and in 28-day mortality (20.6% vs. 38.9%, P = .12). Multiple-organ-dysfunction-free days (median 6 vs 20.5 d, P = .02), respiratory-failure-free days (median 7.5 vs 14.5 d, P = .03), and hemodynamic-failure-free days (median 16 vs 22 d, P = .04) at 28 days were significantly lower in subjects with compliance-guided setting of PEEP. CONCLUSIONS: In ARDS subjects, protective mechanical ventilation with PEEP application according to the highest compliance was associated with less organ dysfunction and a strong nonsignificant trend toward lower mortality. ClinicalTrials.gov Number NCT01119872.

Amerindians show no association of PPAR-γ2 gene Ala12 allele and obesity: an "unthrifty" variant population genetics.

Obesity is for many scholars the most important starting status that gives rise to Metabolic Syndrome (MS) and Type 2 Diabetes (T2D). In the present paper, a genetically homogeneous Amerindian population, as defined by HLA genes, has been genotyped for one of the MS and T2D predisposing genes: PPAR-γ Ala12 and Pro 12 variants. Ala12 has been negatively associated with obesity, but other authors do not find such an association. Notwithstanding, a meta-analysis that used many subjects clearly demonstrated that PPAR-γ Ala12 bearing ones had a reduced risk for T2D. Our results show that Amerindians do not have association of PPAR-γ2 Ala12 and obesity; the latter was measured by waist circumference values after taken specific Amerindian normal waist parameters. Also, a population genetics study indicates that Pro12 allele was the wild allele, which must have occurred before modern humans left Africa. Ala12 may have appeared in Caucasoids later on, according to our comparisons. Negroids tend to show low or null Ala 12 allele frequencies, while most other populations have a significant frequency, particularly European Caucasoids. This may suggest that appearance of Ala12 allele occurred after populations adapted to an agricultural feeding.

Amerindians show association to obesity with adiponectin gene SNP45 and SNP276: population genetics of a food intake control and "thrifty" gene.

Adiponectin gene polymorphisms SNP45 and SNP276 have been related to metabolic syndrome (MS) and related pathologies, including obesity. However results of associations are contradictory depending on which population is studied. In the present study, these adiponectin SNPs are for the first time studied in Amerindians. Allele frequencies are obtained and comparison with obesity and other MS related parameters are performed. Amerindians were also defined by characteristic HLA genes. Our main results are: (1) SNP276 T is associated to low diastolic blood pressure in Amerindians, (2) SNP45 G allele is correlated with obesity in female but not in male Amerindians, (3) SNP45/SNP276 T/G haplotype in total obese/non-obese subjects tends to show a linkage with non-obese Amerindians, (4) SNP45/SNP276 T/T haplotype is linked to obese Amerindian males. Also, a world population study is carried out finding that SNP45 T and SNP276 T alleles are the most frequent in African Blacks and are found significantly in lower frequencies in Europeans and Asians. This together with the fact that there is a linkage of this haplotype to obese Amerindian males suggest that evolutionary forces related to famine (or population density in relation with available food) may have shaped world population adiponectin polymorphism frequencies.

Two-weekly dose-adjusted (DA)-EPOCH-like chemotherapy with high-dose dexamethasone plus rituximab (DA-EDOCH14-R) in poor-prognostic untreated diffuse large B-cell lymphoma.

The activity and safety of two-weekly dose-adjusted (DA)-EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin)-like chemotherapy with high-dose dexamethasone plus rituximab (DA-EDOCH14-R) was explored in 20 patients with previously untreated poor prognosis diffuse large B-cell lymphoma (DLBCL). The main outcomes were compared with those of 27 poor-prognosis patients enrolled into a previous trial of 3-weekly DA-EPOCH-R. Toxicity was manageable and there were no therapy-related deaths. Three-year progression-free survival (PFS) was superior in the DA-EDOCH14-R group (95% vs. 74%, P = 0·08). Importantly, this improvement in PFS with the two-weekly DA-EDOCH14-R was particularly notable in patients with an age-adjusted International Prognostic Index of 3 (100% vs. 30%, P < 0·001).