Valoración mediante Dixon modificado de las lesiones suprarrenales incidentales en RM 3T / Using the modified Dixon technique to evaluate incidental adrenal lesions on 3T MRI

Objetivo: Cuantificar mediante secuencia mDIXON-Quant la fracción grasa (FG) de las lesiones suprarrenales encontradas incidentalmente en estudios de TC. Analizar la relación de la caída de señal entre las secuencias potenciadas en T1 en fase y fase opuesta con la FG en mDIXON-Quant. Comparar la sensibilidad y especificidad de ambos métodos para caracterizar las lesiones suprarrenales. Material y métodos: Se realizó un estudio prospectivo descriptivo que incluyó a 31 pacientes con lesiones suprarrenales incidentales evaluados mediante RM 3T con las secuencias T1 en fase y fase opuesta y mDIXON-Quant. Se midió la FG de las lesiones suprarrenales mediante mDIXON-Quant y la intensidad de señal en secuencias T1 en fase y fase opuesta, calculando su porcentaje de pérdida de señal (PPS). Resultados: El PPS medio fue significativamente mayor en el grupo adenoma (61,3% ± 20,4%) que en el no adenoma (5,1% ± 5,8%) (p < 0,005). La FG media de los adenomas también fue significativamente mayor (26,9% ± 10,8% vs. 3,4% ± 3,0%) (p < 0,005). El área bajo la curva ROC fue 0,99 (0,96-1,00) para el PPS y 0,98 (0,94-1,00) para la FG. El punto de corte obtenido fue de 24,42% para el PPS y de 9,2% para la FG. Los valores diagnósticos fueron iguales para los dos métodos: sensibilidad del 96% (79,6-99,9), especificidad del 100% (39,8-100,0), valor predictivo positivo del 100% (85,8-100,0) y valor predictivo negativo del 80% (28,4-99,5). Conclusión: La FG obtenida mediante técnica Dixon modificada es capaz de diferenciar adenomas de no adenomas con la misma sensibilidad y especificidad que la PPS

Objectives: To use the mDIXON-Quant sequence to quantify the fat fraction of adrenal lesions discovered incidentally on CT studies. To analyze the relation between the signal loss between in-phase and out-of-phase T1-weighted sequences and the fat fraction in mDIXON-Quant. To compare the sensitivity and specificity of the two methods for characterizing adrenal lesions. Material and methods: This prospective descriptive study included 31 patients with incidentally discovered adrenal lesions evaluated with 3T MRI using in-phase and out-of-phase T1-weighted sequences and mDIXON-Quant; the fat fraction of the adrenal lesions was measured by mDIXON-Quant and by calculating the percentage of signal loss between in-phase and out-of-phase T1-weighted sequences. Results: The percentage of signal loss was significantly higher in the group of patients with adenoma (61.3% ± 20.4% vs. 5.1% ± 5.8% in the group without adenoma, p<0.005). The mean fat fraction measured by mDIXON-Quant was also higher for the adenomas (26.9% ±10.8% vs. 3.4% ± 3.0%, p<0.005).The area under the ROC curve was 0.99 (0.96 - 1.00) for the percentage of signal loss and 0.98 (0.94 - 1.00) for the fat fraction measured by mDIXON-Quant. The cutoffs obtained were 24.42% for the percentage of signal loss and 9.2% for the fat fraction measured by mDIXON-Quant. The two techniques had the same values for diagnostic accuracy: sensitivity 96% (79.6 - 99.9), specificity 100% (39.8 - 100.0), positive predictive value 100% (85.8 - 100.0), and negative predictive value 80% (28.4 - 99.5). Conclusion: The fat fraction measured by the modified Dixon technique can differentiate between adenomas and other adrenal lesions with the same sensitivity and specificity as the percentage of signal loss between in-phase and out-of-phase T1-weighted sequences

Using the modified Dixon technique to evaluate incidental adrenal lesions on 3T MRI. / Valoración mediante Dixon modificado de las lesiones suprarrenales incidentales en RM 3T.

OBJECTIVES: To use the mDIXON-Quant sequence to quantify the fat fraction of adrenal lesions discovered incidentally on CT studies. To analyze the relation between the signal loss between in-phase and out-of-phase T1-weighted sequences and the fat fraction in mDIXON-Quant. To compare the sensitivity and specificity of the two methods for characterizing adrenal lesions. MATERIAL AND METHODS: This prospective descriptive study included 31 patients with incidentally discovered adrenal lesions evaluated with 3T MRI using in-phase and out-of-phase T1-weighted sequences and mDIXON-Quant; the fat fraction of the adrenal lesions was measured by mDIXON-Quant and by calculating the percentage of signal loss between in-phase and out-of-phase T1-weighted sequences. RESULTS: The percentage of signal loss was significantly higher in the group of patients with adenoma (61.3% ± 20.4% vs. 5.1% ± 5.8% in the group without adenoma, p<0.005). The mean fat fraction measured by mDIXON-Quant was also higher for the adenomas (26.9% ±10.8% vs. 3.4% ± 3.0%, p<0.005).The area under the ROC curve was 0.99 (0.96 - 1.00) for the percentage of signal loss and 0.98 (0.94 - 1.00) for the fat fraction measured by mDIXON-Quant. The cutoffs obtained were 24.42% for the percentage of signal loss and 9.2% for the fat fraction measured by mDIXON-Quant. The two techniques had the same values for diagnostic accuracy: sensitivity 96% (79.6 - 99.9), specificity 100% (39.8 - 100.0), positive predictive value 100% (85.8 - 100.0), and negative predictive value 80% (28.4 - 99.5). CONCLUSION: The fat fraction measured by the modified Dixon technique can differentiate between adenomas and other adrenal lesions with the same sensitivity and specificity as the percentage of signal loss between in-phase and out-of-phase T1-weighted sequences.

Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia.

Recurrent deletions of the CDKN2A/ARF/CDKN2B genes encoded at chromosome 9p21 have been described in both pediatric and adult acute lymphoblastic leukemia (ALL), but their prognostic value remains controversial, with limited data on adult T-ALL. Here, we investigated the presence of homozygous and heterozygous deletions of the CDKN2A/ARF and CDKN2B genes in 64 adult T-ALL patients enrolled in two consecutive trials from the Spanish PETHEMA group. Alterations in CDKN2A/ARF/CDKN2B were detected in 35/64 patients (55%). Most of them consisted of 9p21 losses involving homozygous deletions of the CDKNA/ARF gene (26/64), as confirmed by single nucleotide polymorphism (SNP) arrays and interphase fluorescence in situ hybridization (iFISH). Deletions involving the CDKN2A/ARF/CDKN2B locus correlated with a higher frequency of cortical T cell phenotype and a better clearance of minimal residual disease (MRD) after induction therapy. Moreover, the combination of an altered copy-number-value (CNV) involving the CDKN2A/ARF/CDKN2B gene locus and undetectable MRD (≤ 0.01%) values allowed the identification of a subset of T-ALL with better overall survival in the absence of hematopoietic stem cell transplantation.

Tratamiento de la enfermedad de injerto contra huésped crónica esclerodermiforme con imatinib: una perspectiva dermatológica / Sclerodermatous Chronic Graft-versus-Host Disease Treated With Imatinib: A Dermatological Perspective

INTRODUCCIÓN: La enfermedad de injerto contra huésped crónica (EICHc) es la causa más importante de mortalidad tardía no relacionada con la recidiva del trasplante alogénico de células progenitoras hematopoyéticas. La EICHc esclerodermiforme suele ser refractaria a los corticosteroides y supone todo un reto terapéutico. Se han descrito anticuerpos activadores contra el RFCDP en pacientes con EICHc esclerodermiforme. Estos anticuerpos inducen la fosforilación del RFCDP, produciendo fibrosis. Hay cada vez más evidencias de la efectividad de imatinib, un inhibidor de la tirosina cinasa, en el tratamiento de la EICHc esclerodermiforme. OBJETIVO: Evaluar la respuesta de la EICHc esclerodermiforme al imatinib. MATERIALES Y MÉTODOS: Estudio retrospectivo de 18 pacientes con EICHc cutánea esclerodermiforme refractaria a inmunosupresores tratada con imatinib en un único centro. La evaluación de la respuesta al tratamiento se realizó mediante valoración clínica del dermatólogo y percepción subjetiva del paciente tras uno, 3, 6, 9, 12 y 18 meses de iniciar el tratamiento con imatinib. La respuesta fue valorada como completa, parcial, significativa, sin cambios o progresión. El descenso de la dosis de esteroides se catalogó como completo, parcial o no posible. RESULTADOS: En nuestra serie, 4 (22%) pacientes lograron una respuesta completa, 9 (50%) alcanzaron una respuesta parcial, 2 (11%) tuvieron un grado significativo de respuesta, 2 (11%) no presentaron ningún cambio y uno (6%) experimentó avance de la enfermedad en el último seguimiento que se llevó a cabo. El tiempo medio transcurrido desde el inicio del imatinib hasta mostrar algún grado de respuesta fue de 2,75 meses (rango 1-9 meses). CONCLUSIONES: Este estudio apoya la evidencia de la utilidad del imatinib en el tratamiento de la EICHc esclerodermiforme

INTRODUCTION: Chronic graft-versus-host disease (cGVHD) is the most important cause of late non-relapse mortality after allogeneic hematopoietic stem cell transplantation. Sclerodermatous cGVHD is usually steroid refractory and remains a therapeutic challenge. Activating antibodies against the PDGFR have been reported in patients with sclerodermatous cGVHD. These antibodies induce PDGFR phosphorylation and lead to fibrosis. There is increasing evidence of successful treatment of sclerodermatous cGVHD with imatinib, a tyrosine kinase inhibitor. OBJECTIVE: To evaluate the response of cutaneous sclerodermatous cGVHD to imatinib. MATERIALS AND METHODS: Retrospective study of 18 patients with sclerodermatous cGVHD refractory to immunosuppressants treated with imatinib in a single center. Evaluation of treatment response was performed by clinicians' assessment and patients' subjective response at one, 3, 6, 9, 12 and 18 months after initiation of imatinib. Response was assessed as complete, partial, significant, no change or progression. Tapper off steroids was complete, partial or not possible. RESULTS: In our series, 4 (22%) patients achieved complete response, 9 (50%) patients partial response, 2 (11%) patients significant response, 2 (11%) patients had no change and one (6%) patient progressive disease at last follow-up. Mean time from initiation of imatinib to any degree of response was 2,75 months (range 1-9 months). CONCLUSIONS: This study provides further evidence of the role of imatinib for the treatment of steroid refractory sclerodermatous cGVHD

Sclerodermatous Chronic Graft-versus-Host Disease Treated With Imatinib: A Dermatological Perspective. / Tratamiento de la enfermedad de injerto contra huésped crónica esclerodermiforme con imatinib: una perspectiva dermatológica.

INTRODUCTION: Chronic graft-versus-host disease (cGVHD) is the most important cause of late non-relapse mortality after allogeneic hematopoietic stem cell transplantation. Sclerodermatous cGVHD is usually steroid refractory and remains a therapeutic challenge. Activating antibodies against the PDGFR have been reported in patients with sclerodermatous cGVHD. These antibodies induce PDGFR phosphorylation and lead to fibrosis. There is increasing evidence of successful treatment of sclerodermatous cGVHD with imatinib, a tyrosine kinase inhibitor. OBJECTIVE: To evaluate the response of cutaneous sclerodermatous cGVHD to imatinib. MATERIALS AND METHODS: Retrospective study of 18 patients with sclerodermatous cGVHD refractory to immunosuppressants treated with imatinib in a single center. Evaluation of treatment response was performed by clinicians' assessment and patients' subjective response at one, 3, 6, 9, 12 and 18 months after initiation of imatinib. Response was assessed as complete, partial, significant, no change or progression. Tapper off steroids was complete, partial or not possible. RESULTS: In our series, 4 (22%) patients achieved complete response, 9 (50%) patients partial response, 2 (11%) patients significant response, 2 (11%) patients had no change and one (6%) patient progressive disease at last follow-up. Mean time from initiation of imatinib to any degree of response was 2,75 months (range 1-9 months). CONCLUSIONS: This study provides further evidence of the role of imatinib for the treatment of steroid refractory sclerodermatous cGVHD.

Long-term outcome of older patients with newly diagnosed de novo acute promyelocytic leukemia treated with ATRA plus anthracycline-based therapy.

Treatment outcome in older patients with acute promyelocytic leukemia (APL) is lower compared with younger patients, mainly because of a higher induction death rate and postremission non-relapse mortality (NRM). This prompted us to design a risk- and age-adapted protocol (Programa Español de Tratamientos en Hematología (PETHEMA)/HOVON LPA2005), with dose reduction of consolidation chemotherapy. Patients aged ⩾60 years reported to the PETHEMA registry and were treated with all-trans retinoic acid (ATRA) plus anthracycline-based regimens according to three consecutive PETHEMA trials that were included. We compared the long-term outcomes of the LPA2005 trial with the preceding PETHEMA trials using non-age-adapted schedules (LPA96&LPA99). From 1996 to 2012, 389 older patients were registered, of whom 268 patients (69%) were eligible. Causes of ineligibility were secondary APL (19%), and unfit for chemotherapy (11%). Median age was 67 years, without relevant differences between LPA2005 and LPA96&LPA99 cohorts. Overall, 216 patients (81%) achieved complete remission with no differences between trials. The 5-year NRM, cumulative incidence of relapse, disease-free survival and overall survival in the LPA2005 vs the LPA96&99 were 5 vs 18% (P=0.15), 7 vs 12% (P=0.23), 87 vs 69% (P=0.04) and 74 vs 60% (P=0.06). A less intensive front-line regimen with ATRA and anthracycline monochemotherapy resulted in improved outcomes in older APL patients.

Impact of NADPH oxidase functional polymorphisms in acute myeloid leukemia induction chemotherapy.

Efficacy and toxicity of anthracycline treatment in acute myeloid leukemia (AML) is mediated by reactive oxygen species (ROS). NADPH oxidase is the major endogenous source of ROS and a key mediator of oxidative cardiac damage. The impact of NADPH oxidase polymorphisms (CYBA:rs4673, NCF4:rs1883112, RAC2:rs13058338) was evaluated in 225 adult de novo AML patients. Variant alleles of NCF4 and RAC2 were related to higher complete remission (P=0.035, P=0.016), and CYBA homozygous variant showed lower overall survival with recessive model (P=0.045). Anthracycline-induced cardiotoxicity was associated to NCF4 homozygous variant (P=0.012) and CYBA heterozygous genotype (P=0.027). Novel associations were found between variant allele of CYBA and lower lung and gastrointestinal toxicities, and a protective effect in nephrotoxicity and RAC2 homozygous variant. Moreover, RAC2 homozygous variant was related to delayed thrombocytopenia recovery. This study supports the interest of NADPH oxidase polymorphisms regarding efficacy and toxicity of AML induction therapy, in a coherent integrated manner.

Characterization of three new HLA Class I Alleles in Spanish Caucasians, HLA-A*02:620, HLA-B*27:150 and HLA-B*07:05:01:02.

Three new HLA class I alleles, HLA-A*02:620, HLA-B*27:150 and HLA-B*07:05:01:02, were described in the Spanish Caucasoid population.

Haplo-Cord transplantation compared to haploidentical transplantation with post-transplant cyclophosphamide in patients with AML.

For patients with AML, the best alternative donor remains to be defined. We analyze outcomes of patients who underwent myeloablative umbilical cord blood or haploidentical hemopoietic stem cell transplantation (HSCT) in Spain. Fifty-one patients underwent single umbilical cord blood transplantation supported by a third party donor (Haplo-Cord) between 1999 and 2012, and 36 patients received an haploidentical HSCT with post-transplant cyclophosphamide (PTCY-haplo) between 2012 and 2014 in GETH centers. The Haplo-Cord cohort included a higher proportion of patients with high disease risk index and use of TBI in the conditioning regimen, and hematopoietic cell transplantation-age Comorbidity Age Index was higher in PTCY-haplo patients. Cumulative incidence of neutrophil engraftment was 97% in the Haplo-Cord and 100% in the PTCY-haplo group, achieved in a median of 12 and 17 days, respectively (P=0.01). Grade II-IV acute GvHD rate was significantly higher in the PTCY-haplo group (9.8% vs 29%, P=0.02) as well as chronic GvHD rates (20% vs 38%, P=0.03). With a median follow-up of 61 months for the Haplo-Cord group and 26 months for the PTCY-haplo cohort, overall survival at 2 years was 55% and 59% (P=0.66), event-free survival was 45% vs 56% (P=0.46), relapse rate was 27% vs 21% (P=0.79), and non-relapse mortality was 17% vs 23% (P=0.54), respectively. In this multicenter experience, Haplo-Cord and PTCY-haplo HSCT offer valid alternatives for patients with AML. Neutrophil engraftment was faster in the Haplo-Cord cohort, with similar survival rates, with higher GvHD rates after haploidentical HSCT.

ABO incompatibility does not influence transfusion requirements in patients undergoing single-unit umbilical cord blood transplantation.

Hematopoietic stem cell transplantation is usually performed without considering the ABO compatibility between donor and recipient. There are few studies analyzing ABO matching impact on transfusion outcome of umbilical cord blood transplantation (UCBT) recipients. The aim of this study was to analyze factors influencing transfusion outcome, highlighting the ABO matching between donor and recipient. This study has reviewed data from 318 patients who underwent single unit UCBT at la Fe University Hospital from January 2000 to December 2014. There were no differences between RBC and platelet (PLT) requirements or RBC and PLT transfusion independence according to ABO matching between donor and recipient. RBC and PLT requirements were statistically correlated (ρ=0,841, P<0.001). A total of 170 and 188 patients achieved RBC and PLT independence, respectively, within 180 days after UCBT. Persistence of recipient isoagglutinins was detected in 6.8% of patients with major ABO incompatibility at median of 176 days (103-269) after UCBT. Autoimmune haemolytic anemia was diagnosed in 15 patients, 12 of them due to cold antibodies. In conclusion, ABO matching has not influenced transfusion requirements of patients undergoing UCBT.

Radiología del oído externo: indicaciones, anatomía normal y procesos patológicos / Radiology of external ear: indications, normal anatomy, and pathological processes

El oído externo (OE) es accesible al examen directo. En la mayor parte de las enfermedades, la historia clínica y la otoscopia son suficientes para su diagnóstico y tratamiento. Nuestro objetivo es describir la anatomía normal del OE, especificar las indicaciones de pruebas de imagen y revisar las manifestaciones clínicas y radiológicas de las enfermedades más frecuentes, que clasificaremos según su origen en patología congénita, inflamatoria e infecciosa, tumoral ósea benigna, traumática y tumoral maligna. Las pruebas de imagen no desempeñan un papel importante en la patología del OE, pero en determinados escenarios clínicos pueden ser cruciales para alcanzar el diagnóstico concreto y establecer el tratamiento idóneo. La tomografía computarizada es la técnica de elección para la mayor parte de las enfermedades. La resonancia magnética es complementaria, permite discriminar tejidos de diferente naturaleza y evaluar con precisión la extensión de la enfermedad (AU)

The external ear is accessible to direct examination; the clinical history and otoscopy are sufficient to diagnose and treat most diseases of the external ear. We aim to describe the normal anatomy of the external ear, specify the indications for imaging tests, and review the clinical and radiological manifestations of the most common diseases affecting the external ear. We classify these diseases according to their origin into congenital, inflammatory, infectious, or traumatic disease or benign bone tumors or malignant tumors. Imaging does not play an important role in diseases of the external ear, but in certain clinical scenarios it can be crucial for reaching a concrete diagnosis and establishing the best treatment. Computed tomography is the first-choice technique for most diseases. Magnetic resonance imaging complements computed tomography and makes it possible to differentiate among different tissue types and to evaluate the extension of disease accurately (AU)

Busulfan-based reduced intensity conditioning regimens for haploidentical transplantation in relapsed/refractory Hodgkin lymphoma: Spanish multicenter experience.

Relapsed or refractory Hodgkin lymphoma (advanced HL) still remains a therapeutic challenge. Recently, unmanipulated haploidentical related donor transplant with reduced conditioning regimen (HAPLO-RIC) and post-transplant cyclophosphamide (PT-Cy) as GvHD prophylaxis has became a promising rescue strategy potentially available to almost every patient. This paper reports our multicenter experience using an IV busulfan-based HAPLO-RIC regimen and PT-Cy in the treatment of 43 patients with advanced HL. Engraftment occurred in 42 patients (97.5%), with a median time to neutrophil and platelet recovery of 18 and 26 days. Cumulative incidences of grades II-IV acute GvHD and chronic GvHD were 39% and 19%, respectively. With a median follow-up of 25.5 months for survivors, 27 patients are alive, with 22 of them disease free. Cumulative incidences of 1-year non-relapse mortality and relapse at 2 years were 21% and 24%, respectively. The estimated 2-year event-free survival (EFS) and overall survival (OS) were 48% and 58%, respectively. CR prior to HAPLO-RIC correlated with better EFS (78.5% vs 33.5%; P=0.015) and OS (86% vs 46%; P=0.044). Our findings further confirm prior reports using HAPLO-RIC in advanced HL in a multicenter approach employing an IV busulfan-based conditioning regimen.

Radiology of external ear: indications, normal anatomy, and pathological processes. / Radiología del oído externo: indicaciones, anatomía normal y procesos patológicos.

The external ear is accessible to direct examination; the clinical history and otoscopy are sufficient to diagnose and treat most diseases of the external ear. We aim to describe the normal anatomy of the external ear, specify the indications for imaging tests, and review the clinical and radiological manifestations of the most common diseases affecting the external ear. We classify these diseases according to their origin into congenital, inflammatory, infectious, or traumatic disease or benign bone tumors or malignant tumors. Imaging does not play an important role in diseases of the external ear, but in certain clinical scenarios it can be crucial for reaching a concrete diagnosis and establishing the best treatment. Computed tomography is the first-choice technique for most diseases. Magnetic resonance imaging complements computed tomography and makes it possible to differentiate among different tissue types and to evaluate the extension of disease accurately.

A systematic review and meta-analysis of the impact of WT1 polymorphism rs16754 in the effectiveness of standard chemotherapy in patients with acute myeloid leukemia.

The polymorphism rs16754 of the WT1 gene has been described as a possible prognostic marker in different acute myeloid leukemia (AML) cohorts; however, it is not supported by all the studies. We performed the first meta-analysis evaluating the effect of this polymorphism upon the effectiveness of standard AML therapy. Fourteen cohort studies were included (3618 patients). Patients with the variant allele showed a significant higher overall survival (OS) at 5 years (OR:1.24, 95% CI: 1.06-1.45, P=0.007, with dominant model). WT1 did not influence complete remission, but a higher disease-free survival was observed with the variant allele. In the subgroup analysis, Caucasians, pediatric and patients treated with idarubicin and etoposide carrying the variant allele showed consistent results in OS, whereas patients with cytogenetically normal AML did not show differences. To verify the effect of this polymorphism upon other outcomes, studies in larger and multiracial populations are needed.

Incidence and risk factors of post-engraftment invasive fungal disease in adult allogeneic hematopoietic stem cell transplant recipients receiving oral azoles prophylaxis.

Studies that analyze the epidemiology and risk factors for invasive fungal disease (IFD) after engraftment in alloSCT are few in number. This single-center retrospective study included 404 alloSCT adult recipients surviving >40 days who engrafted and were discharged without prior IFD. All patients who received ⩾20 mg/day of prednisone were assigned to primary oral prophylaxis (itraconazole or low-dose voriconazole). The primary end point was the cumulative incidence (CI) of probable/proven IFD using the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) criteria. The independent prognostic factors after multivariate analyses were used to construct a post-engraftment IFD risk score. The 1-year CI of IFD was 11%. The non-relapse mortality was 40% in those developing IFD and 16% in those who did not. The intent-to-treat analysis showed that 17% of patients abandoned the assigned prophylaxis. Age >40 years, ⩾1 previous SCT, pre-engraftment neutropenia >15 days, extensive chronic GVHD and CMV reactivation were independent risk factors. The post-engraftment IFD score stratified patients into low risk (0-1 factor, CI 0.7%), intermediate risk (2 factors, CI 9.9%) and high risk (3-5 factors, CI 24.7%) (P<0.0001). The antifungal prophylaxis strategy failed to prevent post-engraftment IFD in 11% of alloSCT. Our risk score could be useful to implement risk-adapted strategies using antifungal prophylaxis after engraftment.

Exploitation of temporal redundancy in compressed sensing reconstruction of fMRI studies with a prior-based algorithm (PICCS).

PURPOSE: Compressed sensing is a technique used to accelerate magnetic resonance imaging (MRI) acquisition without compromising image quality. While it has proven particularly useful in dynamic imaging procedures such as cardiac cine, very few authors have applied it to functional magnetic resonance imaging (fMRI). The purpose of the present study was to check whether the prior image constrained compressed sensing (PICCS) algorithm, which is based on an available prior image, can improve the statistical maps in fMRI better than other strategies that also exploit temporal redundancy. METHODS: PICCS was compared to spatiotemporal total variation (TTV) and k-t FASTER, since they have already demonstrated high performance and robustness in other MRI applications, such as cardiac cine MRI and resting state fMRI, respectively. The prior image for PICCS was the average of all undersampled data. Both PICCS and TTV were solved using the split Bregman formulation. K-t FASTER algorithm relies on matrix completion to reconstruct the undersampled k-spaces. The three algorithms were evaluated using two datasets with high and low signal-to-noise ratio (SNR)-BOLD contrast-acquired in a 7 T preclinical MRI scanner and retrospectively undersampled at various rates (i.e., acceleration factors). The authors evaluated their performance in terms of the sensitivity/specificity of BOLD detection through receiver operating characteristic curves and by visual inspection of the statistical maps. RESULTS: With high SNR studies, PICCS performed similarly to the state-of-the-art algorithms TTV and k-t FASTER and provided consistent BOLD signal at the ROI. In scenarios with low SNR and high acceleration factors, PICCS still provided consistent maps and higher sensitivity/specificity than TTV, whereas k-t FASTER failed to provide significant maps. CONCLUSIONS: The authors performed a comparison between three reconstructions (PICCS, TTV, and k-t FASTER) that exploit temporal redundancy in fMRI. The prior-based algorithm, PICCS, preserved BOLD activation and sensitivity/specificity better than TTV and k-t FASTER in noisy scenarios. The PICCS algorithm can potentially reach an acceleration factor of ×8 and still provide BOLD contrast in the ROI with an area under the curve over 0.99.

FLORENCE: a randomized, double-blind, phase III pivotal study of febuxostat versus allopurinol for the prevention of tumor lysis syndrome (TLS) in patients with hematologic malignancies at intermediate to high TLS risk.

BACKGROUND: Serum uric acid (sUA) control is of key relevance in tumor lysis syndrome (TLS) prevention as it correlates with both TLS and renal event risk. We sought to determine whether febuxostat fixed dose achieves a better sUA control than allopurinol while preserving renal function in TLS prevention. PATIENTS AND METHODS: Patients with hematologic malignancies at intermediate to high TLS risk grade were randomized to receive febuxostat or allopurinol, starting 2 days before induction chemotherapy, for 7-9 days. Study treatment was blinded, whereas daily dose (low/standard/high containing allopurinol 200/300/600 mg, respectively, or fixed febuxostat 120 mg) depended on the investigator's choice. The co-primary end points, sUA area under curve (AUC sUA1-8) and serum creatinine change, were assessed from baseline to day 8 and analyzed through analysis of covariance with two-sided overall significance level of 5%. Secondary end points included treatment responder rate, laboratory and clinical TLS incidence and safety. RESULTS: A total of 346 patients (82.1% intermediate TLS risk; 82.7% assigned to standard dose) were randomized. Mean AUC sUA1-8 was 514.0 ± 225.71 versus 708.0 ± 234.42 mgxh/dl (P < 0.0001) in favor of febuxostat. Mean serum creatinine change was -0.83 ± 26.98% and -4.92 ± 16.70% for febuxostat and allopurinol, respectively (P = 0.0903). No differences among secondary efficacy end points were detected. Drug-related adverse events occurred in 6.4% of patients in both arms. CONCLUSION: In the largest adult trial carried out in TLS prevention, febuxostat achieved a significant superior sUA control with one fixed dose in comparison to allopurinol with comparable renal function preservation and safety profile. CLINICAL TRIAL REGISTRATION: NCT01724528.