Estudio biomecánico comparativo de dos configuraciones de tornillos cementados en una fractura simulada de húmero proximal fijada con placa y tornillos bloqueados / Comparative biomechanical study of two configurations of cemented screws in a simulated proximal humerus fracture fixed with locking plate

Introducción: La utilización de tornillos cementados en la fijación interna de fracturas de húmero proximal con placas bloqueadas parece mejorar la estabilidad del implante y disminuir las complicaciones asociadas al fracaso de síntesis. Sin embargo, la combinación óptima de tornillos cementados se desconoce. El objetivo de este estudio fue analizar la estabilidad relativa de dos configuraciones de tornillos cementados sometidos a una fuerza de compresión axial en una fractura simulada de húmero proximal. Material y métodos: Se realizó una osteotomía del cuello quirúrgico en cinco pares de húmeros embalsamados con una edad media de 74 años (rango 46-93), fijados con una placa de acero inoxidable con tornillos bloqueados. En cada par de húmeros, en el húmero derecho se cementaron los tornillos A y E, y en el lado contralateral se cementaron los tornillos B y D. Cada espécimen fue testado inicialmente mediante una carga cíclica de compresión axial durante 6.000 ciclos para evaluar el movimiento interfragmentario (estudio dinámico). Al final de la prueba, los especímenes se sometieron a una carga de compresión axial progresiva para medir la rigidez de la construcción (estudio estático). Resultados: No se encontraron diferencias estadísticamente significativas en la movilidad interfragmentaria entre las dos configuraciones de tornillos cementados en el estudio dinámico (p=0,463). Cuando se sometieron a rotura, los especímenes con tornillos cementados en las hileras B y D presentaron una carga de rotura mayor (2218N vs. 2105, p=0,901) y una mayor rigidez (125N/mm vs. 106N/mm, p=0,672); sin embargo, ninguna de estas diferencias fue estadísticamente significativa. Conclusiones: La configuración de los tornillos cementados utilizadas en este estudio no influyen en la estabilidad del implante cuando se aplica una carga cíclica de baja energía. La cementación de los tornillos de las hileras B y D proporciona una resistencia similar a la cementación de los tornillos...(AU)

Introduction: Screw tip augmentation with bone cement for fixation of osteoporotic proximal humerus fractures seems to improve stability and to decrease the rate of complications related to implant failure. However, the optimal augmentation combinations are unknown. The aim of this study was to assess the relative stability of two augmentations combinations under axial compression load in a simulated proximal humerus fractures fixed with locking plate. Material and methods: A surgical neck osteotomy was created in five pairs of embalmed humeri with a mean age of 74 years (range 46–93 years), secured with a stainless-steel locking-compression plate. In each pair of humeri, on the right humerus were cemented the screws A and E, and in the contralateral side were cemented screws B and D of the locking plate. The specimens were first tested cyclically in axial compression for 6,000 cycles to evaluate interfragmentary motion (dynamic study). At the end of the cycling test, the specimens were loaded in compression force simulating varus bending with increasing load magnitude until failure of the construct (static study). Results: There were no significant differences in interfragmentary motion between the two configurations of cemented screws in the dynamic study (p=0.463). When tested to failure, the configuration of cemented screws in lines B and D demonstrated higher compression load to failure (2218N vs. 2105, p=0.901) and higher stiffness (125N/mm vs. 106N/mm, p=0.672). However, no statistically significant differences were reported in any of these variables. Conclusions: In simulated proximal humerus fractures, the configuration of the cemented screws does not influence the implant stability when a low-energy cyclical load is applied. Cementing the screws in rows B and D provides similar strength to the previously proposed cemented screws configuration and could avoid complications observed in clinical studies.(AU)

[Translated article] Comparative biomechanical study of two configurations of cemented screws in a simulated proximal humerus fracture fixed with locking plate / Estudio biomecánico comparativo de 2 configuraciones de tornillos cementados en una fractura simulada de húmero proximal fijada con placa y tornillos bloqueados

Introducción: La utilización de tornillos cementados en la fijación interna de fracturas de húmero proximal con placas bloqueadas parece mejorar la estabilidad del implante y disminuir las complicaciones asociadas al fracaso de síntesis. Sin embargo, la combinación óptima de tornillos cementados se desconoce. El objetivo de este estudio fue analizar la estabilidad relativa de dos configuraciones de tornillos cementados sometidos a una fuerza de compresión axial en una fractura simulada de húmero proximal. Material y métodos: Se realizó una osteotomía del cuello quirúrgico en cinco pares de húmeros embalsamados con una edad media de 74 años (rango 46-93), fijados con una placa de acero inoxidable con tornillos bloqueados. En cada par de húmeros, en el húmero derecho se cementaron los tornillos A y E, y en el lado contralateral se cementaron los tornillos B y D. Cada espécimen fue testado inicialmente mediante una carga cíclica de compresión axial durante 6.000 ciclos para evaluar el movimiento interfragmentario (estudio dinámico). Al final de la prueba, los especímenes se sometieron a una carga de compresión axial progresiva para medir la rigidez de la construcción (estudio estático). Resultados: No se encontraron diferencias estadísticamente significativas en la movilidad interfragmentaria entre las dos configuraciones de tornillos cementados en el estudio dinámico (p=0,463). Cuando se sometieron a rotura, los especímenes con tornillos cementados en las hileras B y D presentaron una carga de rotura mayor (2218N vs. 2105, p=0,901) y una mayor rigidez (125N/mm vs. 106N/mm, p=0,672); sin embargo, ninguna de estas diferencias fue estadísticamente significativa. Conclusiones: La configuración de los tornillos cementados utilizadas en este estudio no influyen en la estabilidad del implante cuando se aplica una carga cíclica de baja energía. La cementación de los tornillos de las hileras B y D proporciona una resistencia similar a la cementación de los tornillos...(AU)

Introduction: Screw tip augmentation with bone cement for fixation of osteoporotic proximal humerus fractures seems to improve stability and to decrease the rate of complications related to implant failure. However, the optimal augmentation combinations are unknown. The aim of this study was to assess the relative stability of two augmentations combinations under axial compression load in a simulated proximal humerus fractures fixed with locking plate. Material and methods: A surgical neck osteotomy was created in five pairs of embalmed humeri with a mean age of 74 years (range 46–93 years), secured with a stainless-steel locking-compression plate. In each pair of humeri, on the right humerus were cemented the screws A and E, and in the contralateral side were cemented screws B and D of the locking plate. The specimens were first tested cyclically in axial compression for 6,000 cycles to evaluate interfragmentary motion (dynamic study). At the end of the cycling test, the specimens were loaded in compression force simulating varus bending with increasing load magnitude until failure of the construct (static study). Results: There were no significant differences in interfragmentary motion between the two configurations of cemented screws in the dynamic study (p=0.463). When tested to failure, the configuration of cemented screws in lines B and D demonstrated higher compression load to failure (2218N vs. 2105, p=0.901) and higher stiffness (125N/mm vs. 106N/mm, p=0.672). However, no statistically significant differences were reported in any of these variables. Conclusions: In simulated proximal humerus fractures, the configuration of the cemented screws does not influence the implant stability when a low-energy cyclical load is applied. Cementing the screws in rows B and D provides similar strength to the previously proposed cemented screws configuration and could avoid complications observed in clinical studies.(AU)

[Translated article] Comparative biomechanical study of two configurations of cemented screws in a simulated proximal humerus fracture fixed with locking plate.

INTRODUCTION: Screw tip augmentation with bone cement for fixation of osteoporotic proximal humerus fractures seems to improve stability and to decrease the rate of complications related to implant failure. However, the optimal augmentation combinations are unknown. The aim of this study was to assess the relative stability of two augmentations combinations under axial compression load in a simulated proximal humerus fractures fixed with locking plate. MATERIAL AND METHODS: A surgical neck osteotomy was created in five pairs of embalmed humeri with a mean age of 74 years (range 46-93 years), secured with a stainless-steel locking-compression plate. In each pair of humeri, on the right humerus were cemented the screws A and E, and in the contralateral side were cemented screws B and D of the locking plate. The specimens were first tested cyclically in axial compression for 6000 cycles to evaluate interfragmentary motion (dynamic study). At the end of the cycling test, the specimens were loaded in compression force simulating varus bending with increasing load magnitude until failure of the construct (static study). RESULTS: There were no significant differences in interfragmentary motion between the two configurations of cemented screws in the dynamic study (p=0.463). When tested to failure, the configuration of cemented screws in lines B and D demonstrated higher compression load to failure (2218N vs. 2105, p=0.901) and higher stiffness (125N/mm vs. 106N/mm, p=0.672). However, no statistically significant differences were reported in any of these variables. CONCLUSIONS: In simulated proximal humerus fractures, the configuration of the cemented screws does not influence the implant stability when a low-energy cyclical load is applied. Cementing the screws in rows B and D provides similar strength to the previously proposed cemented screws configuration and could avoid complications observed in clinical studies.

Comparative biomechanical study of two configurations of cemented screws in a simulated proximal humerus fracture fixed with locking plate. / Estudio biomecánico comparativo de dos configuraciones de tornillos cementados en una fractura simulada de húmero proximal fijada con placa y tornillos bloqueados.

INTRODUCTION: Screw tip augmentation with bone cement for fixation of osteoporotic proximal humerus fractures seems to improve stability and to decrease the rate of complications related to implant failure. However, the optimal augmentation combinations are unknown. The aim of this study was to assess the relative stability of two augmentations combinations under axial compression load in a simulated proximal humerus fractures fixed with locking plate. MATERIAL AND METHODS: A surgical neck osteotomy was created in five pairs of embalmed humeri with a mean age of 74 years (range 46-93 years), secured with a stainless-steel locking-compression plate. In each pair of humeri, on the right humerus were cemented the screws A and E, and in the contralateral side were cemented screws B and D of the locking plate. The specimens were first tested cyclically in axial compression for 6,000 cycles to evaluate interfragmentary motion (dynamic study). At the end of the cycling test, the specimens were loaded in compression force simulating varus bending with increasing load magnitude until failure of the construct (static study). RESULTS: There were no significant differences in interfragmentary motion between the two configurations of cemented screws in the dynamic study (p=0.463). When tested to failure, the configuration of cemented screws in lines B and D demonstrated higher compression load to failure (2218N vs. 2105, p=0.901) and higher stiffness (125N/mm vs. 106N/mm, p=0.672). However, no statistically significant differences were reported in any of these variables. CONCLUSIONS: In simulated proximal humerus fractures, the configuration of the cemented screws does not influence the implant stability when a low-energy cyclical load is applied. Cementing the screws in rows B and D provides similar strength to the previously proposed cemented screws configuration and could avoid complications observed in clinical studies.

An approach to evaluating and benchmarking the mechanical behavior of a surgical mesh prototype designed for the repair of abdominal wall defects.

Ventral hernia repair is a common surgical procedure in abdominal surgery in which surgical mesh has become an essential tool to improve outcomes. To avoid recurrences the mesh needs to mimic the mechanical behavior of the abdominal wall. In this scenario the mechanical properties at the interface between the mesh and its surrounding tissue is critical for the performance of the device and, therefore, the success after surgery. We aimed to characterize and compare the mechanical behavior of the patented prototype mesh Spider and four commercial meshes at the mesh-tissue interface. The prototype mesh was designed based on the hypothesis that the best performance for a large-sized defect in a ventral hernia is obtained when the mesh presents an isotropic behavior. In contrast, commercial meshes presented significant anisotropic behavior. Mechanical properties of the meshes were characterized through uniaxial tensile tests. Longitudinal and transverse axes were defined for each mesh, and samples were cut in each axis orientation. Samples underwent uniaxial tensile testing, from which the elastic modulus in each axis was determined. The degree of anisotropy was calculated as the ratio between the elastic modulus in each axis. An in silico model of the ventral hernia defect was designed to simulate the mesh-tissue interface behavior via finite element method. Meshes were modeled by an hyperelastic orthotropic constitutive model, which allowed isotropic symmetry as particular case for the prototype mesh. Abdominal wall was modeled using a Neo-Hookean model. Once the simulations were launched, mesh-tissue interface behavior was evaluated through the difference between Von Mises stress values on either size of the interface, both on the external and the internal face of the mesh and abdominal wall. Mechanical response was anisotropic for all commercial meshes and isotropic for the Spider prototype. Among commercial, Ultrapro® was highly anisotropic. Tests revealed Gore-Tex® to be the stiffest, followed by Repol Angimesh®, Spider and Ultrapro®; Duramesh™  was found to be the most compliant. Concerning mesh-tissue behavior, simulation results revealed the Spider prototype and Duramesh™  to be the best; Spider due to its uniformity and lower stress difference thanks to its nearly isotropic behavior, and Duramesh™  due to its compliant behavior. Our results suggest that the compromise between stiffness and anisotropy must be considered in order to improve the mechanical performance of the meshes, bearing in mind that for large-sized ventral defects, nearly isotropic mesh ensures better performance.

Clinical assessment of W-band spectroscopy for non-invasive detection and monitoring of sustained hyperglycemia.

HbA1c is the gold standard test for monitoring medium/long term glycemia conditions in diabetes care, which is a critical factor in reducing the risk of chronic diabetes complications. Current technologies for measuring HbA1c concentration are invasive and adequate assays are still limited to laboratory-based methods that are not widely available worldwide. The development of a non-invasive diagnostic tool for HbA1c concentration can lead to the decrease of the rate of undiagnosed cases and facilitate early detection in diabetes care. We present a preliminary validation diagnostic study of W-band spectroscopy for detection and monitoring of sustained hyperglycemia, using the HbA1c concentration as reference. A group of 20 patients with type 1 diabetes mellitus and 10 healthy subjects were non-invasively assessed at three different visits over a period of 7 months by a millimeter-wave spectrometer (transmission mode) operating across the full W-band. The relationship between the W-band spectral profile and the HbA1c concentration is studied using longitudinal and non-longitudinal functional data analysis methods. A potential blind discrimination between patients with or without diabetes is obtained, and more importantly, an excellent relation (R-squared = 0.97) between the non-invasive assessment and the HbA1c measure is achieved. Such results support that W-band spectroscopy has great potential for developing a non-invasive diagnostic tool for in-vivo HbA1c concentration monitoring in humans.

Evaluation of the American Society of Anesthesiologists Physical Status Classification System in Risk Assessment for Lower Extremity Reconstruction with Free Tissue Transfer.

BACKGROUND: The applicability of free flap reconstruction for lower extremity (LE) defects in high-risk patients continues to require ongoing review. The aim of this study was to analyze the risk factors, management, and outcome of LE free flap reconstruction in high-risk (American Society of Anesthesiologists [ASA] class 3 or 4) patients. METHODS: A retrospective chart review was performed for all patients who underwent LE reconstruction in our Institution (Level I Trauma Center) from 2013 to 2019. Medical records and the authors' prospectively maintained database were analyzed with respect to ASA class, comorbidities, and postoperative complications. All patients were treated using the same pre-, intra-, and postoperative multidisciplinary approach. RESULTS: A total of 199 patients were analyzed. Sixty-six flaps were transferred in 60 patients with an ASA class 3 or higher. High-risk patients did not present a higher rate of flap loss or LE amputation. The overall flap success rate was 92%. There were five flap losses in high-risk patients. Three of these five patients underwent a successful second free flap reconstruction. The overall success rate of LE reconstruction in high-risk patients was 90%. Four patients with successful free flap ended up in LE amputation due to bone infection and two patients underwent an amputation after the first free flap failure. CONCLUSION: Free flap reconstruction for LE defects in high-risk patients is a safe and reliable procedure for selected patients when an experienced multidisciplinary team is involved. Bone infection was the only variable associated with LE amputation.

Variable selection with P-splines in functional linear regression: Application in graft-versus-host disease.

This paper focuses on the problems of estimation and variable selection in the functional linear regression model (FLM) with functional response and scalar covariates. To this end, two different types of regularization (L1 and L2 ) are considered in this paper. On the one hand, a sample approach for functional LASSO in terms of basis representation of the sample values of the response variable is proposed. On the other hand, we propose a penalized version of the FLM by introducing a P-spline penalty in the least squares fitting criterion. But our aim is to propose P-splines as a powerful tool simultaneously for variable selection and functional parameters estimation. In that sense, the importance of smoothing the response variable before fitting the model is also studied. In summary, penalized (L1 and L2 ) and nonpenalized regression are combined with a presmoothing of the response variable sample curves, based on regression splines or P-splines, providing a total of six approaches to be compared in two simulation schemes. Finally, the most competitive approach is applied to a real data set based on the graft-versus-host disease, which is one of the most frequent complications (30% -50%) in allogeneic hematopoietic stem-cell transplantation.

Prognostic factors in patients with primary cutaneous anaplastic large cell lymphoma: a multicentric, retrospective analysis of the Spanish Group of Cutaneous Lymphoma.

BACKGROUND: Reliable prognostic factors for patients with primary cutaneous anaplastic large cell lymphoma (PCALCL) are lacking. OBJECTIVE: To identify prognostic factors for specific survival in patients with PCALCL. METHODS: Using the convenience sampling method, patients with PCALCL diagnosed from May 1986 to August 2017 in 16 University Departments were retrospectively reviewed. RESULTS: One hundred eight patients were included (57 males). Median age at diagnosis was 58 years. All of them showed T1-3N0M0 stages. Seventy per cent of the cases presented with a solitary lesion, mostly at the limbs. Complete response rate after first-line treatment was 87%, and no advantage was observed for any of them (surgery, radiotherapy, chemotherapy or other approaches). Nodal and visceral progression rate was 11% and 2%, respectively. 5-year specific survival (SSV) reached 93%; 97% for T1 patients and 84% for T2/T3 patients (P = 0.031). Five-year SSV for patients developing early cutaneous relapse was 64%; for those with late or no relapse, 96% (P = 0.001). Estimated median SSV for patients showing nodal progression was 103 months (95% CI: 51-155 months); for patients without nodal progression, estimated SSV did not reach the median (P < 0.001). Nodal progression was an independent predictive parameter for shorter survival (P = 0.011). CONCLUSION: Multiple cutaneous lesions at presentation, early skin relapse and nodal progression portrait worse prognosis in patients with PCALCL.

Osteomielitis crónica multifocal recurrente en pediatría: un reto diagnóstico / Chronic recurrent multifocal osteomyelitis in pediatrics: a diagnostic challenge

La osteomielitis crónica multifocal recurrente (OMCR) es una enfermedad autoinflamatoria que cursa con inflamación ósea aséptica y puede acompañarse de clínica multisistémica. Presentamos el caso de un varón de 14 años con dolor a nivel de la metáfisis tibial de 2 semanas de evolución y fiebre. En la radiografía se objetivó lesión lítica en metáfisis tibial. Se realizó RM que mostró lesión ósea intramedular con edema óseo perilesional. Se realizó biopsia guiada por TAC descartando malignidad y siendo los cultivos microbiológicos negativos. Posterior a la punción presentó empeoramiento clínico y fiebre por lo que iniciaron antibioterapia ante sospecha de sobreinfección. Ante la persistencia de fiebre se realizó RM-body que halló segunda lesión activa a nivel vertebral, diagnosticándose de OMCR y evolucionando bien con antinflamatorios. La OMCR es una entidad de difícil diagnóstico. El diagnóstico diferencial es extenso con enfermedades infecciosas, tumores y otras enfermedades autoinflamatorias. Es crucial su diagnóstico precoz y tratamiento adecuado para prevenir sus secuelas derivadas

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disease that presents with aseptic bone inflammation and can be accompanied by multisystemic symptoms. We present the case of a 14-year-old male with a 2-week history of pain located at the tibial metaphysis and fever. X-ray revealed a lytic lesion in the tibial metaphysis. MRI revealed an intramedullary bone lesion with perilesional bone oedema. CT-guided biopsy discounted malignancy and microbiological cultures were negative. The patient's symptoms and fever worsened after the biopsy; therefore antibiotherapy was commenced for a suspected superinfection. A body MRI was performed given the persistence of the fever, which found a second active lesion in the spine that was diagnosed as CRMO and progressed well with anti-inflammatories. CRMO is an entity that is difficult to diagnose. Differential diagnosis is extensive with infectious diseases, tumours and other autoinflammatory diseases. Prompt diagnosis and appropriate treatment are crucial to prevent sequelae

Early, Non-Invasive Sensing of Sustained Hyperglycemia in Mice Using Millimeter-Wave Spectroscopy.

Diabetes is a very complex condition affecting millions of people around the world. Its occurrence, always accompanied by sustained hyperglycemia, leads to many medical complications that can be greatly mitigated when the disease is treated in its earliest stage. In this paper, a novel sensing approach for the early non-invasive detection and monitoring of sustained hyperglycemia is presented. The sensing principle is based on millimeter-wave transmission spectroscopy through the skin and subsequent statistical analysis of the amplitude data. A classifier based on functional principal components for sustained hyperglycemia prediction was validated on a sample of twelve mice, correctly classifying the condition in diabetic mice. Using the same classifier, sixteen mice with drug-induced diabetes were studied for two weeks. The proposed sensing approach was capable of assessing the glycemic states at different stages of induced diabetes, providing a clear transition from normoglycemia to hyperglycemia typically associated with diabetes. This is believed to be the first presentation of such evolution studies using non-invasive sensing. The results obtained indicate that gradual glycemic changes associated with diabetes can be accurately detected by non-invasively sensing the metabolism using a millimeter-wave spectral sensor, with an observed temporal resolution of around four days. This unprecedented detection speed and its non-invasive character could open new opportunities for the continuous control and monitoring of diabetics and the evaluation of response to treatments (including new therapies), enabling a much more appropriate control of the condition.

Chronic recurrent multifocal osteomyelitis in pediatrics: A diagnostic challenge. / Osteomielitis crónica multifocal recurrente en pediatría: un reto diagnóstico.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disease that presents with aseptic bone inflammation and can be accompanied by multisystemic symptoms. We present the case of a 14-year-old male with a 2-week history of pain located at the tibial metaphysis and fever. X-ray revealed a lytic lesion in the tibial metaphysis. MRI revealed an intramedullary bone lesion with perilesional bone oedema. CT-guided biopsy discounted malignancy and microbiological cultures were negative. The patient's symptoms and fever worsened after the biopsy; therefore antibiotherapy was commenced for a suspected superinfection. A body MRI was performed given the persistence of the fever, which found a second active lesion in the spine that was diagnosed as CRMO and progressed well with anti-inflammatories. CRMO is an entity that is difficult to diagnose. Differential diagnosis is extensive with infectious diseases, tumours and other autoinflammatory diseases. Prompt diagnosis and appropriate treatment are crucial to prevent sequelae.

Registro de linfomas cutáneos primarios de la AEDV: primer año de funcionamiento / The First Year of the AEVD Primary Cutaneous Lymphoma Registry

ANTECEDENTES Y OBJETIVO: Los linfomas primarios cutáneos son enfermedades poco frecuentes. Este artículo describe el Registro de linfomas cutáneos primarios de la AEDV y sus primeros resultados. PACIENTES Y MÉTODOS: Registro de enfermedad de pacientes con linfomas cutáneos primarios. Los centros participantes recogieron datos prospectivamente de todos los pacientes, incluyendo datos del diagnóstico, de los tratamientos, de las pruebas realizadas y del estado actual del paciente. Se realizó un análisis descriptivo. RESULTADOS: En diciembre del 2017 el registro tenía datos de 639 pacientes pertenecientes a 16 hospitales universitarios. Un 60% eran hombres y los diagnósticos, por orden de frecuencia, fueron: micosis fungoide/síndrome de Sézary (MF/SS) (348 casos; 55%), linfoma cutáneo primario de células B (LCCB) (184; 29%), trastorno linfoproliferativo de células T CD30+ (LTCD30+) (70; 11%) y otro tipo de linfoma T (OLT) (37; 5%). El número de casos incidentes recogidos durante el primer año fue de 105 (16,5%). En los pacientes con MF/SS, el diagnóstico más frecuente fue MF clásica (77,3%). La mitad de estos casos se diagnosticaron en estadio IA. La mayoría de los pacientes estaban en remisión parcial (32,5%) o enfermedad estable (33,1%). Los tratamientos más usados fueron los corticoides tópicos (90,8%) seguidos de fototerapia. En los pacientes con LCCB el diagnóstico más frecuente fue el linfoma de la zona marginal (50%). Casi todos los pacientes tuvieron afectación exclusivamente cutánea y casi la mitad fue T1a. La mayoría (76,1%) estaba en remisión completa. Los tratamientos más utilizados fueron la cirugía (55,4%) y la radioterapia (41,9%). En los pacientes con LTCD30+, el diagnóstico más frecuente fue la papulosis linfomatoide (68,6%). La mayoría fueron clasificados T3b (31,4%). La mitad de los casos estaban en remisión completa. Los tratamientos más frecuentes fueron los esteroides tópicos (68,6%), seguidos de la quimioterapia sistémica (32,9%). CONCLUSIÓN: Las características del paciente con linfoma cutáneo primario en España no difieren de otras series descritas en la literatura. El registro facilitará al grupo de linfomas de la AEDV realizar investigación clínica

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas are uncommon. This article describes the Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV) and reports on the results from the first year. PATIENTS AND METHODS: Disease registry for patients with primary cutaneous lymphoma. The participating hospitals prospectively recorded data on diagnosis, treatment, tests, and disease stage for all patients with primary cutaneous lymphoma. A descriptive analysis was performed. RESULTS: In December 2017, the registry contained data on 639 patients (60% male) from 16 university hospitals. The most common diagnoses, in order of frequency, were mycosis fungoides/Sézary syndrome (MF/SS) (348 cases, 55%), primary cutaneous B-cell lymphoma (CBCL) (184 cases, 29%), primary cutaneous CD30+ T-cell lymphoproliferative disorder (CD30+ CLPD) (70 cases, 11%), and other types of T-cell lymphoma (37 cases, 5%). In total, 105 (16.5%) of the cases recorded were incident cases. The most common diagnosis in the MF/SS group was classic MF (77.3%). Half of the patients with MF had stage IA disease when diagnosed, and the majority were either in partial remission (32.5%) or had stable disease (33.1%). The most widely used treatments were topical coricosteroids (90.8%) and phototherapy. The most common form of primary CBCL was marginal zone lymphoma (50%). Almost all of the patients had cutaneous involvement only and nearly half had stage T1a disease. Most (76.1%) were in complete remission. The main treatments were surgery (55.4%) and radiotherapy (41.9%). The most common diagnosis in patients with CD30+ CLPD was lymphomatoid papulosis (68.8%). Most of the patients (31.4%) had stage T3b disease and half were in complete remission. The most common treatments were topical corticosteroids (68.8%) and systemic chemotherapy (32.9%). CONCLUSION: The characteristics of patients with primary cutaneous lymphoma in Spain do not differ from those described in other series in the literature. The registry will facilitate clinical research by the AEDV's lymphoma group

A novel predictive approach for GVHD after allogeneic SCT based on clinical variables and cytokine gene polymorphisms.

Despite considerable advances in our understanding of the pathophysiology of graft-versus-host disease (GVHD), its prediction remains unresolved and depends mainly on clinical data. The aim of this study is to build a predictive model based on clinical variables and cytokine gene polymorphism for predicting acute GVHD (aGVHD) and chronic GVHD (cGVHD) from the analysis of a large cohort of HLA-identical sibling donor allogeneic stem cell transplant (allo-SCT) patients. A total of 25 SNPs in 12 cytokine genes were evaluated in 509 patients. Data were analyzed using a linear regression model and the least absolute shrinkage and selection operator (LASSO). The statistical model was constructed by randomly selecting 85% of cases (training set), and the predictive ability was confirmed based on the remaining 15% of cases (test set). Models including clinical and genetic variables (CG-M) predicted severe aGVHD significantly better than models including only clinical variables (C-M) or only genetic variables (G-M). For grades 3-4 aGVHD, the correct classification rates (CCR1) were: 100% for CG-M, 88% for G-M, and 50% for C-M. On the other hand, CG-M and G-M predicted extensive cGVHD better than C-M (CCR1: 80% vs. 66.7%, respectively). A risk score was calculated based on LASSO multivariate analyses. It was able to correctly stratify patients who developed grades 3-4 aGVHD (P < .001) and extensive cGVHD (P < .001). The novel predictive models proposed here improve the prediction of severe GVHD after allo-SCT. This approach could facilitate personalized risk-adapted clinical management of patients undergoing allo-SCT.

The First Year of the AEVD Primary Cutaneous Lymphoma Registry. / Registro de linfomas cutáneos primarios de la AEDV: primer año de funcionamiento.

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas are uncommon. This article describes the Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV) and reports on the results from the first year. PATIENTS AND METHODS: Disease registry for patients with primary cutaneous lymphoma. The participating hospitals prospectively recorded data on diagnosis, treatment, tests, and disease stage for all patients with primary cutaneous lymphoma. A descriptive analysis was performed. RESULTS: In December 2017, the registry contained data on 639 patients (60% male) from 16 university hospitals. The most common diagnoses, in order of frequency, were mycosis fungoides/Sézary syndrome (MF/SS) (348 cases, 55%), primary cutaneous B-cell lymphoma (CBCL) (184 cases, 29%), primary cutaneous CD30+ T-cell lymphoproliferative disorder (CD30+ CLPD) (70 cases, 11%), and other types of T-cell lymphoma (37 cases, 5%). In total, 105 (16.5%) of the cases recorded were incident cases. The most common diagnosis in the MF/SS group was classic MF (77.3%). Half of the patients with MF had stage IA disease when diagnosed, and the majority were either in partial remission (32.5%) or had stable disease (33.1%). The most widely used treatments were topical corticosteroids (90.8%) and phototherapy. The most common form of primary CBCL was marginal zone lymphoma (50%). Almost all of the patients had cutaneous involvement only and nearly half had stage T1a disease. Most (76.1%) were in complete remission. The main treatments were surgery (55.4%) and radiotherapy (41.9%). The most common diagnosis in patients with CD30+ CLPD was lymphomatoid papulosis (68.8%). Most of the patients (31.4%) had stage T3b disease and half were in complete remission. The most common treatments were topical corticosteroids (68.8%) and systemic chemotherapy (32.9%). CONCLUSION: The characteristics of patients with primary cutaneous lymphoma in Spain do not differ from those described in other series in the literature. The registry will facilitate clinical research by the AEDV's lymphoma group.

First-line treatment in lymphomatoid papulosis: a retrospective multicentre study.

BACKGROUND: Data regarding response to treatment in lymphomatoid papulosis (LyP) are scarce. AIM: To assess the daily clinical practice approach to LyP and the response to first-line treatments. METHODS: This was a retrospective study enrolling 252 patients with LyP. RESULTS: Topical steroids, methotrexate and phototherapy were the most common first-line treatments, prescribed for 35%, 20% and 14% of the patients, respectively. Complete response (CR) was achieved in 48% of treated patients. Eczematous lesions significantly increased relative risk (RR) of not achieving CR (RR = 1.76; 95% CI 1.16-2.11). Overall median time to CR was 10 months (95% CI 6-13 months), and 78% of complete responders showed cutaneous relapse; both results were similar for all treatment groups (P > 0.05). Overall estimated median disease-free survival (DFS) was 11 months (95% CI 9-13 months) but DFS for patients treated with phototherapy was 23 months (95% CI 10-36 months; P < 0.03). Having the Type A LyP variant (RR = 2.04; 95% CI 0.96-4.30) and receiving a first-line treatment other than phototherapy (RR = 5.33; 95% CI 0.84-33.89) were significantly associated with cutaneous early relapse. Of the 252 patients, 31 (13%) had associated mycosis fungoides unrelated to therapeutic approach, type of LyP or T-cell receptor clonality. CONCLUSIONS: Current epidemiological, clinical and pathological data support previous results. Topical steroids, phototherapy and methotrexate are the most frequently prescribed first-line treatments. Although CR and cutaneous relapse rates do not differ between them, phototherapy achieves a longer DFS. Presence of Type A LyP and use of topical steroid or methotrexate were associated with an increased risk of early relapse.

Tuberculosis drug resistance in Southern Mozambique: results of a population-level survey in the district of Manhiça.

SETTING: Mozambique, one of the world's high tuberculosis (TB) burden countries, has conducted only one national-level drug resistance survey, in 2007-2008. OBJECTIVE: To determine the drug resistance patterns of laboratory-confirmed TB cases. DESIGN: This was a population-level survey conducted over a 1-year period in the district of Manhiça. All laboratory-confirmed cases were evaluated for first-line anti-tuberculosis drug susceptibility testing using liquid culture. RESULTS: Resistance to at least one first-line drug was observed in 44 of 276 isolates (15.9%). Prevalence of drug resistance to each of the five anti-tuberculosis drugs tested was 4.0% for streptomycin, 10.1% for isoniazid (INH), 6.2% for rifampicin, 3.6% for ethambutol and 1.1% for pyrazinamide. The overall prevalence of multidrug-resistant TB (MDR-TB) was 5.1%: 3.8% (95%CI 2.0-7.0) in new and 13.2% (95%CI 5.8-27.3) in retreatment cases. Respectively 4.6% and 2.6% of new and retreatment cases were INH-monoresistant. Previous history of anti-tuberculosis treatment was associated with having MDR-TB (OR 4.3, 95%CI 1.3-14.1). CONCLUSION: The prevalence of drug resistance in the district of Manhiça is slightly higher than, but still compatible with, previous national estimates. INH monoresistance was high, posing the risk of hidden monotherapy in the continuation phase.

Identificación de variantes genéticas asociadas con la densidad mineral ósea (DMO) en el gen FLJ42280 / Identification of genetic variants associated with bone mineral density (BMD) in the FLJ42280 gene

FLJ42280 es un posible gen de susceptibilidad a la osteoporosis. Distintos estudios de GWAs han identificado 4 SNPs no-codificantes en este gen que se asocian a la densidad mineral ósea (DMO) y el riesgo de fractura. Para descubrir la causa de la asociación entre estos SNPs y la osteoporosis, se realizó una búsqueda de variantes genéticas mediante resecuenciación de 28 kb que contienen el gen, en una selección truncada de mujeres con DMO muy baja (n=50) o muy alta (n=50) de la cohorte BARCOS (Barcelona Cohorte Osteoporosis, cohorte de mujeres postmenopáusicas de Barcelona). Las variantes encontradas se filtraron y se analizó su frecuencia en cada grupo. Se analizó el solapamiento de las variantes con elementos funcionales del proyecto ENCODE y también se calculó el desequilibrio de ligamiento entre los SNPs de la región. Finalmente, se hizo un análisis de eQTL de los 4 SNPs no-codificantes respecto a los niveles de expresión de genes cercanos a FLJ42280 en linfoblastos. Se seleccionaron 110 variantes. Las diferencias de sus frecuencias entre los dos grupos estuvieron por debajo del poder estadístico del diseño experimental. Sin embargo, 3 variantes solaparon con posibles enhancers y una solapó con un enhancer activo en osteoblastos (rs4613908). Se observó un fuerte desequilibrio de ligamiento entre los 4 SNPs no-codificantes y el SNP rs4613908, que pertenecen a un bloque que abarca el gen casi por completo. Ninguno de los SNPs no-codificantes mostró asociación con los niveles de expresión de genes cercanos a FLJ42280. En conclusión, el SNP rs4613908 podría estar implicado funcionalmente en la determinación de la DMO. Serán necesarios experimentos concretos para confirmarlo (AU)

FLJ42280 is a possible gene for susceptibility to osteoporosis. Different studies of GWAs have identified 4 non-coding SNPs in this gene associated with bone mineral density (BMD) and fracture risk. In order to ascertain the cause of the association between these SNPs and osteoporosis, we searched for genetic variants by resequencing the 28-kb gene, in a truncated selection of women with very low (n=50) or very high BMD (N=50) of the BARCOS cohort (Barcelona Cohort Osteoporosis, cohort of postmenopausal women in Barcelona). The variants found were filtered and their frequency analyzed in each group. The overlap of the variants with functional elements of the ENCODE project was calculated. Finally, an eQTL analysis of the 4 SNPs-coding was performed on the expression levels of FLJ42280 neighbor genes in lymphoblasts. In all, 110 variants were selected. The differences in their frequencies between the two groups were below the statistical power of the experimental design. However, three variants overlapped with possible enhancers and one overlapped with an active enhancer in osteoblasts (rs4613908). A strong linkage disequilibrium was observed between the 4 non-coding SNPs and the SNP rs4613908, which belong to a block spanning the gene almost completely. None of the non-coding SNPs showed association with the expression levels of FLJ42280 neighbor genes. In conclusion, the SNP rs4613908 could be involved functionally in determining BMD. Tangible experiments will be required to confirm this (AU)

Desprendimiento viteliforme adquirido en paciente con drusas cuticulares tratado con bevacizumab / Bevacizumab treatment for acquired vitelliform detachment in patient with cuticular drusen

Caso clínico: Varón de 30 años, diagnosticado de desprendimiento viteliforme adquirido (DVA) secundario a drusas cuticulares que presentaba metamorfopsias en su OD. Se trató con inyecciones intravítreas de bevacizumab (Avastin), respondiendo favorablemente. Discusión: Enfermedad independiente, de fenotipo genético aún desconocido, debida a una disfunción generalizada del epitelio pigmentario retiniano (EPR). Evoluciona en un 50% a DVA; con la ayuda de nuevas pruebas complementarias llegamos a un diagnóstico certero. Sin tratamiento efectivo hasta el momento. Dada la frecuencia con la que se desarrolla neovascularización coroidea (NVC), creemos que el tratamiento con fármacos anti-VEGF podría ayudarnos en la estabilización o mejoría funcional y/o anatómica del cuadro (AU)

Case report: We report a case of a 30-year-old male with acquired vitelliform detachment (AVD) secondary to cuticular drusen and suffering from metamorphopsia in his right eye. Intravitreal bevacizumab (Avastin) was administered, achieving successful results. Discussion: An independent disease, of unknown genetic phenotype, caused by a generalized dysfunction of the retinal pigment epithelium (RPE). About 50% of patients develop AVD, and a correct diagnosis can be made with the help of new complementary tests. With no effective treatment currently available, and because of the incidence of developing choroidal neovascularization (NVC), treatment with anti-VEGF could help stabilize or improve the disease functionally and/or anatomically (AU)