Tratamiento de reperfusión en el ictus isquémico agudo por disección arterial cervicocerebral: descripción de los resultados de un estudio nacional multicéntrico / Reperfusion treatment in acute ischaemic stroke due to cervical and cerebral artery dissection: results of a Spanish national multicentre study

Introducción: El ictus isquémico (II) por disección arterial cervicocerebral (DAC) es una entidadinfrecuente y existen pocos datos sobre el uso de terapias de reperfusión como la fibrinólisis intravenosa y la trombectomía mecánica. Se analizó el uso de dichas terapias en pacientes conII por DAC y se comparó con aquellos pacientes reperfundidos con II por otras causas.Método: Estudio observacional retrospectivo multicéntrico de pacientes con II por DAC basadoen el Registro Nacional de Ictus de la Sociedad Espa˜nola de Neurología durante el periodo 2011-2019. Se realizaron análisis comparativos entre: a) pacientes con DAC tratados y no tratados conterapias de reperfusión y b) pacientes reperfundidos con II por DAC y pacientes reperfundidoscon II por otras causas. Se incluyeron variables epidemiológicas, del ictus y resultados al alta ya los 3 meses.Resultados: Un total de 21.037 pacientes con II fueron incluidos; 223 (1%) fueron por DAC y 68(30%) recibieron tratamiento de reperfusión. El uso de tratamientos de reperfusión fue menor enlos casos de DAC de arteria vertebral y mayor en los casos de oclusión carotídea. Los pacientescon II por DAC reperfundidos respecto a aquellos con II reperfundidos por otras causas fueronmás jóvenes, la trombectomía mecánica se utilizó más y la fibrinólisis intravenosa menos. Lascomplicaciones hemorrágicas, la mortalidad y la autonomía a los 3 meses fueron similares.Conclusiones: Las terapias de reperfusión se usan con frecuencia en los pacientes con II porDAC. Los resultados demuestran eficacia y seguridad y son equiparables a los pacientes tratadoscon terapias de reperfusión por II de otras causas.(AU)

Introduction: Ischaemic stroke (IS) due to cervical and cerebral artery dissection (CAD) is arare entity, and few data are available on the use of such reperfusion therapies as intravenousfibrinolysis and mechanical thrombectomy in these patients. We analysed the use of these treat-ments in patients with IS due to CAD and compared them against patients receiving reperfusiontreatment for IS of other aetiologies.Method: We conducted an observational, retrospective, multicentre study of patients with ISdue to CAD recorded in the National Stroke Registry of the Spanish Society of Neurology duringthe period 2011-2019. Comparative analyses were performed between: a) patients with CADtreated and not treated with reperfusion therapies and b) patients treated with reperfusion forIS due to CAD and patients treated with reperfusion for IS due to other causes. Epidemiologicaldata, stroke variables, and outcomes at discharge and at 3 months were included in the analysis.Results: The study included 21,037 patients with IS: 223 (1%) had IS due to CAD, of whom68 (30%) received reperfusion treatment. Reperfusion treatments were used less frequently incases of vertebral artery dissection and more frequently in patients with carotid artery occlu-sion. Compared to patients with IS due to other causes, patients with CAD were younger, morefrequently underwent mechanical thrombectomy, and less frequently received intravenous fibri-nolysis. Rates of haemorrhagic complications, mortality, and independence at 3 months weresimilar in both groups.Conclusions: Reperfusion therapy is frequently used in patients with IS due to CAD. The outco-mes of these patients demonstrate the efficacy and safety of reperfusion treatments, and arecomparable to the outcomes of patients with IS due to other aetiologies.(AU)

Lenalidomide in combination with R-ESHAP in patients with relapsed or refractory diffuse large B-cell lymphoma: A phase 2 study from GELTAMO.

Diffuse large B-cell lymphoma (DLBCL) patients with relapsed or refractory (RR) disease have poor outcomes with current salvage regimens. We conducted a phase 2 trial to analyse the safety and efficacy of adding lenalidomide to R-ESHAP (LR-ESHAP) in patients with RR DLBCL. Subjects received 3 cycles of lenalidomide 10 mg/day on days 1-14 of every 21-day cycle, in combination with R-ESHAP at standard doses. Responding patients underwent autologous stem-cell transplantation (ASCT). The primary endpoint was the overall response rate (ORR) after 3 cycles. Centralized cell-of-origin (COO) classification was performed. Forty-six patients were included. The ORR after LR-ESHAP was 67% (35% of patients achieved complete remission). Patients with primary refractory disease (n = 26) had significantly worse ORR than patients with non-refractory disease (54% vs. 85%, p = 0.031). No differences in response rates according to the COO were observed. Twenty-eight patients (61%) underwent ASCT. At a median follow-up of 41 months, the estimated 3-year PFS and OS were 42% and 48%, respectively. The most common grade ≥3 adverse events were thrombocytopenia (70% of patients), neutropenia (67%) and anaemia (35%). There were no treatment-related deaths during LR-ESHAP cycles. In conclusion, LR-ESHAP is a feasible salvage regimen with promising efficacy results for patients with RR DLBCL.

Reperfusion therapy in acute ischaemic stroke due to cervical and cerebral artery dissection: Results from a Spanish multicentre study.

INTRODUCTION: Ischaemic stroke (IS) due to cervical and cerebral artery dissection (CAD) is a rare entity, and few data are available on the use of such reperfusion therapies as intravenous fibrinolysis and mechanical thrombectomy in these patients. We analysed the use of these treatments in patients with IS due to CAD and compared them against patients receiving reperfusion treatment for IS of other aetiologies. METHODS: We conducted an observational, retrospective, multicentre study of patients with IS due to CAD recorded in the National Stroke Registry of the Spanish Society of Neurology during the period 2011-2019. Comparative analyses were performed between: a) patients with CAD treated and not treated with reperfusion therapies and b) patients treated with reperfusion for IS due to CAD and patients treated with reperfusion for IS due to other causes. Epidemiological data, stroke variables, and outcomes at discharge and at 3 months were included in the analysis. RESULTS: The study included 21,037 patients with IS: 223 (1%) had IS due to CAD, of whom 68 (30%) received reperfusion treatment. Reperfusion treatments were used less frequently in cases of vertebral artery dissection and more frequently in patients with carotid artery occlusion. Compared to patients with IS due to other causes, patients with CAD were younger, more frequently underwent mechanical thrombectomy, and less frequently received intravenous fibrinolysis. Rates of haemorrhagic complications, mortality, and independence at 3 months were similar in both groups. CONCLUSIONS: Reperfusion therapy is frequently used in patients with IS due to CAD. The outcomes of these patients demonstrate the efficacy and safety of reperfusion treatments, and are comparable to the outcomes of patients with IS due to other aetiologies.

Basal Extended Mentoplasty.

Introduction: The chin is one of the most visible facial structures. Chin surgery, was initially described, for, the treatment of facial abnormalities, advancing the mandibular symphysis; achieved anterior displacement of the base of the tongue showing some value in the treatment of snoring and obstructive sleep apnea, and achieved adequate lip competence. We designed the Basal Extended Mentoplasty (BEM) based on the needs of patients orthodontically compensated, but dissatisfied with the appearance of his face as well as upper airway problems looking for a solution to this, design and planning the advances of the chin. Materials and Methods: Patients operated in the service of Maxillofacial Surgery, Specialist Hospital, "Dr. Bernardo Sepulveda "XXI Century National Medical Center, during the period of 2015-2019, orthodontically compensated patients, with labial incompetence and Class II skeletal. Sixty-five patients were operated during this period, and eight cases are presented. Results: Lip competition, osseointegration of the segments is observed, with a proper projection of the lower third, no nerve or vascular damage in the area. Conclusions: The design of the osteotomy is for orthodontically compensated patients with labial incompetence and Class II skeletal, giving a result mandibular lengthening. The BEM achieved adequate lip competence demonstrated by an interlabial gap of 0 mm, achieved adequate osseous consolidation of the fracture site with a more harmonious facial balance and profile, without nerve or vascular damage with spectacular results.

Attention to acute cerebrovascular disease in Guipúzcoa: description of the results of a reference hospital in a centralized care model.

INTRODUCTION: In the last 15 years, considerable improvements have been made in acute stroke care in Guipuzkoa, including the implementation of a centralised care model at Hospital Universitario Donostia (HUD), improved coordination between professionals, early detection campaigns, new treatments, a stroke unit, and specific rehabilitation. The aim of this work is to describe the results of a reference hospital (HUD) in a centralised care model. MATERIAL AND METHODS: We performed a retrospective observational study of a sample of patients discharged between August and December 2015 from the HUD with a diagnosis of acute stroke (ICD-9-CM codes 430-436, except 433.10). We review patients' baseline characteristics, acute-phase care, and functional outcomes and mortality at discharge and at one year. RESULTS AND DISCUSSION: We identified 536 patients, with a mean age of 73.6 years and a high comorbidity rate. Ischaemic stroke accounted for 64.8% of patients, followed by haemorrhagic stroke (20%) and transient ischaemic attack (14.8%). A total of 53% of patients were attended in < 6 hours, with code stroke being activated in 37.1%; 52.2% of patients were admitted to the stroke unit. Intravenous therapy was administered to 8.3% of patients with ischaemic stroke, and 9.5% underwent mechanical thrombectomy. Surgery was performed in 12.1% patients with haemorrhagic stroke. Rehabilitation was started at hospital in 56% of patients, and 39.6% continued with this treatment at discharge. Mortality was 13.8% at discharge and 25.9% at one year (ischaemic stroke, 25.3%; haemorrhagic stroke, 47.5%); these figures are lower than those previously reported in Guipuzkoa. At one year, 62.5% of patients had a Barthel Index score of 95-100, and 50% a modified Rankin Scale score of 0-2. CONCLUSIONS: After the strategic changes implemented in acute stroke care in Guipuzkoa, including the centralisation of the acute stroke care model, mortality rates at discharge and at one year are lower in 2015 than the previously reported rates, with similar rates of independence. These results are consistent with those published by other Spanish and European centres.

The Tumor Microenvironment: An Introduction to the Development of Microfluidic Devices.

The tumor microenvironment (TME) is like the Referee of a soccer match who has constant eyes on the activity of all players, such as cells, acellular stroma components, and signaling molecules for the successful completion of the game, that is, tumorigenesis. The cooperation among all the "team members" determines the characteristics of tumor, such as the hypoxic and acidic niche, stiffer mechanical properties, or dilated vasculature. Like in soccer, each TME is different. This heterogeneity makes it challenging to fully understand the intratumor dynamics, particularly among different tumor subpopulations and their role in therapeutic response or resistance. Further, during metastasis, tumor cells can disseminate to a secondary organ, a critical event responsible for approximately 90% of the deaths in cancer patients. The recapitulation of the rapidly changing TME in the laboratory is crucial to improve patients' prognosis for unraveling key mechanisms of tumorigenesis and developing better drugs. Hence, in this chapter, we provide an overview of the characteristic features of the TME and how to model them, followed by a brief description of the limitations of existing in vitro platforms. Finally, various attempts at simulating the TME using microfluidic platforms are highlighted. The chapter ends with the concerns that need to be addressed for designing more realistic and predictive tumor-on-a-chip platforms.

Atención a la enfermedad cerebrovascular aguda en Guipúzcoa: descripción de los resultados de un hospital de referencia en un modelo de atención centralizado / Attention to acute cerebrovascular disease in Guipúzcoa: Description of the results of a reference hospital in a centralized care model

Introducción: En los últimos 15 años se han introducido importantes mejoras en la atención de la enfermedad cerebrovascular aguda (ECVA) en Guipúzcoa, que incluyen la implementación de un modelo centralizado en el Hospital Universitario Donostia (HUD), una mejor coordinación entre profesionales, campañas para su detección precoz, nuevos tratamientos, Unidad de Ictus y una rehabilitación específica. El objetivo de este trabajo es describir los resultados de un hospital de referencia (HUD) en un modelo de atención centralizado. Material y métodos: Estudio observacional retrospectivo de una muestra de pacientes dados de alta en el periodo de agosto-diciembre del año 2015 del HUD con diagnóstico de ECVA (CIE-9-MC-430-436 excepto 43310). Revisión de las características basales, atención en fase aguda y resultados funcionales y de mortalidad al alta y al año. Resultados y discusión: Se incluyó a 536 pacientes cuya media de edad fue de 73,6 años y cuya comorbilidad era elevada. El ictus isquémico supuso el 64,8% de las altas, seguido de la ECVA hemorrágica (20%) y del accidente isquémico transitorio (14,8%). Se atendió en < 6 h a un 53% de pacientes, activándose el «código ictus» en un 37,1%. Un 52,2% ingresó en la Unidad de Ictus. Un 11,34% de los pacientes con ictus isquémico recibió terapia por vía intravenosa y un 9,5% trombectomía mecánica. Un 12,1% de los pacientes con ECVA hemorrágica fue intervenido quirúrgicamente. El 56% inició rehabilitación en el hospital y un 39,6% la mantuvo al alta. La mortalidad al alta fue de un 13,8% y al año de un 25,9% (ictus isquémico: 25,3% y ECVA hemorrágica: 47,5%), menor a la descrita previamente en Guipúzcoa. Al año, un 62,5% de los pacientes tenían un ÿndice de Barthel 95-100 y un 50% una puntuación en escala de Rankin modificada 0-2. [...] (AU)

Introduction: In the last 15 years, considerable improvements have been made in acute stroke care in Guipuzkoa, including the implementation of a centralised care model at Hospital Universitario Donostia (HUD), improved coordination between professionals, early detection campaigns, new treatments, a stroke unit, and specific rehabilitation. The aim of this work is to describe the results of a reference hospital (HUD) in a centralised care model. Material and methods: We performed a retrospective observational study of a sample of patients discharged between August and December 2015 from the HUD with a diagnosis of acute stroke (ICD-9-CM codes 430-436, except 433.10). We review patients’ baseline characteristics, acute-phase care, and functional outcomes and mortality at discharge and at one year. Results and discussion: We identified 536 patients, with a mean age of 73.6 years and a high comorbidity rate. Ischaemic stroke accounted for 64.8% of patients, followed by haemorrhagic stroke (20%) and transient ischaemic attack (14.8%). A total of 53% of patients were attended in < 6 hours, with code stroke being activated in 37.1%; 52.2% of patients were admitted to the stroke unit. Intravenous therapy was administered to 8.3% of patients with ischaemic stroke, and 9.5% underwent mechanical thrombectomy. Surgery was performed in 12.1% patients with haemorrhagic stroke. Rehabilitation was started at hospital in 56% of patients, and 39.6% continued with this treatment at discharge. Mortality was 13.8% at discharge and 25.9% at one year (ischaemic stroke, 25.3%; haemorrhagic stroke, 47.5%); these figures are lower than those previously reported in Guipuzkoa. At one year, 62.5% of patients had a Barthel Index score of 95-100, and 50% a modified Rankin Scale score of 0-2. [...] (AU)

Modulation of inflammation by anti-TNF α mAb-dendrimer nanoparticles loaded in tyramine-modified gellan gum hydrogels in a cartilage-on-a-chip model.

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease characterized by joint inflammation. Since the inflammatory condition plays an important role in the disease process, it is important to develop and test new therapeutic approaches that specifically target and treat joint inflammation. In this study, a human 3D inflammatory cartilage-on-a-chip model was established to test the therapeutic efficacy of anti-TNFα mAb-CS/PAMAM dendrimer NPs loaded-Tyramine-Gellan Gum in the treatment of inflammation. The results showed that the proposed therapeutic approach applied to the human monocyte cell line (THP-1) and human chondrogenic primary cells (hCH) cell-based inflammation system revealed an anti-inflammatory capacity that increased over 14 days. It was also possible to observe that Coll type II was highly expressed by inflamed hCH upon the culture with anti-TNF α mAb-CS/PAMAM dendrimer NPs, indicating that the hCH cells were able maintain their biological function. The developed preclinical model allowed us to provide more robust data on the potential therapeutic effect of anti-TNF α mAb-CS/PAMAM dendrimer NPs loaded-Ty-GG hydrogel in a physiologically relevant model.

Outcomes After Vascular Surgery Procedures in Patients with COVID-19 Infection: A National Multicenter Cohort Study (COVID-VAS).

OBJECTIVES: To analyze the outcome of vascular procedures performed in patients with COVID-19 infection during the 2020 pandemic. METHODS: This is a multicenter, prospective observational cohort study. We analyzed data from 75 patients with COVID-19 infection undergoing vascular surgery procedures in 17 hospitals across Spain and Andorra between March and May 2020. The primary end point was 30-day mortality. Clinical Trials registry number NCT04333693. RESULTS: The mean age was 70.9 (45-94) and 58 (77.0%) patients were male. Around 70.7% had postoperative complications, 36.0% of patients experienced respiratory failure, 22.7% acute renal failure, and 22.7% acute respiratory distress syndrome (ARDS). All-cause 30-days mortality rate was 37.3%. Multivariate analysis identified age >65 years (P = 0.009), American Society of Anesthesiologists (ASA) classification IV (P = 0.004), preoperative lymphocyte count <0.6 (×109/L) (P = 0.001) and lactate dehydrogenase (LDH) >500 (UI/L) (P = 0.004), need for invasive ventilation (P = 0.043), postoperative acute renal failure (P = 0.001), ARDS (P = 0.003) and major amputation (P = 0.009) as independent variables associated with mortality. Preoperative coma (P = 0.001), quick Sepsis Related Organ Failure Assessment (qSOFA) score ≥2 (P = 0.043), lymphocytes <0.6 (×109/L) (P = 0.019) leucocytes >11.5 (×109/L) (P = 0.007) and serum ferritin >1800 mg/dL (P = 0.004), bilateral lung infiltrates on thorax computed tomography (P = 0.025), and postoperative acute renal failure (P = 0.009) increased the risk of postoperative ARDS. qSOFA score ≥2 was the only risk factor associated with postoperative sepsis (P = 0.041). CONCLUSIONS: Patients with COVID-19 infection undergoing vascular surgery procedures showed poor 30-days survival. Age >65 years, preoperative lymphocytes <0.6 (x109/L) and LDH >500 (UI/L), and postoperative acute renal failure, ARDS and need for major amputation were identified as prognostic factors of 30-days mortality.

Reperfusion treatment in acute ischaemic stroke due to cervical and cerebral artery dissection: results of a Spanish national multicentre study. / Tratamiento de reperfusión en el ictus isquémico agudo por disección arterial cervicocerebral: descripción de los resultados de un estudio nacional multicéntrico.

INTRODUCTION: Ischaemic stroke (IS) due to cervical and cerebral artery dissection (CAD) is a rare entity, and few data are available on the use of such reperfusion therapies as intravenous fibrinolysis and mechanical thrombectomy in these patients. We analysed the use of these treatments in patients with IS due to CAD and compared them against patients receiving reperfusion treatment for IS of other aetiologies. METHOD: We conducted an observational, retrospective, multicentre study of patients with IS due to CAD recorded in the National Stroke Registry of the Spanish Society of Neurology during the period 2011-2019. Comparative analyses were performed between: a) patients with CAD treated and not treated with reperfusion therapies and b) patients treated with reperfusion for IS due to CAD and patients treated with reperfusion for IS due to other causes. Epidemiological data, stroke variables, and outcomes at discharge and at 3 months were included in the analysis. RESULTS: The study included 21,037 patients with IS: 223 (1%) had IS due to CAD, of whom 68 (30%) received reperfusion treatment. Reperfusion treatments were used less frequently in cases of vertebral artery dissection and more frequently in patients with carotid artery occlusion. Compared to patients with IS due to other causes, patients with CAD were younger, more frequently underwent mechanical thrombectomy, and less frequently received intravenous fibrinolysis. Rates of haemorrhagic complications, mortality, and independence at 3 months were similar in both groups. CONCLUSIONS: Reperfusion therapy is frequently used in patients with IS due to CAD. The outcomes of these patients demonstrate the efficacy and safety of reperfusion treatments, and are comparable to the outcomes of patients with IS due to other aetiologies.

Attention to acute cerebrovascular disease in Guipúzcoa: Description of the results of a reference hospital in a centralized care model. / Atención a la enfermedad cerebrovascular aguda en Guipúzcoa: descripción de los resultados de un hospital de referencia en un modelo de atención centralizado.

INTRODUCTION: In the last 15 years, considerable improvements have been made in acute stroke care in Guipuzkoa, including the implementation of a centralised care model at Hospital Universitario Donostia (HUD), improved coordination between professionals, early detection campaigns, new treatments, a stroke unit, and specific rehabilitation. The aim of this work is to describe the results of a reference hospital (HUD) in a centralised care model. MATERIAL AND METHODS: We performed a retrospective observational study of a sample of patients discharged between August and December 2015 from the HUD with a diagnosis of acute stroke (ICD-9-CM codes 430-436, except 433.10). We review patients' baseline characteristics, acute-phase care, and functional outcomes and mortality at discharge and at one year. RESULTS AND DISCUSSION: We identified 536 patients, with a mean age of 73.6 years and a high comorbidity rate. Ischaemic stroke accounted for 64.8% of patients, followed by haemorrhagic stroke (20%) and transient ischaemic attack (14.8%). A total of 53% of patients were attended in <6 hours, with code stroke being activated in 37.1%; 52.2% of patients were admitted to the stroke unit. Intravenous therapy was administered to 8.3% of patients with ischaemic stroke, and 9.5% underwent mechanical thrombectomy. Surgery was performed in 12.1% patients with haemorrhagic stroke. Rehabilitation was started at hospital in 56% of patients, and 39.6% continued with this treatment at discharge. Mortality was 13.8% at discharge and 25.9% at one year (ischaemic stroke, 25.3%; haemorrhagic stroke, 47.5%); these figures are lower than those previously reported in Guipuzkoa. At one year, 62.5% of patients had a Barthel Index score of 95-100, and 50% a modified Rankin Scale score of 0-2. CONCLUSIONS: After the strategic changes implemented in acute stroke care in Guipuzkoa, including the centralisation of the acute stroke care model, mortality rates at discharge and at one year are lower in 2015 than the previously reported rates, with similar rates of independence. These results are consistent with those published by other Spanish and European centres.

[Extensive encephalomyelitis due to Borrelia: an atypical form of neuroborreliosis]. / Encefalomielitis extensa por Borrelia: una forma atipica de neuroborreliosis.

TITLE: Encefalomielitis extensa por Borrelia: una forma atipica de neuroborreliosis.

Classifying different Iberian pig genetic lines by applying chemical-instrumental parameters of dry-cured Iberian shoulders.

Iberian pigs are an autochthonous porcine breed mainly bred in southwestern of Iberian Peninsula, this herd traditionally feeds on acorn and pasture, in an extensive production system. In this study, the main objective was for classifying Iberian shoulders from different genetic lines of pigs and their crossed genetic lines. For that, morphology parameters, fatty acid profile and volatile compounds were determined on two batches of dry-cured Iberian shoulders. The samples were acquired from the same place of the dry-cured Iberian shoulders. From these data, two databases were created, for training and validation purpose. Results on this study, firstly demonstrate the capability of data mining techniques in order to classify shoulder as function as Iberian pig genetic lines by using of different quality characteristics. Four classification models were developed and tested in the training database and all models achieved a percentage of correct classification higher than 75%. Then, the same four classification models were performed in the validation database and the model of J48 decision tree and fatty acid profile reached the highest correct classification percentage (91.67%), and from Retinto genetic line (95.65%). From this classification model, a software application was developed in order to determine in a semi-automatic way the genetic line of the dry-cured Iberian shoulder. This application could be used in the meat industries for determining relationships between genetic line and meat quality or performance of noble parts.

Organ-on-chip models of cancer metastasis for future personalized medicine: From chip to the patient.

Most cancer patients do not die from the primary tumor but from its metastasis. Current in vitro and in vivo cancer models are incapable of satisfactorily predicting the outcome of various clinical treatments on patients. This is seen as a serious limitation and efforts are underway to develop a new generation of highly predictive cancer models with advanced capabilities. In this regard, organ-on-chip models of cancer metastasis emerge as powerful predictors of disease progression. They offer physiological-like conditions where the (hypothesized) mechanistic determinants of the disease can be assessed with ease. Combined with high-throughput characteristics, the employment of organ-on-chip technology would allow pharmaceutical companies and clinicians to test new therapeutic compounds and therapies. This will permit the screening of a large battery of new drugs in a fast and economic manner, to accelerate the diagnosis of the disease in the near future, and to test personalized treatments using cells from patients. In this review, we describe the latest advances in the field of organ-on-chip models of cancer metastasis and their integration with advanced imaging, screening and biosensing technologies for future precision medicine applications. We focus on their clinical applicability and market opportunities to drive us forward to the next generation of tumor models for improved cancer patient theranostics.

18F-FDG PET/TC en el manejo clínico de los linfomas / 18F-FDG PET/CT in the clinical management of patients with lymphoma

El objetivo de la presente revisión es actualizar las recomendaciones sobre el papel de la tomografía por emisión de positrones (PET)/tomografía computarizada (TC) en la estadificación y valoración de la respuesta tras quimioterapia y/o trasplante de progenitores hematopoyéticos en pacientes con linfoma de Hodgkin (LH) y linfoma no-Hodgkin (LNH) en la práctica clínica habitual. En la primera reunión internacional sobre PET en linfoma, celebrada en 2009 en Deauville (Francia), se estableció una escala de 5 puntos para la valoración de la respuesta en pacientes con linfoma mediante la 18F-Fluordeoxiglucosa (FDG) PET/TC. Posteriormente, tras celebrarse la 11.a y 12.a Conferencia Internacional sobre Linfomas en Lugano (Suiza) en 2011 y 2013, respectivamente, se alcanzó un acuerdo en cuanto al uso de la PET/TC para la estadificación y se revisaron los criterios de respuesta en linfoma ávidos por la FDG en la práctica clínica y en ensayos clínicos; son los denominados criterios de valoración de respuesta de Lugano. Los principales consensos alcanzados fueron: I) la PET/TC con 18F-FDG fue formalmente incorporada en la estadificación de los linfomas con avidez por la FDG; II) la biopsia de médula ósea ya no está indicada en la estadificación rutinaria de pacientes con LH y en la mayoría de los pacientes con linfoma B difuso de células grandes (LBDCG), y III) la valoración de respuesta al tratamiento se hará mediante la PET/TC usando la escala de 5 puntos y la clasificación de Lugano. Actualmente, con la introducción de terapias basadas en agentes biológicos con mecanismos inmunes, los criterios de Lugano para valoración de la respuesta requieren una flexibilización y modificación, debido a que estos agentes pueden producir cambios en las técnicas de imagen que sugieren progresión de la enfermedad, a pesar de una respuesta clínica evidente (pseudoprogresión o tumor flare). Ello ha llevado a la adopción provisional de los criterios LYRIC (LYmphoma Response to Inmunomodulatory Therapy Criteria), con la introducción del término «respuesta indeterminada» para definir estos cambios hasta que sean confirmados o descartados como progresión de la enfermedad. El uso generalizado de todas estas recomendaciones mejorará la evaluación de pacientes con linfoma y hará posible la comparación de resultados procedentes de ensayos clínicos (AU)

The aim of this work was to review the current recommendations for staging and response assessment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) in routine clinical practice after chemotherapy and/or stem cell transplantation. A five-point scale (5-PS) from the First International Workshop on PET in Lymphoma in Deauville, France, in 2009, was recommended as the standard tool to score imaging to assess treatment response in patients with lymphoma using 18F-Fluorodeoxyglucose (FDG) PET/CT. Following the recommendations of the 11th and 12th International Conferences on Malignant Lymphoma held in Lugano (Switzerland), in 2011 and 2013, respectively, a consensus (the so-called Lugano Classification) was reached regarding the use of PET/CT for staging and response assessment in FDG-avid lymphomas. As a result, 18F-FDG PET/CT was formally incorporated into standard staging for FDG-avid lymphomas. A bone marrow biopsy is no longer indicated for the routine staging of HL and most diffuse large B-cell lymphomas. PET/CT will be used to assess response in FDG-avid histologies using the 5-point scale. The recent introduction of biological agents with immune mechanisms requires flexibility in interpretations of the Lugano criteria due to tumour flare or a pseudo-progression effect produced by these agents. Provisional criteria have been proposed (Lymphoma Response to Immunomodulatory Therapy Criteria) with the introduction of the term ‘Indeterminate Response’ in order to identify this phenomenon until confirmed as flare/pseudoprogression or true progression. All these recommendations will improve evaluations of patients with lymphoma, and allow comparison of results from clinical practice and trials (AU)

18F-FDG PET/CT in the clinical management of patients with lymphoma. / 18F-FDG PET/TC en el manejo clínico de los linfomas.

The aim of this work was to review the current recommendations for staging and response assessment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) in routine clinical practice after chemotherapy and/or stem cell transplantation. A five-point scale (5-PS) from the First International Workshop on PET in Lymphoma in Deauville, France, in 2009, was recommended as the standard tool to score imaging to assess treatment response in patients with lymphoma using 18F-Fluorodeoxyglucose (FDG) PET/CT. Following the recommendations of the 11th and 12th International Conferences on Malignant Lymphoma held in Lugano (Switzerland), in 2011 and 2013, respectively, a consensus (the so-called Lugano Classification) was reached regarding the use of PET/CT for staging and response assessment in FDG-avid lymphomas. As a result, 18F-FDG PET/CT was formally incorporated into standard staging for FDG-avid lymphomas. A bone marrow biopsy is no longer indicated for the routine staging of HL and most diffuse large B-cell lymphomas. PET/CT will be used to assess response in FDG-avid histologies using the 5-point scale. The recent introduction of biological agents with immune mechanisms requires flexibility in interpretations of the Lugano criteria due to tumour flare or a pseudo-progression effect produced by these agents. Provisional criteria have been proposed (Lymphoma Response to Immunomodulatory Therapy Criteria) with the introduction of the term 'Indeterminate Response' in order to identify this phenomenon until confirmed as flare/pseudoprogression or true progression. All these recommendations will improve evaluations of patients with lymphoma, and allow comparison of results from clinical practice and trials.

Radioinmunoterapia en el linfoma no Hodgkin, posicionamiento, seguridad y eficacia de 90Y-ibritumomab. Experiencia y seguimiento a los 10 años / Radioimmunotherapy for non-Hodgkin's lymphoma; positioning, safety, and efficacy of 90Y-Ibritumomab. 10 years of experience and follow-up

Introducción. La radioinmunoterapia (RIT) es uno de los tratamientos dirigidos contra dianas moleculares del linfoma no Hodgkin (LNH). Objetivo. Evaluar el posicionamiento de la RIT con 90Y-ibritumomab en pacientes con LNH, así como su seguridad y efectividad. Método. Estudio retrospectivo de pacientes con LNH que recibieron RIT con 90Y-ibritumomab. Se evaluaron la concordancia con las guías clínicas, la toxicidad según la clasificación Common Terminology Criteria for Adverse Events (CTCAE) y la efectividad en función de la respuesta al tratamiento y de la supervivencia global (SG) y la supervivencia libre de progresión (SLP). Resultados. Se solicitó RIT en 26 pacientes, de los que 21 (11 mujeres, edad media ± desviación estándar 56±10 años) fueron incluidos en el estudio, con la siguiente distribución: LNH folicular 67%, LNH del manto 14%, LNH difuso de células B grandes 9,5% y LNH transformado 9,5%. Se trató a 12 pacientes con LNH refractario, 7 para consolidación de respuesta y 2 para acondicionamiento a trasplante. El 71% de los pacientes presentó efectos adversos, generalmente manejables y transitorios, siendo la trombocitopenia el más frecuente. A los 3-4 meses, se obtuvo una tasa de respuesta global del 76,2% (completa en 71,4% y parcial en 4,8%) y el 19% mostró progresión de su enfermedad. Con una mediana de seguimiento de 70 meses, la SG fue 96±8 y la SLP de 54±11 meses. Conclusiones. La RIT presentó una moderada correlación con las guías clínicas y probablemente esté infrautilizada. Los efectos adversos fueron frecuentes, leves y manejables. Los datos muestran una alta tasa de respuesta completa y una prolongación de la SG y la SLP (AU)

Introduction. Radioimmunotherapy (RIT) is one of the therapies directed against molecular targets in non-Hodgkin's lymphoma (NHL). Objective. To evaluate the positioning, safety, and effectiveness of RIT with 90Y-Ibritumomab in NHL patients. Method. A retrospective study was conducted on patients with NHL who received RIT with 90Y-Ibritumomab. An evaluation was made of the concordance with clinical guidelines, toxicity as rated by the Common Terminology Criteria for Adverse Events (CTCAE), and effectiveness was assessed based on response to treatment, overall survival (OS), and progression-free survival (PFS). Results. RIT was requested in 26 patients, of whom 21 (11 women, mean age 56±10 years) were included in the study, with the following distribution: Follicular NHL, 67%, Mantle NHL, 14%, Diffuse large B-cell NHL, 9.5%, and Transformed NHL 9.5%. Twelve patients with refractory NHL, 7 for consolidation response, and 2 transplant conditioning, were treated. Adverse effects were observed in 71% of patients, which were usually manageable and transient, and with the most common being thrombocytopenia. At 3-4 months, overall response rate was 76.2% (71.4% complete and 4.8% partial response), and 19% had progression of disease. With a median follow up of 70 months, the OS was 96±8 months, and the PFS was 54±11 months. Conclusion. RIT showed a moderate correlation with clinical guidelines, and is probably underused. Adverse effects were common, mild, and manageable. The data show a high complete response rate and an increase in the OS and PFS (AU)

Long-term survival of patients with CLL after allogeneic transplantation: a report from the European Society for Blood and Marrow Transplantation.

Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25-31), 35% (95% CI, 32-38) and 40% (95% CI, 37-42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73-85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients.

Tacrolimus plus sirolimus with or without ATG as GVHD prophylaxis in HLA-mismatched unrelated donor allogeneic stem cell transplantation.

HLA-matched related or unrelated donors are not universally available. Consequently, patients can be offered hematopoietic stem cell transplantation (HSCT) from alternative donors, including mismatched unrelated donors (MMURD), known to cause a higher incidence of acute GVHD (aGVHD) and chronic GVHD. In vivo T-cell-depletion strategies, such as antithymocyte globulin (ATG) therapy, significantly decrease the risk of GVHD. We performed a multicenter, retrospective study comparing tacrolimus (TAC) and sirolimus (SIR) with or without ATG in 104 patients (TAC-SIR=45, TAC-SIR-ATG=59) who underwent MMURD HSCT. Use of ATG was associated with a lower incidence, albeit not statistically significant, of grades 2-4 aGVHD (46% vs 64%, P=0.09), no difference in grades 3-4 aGVHD (10% vs 15%, P=0.43), a trend for a lower incidence of moderate/severe chronic GVHD (16% vs 37%, P=0.09) and more frequent Epstein-Barr virus reactivation (54% vs 18%, P=0.0002). There were no statistically significant differences in 3-year overall survival (OS) (TAC-SIR-ATG=40% (95% confidence interval (CI)=24-56%) vs TAC-SIR=54% (95% CI=37-70%), P=0.43) or 3-year cumulative incidence of relapse/progression (TAC-SIR-ATG=40% (95% CI=28-58%) vs TAC-SIR=22% (95% CI=13-39%), P=0.92). An intermediate Center for International Blood & Marrow Transplant Research disease risk resulted in a significantly lower non-relapse mortality and better OS at 3 years. Our study suggests that addition of ATG to TAC-SIR in MMURD HSCT does not affect OS when compared with TAC-SIR alone.