Fostamatinib effectiveness and safety for immune thrombocytopenia in clinical practice.

Fostamatinib, a recently approved syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here 138 ITP patients (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively. The median age of our cohort (55.8% women) was 66 years (interquartile range, IQR, 56-80 years). The median time since ITP diagnosis at fostamatinib initiation was 51 months (IQR, 10-166 months). The median number of therapies prior to fostamatinib initiation was 4 (IQR, 2-5), including eltrombopag (76.1%), romiplostim (57.2%) and intravenous immunoglobulins (IVIG) (44.2%). Fifty-eight patients (42.0%) had signs/symptoms of bleeding in the month prior to treatment initiation. 79.0% of patients responded to fostamatinib with 53.6% complete responses (platelet count > 100 x 109 /L). Eighty-three patients (60.1%) received fostamatinib monotherapy achieving a high response rate (85.4%). The proportion of time in response during the 27-month period examined was 83.3%. The median time to platelet response was 11 days (IQR, 7-21 days). Sixty-seven patients (48.5%) experienced adverse events, mainly grade 1-2, the commonest of which were diarrhea (n = 28) and hypertension (n = 21). One patient had deep venous thrombosis and one patient developed acute myocardial infarction. Fostamatinib was shown to be effective with good safety profile in patients with primary and secondary ITP across a wide age spectrum in this real-world study.

Association of Cytogenetics Aberrations and IGHV Mutations with Outcome in Chronic Lymphocytic Leukemia Patients in a Real-World Clinical Setting.

Immunoglobulin heavy chain variable ( IGHV ) region mutations, TP53 mutation, fluorescence in situ hybridization (FISH), and cytogenetic analysis are the most important prognostic biomarkers used in chronic lymphocytic leukemia (CLL) patients in our daily practice. In real-life environment, there are scarce studies that analyze the correlation of these factors with outcome, mainly referred to time to first treatment (TTFT) and overall survival (OS). This study aimed to typify IGHV mutation status, family usage, FISH aberrations, and complex karyotype (CK) and to analyze the prognostic impact in TTFT and OS in retrospective study of 375 CLL patients from a Spanish cohort. We found unmutated CLL (U-CLL) was associated with more aggressive disease, shorter TTFT (48 vs. 133 months, p < 0.0001), and shorter OS (112 vs. 246 months, p < 0.0001) than the mutated CLL. IGHV3 was the most frequently used IGHV family (46%), followed by IGHV1 (30%) and IGHV4 (16%). IGHV5-51 and IGHV1-69 subfamilies were associated with poor prognosis, while IGHV4 and IGHV2 showed the best outcomes. The prevalence of CK was 15% and was significantly associated with U-CLL. In the multivariable analysis, IGHV2 gene usage and del13q were associated with longer TTFT, while VH1-02, +12, del11q, del17p, and U-CLL with shorter TTFT. Moreover, VH1-69 usage, del11q, del17p, and U-CLL were significantly associated with shorter OS. A comprehensive analysis of genetic prognostic factors provides a more precise information on the outcome of CLL patients. In addition to FISH cytogenetic aberrations, IGHV and TP53 mutations, IGHV gene families, and CK information could help clinicians in the decision-making process.

Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY.

Background: Patients with chronic lymphocytic leukemia (CLL) have a higher risk of developing other malignancies (OMs) compared to the general population. However, the impact of CLL-related risk factors and CLL-directed treatment is still unclear and represents the focus of this work. Methods: We conducted a retrospective international multicenter study to assess the incidence of OMs and detect potential risk factors in 19,705 patients with CLL, small lymphocytic lymphoma, or high-count CLL-like monoclonal B-cell lymphocytosis, diagnosed between 2000 and 2016. Data collection took place between October 2020 and March 2022. Findings: In 129,254 years of follow-up after CLL diagnosis, 3513 OMs were diagnosed (27.2 OMs/1000 person-years). The most common hematological OMs were Richter transformation, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Non-melanoma skin (NMSC) and prostate cancers were the most common solid tumors (STs).The only predictor for MDS and AML development was treatment with fludarabine and cyclophosphamide with/without rituximab (FC ± R) (OR = 3.7; 95% CI = 2.79-4.91; p < 0.001). STs were more frequent in males and patients with unmutated immunoglobulin heavy variable genes (OR = 1.77; 95% CI = 1.49-2.11; p < 0.001/OR = 1.89; 95% CI = 1.6-2.24; p < 0.001).CLL-directed treatment was associated with non-melanoma skin and prostate cancers (OR = 1.8; 95% CI = 1.36-2.41; p < 0.001/OR = 2.11; 95% CI = 1.12-3.97; p = 0.021). In contrast, breast cancers were more frequent in untreated patients (OR = 0.17; 95% CI = 0.08-0.33; p < 0.001).Patients with CLL and an OM had inferior overall survival (OS) than those without. AML and MDS conferred the worst OS (p < 0.001). Interpretation: OMs in CLL impact on OS. Treatment for CLL increased the risk for AML/MDS, prostate cancer, and NMSC. FCR was associated with increased risk for AML/MDS. Funding: AbbVie, and EU/EFPIAInnovative Medicines Initiative Joint Undertaking HARMONY grant n° 116026.

The Five "Ws" of Frailty Assessment and Chronic Lymphocytic Leukemia: Who, What, Where, Why, and When.

Chronic lymphocytic leukemia (CLL) is a disease of the elderly, but chronological age does not accurately discriminate frailty status at the inter-individual level. Frailty describes a person's overall resilience. Since CLL is a stressful situation, it is relevant to assess the patient´s degree of frailty, especially before starting antineoplastic treatment. We are in the era of targeted therapies, which have helped to control the disease more effectively and avoid the toxicity of chemo (immuno) therapy. However, these drugs are not free of side effects and other aspects arise that should not be neglected, such as interactions, previous comorbidities, or adherence to treatment, since most of these medications are taken continuously. The challenge we face is to balance the risk of toxicity and efficacy in a personalized way and without forgetting that the most frequent cause of death in CLL is related to the disease. For this purpose, comprehensive geriatric assessment (GA) provides us with the opportunity to evaluate multiple domains that may affect tolerance to treatment and that could be improved with appropriate interventions. In this review, we will analyze the state of the art of GA in CLL through the five Ws.

Challenging Diagnosis of Invasive Sinus Aspergillosis Mimicking Gradenigo's Syndrome in an Elderly Patient with T-Cell Lymphoma.

(1) Background: Gradenigo's Syndrome (GS) is a rare complication of acute otitis media characterized by the triad of diplopia, otitis, and facial pain. The widespread use of antibiotics has significantly reduced its occurrence. (2) Case summary: We present the case of an elderly patient with T-cell lymphoma who developed neurological deficits resembling GS. The patient was ultimately diagnosed with invasive sinus aspergillosis. The diagnostic process was challenging due to the atypical clinical presentation and the lack of specific imaging findings. A biopsy was the most important test for clarifying the diagnosis. (3) Conclusions: The prognosis for this complication is extremely poor without surgery, and the patient died despite adequate antifungal coverage. Therefore, maintaining high clinical suspicion is paramount to avoid adverse outcomes in similar cases, particularly in the geriatric population, wherein this syndrome's occurrence may not be expected.

Factors associated with the duration of breastfeeding in mothers of babies cared for in a kangaroo family program / Factores asociados a la duración de la lactancia en madres de bebés atendidos en un programa de familia canguro / Fatores associados à duração do aleitamento materno em mães de bebês atendidos em programa família canguru

Goal. To determine the factors associated with the duration of breastfeeding in mothers of babies cared for in a kangaroo family program. Methods. Quantitative, observational study with a secondary source of a retrospective cohort of 707 babies with monitoring at admission, at 40 weeks, at three and at six months of corrected age in the kangaroo family program of a public hospital in the municipality of Rionegro (Antioquia, Colombia) from 2016 to 2019. Results. 49.6% of babies were born with low weight for gestational age and 51.5% were female. 58.3% of the mothers were unemployed and 86.2% of them lived with their partner. When entering the kangaroo family program, 94.2% of the babies received breastfeeding and at six months they were 44.7%. The variables that were associated with the duration of breastfeeding up to six months according to the explanatory model were: the mother's cohabitation with her partner (adjusted prevalence ratio - APR: 1.34) and receiving breastfeeding when entering the kangaroo family program (APR: 2.30). Conclusion. The factors related to the duration of breastfeeding in mothers of babies cared for in the kangaroo family program were that the mother lived with her partner and that the mother was breastfeeding when she entered the program, therefore they received education and support from the interdisciplinary team, which could favor confidence and willingness towards breastfeeding.

Objetivo.Determinar los factores asociados a la duración de la lactancia en madres de bebés atendidos en un programa de familia canguro. Métodos. Estudio cuantitativo, observacional con fuente secundaria de una cohorte retrospectiva de 707 bebés con seguimiento al ingreso, a las 40 semanas, a los tres y a los seis meses de edad corregida en el programa familia canguro de un hospital público del municipio de Rionegro (Antioquia, Colombia) entre 2016 y 2019. Resultados. El 49.6 % de los bebés nacieron con bajo peso para la edad gestacional y 51.5% eran de sexo femenino. El 58.3% de las madres eran desempleadas y un 86.2 % de ellas convivía con su pareja. Al ingresar al programa familia canguro, el 94.2 % de los bebés recibían lactancia materna y a los seis meses correspondió al 44.7%. Las variables que se asociaron con la duración de la lactancia materna hasta los seis meses según el modelo explicativo fueron: la convivencia de la madre con la pareja (razón de prevalencia ajustada - RPa: 1.34) y recibir lactancia al ingresar al programa familia canguro (RPa: 2.30). Conclusión. Los factores que se relacionaron con la duración de la lactancia en madres de bebés atendidos en el programa de familia canguro fueron, por un lado, que la madre conviviera con su pareja y, por otro, que la madre estuviera lactando al ingreso al programa, por lo que recibieron educación y acompañamiento por parte del equipo interdisciplinario, lo cual pudo favorecer la confianza y disposición hacia la lactancia.

Objetivo.Determinar os fatores associados à duração do aleitamento materno em mães de bebês atendidos em um programa família canguru. Métodos.Estudo quantitativo, observacional com fonte secundária de uma coorte retrospectiva de 707 bebês com acompanhamento na admissão, às 40 semanas, aos três e seis meses de idade corrigida no programa família canguru de um hospital público do município de Rionegro (Antioquia, Colômbia) entre 2016 e 2019. Resultados.49.6% dos bebês nasceram com baixo peso para a idade gestacional e 51.5% eram do sexo feminino. 58.3% das mães estavam desempregadas e 86.2% delas moravam com o companheiro. Ao ingressar no programa família canguru, 94.2% dos bebês receberam aleitamento materno e aos seis meses correspondeu a 44.7%. As variáveis que se associaram à duração do aleitamento materno até seis meses segundo o modelo explicativo foram: a coabitação da mãe com o companheiro (razão de prevalência ajustada - TAEG: 1.34) e receber aleitamento materno ao ingressar no programa família canguru (RPa: 2.30). Conclusão. Os fatores que se relacionaram com a duração do aleitamento materno em mães de bebês atendidos no programa família canguru foram que a mãe morava com o companheiro e que a mãe estava amamentando quando ingressou no programa, para o qual receberam educação e apoio da da equipe interdisciplinar, o que poderia favorecer a confiança e disposição para a amamentação.

TRAF3 alterations are frequent in del-3'IGH chronic lymphocytic leukemia patients and define a specific subgroup with adverse clinical features.

Interstitial 14q32 deletions involving IGH gene are infrequent events in chronic lymphocytic leukemia (CLL), affecting less than 5% of patients. To date, little is known about their clinical impact and molecular underpinnings, and its mutational landscape is currently unknown. In this work, a total of 871 CLLs were tested for the IGH break-apart probe, and 54 (6.2%) had a 300 kb deletion of 3'IGH (del-3'IGH CLLs), which contributed to a shorter time to first treatment (TFT). The mutational analysis by next-generation sequencing of 317 untreated CLLs (54 del-3'IGH and 263 as the control group) showed high mutational frequencies of NOTCH1 (30%), ATM (20%), genes involved in the RAS signaling pathway (BRAF, KRAS, NRAS, and MAP2K1) (15%), and TRAF3 (13%) within del-3'IGH CLLs. Notably, the incidence of TRAF3 mutations was significantly higher in del-3'IGH CLLs than in the control group (p < .001). Copy number analysis also revealed that TRAF3 loss was highly enriched in CLLs with 14q deletion (p < .001), indicating a complete biallelic inactivation of this gene through deletion and mutation. Interestingly, the presence of mutations in the aforementioned genes negatively refined the prognosis of del-3'IGH CLLs in terms of overall survival (NOTCH1, ATM, and RAS signaling pathway genes) and TFT (TRAF3). Furthermore, TRAF3 biallelic inactivation constituted an independent risk factor for TFT in the entire CLL cohort. Altogether, our work demonstrates the distinct genetic landscape of del-3'IGH CLL with multiple molecular pathways affected, characterized by a TRAF3 biallelic inactivation that contributes to a marked poor outcome in this subgroup of patients.

Factors associated with the duration of breastfeeding in mothers of babies cared for in a kangaroo family program.

OBJECTIVES: To determine the factors associated with the duration of breastfeeding in mothers of babies cared for in a kangaroo family program. METHODS: Quantitative, observational study with a secondary source of a retrospective cohort of 707 babies with monitoring at admission, at 40 weeks, at three and at six months of corrected age in the kangaroo family program of a public hospital in the municipality of Rionegro (Antioquia, Colombia) from 2016 to 2019. RESULTS: 49.6% of babies were born with low weight for gestational age and 51.5% were female. 58.3% of the mothers were unemployed and 86.2% of them lived with their partner. When entering the kangaroo family program, 94.2% of the babies received breastfeeding and at six months they were 44.7%. The variables that were associated with the duration of breastfeeding up to six months according to the explanatory model were: the mother's cohabitation with her partner (adjusted prevalence ratio - APR: 1.34) and receiving breastfeeding when entering the kangaroo family program (APR: 2.30). CONCLUSIONS: The factors related to the duration of breastfeeding in mothers of babies cared for in the kangaroo family program were that the mother lived with her partner and that the mother was breastfeeding when she entered the program, therefore they received education and support from the interdisciplinary team, which could favor confidence and willingness towards breastfeeding.

Hypermetabolic abdominal and cervical lymph nodes mimicking Hodgkin lymphoma relapse on FDG PET/CT after adenovirus-vectored COVID-19 vaccine.

Vaccine-associated hypermetabolic lymphadenopathy (VAHL) has been reported as a common post-vaccination side effect, especially with mRNA-based COVID-19 vaccines. Most VAHL cases present normal or enlarged regional lymph nodes close to the injection site, usually with mild-moderate FDG (18 F-Fluorodeoxyglucose) uptake on FDG positron emission tomography (PET)/CT. Here, we describe the case of a 33-year-old woman with past history of Classic Hodgkin Lymphoma (CHL) who underwent follow-up FDG PET/CT 3 days (d) after the first dose of the adenovirus-vectored Oxford-AstraZeneca COVID-19 vaccine. FDG PET/CT showed unexpected small hypermetabolic cervical and abdominal lymph nodes in the same location as at the onset of the disease, suggesting radiological relapse. Considering temporal relationship and other cases of VAHL, a new image was performed 2 months later, which revealed decreased lymph nodes and normalization of FDG uptake. This case illustrates that the possibility of a false-positive should always be considered by physicians in this new context, even when hypermetabolic lymph nodes appear far from the vaccination site.

Síndrome de Cushing secundario a administración tópica decorticoesteroides / Cushing Syndrome due to topical corticosteroid misuse

Los corticoesteroides tópicos son drogas muy comunes, frecuentemente utilizadas en patologías dermatológicas. Su mal uso puede causar efectos sistémicos, como el síndrome de Cushing y la supresión del eje hipotalámico ­ hipofisiario ­ adrenal. Presentamos un caso de un lactante menor de siete meses quien desarrolla un síndrome de Cushing secundario al uso de Clobetasol por una dermatitis en el área del pañal, por tiempo prolongado, sin prescripción médica. Al examen físico se evidencia obesidad a predominio central, con fascie de luna llena, hipertricosis en región frontal, telangiectasias aisladas en mejillas y cuello de búfalo. Los paraclínicos demuestran una hipercolesterolemia, hipertrigliceridemia, elevación de las transaminasas y cortisol sérico en la mañana disminuido. Se concluye que se debe informar a los padres de los efectos adversos sistémicos de los esteroides tópicos y se sugiere evitar en pacientes pediátrico(AU)

Topical corticosteroids are very common drugs used in the treatment of inflammatory skin diseases. Prolonged ormisuse of them may cause systemic adverse effects, including Cushing syndrome and hypothalamic-pituitary-adrenal axissuppression. We present a case of a seven months old maleinfant who developed iatrogenic Cushing syndrome after diaperdermatitis treatment through misuse of Clobetasol, withoutdoctor's prescription. We observe redness and a moon face, abuffalo hump, central obesity and hirsutism. Laboratory values revealed hypercholesterolemia, hypertriglyceridemia, elevationin liver enzymes and low early morning cortisol. To conclude,parents must be informed by physicians about the adverse effect of steroids and the should be avoided in very young infant(AU)

Biological significance of monoallelic and biallelic BIRC3 loss in del(11q) chronic lymphocytic leukemia progression.

BIRC3 is monoallelically deleted in up to 80% of chronic lymphocytic leukemia (CLL) cases harboring del(11q). In addition, truncating mutations in the remaining allele of this gene can lead to BIRC3 biallelic inactivation, which has been shown to be a marker for reduced survival in CLL. Nevertheless, the biological mechanisms by which these lesions could contribute to del(11q) CLL pathogenesis and progression are partially unexplored. We implemented the CRISPR/Cas9-editing system to generate isogenic CLL cell lines harboring del(11q) and/or BIRC3 mutations, modeling monoallelic and biallelic BIRC3 loss. Our results reveal that monoallelic BIRC3 deletion in del(11q) cells promotes non-canonical NF-κB signaling activation via RelB-p52 nuclear translocation, being these effects allelic dose-dependent and therefore further enhanced in del(11q) cells with biallelic BIRC3 loss. Moreover, we demonstrate ex vivo in primary cells that del(11q) cases including BIRC3 within their deleted region show evidence of non-canonical NF-κB activation which correlates with high BCL2 levels and enhanced sensitivity to venetoclax. Furthermore, our results show that BIRC3 mutations in del(11q) cells promote clonal advantage in vitro and accelerate leukemic progression in an in vivo xenograft model. Altogether, this work highlights the biological bases underlying disease progression of del(11q) CLL patients harboring BIRC3 deletion and mutation.

The Evolving Landscape of Chronic Lymphocytic Leukemia on Diagnosis, Prognosis and Treatment.

The knowledge of chronic lymphocytic leukemia (CLL) has progressively deepened during the last forty years. Research activities and clinical studies have been remarkably fruitful in novel findings elucidating multiple aspects of the pathogenesis of the disease, improving CLL diagnosis, prognosis and treatment. Whereas the diagnostic criteria for CLL have not substantially changed over time, prognostication has experienced an expansion with the identification of new biological and genetic biomarkers. Thanks to next-generation sequencing (NGS), an unprecedented number of gene mutations were identified with potential prognostic and predictive value in the 2010s, although significant work on their validation is still required before they can be used in a routine clinical setting. In terms of treatment, there has been an impressive explosion of new approaches based on targeted therapies for CLL patients during the last decade. In this current chemotherapy-free era, BCR and BCL2 inhibitors have changed the management of CLL patients and clearly improved their prognosis and quality of life. In this review, we provide an overview of these novel advances, as well as point out questions that should be further addressed to continue improving the outcomes of patients.

From Biomarkers to Models in the Changing Landscape of Chronic Lymphocytic Leukemia: Evolve or Become Extinct.

Chronic lymphocytic leukemia (CLL) is an extremely heterogeneous disease. With the advent of oral targeted agents (Tas) the treatment of CLL has undergone a revolution, which has been accompanied by an improvement in patient's survival and quality of life. This paradigm shift also affects the value of prognostic and predictive biomarkers and prognostic models, most of them inherited from the chemoimmunotherapy era but with a different behavior with Tas. This review discusses: (i) the role of the most relevant prognostic and predictive biomarkers in the setting of Tas; and (ii) the validity of classic and new scoring systems in the context of Tas. In addition, a critical point of view about predictive biomarkers with special emphasis on 11q deletion, novel resistance mutations, TP53 abnormalities, IGHV mutational status, complex karyotype and NOTCH1 mutations is stated. We also go over prognostic models in early stage CLL such as IPS-E. Finally, we provide an overview of the applicability of the CLL-IPI for patients treated with Tas, as well as the emergence of new models, generated with data from patients treated with Tas.

Blood transfusion activity in a general hospital during the COVID-19 pandemic.

BACKGROUND: The COVID-19 outbreak has affected almost all hospital departments, including transfusion services. However, the demand for transfusions in a general hospital designated to deal with COVID-19 patients has not been analysed before. STUDY DESIGN AND METHODS: A retrospective study was conducted to evaluate blood transfusion practices from 15 March to 14 April 2020 at Hospital Universitario Infanta Leonor (Madrid, Spain). During this month, with few exceptions, the hospital became a 'COVID-19' centre. In addition, transfusion rates during this time frame and the same period over the last 4 years were compared. RESULTS: From 15 March to 14 April 2020, only 254 blood components were transfused, resulting in a 49·3% reduction over the previous year. Interestingly, in critically ill patients, the red blood cell (RBC) transfusion/bed ratio significantly decreased during this period (0·92) compared to the same ratio over the past 4 years (2·70) (P = 0·02). Of note, 106 blood components (95 RBC; 11 platelet concentrates) were transfused to only 36 out of 1348 COVID-19 patients (2·7%). The main reason for RBC transfusion in COVID-19 patients was a previous underlying disease (44%) followed by bleeding (25%) and inflammatory anaemia (25%). CONCLUSION: This is the first study to report a decrease in blood transfusions during the COVID-19 pandemic in a general hospital and especially in the intensive care unit. The results of this study suggest that COVID-19 does not generally induce transfusion requiring anaemia, being the main causes for transfusion in these patients underlying conditions or bleeding.

Non-pharmaceutical interventions for containment, mitigation and suppression of COVID-19 infection.

BACKGROUND: The best scientific evidence is required to design effective Non-pharmaceutical interventions to help policymakers to contain COVID-19. AIM: To describe which Non-pharmaceutical interventions used different countries and a when they use them. It also explores how Non-pharmaceutical interventions impact the number of cases, the mortality, and the capacity of health systems. METHODS: We consulted eight web pages of transnational organizations, 17 of international media, 99 of government institutions in the 19 countries included, and besides, we included nine studies (out of 34 identified) that met inclusion criteria. RESULT: Some countries are focused on establishing travel restrictions, isolation of identified cases, and high-risk people. Others have a combination of mandatory quarantine and other drastic social distancing measures. The timing to implement the interventions varied from the first fifteen days after detecting the first case to more than 30 days. The effectiveness of isolated non-pharmaceutical interventions may be limited, but combined interventions have shown to be effective in reducing the transmissibility of the disease, the collapse of health care services, and mortality. When the number of new cases has been controlled, it is necessary to maintain social distancing measures, self-isolation, and contact tracing for several months. The policy decision-making in this time should be aimed to optimize the opportunities of saving lives, reducing the collapse of health services, and minimizing the economic and social impact over the general population, but principally over the most vulnerable. The timing of implementing and lifting interventions could have a substantial effect on those objectives.

Antecedentes: Se requiere la mejor evidencia científica para diseñar intervenciones no farmacológicas efectivas para ayudar a los formuladores de políticas a contener COVID-19. OBJETIVO: Describir qué intervenciones no farmacológicas utilizaron diferentes países y cuándo las implementaron. También explora cómo las intervenciones no farmacológicas afectan el número de casos, la mortalidad y la capacidad de los sistemas de salud. MÉTODOS: Consultamos ocho páginas web de organizaciones transnacionales, 17 de medios internacionales, 99 de instituciones gubernamentales en los 19 países incluidos, y además, incluimos nueve estudios (de 34 identificados) que cumplían con los criterios de inclusión. RESULTADOS: Algunos países implementaron restricciones de viaje, aislamiento de casos identificados y personas de alto riesgo. Otros combinaron varias medidas más drásticas de distanciamiento social. El tiempo para implementar las intervenciones varió desde los primeros quince días después de detectar el primer caso hasta más de 30 días. La efectividad de las intervenciones no farmacológicas combinadas ha demostrado ser efectivas para reducir la transmisibilidad de la enfermedad, el colapso de los servicios de salud y la mortalidad. Cuando se controle el número de casos nuevos, es necesario mantener medidas de distanciamiento social, autoaislamiento y rastreo de contactos durante varios meses. La toma de decisiones políticas en este momento debe tener como objetivo optimizar las oportunidades de salvar vidas, reducir el colapso de los servicios de salud y minimizar el impacto económico y social sobre la población en general, pero principalmente sobre los más vulnerables.

Prognosis Assessment of Early-Stage Chronic Lymphocytic Leukemia: Are We Ready to Predict Clinical Evolution Without a Crystal Ball?

BACKGROUND: The discovery of new biologic variables with high prognostic effect has been accompanied by the emergence of different prognostic indexes (PIs) to assess the time to first treatment in patients with early-stage (Binet A) chronic lymphocytic leukemia (CLL). The present study compared the prognostic value of 5 PIs: CLL international prognostic index (CLL-IPI), Barcelona-Brno, international prognostic score-A (IPS-A), CLL-01, and a tailored approach. PATIENTS AND METHODS: We applied the 5 PIs to a cohort of 428 unselected patients with Binet A CLL from a multicenter Spanish database with clinical and biologic information available. The predictive value of the scores was assessed using Harrell's concordance index (C index) and area under the receiver operating characteristic curve (AUC). RESULTS: We found a significant association between time to first treatment and risk subgroups for all 5 PIs used. The most accurate PI was the IPS-A (C-index, 0.72; AUC, 0.76), closely followed by CLL-01 (C-index, 0.69; AUC, 0.70), CLL-IPI (C-index, 0.69; AUC, 0.69), Barcelona-Brno (C-index, 0.67; AUC, 0.69), and the tailored approach (C-index, 0.61 and 0.58; AUC, 0.58 and 0.54). CONCLUSIONS: The concordance between the PIs was low (44%), suggesting that although all these PIs improve clinical staging and help physicians in routine clinical practice, it will be necessary to harmonize larger cohorts of patients to define the best PI for treatment decision-making in the real world.

Aplicación del diagnóstico genético preimplantacional en la distrofia miotónica tipo 1 o enfermedad de Steinert / Application of pre-implantation genetic diagnosis in Myotonic dystrophy type 1 - Steinert's disease

La distrofia miotónica tipo 1 (DM1) es la forma más común de distrofia muscular en adultos causada por la expansión de una repetición de trinucleótidos CTG en el gen DMPK (Distrofia miotónica proteína quinasa) y su herencia es autosómica dominante. Hasta el momento, la técnica de Diagnóstico Genético Preimplantacional parece ser la aproximación reproductiva más eficaz para aquellas parejas en las que alguno de sus progenitores es afecto de DM1. En este estudio se evaluó la técnica de Diagnóstico Genético Preimplantacional en función del sexo del progenitor afecto y el número de repeticiones CTG y su influencia sobre el resultado reproductivo de la misma. Un total de 13 parejas, del programa de Diagnóstico Genético Preimplantacional de la Unidad de Reproducción Asistida del Hospital Universitari i Politècnic La Fe, fueron incluidas en el estudio. En 8 de éstas la afecta es la mujer, mientras que en las 5 restantes es el hombre el portador de la enfermedad. En todas ellas se llevaron a cabo todos los pasos del programa. Los embriones fueron analizados mediante mTP-PCR y PCR multiplex. El efecto de ambas variables se analizó mediante análisis bivariado (prueba T, Chi-cuadrado, regresión lineal y test Anova) y análisis multivariante utilizando análisis de correlación (Rho de Spearman). Los resultados obtenidos revelaron una transmisión preferencial de los alelos expandidos en DM1, independiente del sexo del progenitor afecto. A pesar de ello, no mostraron ninguna relación estadísticamente significativa entre el sexo del progenitor afecto ni el número de repeticiones CTG y el resultado reproductivo de la técnica. De modo que, atendiendo a nuestros resultados, el Diagnóstico Genético Preimplantacional sería una buena aproximación reproductiva en casos de DM1 con una tasa de gestación de 53,8 % y de nacidos sanos de 38,5 %, independientemente del sexo del progenitor afecto y del número de repeticiones CTG

Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy in adults caused by the expansion of a CTG trinucleotide repeat in the DMPK gene (dystrophia myotonica-protein kinase gene) and its inheritance is autosomal dominant. So far, the technique of Preimplantation Genetic Diagnosis (PGD) seems to be the most effective reproductive approach for those couples in which one of their parents is affected by DM1. In this study, the Preimplantation Genetic Diagnosis technique was evaluated according to the sex of the affected progenitor and the number of CTG repetitions and their influence on the reproductive result of itself. A total of 13 couples from the Preimplantation Genetic Diagnosis program of the Assisted Reproduction Unit of the Hospital Universitario i Politècnic La Fe were included in the study were included in the study. In 8 of them the affected parent is the woman, whereas the 5 remaining is the man who is the disease carrier. In all of them, all the steps of the program were followed. The embryos were analyzed by mTP-PCR and multiplex PCR. The variables effect was analyzed by bivariate analysis (T-test, Chi-square, linear regression and Anova test) and multivariate analysis using correlation analysis (Spearman's rho). The results obtained revealed a preferential transmission of the expanded alleles in DM1, regardless of the sex of the affected parent. In spite of, the results obtained do not show any statistically significant relation between the sex of the progenitor and the number of repetitions and the reproductive result of the technique. Thus, according to our results, Preimplantation Genetic Diagnosis would be a good reproductive approach in cases of DM1 with a gestation rate of 53.8% and healthy births of 38.5%, regardless of the sex of the affected parent and the number of CTG repetitions

Composite Lymphoma Containing Mantle Cell and Peripheral T-cell Lymphoma, Not Otherwise Specified: A Report of 2 Cases Treated With Up-front Autologous Stem Cell Transplantation.

We report 2 cases of composite lymphoma comprising mantle cell lymphoma and peripheral T-cell lymphoma, not otherwise specified, a rare association that has only been reported twice in the literature. In case 1, a 64-year-old woman presented with massive splenomegaly and lymphadenopathy. Immunohistochemical studies of the lymph node biopsy suggested the presence of 2 lymphomas, a predominant component of a peripheral T-cell lymphoma, not otherwise specified and an in situ mantle cell neoplasia. These suspicions were confirmed with polymerase chain reaction and fluorescence in situ hybridization studies. In case 2, a 45-year-old man presented with an enlarged right tonsil. Contrary to case 1, the biopsy suggested a predominant infiltration of a classical mantle cell lymphoma and an atypical proliferation of T cells. Biclonality was also confirmed with fluorescence in situ hybridization and molecular techniques. Both cases were treated with an up-front autologous stem cell transplantation after achieving first complete remission, and they remained free of disease for a long period of time.