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.

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.

Dyspareunia and lubrication in premature ovarian failure using hormonal therapy and vaginal health.

OBJECTIVE: To evaluate vaginal microbiological and functional aspects in women with and without premature ovarian failure (POF) and the relationship with sexual function. METHODS: A cross-sectional study of 36 women with POF under hormonal therapy who were age-matched with 36 women with normal gonadal function. The vaginal tropism was assessed through hormonal vaginal cytology, vaginal pH and vaginal health index (VHI). Vaginal flora were assessed by the amine test, bacterioscopy and culture for fungi. Sexual function was evaluated through the questionnaire Female Sexual Function Index (FSFI). RESULTS: Women in both groups were of similar age and showed similar marital status. The two groups presented vaginal tropic scores according to the VHI but the tropism was worse among women in the POF group. No difference was observed with respect to hormonal cytology and pH. Vaginal flora was similar in both groups. Women with POF showed worse sexual performance with more pain and poorer lubrication than women in the control group. The VHI, the only parameter evaluated showing statistical difference between the groups, did not correlate with the domains of pain and lubrication in the FSFI questionnaire. CONCLUSION: These findings suggest that the use of systemic estrogen among women with POF is not enough to improve complaints of lubrication and pain despite conferring similar tropism and vaginal flora. Other therapeutic options need to be evaluated.

MYD88 L265P is a marker highly characteristic of, but not restricted to, Waldenström's macroglobulinemia.

We evaluated the MYD88 L265P mutation in Waldenström's macroglobulinemia (WM) and B-cell lymphoproliferative disorders by specific polymerase chain reaction (PCR) (sensitivity ∼10(-3)). No mutation was seen in normal donors, while it was present in 101/117 (86%) WM patients, 27/31 (87%) IgM monoclonal gammapathies of uncertain significance (MGUS), 3/14 (21%) splenic marginal zone lymphomas and 9/48 (19%) non-germinal center (GC) diffuse large B-cell lymphomas (DLBCLs). The mutation was absent in all 28 GC-DLBCLs, 13 DLBCLs not subclassified, 35 hairy cell leukemias, 39 chronic lymphocytic leukemias (16 with M-component), 25 IgA or IgG-MGUS, 24 multiple myeloma (3 with an IgM isotype), 6 amyloidosis, 9 lymphoplasmacytic lymphomas and 1 IgM-related neuropathy. Among WM and IgM-MGUS, MYD88 L265P mutation was associated with some differences in clinical and biological characteristics, although usually minor; wild-type MYD88 cases had smaller M-component (1.77 vs 2.72 g/dl, P=0.022), more lymphocytosis (24 vs 5%, P=0.006), higher lactate dehydrogenase level (371 vs 265 UI/L, P=0.002), atypical immunophenotype (CD23-CD27+ +FMC7+ +), less Immunoglobulin Heavy Chain Variable gene (IGHV) somatic hypermutation (57 vs 97%, P=0.012) and less IGHV3-23 gene selection (9 vs 27%, P=0.014). These small differences did not lead to different time to first therapy, response to treatment or progression-free or overall survival.

Prognostic significance of FLT3 mutational status and expression levels in MLL-AF4+ and MLL-germline acute lymphoblastic leukemia.

There is barely any information about the prognostic significance of FLT3 expression and mutational status in cytogenetically distinct subgroups of acute lymphoblastic leukemia (ALL). We analyzed the presence of FLT3-tyrosine kinase domain (TKD) and FLT3-internal tandem duplication (ITD) mutations as well as FLT3 expression levels in 54 newly diagnosed patients with B-ALL (n=49) or T-ALL (n=5). All B/T-ALL samples tested negative for the presence of FLT3-TKD or FLT3-ITD. None of the T-ALL and E2A-PBX1+ B-ALL overexpressed FLT3. In contrast, mainly MLL-AF4+ B-ALL but also ETV6-RUNX1+, BCR-ABL+ or B-ALL displaying normal cytogenetics exhibited significantly higher FLT3 expression levels than normal bone marrow, supporting that aberrantly increased transcription of FLT3, rather than activating FLT3 mutations, contributes to the pathogenesis of these B-ALL. Using the median FLT3 expression as cut-off value we found that high-level FLT3 expression is associated with an extremely poor 1-year overall survival (OS; 0 vs 71%; P=0.002) and disease-free survival (DFS; 0 vs 43%; P=0.03) in MLL-AF4+ B-ALL but not in MLL-germline B-ALL. Cox regression analysis with OS/DFS as end points showed that age>14 years and high-level FLT3 expression were independent prognostic factors when all ALL patients were analyzed together. Importantly, when the MLL-AF4+ B-ALL subgroup was analyzed separately, high-level FLT3 expression was the only independent prognostic factor for OS and treatment outcome. These findings indicate that high FLT3 expression identifies MLL-AF4+ ALL patients at very high risk of treatment failure and poor survival, emphasizing the value of ongoing/future clinical trials for FLT3 inhibitors.

SNP-based mapping arrays reveal high genomic complexity in monoclonal gammopathies, from MGUS to myeloma status.

Genetic events mediating transformation from premalignant monoclonal gammopathies (MG) to multiple myeloma (MM) are unknown. To obtain a comprehensive genomic profile of MG from the early to late stages, we performed high-resolution analysis of purified plasma cells from 20 MGUS, 20 smoldering MM (SMM) and 34 MM by high-density 6.0 SNP array. A progressive increase in the incidence of copy number abnormalities (CNA) from MGUS to SMM and to MM (median 5, 7.5 and 12 per case, respectively) was observed (P=0.006). Gains on 1q, 3p, 6p, 9p, 11q, 19p, 19q and 21q along with 1p, 16q and 22q deletions were significantly less frequent in MGUS than in MM. Although 11q and 21q gains together with 16q and 22q deletions were apparently exclusive of MM status, we observed that these abnormalities were also present in minor subclones in MGUS. Overall, a total of 65 copy number-neutral LOH (CNN-LOH) were detected. Their frequency was higher in active MM than in the asymptomatic entities (P=0.047). A strong association between genetic lesions and fragile sites was also detected. In summary, our study shows an increasing genomic complexity from MGUS to MM and identifies new chromosomal regions involved in CNA and CNN-LOH.

[Resistance to first line chemotherapy treatment in a patient diagnosed of nodular lymphocyte-predominant Hodgkin's lymphoma identified by 18F-FDG PET/CT: diagnostic and therapeutic implications]. / Resistencia al tratamiento de primera línea de quimioterapia en un paciente diagnosticado de linfoma de Hodgkin de predominio linfocítico nodular identificada mediante (18)F-FDG PET/TAC: implicaciones diagnósticas y terapéuticas.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare entity that accounts for less than 5% of the cases of Hodgkin lymphoma (HL) with morphological, immunophenotypical, genetic and clinical behavior traits different from the classic HL. In a minority of patients, the NLPHL course is complicated by a transformation to a non-Hodgkin diffuse large B-cell lymphoma (NHDLBCL) with prognostic and therapeutic implications. Early metabolic changes observed by (18)F-FDG PET in patients with HL and NHL, after 1-3 cycles of chemotherapy, predict the final response to treatment and progression-free survival. In the case we are presenting herein, whether NLPHL is transformed to NHDLBCL or the two types of lymphoma co-exist in the same patient, the (18)F-FDG PET/CT scan was crucial for the identification of tumor resistance to first line chemotherapy and to guide a second biopsy decision and therefore modify the chemotherapy regimen.

IgM monoclonal component associated with type I Gaucher disease resolved after enzyme replacement therapy: a case report.

The frequency of monoclonal gammopathy of undetermined significance (MGUS) is higher in patients with type I Gaucher disease (GD I) than in the general population. Although enzyme replacement therapy is effective in the control of the disease, its effect on MGUS is still controversial. We present the case of a 65-year-old woman with extensive GD I associated with IgM MGUS, in whom enzyme replacement therapy succeeded in eradicating the monoclonal component. This observation further supports the idea that enzyme replacement therapy decreases the chronic antigenic stimulation responsible for gammopathies in Gaucher disease.