Randomized clinical trial on the usefulness of 3D printing in intra-articular fractures of the distal radius. / Ensayo clínico aleatorizado sobre la utilidad de la impresión 3D en las fracturas intraarticulares de radio distal.

OBJECTIVES: We evaluated the utility of 3D printing technology for preoperative planning in the treatment of intra-articular fractures of the distal radius in relation to the improvement of surgical technique, radiological and clinical results. MATERIAL AND METHODS: A total of 30 patients with 2B and C fractures of the AO classification were operated on by a single surgeon with a volar plate, randomly divided into two groups, 15 of them with conventional planning (Rx and CT) and 15 adding a 3D model of the fracture and the previous simulation of the intervention. Simulation time, surgical time in minutes, radioscopy time in minutes, loss of material expressed in lost screws were recorded. Clinical evaluation based PRWE questionnaire and full radiographic analysis was done for all patients with a mean follow-up of 6 months by an independent, blinded observed. RESULTS: No statistically significant differences were observed in the PRWE questionnaire (p=0.22), nor were we observed differences in the radiological values, except in relation to the articular step (p=0.028), which represents statistical significance, but in both groups the median was of 0.0 (0.0-0.0). We also did not see statistically significant differences in surgical times (p=0.745), radioscopy (p=0.819) or in the loss of synthesis material (p=0.779). CONCLUSIONS: 3D printing has not improved the parameters studied in relation to routinely operated patients.

Real-life analysis on safety and efficacy of asciminib for ponatinib pretreated patients with chronic myeloid leukemia.

Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.

Neonatal cholestasis and Niemann-pick type C disease: A literature review.

BACKGROUND: Neonatal cholestasis (NC) is one of the most serious diseases in newborns and infants and results from metabolic disorders, such as Niemann-Pick type C (NPC), among other causes. OBJECTIVE: We evaluated the incidence of NPC in our NC plus lysosomal storage disease (LSD) suspicious neonates and infants series. METHODS: The study included children (≤3 years old) with a history of NC together with a suspicion of LSD, referred from Spanish Hospitals during the period 2011-2020. Screening for NPC was done by plasma biomarker assay (chitotriosidase activity and 7-ketocholesterol), and Sanger sequencing for NPC1 and NPC2 genes. RESULTS: We screened NPC disease in 17 patients with NC plus organomegaly and that were LSD suspicious, finding 5 NPC patients (29.4%) and 2 carriers. CONCLUSIONS: Our results emphasize the need to study NPC when NC and visceral enlargement arise in a newborn or infant.

Metabolizing profile of the cytochrome pathway CYP2D6, CYP3A4 and the ABCB 1 transporter in Spanish patients affected by Gaucher disease.

Several therapeutic options are available for type 1 Gaucher disease (GD1), including enzymatic replacement therapy (ERT) and substrate reduction therapy (SRT). Eliglustat is a selective inhibitor of glucosylceramide synthase that is extensively metabolized by CYP2D6 and, to a lesser extent by CYP3A4; it is also an inhibitor of the P-gp transporter. The aim of this study is to evaluate the metabolizer profile of these cytochrome isoforms in 61 GD1 patients, and to analyze interferences with concomitant therapies. Patients were selected from the Spanish Gaucher Disease Registry considering clinical data, GBA genotype, severity score index, comorbidities, concomitant drugs, type and response to therapy and adverse effects. The polymorphisms of CYP2D6, CYP3A4 and three ABCB1 transporter variants were analyzed by Polymerase Chain Reaction (PCR). The most frequent metabolizer profile was extensive or intermediate for CYP2D6, extensive for CYP3A4*1B and CYP3A4*22 and normal activity for ABCB1. Correlations between metabolizer profile and other variables were analyzed by multiple regression study. Twenty-eight patients received ERT, 17 eliglustat and seven miglustat. Forty-two patients (68.8%) had associated diseases and 54.5% were taking daily concomitant medication. Nine patients under eliglustat therapy received concomitant drugs that interact with the CYPs and/or ABCB1, five of these did not reach therapeutic goals and three presented mild or moderate adverse effects (headache and gastrointestinal disorders). Detailed analysis in four patients with TTT haplotype, corresponding to lack of activity of the transporter, was performed. In order to apply personalized medicine and avoid interferences and adverse effects, the individual CYP metabolizer profile and transporter must be considered when choosing the concomitant medication and/or making dose adjustments.

Nueva variante asociada a enfermedad de Niemann-Pick tipo C: manifestaciones neurológicas y caracterización bioquímica, molecular y celular / New variant associated with Niemann-Pick disease type C: Neurological manifestations and biochemical, molecular, and cellular characterisation

No disponible

Treatment patterns from 647 patients with Gaucher disease: An analysis from the Gaucher Outcome Survey.

The Gaucher Outcome Survey (GOS) is an international disease-specific registry established in 2010 for patients with a confirmed diagnosis of Gaucher disease (GD), regardless of GD type or treatment status. For insight into how GD management varies among countries, we analyzed treatment patterns in GOS. As of October 30, 2015, data on GD-specific treatment (enzyme replacement therapy, substrate reduction therapy, or chemical chaperone therapy) received at any time were available for 647 patients. At analysis, velaglucerase alfa (316/573, 55.1%) and imiglucerase (184/573, 32.1%) were the treatments most widely used. Of the 647 treated patients, 446 (68.9%) had been treated for >5years and 368 (56.9%) had received only one GD-specific drug therapy. There were 377 patients who received velaglucerase alfa. Velaglucerase alfa was most widely used at 60U/kg every other week (134/492 dose entries, 27.2%), but there were differences in dosing between the three highest-enrolling countries (defined as >100 GOS patients enrolled in each), with most patients in Israel receiving <20U/kg, most patients in the United Kingdom receiving 20 to <40U/kg, and most in the United States receiving 60U/kg. This analysis provides a foundation upon which to examine real-life outcomes data from different treatment regimens globally.

Management goals for type 1 Gaucher disease: An expert consensus document from the European working group on Gaucher disease.

Gaucher Disease type 1 (GD1) is a lysosomal disorder that affects many systems. Therapy improves the principal manifestations of the condition and, as a consequence, many patients show a modified phenotype which reflects manifestations of their disease that are refractory to treatment. More generally, it is increasingly recognised that information as to how a patient feels and functions [obtained by patient- reported outcome measurements (PROMs)] is critical to any comprehensive evaluation of treatment. A new set of management goals for GD1 in which both trends are reflected is needed. To this end, a modified Delphi procedure among 25 experts was performed. Based on a literature review and with input from patients, 65 potential goals were formulated as statements. Consensus was considered to be reached when ≥75% of the participants agreed to include that specific statement in the management goals. There was agreement on 42 statements. In addition to the traditional goals concerning haematological, visceral and bone manifestations, improvement in quality of life, fatigue and social participation, as well as early detection of long-term complications or associated diseases were included. When applying this set of goals in medical practice, the clinical status of the individual patient should be taken into account.

Reducing rumen starch fermentation of wheat with three percent sodium hydroxide has the potential to ameliorate the effect of heat stress in grain-fed wethers.

Selection for high productivity has resulted in ruminants adversely affected by heat stress (HS) due to their high metabolic rate and feed intake. One mechanism to ameliorate HS is to reduce the forage-to-concentrate ratio in the diet, although the inclusion of readily fermentable grains can reduce heat tolerance. The aim of these experiments was to investigate a chemical method for reducing the rate of fermentation of wheat and its effect on improving heat tolerance in sheep. In the first experiment, fermentation kinetics and buffered rumen fluid pH variation during in vitro incubation of corn, wheat, and 3% NaOH-treated wheat grains were compared. This experiment showed that corn and 3% NaOH-treated wheat had a slower (-23 and -22%, respectively; < 0.001) rate of gas production and elevated buffered rumen fluid pH ( < 0.001) compared with wheat. In the second experiment, 31 Merino × Poll Dorset wethers were housed in 2 climate-controlled rooms and were fed either corn grain plus forage (42.7% starch; were fed either corn grain plus forage (CD), wheat grain plus forage (WD) or 3 % NaOH-treated wheat plus forage (TWD) during 3 experimental periods: period 1 (P1), which consisted of 7 d of thermoneutral conditions (18 to 21°C and 40 to 50% relative humidity) and 1.7 times maintenance feed intake; period 2 (P2), which consisted of 7 d of HS (28 to 38°C and 30 to 50% relative humidity) and the same feed intake as in P1; and period 3 (P3), which consisted of 7 d of HS as in P2 and 2 times maintenance feed intake in a randomized control experiment. Water was offered ad libitum. The impact of HS was quantified by increases in rectal temperature, respiration rate (RR), and flank skin temperature (FT); variations in blood acid-base balance; and glucose, NEFA, and heat shock protein 70 (HSP-70) plasma concentrations. All physiological variables were elevated during HS, especially when wethers had greater feed intake (P3). Wethers fed CD had lower RR, rectal temperature, and FT than wethers fed WD ( < 0.001) and wethers fed TWD had lower RR and FT than wethers fed WD during HS ( < 0.05). There were reductions in blood CO, HCO3, and base excess concurrent with increases in blood partial pressure of O and pH during HS ( < 0.05). Heat stress reduced plasma NEFA and glucose concentrations whereas it increased prolactin ( < 0.05). Prolactin and HSP-70 plasma concentrations were greater for WD-fed wethers ( < 0.001) associated with Prolactin and HSP-70 plasma concentrations were greater for WD fed wethers (P < 0.001) during HS. These data indicate that the slow rate of rumen fermentation of CD and TWD can reduce the heat released during feed fermentation in the rumen, improving heat tolerance in sheep.

Leucemia mieloide crónica en España: sus características de presentación han cambiado. Sección española del registro poblacional EUTOS / Chronic myeloid leukaemia in Spain: Its presentation characteristics have changed. Spanish section of the EUTOS population-based registry

Objetivos. Pretendemos aportar datos más fiables sobre la epidemiología de la leucemia mieloide crónica (LMC) en España que los disponibles hasta la fecha. Material y métodos. El registro poblacional EUTOS, de la European LeukemiaNet, es un registro de casos nuevos de LMC en pacientes ≥ de 18 años de 22 áreas europeas. La sección española incluyó las comunidades autónomas de Madrid, Castilla-La Mancha y Aragón, en el periodo comprendido entre el 1-2-2010 y el 31-12-2012. Resultados. Se registraron 250 casos en 35 meses. La incidencia global fue de 1,08 casos/105 habitantes-año, con predominio masculino (58% de varones) y claras diferencias entre comunidades autónomas. La incidencia estandarizada por edad fue similar (global 1,04, varones 1,31, mujeres 0,81). La mediana de edad fue de 54 años. La incidencia aumentó con la edad, siendo máxima en>65 años, aunque un 31,7% de los casos aparecieron entre los 20 y los 44 años. Un 4% se diagnosticaron en fases avanzadas (2,4% en fase acelerada, 1,6% en crisis blástica), el 56% estaban asintomáticos, el 38% tenían esplenomegalia, y el score Sokal era alto en el 11% (inferior a lo previamente reflejado en la literatura). Conclusiones. La incidencia actual de LMC en España es superior a la previamente descrita y similar a la de los estudios europeos. A diferencia de las descripciones clásicas, la LMC se presenta mayoritariamente de forma asintomática, sin esplenomegalia, con menor leucocitosis y en estadios con mejor pronóstico (AU)

Objectives. To provide more reliable data on the epidemiology of chronic myeloid leukaemia (CML) in Spain than are currently available. Material and methods. The EUTOS population-based project of European LeukemiaNet is a population registry of new CML cases in patients 18 years of age or older from 22 European areas. The Spanish section included the autonomous communities of Madrid, Castilla-La Mancha and Aragon, from 1-2-2010 to 31-12-2012. Results. A total of 250 cases were recorded in 35 months. The overall incidence was 1.08 cases/105 inhabitants-year, with a predominance of men (58%) and clear differences among the communities. The incidence standardised by age was similar (overall, 1.04; men, 1.31; women, 0.81). The median age was 54 years. The incidence increased with age, reaching a peak at>65 years, although 31.7% of cases appeared between the ages of 20 and 44 years. Four percent of cases were diagnosed in advanced stages (2.4% in accelerated phase, 1.6% in blast crisis), 56% were asymptomatic, 38% had splenomegaly, and the Sokal score was high in 11% (lower than what was previously reflected in the literature). Conclusions. The current incidence of CML in Spain is higher than previously reported and similar to that of the European studies. Unlike the classical descriptions, CML presented mostly in asymptomatic form, with no splenomegaly, less leucocytosis and in stages with better prognosis (AU)

Diagnóstico diferencial de parálisis flácida en pediatría / Differential diagnosis of flaccid paralysis in paediatric medicine

No disponible

Chronic myeloid leukaemia in Spain: Its presentation characteristics have changed. Spanish section of the EUTOS population-based registry. / Leucemia mieloide crónica en España: sus características de presentación han cambiado. Sección española del registro poblacional EUTOS.

OBJECTIVES: To provide more reliable data on the epidemiology of chronic myeloid leukaemia (CML) in Spain than are currently available. MATERIAL AND METHODS: The EUTOS population-based project of European LeukemiaNet is a population registry of new CML cases in patients 18 years of age or older from 22 European areas. The Spanish section included the autonomous communities of Madrid, Castilla-La Mancha and Aragon, from 1-2-2010 to 31-12-2012. RESULTS: A total of 250 cases were recorded in 35 months. The overall incidence was 1.08 cases/10(5) inhabitants-year, with a predominance of men (58%) and clear differences among the communities. The incidence standardised by age was similar (overall, 1.04; men, 1.31; women, 0.81). The median age was 54 years. The incidence increased with age, reaching a peak at>65 years, although 31.7% of cases appeared between the ages of 20 and 44 years. Four percent of cases were diagnosed in advanced stages (2.4% in accelerated phase, 1.6% in blast crisis), 56% were asymptomatic, 38% had splenomegaly, and the Sokal score was high in 11% (lower than what was previously reflected in the literature). CONCLUSIONS: The current incidence of CML in Spain is higher than previously reported and similar to that of the European studies. Unlike the classical descriptions, CML presented mostly in asymptomatic form, with no splenomegaly, less leucocytosis and in stages with better prognosis.

Protein-Derived Acetaminophen-Cysteine Can Be Detected After Repeated Supratherapeutic Ingestion of Acetaminophen in the Absence of Hepatotoxicity.

UNLABELLED: Generation of protein-derived acetaminophen-cysteine (APAP-CYS) is reported after ingestion of large and therapeutic dosages of acetaminophen in healthy and in liver-damaged patients. The incidence of protein-derived APAP-CYS adducts in repeated supratherapeutic dosages of APAP is not known. METHODS: for 12 months, a standardized and comprehensive questionnaire was used to interview every consecutive patient at a pain management clinic. Patients found to ingest more than 4 g of APAP per day for a minimum of 14 consecutive days at the time of the encounter were invited to have blood drawn for hepatic transaminases and APAP-CYS adduct levels. Twelve subjects out of 990 interviewees met inclusion criteria. Ten of the 12 had measurable protein-derived APAP-CYS, none had evidence of liver injury. Patients that ingest repeated supratherapeutic amounts of APAP over several weeks may generate APAP-CYS protein adducts in the absence of hepatic injury.

Cromotubación histeroscópica: técnica alternativa para la evaluación de la permeabilidad tubárica y la cavidad uterina en un solo paso / Hysteroscopic chromotubation: an alternative technique for the evaluation of tubal patency and uterine cavity in a single step

La evaluación de la permeabilidad tubárica es un paso esencial en el estudio de la infertilidad femenina. Existen varios métodos que permiten realizar esta evaluación. La histerosalpingografía (HSG) se ha considerado el método estándar, sin embargo es conocida su limitación en la evaluación de la obstrucción proximal con alta tasa de falsos positivos. Presentamos una técnica alternativa para la evaluación por medio de cromotubación histeroscópica, que tiene entre otras, la ventaja de permitir la evaluacion del factor uterino y tubárico en un solo paso y además, supera la dificultad de los falsos positivos de la HSG, en cuanto a la obstrucción proximal.

The evaluation of tubal patency is an essential step in the study of female infertility. There are several methods to perform this evaluation. Hysterosalpingography (HSG) has been considered the standard method, however it is known to limitations in the assessment of proximal obstruction with high false positive rate. We present an alternative technique for evaluation by hysteroscopic chromo tubation, which has among others, the advantage of allowing the evaluation of uterine and tubal factor in one step and also overcomes the difficulty of false-positive HSG, as to the proximal obstruction.

Differential expression of lactic acid isomers, extracellular matrix metalloproteinase inducer, and matrix metalloproteinase-8 in vaginal fluid from women with vaginal disorders.

OBJECTIVE: Do metabolites in vaginal samples vary between women with different vaginal disorders. DESIGN: Cross-sectional study. SETTING: Campinas, Brazil. SAMPLE: Seventy-seven women (39.9%) with no vaginal disorder, 52 women (26.9%) with vulvovaginal candidiasis (VVC), 43 women (22.3%) with bacterial vaginosis (BV), and 21 women (10.9%) with cytolytic vaginosis (CTV). METHOD: Concentrations of D- and L-lactic acid, extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinase-8 (MMP-8), and the influence of Candida albicans on EMMPRIN production by cultured vaginal epithelial cells, were determined by enzyme-linked immunosorbent assay (ELISA). Associations were determined by the Mann-Whitney U-test and by Spearman's rank correlation test. MAIN OUTCOME MEASURES: Metabolite levels and their correlation with diagnoses. RESULTS: Vaginal concentrations of D- and L-lactic acid were reduced from control levels in BV (P < 0.0001); L-lactic acid levels were elevated in CTV (P = 0.0116). EMMPRIN and MMP-8 concentrations were elevated in VVC (P < 0.0001). EMMPRIN and L-lactic acid concentrations (P ≤ 0.008), but not EMMPRIN and D-lactic acid, were correlated in all groups. EMMPRIN also increased in proportion with the ratio of L- to D-lactic acid in controls and in women with BV (P ≤ 0.009). Concentrations of EMMPRIN and MMP-8 were correlated in controls and women with VVC (P ≤ 0.0002). Candida albicans induced EMMPRIN release from vaginal epithelial cells. CONCLUSIONS: Vaginal secretions from women with BV are deficient in D- and L-lactic acid, women with VVC have elevated EMMPRIN and MMP-8 levels, and women with CTV have elevated L-lactic acid levels. These deviations may contribute to the clinical signs, symptoms, and sequelae that are characteristic of these disorders.

Iron homeostasis and infIammatory biomarker analysis in patients with type 1 Gaucher disease.

Gaucher disease induces some metabolic abnormalities so increased serum ferritin appears in more than 60% at diagnosis. The storage of glucosylceramide in macrophages produces an inflammatory response with iron recycling deregulation and release of cytokines. Iron homeostasis is controlled by the circulating peptide hepcidin and its production is influenced by inflammatory cytokines. Iron damages cells by excess of catalyzing reactive oxygen species, removal of the excess iron has a positive influence on the response to treatment and survival in patients with iron overload. We have analyzed some inflammatory biomarkers of macrophage activation and related to the iron profile, including hepcidin and liver iron deposits determined by MRI, in 8 type 1 GD patients with hyperferritinemia. We have explored the changes in this profile after 4 months under therapy with two different iron chelators, deferoxamine or deferasirox, by evaluating response, adverse events and quality of life. We observed a significant reduction in serum ferritin and hepcidin levels and in liver iron deposits. No differences were observed in chitotriosidase activity, CCL18/PARC concentration and IL-4, IL-6, IL-7, IL-10, IL-13, MIP-1α, MIP-1ß,TNF-α cytokine levels. After two years on follow-up, clinical and analytical data were improved and stable ferritin levels maintained less than 700 ng/dL.

Habitar bajo los puentes: vida y muerte, dos formas de comenzar algo / Living under the bridges: life and death, two ways of begining something

OBJETIVO: comprender los significados que las personas que habitan bajo los puentes de la quebrada La Picacha le dan a las experiencias, relacionadas con la vida, la salud, la enfermedad y la muerte. METODOLOGIA:estudio cualitativo-etnográfico. Se utilizó muestreo teórico. Se aplicaron las técnicas de observación y entrevista abierta no estructurada. Para el análisis de la información se codificó y categorizó. RESULTADOS : la vida significa la fuerza para salir adelante; la salud es el motor para vivir; el cuidado de la salud lo consideran imposible por las condiciones de vida; la enfermedad significa el inicio de la muerte; la muerte significa el descanso del cuerpo a la que no se le tiene miedo. CONCLUSION:las concepciones sobre vida, salud, enfermedad y muerte no son muy diferentes a las que tienen los habitantes de la calle. Los programas de promoción de la salud deben tener en cuenta el significado de los habitantes de los puentes.

OBJECTIVE: to understand the meanings of vital human process in street people from the riverside of brook la Picacha, Medellín 2012. METHODOLOGY: qualitative-ethnographic study. It was used a theorist sampling, according to convenience criteria. It was applied techniques like: field diary and interview. For the information analysis, this one was codified and categorized. RESULTS :living under bridges represents an opportunity for developing their lives, for this they require energy that is given them for the health and when they lose it, they know that’s the beginning of a path toward death. CONCLUSSION:for the participants, living under bridges lets them to shelter themselves from the street dangers and it is an opportunity for developing their lives with the conditions and resources that the environment provides them.

Ser niño en situación de calle: un riesgo permanente / Homeless children: a permanent risk

Este trabajo se realizó con niños en situación de calle en la ciudad de Medellín, Colombia. OBJETIVO: comprender las experiencias y significados que tienen las situaciones de riesgo que viven en su cotidianeidad. METODOLOGIA: estudio cualitativo, enfoque etnográfico, se realizaron entrevistas, observaciones y diario de campo. Se garantizó la confidencialidad en la divulgación de los datos. RESULTADOS : para los niños la calle significa un riesgo representado por circunstancias que favorecen la ocurrencia de una situación generadora de daño físico y emocional, está condicionado por los lugares en los que se encuentren, las instituciones a las que tienen acceso, las personas con quienes interactúan, las ocupaciones que realizan y el consumo de drogas. CONCLUCUSION:los niños consideran que el medio en el cual se mueven representa un riesgo, lo que los convierte en personas vulnerables que deben protegerse a sí mismos.

This study was conducted with homeless children in Medellin, Colombia. OBJECTIVE: to understand the experiences and meanings of the risky situations that homeless children experience every day. METHODOLOGY: a qualitative study with an ethnographic approach. Interviews, observations and field journals were used for data collection. RESULTS :the streets are a risk for children because their circumstances favor the occurrence of physical and emotional damage. This damage depends on the places the children are in, the institutions to which they have access, the people with whom they interact, their occupations and the drugs they use. CONCLUSSION:children believe that the environment in which they live is risk-filled, and this makes them vulnerable people who must protect themselves.