Tomografía computarizada coronaria en urgencias: importancia de la experiencia del radiólogo / Coronary computed tomography in emergencies: the importance of the radiologist's experience

Introducción: La incorporación de la angiografía coronaria por tomografía computarizada (ACTC) a la atención sanitaria en las urgencias hospitalarias hace necesaria una adecuada capacitación para la interpretación de esta prueba de imagen. Esta capacitación puede afectar al grado de concordancia interobservador de los radiólogos que evalúan dichos estudios. Objetivo: Evaluar la concordancia interobservador en función de la experiencia en la interpretación de ACTC realizadas a pacientes que acuden a urgencias por dolor torácico agudo (DTA) con probabilidad baja-intermedia de síndrome coronario agudo (SCA). Materiales y método: Estudio de concordancia interobservador en la evaluación de ACTC realizadas en contexto urgente utilizando CAD-RADS como registro de resultados. Se crearon parejas de observadores entre un total de 8 evaluadores (4 staff y 4 en formación). Se estimó el grado de concordancia global y entre subgrupos de acuerdo con su experiencia mediante el coeficiente kappa. Resultados: La concordancia fue sustancial entre radiólogos experimentados y en formación (k= 0,627; IC95%: 0,436-0,826), así como para todas las parejas de evaluadores (k=0,661; IC95%: 0,506-0,823) para todas las categorías CAD-RADS en conjunto. El grado de acuerdo del grupo de radiólogos experimentados fue superior al de los radiólogos en formación en todos los análisis realizados. La concordancia fue excelente para CAD-RADS global (k= 0,950; IC95%: 0,896-1) y para CAD-RADS ≥ 4 (k = 1), observando un menor acuerdo para CAD-RADS ≥ 3 (k= 0,754; IC95%: 0,246-1,255). Los valores del personal en formación para estas categorías fueron k= 0,623, k= 0,596 y k= 0,473, respectivamente. Conclusión: La concordancia entre radiólogos staff en la evaluación de ACTC realizadas a pacientes en el contexto de urgencias es excelente. El grado de acuerdo es menor cuando el personal inexperto forma parte de las parejas analizadas...(AU)

Introduction: Incorporating coronary computed tomography angiography (CTA) in the hospital workup for suspected acute coronary syndrome requires appropriate skills for interpreting this imaging test. Radiologists’ skills can affect the interobserver agreement in evaluating these studies. Objective: To determine the interobserver agreement according to radiologists’ experience in the interpretation of coronary CTA studies done in patients who present at the emergency department with acute chest pain and low-to-intermediate probability of acute coronary syndrome. Materials and methods: We studied the interobserver agreement in the urgent evaluation of coronary CTA studies in which CAD-RADS was used to register the findings. We created pairs of observers among a total of 8 assessors (4 attending radiologists and 4 radiology residents). We used the kappa coefficient to estimate the overall concordance and the concordance between subgroups according to their experience. Results: The agreement was substantial between experienced radiologists and residents (k = 0.627; 95%CI: 0.436 – 0.826) as well as between all the pairs of observers (k=0.661; 95%CI: 0.506 – 0.823) for all the CAD-RADS together. The degree of agreement within the group of experienced radiologists was greater than that within the group of residents in all the analyses. The agreement was excellent for the overall CAD-RADS (k=0.950; 95% CI: 0.896 – 1) and for CAD-RADS ≥ 4 (k=1); the agreement was lower for CAD-RADS ≥ 3 (k = 0.754; 95% CI: 0.246 – 1.255). The agreement for the residents for these categories was k= 0.623, k=0.596, and k=0.473, respectively. Conclusion: The agreement among attending radiologists regarding the assessment of urgent coronary CTA studies is excellent. The agreement is lower when residents are paired with attending radiologists...(AU)

Coronary computed tomography in emergencies: The importance of the radiologist's experience.

INTRODUCTION: Incorporating coronary computed tomography angiography (CTA) in the hospital workup for suspected acute coronary syndrome requires appropriate skills for interpreting this imaging test. Radiologists' skills can affect the interobserver agreement in evaluating these studies. OBJECTIVE: To determine the interobserver agreement according to radiologists' experience in the interpretation of coronary CTA studies done in patients who present at the emergency department with acute chest pain and low-to-intermediate probability of acute coronary syndrome. MATERIALS AND METHODS: We studied the interobserver agreement in the urgent evaluation of coronary CTA studies in which CAD-RADS was used to register the findings. We created pairs of observers among a total of 8 assessors (4 attending radiologists and 4 radiology residents). We used the kappa coefficient to estimate the overall concordance and the concordance between subgroups according to their experience. RESULTS: The agreement was substantial between experienced radiologists and residents (k=0.627; 95%CI: 0.436-0.826) as well as between all the pairs of observers (k=0.661; 95%CI: 0.506-0.823) for all the CAD-RADS together. The degree of agreement within the group of experienced radiologists was greater than that within the group of residents in all the analyses. The agreement was excellent for the overall CAD-RADS (k=0.950; 95% CI: 0.896-1) and for CAD-RADS ≥ 4 (k=1); the agreement was lower for CAD-RADS ≥ 3 (k=0.754; 95% CI: 0.246-1.255). The agreement for the residents for these categories was k=0.623, k=0.596, and k=0.473, respectively. CONCLUSION: The agreement among attending radiologists regarding the assessment of urgent coronary CTA studies is excellent. The agreement is lower when residents are paired with attending radiologists. These findings should be taken into consideration when implementing coronary CTA in emergency departments and in the organisation of radiological staff for interpreting and reporting this imaging test.

Manejo de un brote de COVID-19 en un despliegue / Covid-19 outbreak management in a deployed setting

Antecedentes y objetivos: la pandemia por COVID-19 ha afectado a todos los ámbitos de la sociedad, las misiones internacionales no son una excepción. Con este trabajo pretendemos compartir nuestra experiencia con un brote de COVID-19 en zona de operaciones (ZO). Material y métodos: estudio observacional prospectivo del 23 de noviembre de 2021 al 22 de febrero de 2022. Las variables estudiadas fueron: sexo, edad, días desde la última dosis de vacuna, tipo de vacuna en primera y segunda dosis (Moderna, Pfizer o Astrazeneca), despliegue a zona de operaciones con una dosis o dos dosis, covid-19 previo a despliegue, covid-19 en despliegue, sintomatología (asintomático, anosmia, tos, fiebre, malestar general, cefalea, mucosidad) y voluntariedad para la vacunación en zona de operaciones. Resultados: un total de 188 (31,6% del contingente) resultaron positivos en el periodo estudiado, generando un total de 183 contactos estrechos. Del contingente, 23 (3,9%) fueron mujeres y 572 (96,1%) varones, con una media de edad de 32 años. El 64,4% fueron asintomáticos. Los síntomas presentados fueron: 10,9% anosmia, 35,9% tos, 9,4% mucosidad, 32,8% cefalea, 57,8% malestar general y 20,3% fiebre. Todos fueron casos leves. De los casos positivos, el 90% de los vacunados con una sola dosis fueron asintomáticos al diagnóstico versus un 64% de los vacunados con dos dosis (p = 0,01). Conclusiones: la experiencia con un brote de COVID-19 en zona de operaciones refleja la importancia de tomar medidas de prevención y control para el correcto desarrollo de la misión. Es fundamental el uso de mascarillas, así como intentar respetar la distancia social en las bases. El uso de test rápido de detección de antígeno como diagnóstico y cribado es una medida útil y asequible. Protocolos de cuarentena laxos permiten continuar con las operaciones sin aumentar en exceso el riesgo de infección. (AU)

Background and objectives: The COVID-19 pandemic has affected all areas of our society, and international missions are not an exception. With this study we intended to share our experience with an outbreak of COVID-19 in an area of operations. Material and methods: A prospective observational study was performed from 11/23/2021 - 02/22/2022. The variables studied were: sex, age, days since the last vaccine dose, type of vaccine in the first and second doses (Moderna, Pfizer or Astrazeneca), in-theatre deployment with one or two doses, covid-19 prior to deployment, covid-19 during deployment, symptomatology (asymptomatic, anosmia, cough, fever, malaise, headache, runny nose) and volunteering for vaccination in area of operations. Results: A total of 188 (32.1% of the contingent) were positive during the period studied, with 183 close contacts. Of the contingent, 23 (3.9%) were women and 572 (96.1%) men, with a mean age of 32 years. 64.4% were asymptomatic. The symptoms presented were: 10.9% anosmia, 35.9% cough, 9.4% runny nose, 32.8% headache, 57.8% malaise and 20.3% fever. They were all mild cases. Of the positive cases, 90% of those who were vaccinated with a single dose were asymptomatic at diagnosis versus 64% of those vaccinated with two doses (p = 0.01). Conclusions: Our experience with a COVID-19 outbreak during a mission reflects the importance of prevention and control measures for the correct development of the mission. Use of masks is essential, as well as trying to maintain social distancing in the bases. The use of rapid antigen test for diagnosis and screening is a useful and affordable tool. Lax quarantine protocols allow the correct development of the operations without an increase in the risk of infection. (AU)

Contamination of N-poor wastewater with emerging pollutants does not affect the performance of purple phototrophic bacteria and the subsequent resource recovery potential.

Propagation of emerging pollutants (EPs) in wastewater treatment plants has become a warning sign, especially for novel resource-recovery concepts. The fate of EPs on purple phototrophic bacteria (PPB)-based systems has not yet been determined. This work analyzes the performance of a photo-anaerobic membrane bioreactor treating a low-N wastewater contaminated with 25 EPs. The chemical oxygen demand (COD), N and P removal efficiencies were stable (76 ±â€¯8, 62 ±â€¯15 and 36 ±â€¯8 %, respectively) for EPs loading rate ranging from 50 to 200 ng L-1 d-1. The PPB community adapted to changes in both the EPs concentration and the organic loading rate (OLR) and maintained dominance with >85 % of total 16S gene copies. Indeed, an increment of the OLR caused an increase of the biomass growth and activity concomitantly with a higher EPs removal efficiency (30 ±â€¯13 vs 54 ±â€¯11 % removal for OLR of 307 ±â€¯4 and 590 ±â€¯8 mgCOD L-1 d-1, respectively). Biodegradation is the main mechanism of EPs removal due to low EPs accumulation on the biomass, the membrane or the reactor walls. Low EPs adsorption avoided biomass contamination, resulting in no effect on its biological methane potential. These results support the use of PPB technologies for resource recovery with low EPs contamination of the products.

[Meconium periorchitis prenatal diagnosis: review of the literature, about 3 cases]. / Periorquitis meconial diagnóstico prenatal: revisión de la literatura, a propósito de 3 casos.

OBJECTIVE: To assess the importance of prenatal ultrasound diagnosis of the fetus carrying meconium periorchitis and its predictive relevance for fetal monitoring and prognosis in the context of acute fetal intestinal disease. MATERIAL AND METHODS: Three male fetuses have been diagnosed of meconium periorchitis in our Unit of Fetal Medicine in the last 5 years. Their prenatal ultrasound diagnoses were: testicular tumor (n=1); Meconium periorchitis with acute fetal intestinal perforation (n=2). Gestational age at diagnosis was 33, 34 and 35 weeks. Ultrasound signs at diagnosis were: Increased size of scrotal zone, with hyperechogenic lesions inside and permanence of peritoneum-vaginal canal; at abdominal zone, echographic signs of intestinal disease with or without meconium peritonitis were found (hyperechogenic lesions, edema of intestinal loops and ascites). All three neonates were assessed postnatally by ultrasound and therapeutic indication. RESULTS: Fetal ultrasound findings influenced both evolution and termination of pregnancy. The diagnosis of meconium periorchitis was confirmed postnatally in all cases: in the 1st case, delivered at term, scrotal tumoral pathology was ruled out and did not require abdominal surgery; the other 2 patients were delivered at the same week of prenatal diagnosis and an inguinal-scrotal surgery with intestinal approach because of meconium peritonitis was performed. No patient underwent orchiectomy, maintaining the teste-epididymal binomial intact. CONCLUSION: Prenatal ultrasound diagnosis of meconium periorchitis requires a strict ultrasound follow-up of the fetus as it is a specific marker of intestinal perforation, which can lead to the termination of pregnancy and avoid appearance of complicated meconium peritonitis.

OBJETIVO: Evaluar la importancia del diagnóstico ecográfico prenatal del feto portador de periorquitis meconial y su relevancia predictiva del seguimiento y pronóstico fetal en el contexto de una enfermedad intestinal fetal aguda. MATERIAL Y METODOS: En los últimos 5 años en la Unidad de Medicina Fetal se han diagnosticado tres fetos varones de periorquitis meconial cuyos diagnósticos ecográficos prenatales fueron: tumor testicular (n=1); y periorquitis meconial con perforación intestinal aguda fetal (n=2). La edad gestacional al diagnóstico fue de 33, 34 y 35 semanas. Los signos ecográficos al diagnóstico fueron: a nivel escrotal, aumento del tamaño, lesiones hiperecogénicas y permanencia del conducto peritoneo-vaginal; a nivel abdominal pueden existir signos ecográficos de enfermedad intestinal con o sin peritonitis meconial (lesiones hiperecogénicas, edemas de asas y ascitis). Los tres neonatos fueron evaluados postnatalmente mediante ecografía comparativa de los hallazgos prenatales e indicación terapéutica. RESULTADOS: Los hallazgos ecográficos fetales influyeron en la evolución y finalización de la gestación. El diagnóstico de periorquitis meconial fue confirmado postnatalmente en los tres casos: en el 1er caso a término, se descartó patología tumoral escrotal y no requirió cirugía abdominal; en los otros dos pacientes se indicó finalizar la gestación tras el diagnóstico prenatal y se realizó cirugía inguino-escrotal y abordaje intestinal por la peritonitis meconial. CONCLUSION: El diagnóstico ecográfico prenatal de periorquitis meconial obliga a un seguimiento ecográfico estricto del feto al ser un marcador específico de perforación intestinal, que puede conllevar la finalización de la gestación y evitar la aparición de una peritonitis meconial complicada.

Periorquitis meconial diagnóstico prenatal: revisión de la literatura, a propósito de 3 casos / Meconium periorchitis prenatal diagnosis: review of the literature, about 3 cases

Objetivo: Evaluar la importancia del diagnóstico ecográfico prenatal del feto portador de periorquitis meconial y su relevancia predictiva del seguimiento y pronóstico fetal en el contexto de una enfermedad intestinal fetal aguda. Material y métodos: En los últimos 5 años en la Unidad de Medicina Fetal se han diagnosticado tres fetos varones de periorquitis meconial cuyos diagnósticos ecográficos prenatales fueron: tumor testicular (n=1); y periorquitis meconial con perforación intestinal aguda fetal (n=2). La edad gestacional al diagnóstico fue de 33, 34 y 35 semanas. Los signos ecográficos al diagnóstico fueron: a nivel escrotal, aumento del tamaño, lesiones hiperecogénicas y permanencia del conducto peritoneo-vaginal; a nivel abdominal pueden existir signos ecográficos de enfermedad intestinal con o sin peritonitis meconial (lesiones hiperecogénicas, edemas de asas y ascitis). Los tres neonatos fueron evaluados postnatalmente mediante ecografía comparativa de los hallazgos prenatales e indicación terapéutica. Resultados: Los hallazgos ecográficos fetales influyeron en la evolución y finalización de la gestación. El diagnóstico de periorquitis meconial fue confirmado postnatalmente en los tres casos: en el 1er caso a término, se descartó patología tumoral escrotal y no requirió cirugía abdominal; en los otros dos pacientes se indicó finalizar la gestación tras el diagnóstico prenatal y se realizó cirugía inguino-escrotal y abordaje intestinal por la peritonitis meconial. Conclusión: El diagnóstico ecográfico prenatal de periorquitis meconial obliga a un seguimiento ecográfico estricto del feto al ser un marcador específico de perforación intestinal, que puede conllevar la finalización de la gestación y evitar la aparición de una peritonitis meconial complicada

Objective: To assess the importance of prenatal ultrasound diagnosis of the fetus carrying meconium periorchitis and its predictive relevance for fetal monitoring and prognosis in the context of acute fetal intestinal disease. Material and methods: Three male fetuses have been diagnosed of meconium periorchitis in our Unit of Fetal Medicine in the last 5 years. Their prenatal ultrasound diagnoses were: testicular tumor (n=1); Meconium periorchitis with acute fetal intestinal perforation (n=2). Gestational age at diagnosis was 33, 34 and 35 weeks. Ultrasound signs at diagnosis were: Increased size of scrotal zone, with hyperechogenic lesions inside and permanence of peritoneum-vaginal canal; at abdominal zone, echographic signs of intestinal disease with or without meconium peritonitis were found (hyperechogenic lesions, edema of intestinal loops and ascites). All three neonates were assessed postnatally by ultrasound and therapeutic indication. Results: Fetal ultrasound findings influenced both evolution and termination of pregnancy. The diagnosis of meconium periorchitis was confirmed postnatally in all cases: in the 1st case, delivered at term, scrotal tumoral pathology was ruled out and did not require abdominal surgery; the other 2 patients were delivered at the same week of prenatal diagnosis and an inguinal-scrotal surgery with intestinal approach because of meconium peritonitis was performed. No patient underwent orchiectomy, maintaining the teste-epididymal binomial intact. Conclusion: Prenatal ultrasound diagnosis of meconium periorchitis requires a strict ultrasound follow-up of the fetus as it is a specific marker of intestinal perforation, which can lead to the termination of pregnancy and avoid appearance of complicated meconium peritonitis

Novel concept for visible and near infrared spectro-interferometry: laser-written layered arrayed waveguide gratings.

With the growing complexity of astronomical instruments devoted to interferometry, such as MATISSE (a 4 telescope beam combiner) or FIRST (a 9 sub-apertures beam combiner), and the rebirth of space projects such as LIFE (a mid-infrared interferometer), integrated optics devices can be an interesting and complementary approach for beam combination of a large number of apertures. Moreover, one of the approaches for beam combination is pairwise combination of the inputs (either from individual telescopes or from aperture masking on a single telescope), which scales as N(N-1)/2 for an N input system. Astrophotonics devices are attractive to reduce mass and system complexity, while achieving all the beam combination in a single chip, even for a high number of inputs. The aim of this work is to develop a compact photonic device for astronomical applications and demonstrate a proof-of-concept of a spectro-interferometer. In this paper ultrafast laser inscription is used to fabricate three arrayed waveguide gratings (AWGs) stacked vertically. This arrangement enables spectral dispersion and interferometry to be measured simultaneously. Individual AWGs were designed for operation at 633 nm, and demonstrated at 633nm and 830nm. A scan between 790 and 830nm was also achieved to study the wavelength behavior of the AWG. Using a segmented mirror, light at 633nm or 830nm was injected simultaneously into three AWGs layered 40 µm apart, showing analogous behavior for all three layers and no unexpected crosstalk. Finally the three outputs were vertically combined to obtain interference fringes, showing the feasibility of spectro-interferometry and opening the way for compact astrophotonic devices devoted to phase closure studies, used in astronomy to reduce the effect of atmospheric turbulence.

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.

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.

The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML.

Severe infections after single umbilical cord blood transplantation in adults with or without the co-infusion of CD34+ cells from a third-party donor: results of a multicenter study from the Grupo Español de Trasplante Hematopoyético (GETH).

BACKGROUND: Umbilical cord blood transplantation (CBT) is an established alternative source of stem cells in the setting of unrelated transplantation. When compared with other sources, single-unit CBT (sCBT) is associated with a delayed hematologic recovery, which may lead to a higher infection-related mortality (IRM). Co-infusion with the sCBT of CD34+ peripheral blood stem cells from a third-party donor (TPD) (sCBT + TPDCD34+) has been shown to markedly accelerate leukocyte recovery, potentially reducing the IRM. However, to our knowledge, no comparative studies have focused on severe infections and IRM with these 2 sCBT strategies. METHODS: A total of 148 consecutive sCBT (2000-2010, median follow-up 4.5 years) were included in a multicenter retrospective study to analyze the incidence and risk factors of IRM and severe viral and invasive fungal infections (IFIs). Neutrophil engraftment occurred in 90% of sCBT (n = 77) and 94% sCBT + TPDCD34+ (n = 71) recipients at a median of 23 and 12 days post transplantation, respectively (P < 0.01). RESULTS: The 4-year IRM was 24% and 20%, respectively (P = 0.7), with no differences at day +30 (5% and 4%, respectively) and day +100 (10% and 8%, respectively). In multivariate analysis early status of the underlying malignancy, cytomegalovirus (CMV)-seronegative recipient and high CD34+ cell content in the cord blood unit before cryostorage (≥1.4 × 10(5) /kg) were protective of IRM. Among the causes of IRM, bacterial infections and IFIs were more common in sCBT (15% vs. 4%), while CMV disease and parasitic infections were more common in the sCBT + TPDCD34+ cohort (5% vs. 16%). CONCLUSION: These data show that sCBT supported with TPDCD34(+) cells results in much shorter periods of post-transplant leukopenia, but the short- and long-term rates of IRM were comparable to those of sCBT, presumably because immune recovery is equally delayed in both graft types.

Fungal and viral infections after allogeneic hematopoietic transplantation from unrelated donors in adults: improving outcomes over time.

Umbilical cord blood (CB) is increasingly used as an alternative source of stem cells in adult unrelated transplantation. Although registry studies report similar overall outcomes in comparison with BM/PB, comparative studies focusing on severe infections and infection-RM (IRM) with a long follow-up are scarce. A total of 434 consecutive unrelated transplants (1997-2009) were retrospectively analyzed to compare overall outcomes, incidence and risk factors of severe viral and invasive fungal infections in CB (n=65) vs BM/PB recipients (n=369). The 5-year OS was 38 vs 43%, respectively (P=0.2). CB transplantation (CBT) was associated with a higher risk of invasive aspergillosis (100-days-cumulative incidence 16 vs 6%, P=0.04) and CMV infection without differences in RM. No statistically significant differences were found regarding NRM (NRM of 38% in CB vs 37% in BM/PB at 1 year) nor IRM (30% in CB vs 27% in BM/PB at 1 year). In the overall population, NRM and IRM improved in more recent years. In adults who receive a single CBT, the risk of severe infections is increased when compared with unrelated BM/PB recipients, but mortality from infections is similar, leading to similar NRM and survival.

MicroRNA expression at diagnosis adds relevant prognostic information to molecular categorization in patients with intermediate-risk cytogenetic acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease, and optimal treatment varies according to cytogenetic risk factors and molecular markers. Several studies have demonstrated the prognostic importance of microRNAs (miRNAs) in AML. Here we report a potential association between miRNA expression and clinical outcome in 238 intermediate-risk cytogenetic AML (IR-AML) patients from 16 institutions in the CETLAM cooperative group. We first profiled 670 miRNAs in a subset of 85 IR-AML patients from a single institution and identified 10 outcome-related miRNAs. We then validated these 10 miRNAs by individual assays in the total cohort and confirmed the prognostic impact of 4 miRNAs. High levels of miR-196b and miR-644 were independently associated with shorter overall survival, and low levels of miR-135a and miR-409-3p with a higher risk of relapse. Interestingly, miR-135a and miR-409-3p maintained their independent prognostic value within the unfavorable molecular subcategory (wild-type NPM1 and CEBPA and/or FLT3-ITD), and miR-644 retained its value within the favorable molecular subcategory. miR-409-3p, miR-135a, miR-196b and mir-644 arose as prognostic markers for IR-AML, both overall and within specific molecular subgroups.

Bone marrow WT1 levels at diagnosis, post-induction and post-intensification in adult de novo AML.

We retrospectively assessed whether normalized bone marrow WT1 levels could be used for risk stratification in a consecutive series of 584 acute myeloid leukemia (AML) patients. A cutoff value of 5065 copies at diagnosis identified two prognostic groups (overall survival (OS): 44 ± 3 vs 36 ± 3%, P=0.023; leukemia-free survival (LFS): 47 ± 3 vs 36 ± 4%, P=0.038; and cumulative incidence of relapse (CIR): 37 ± 3 vs 47 ± 4%, P=:0.043). Three groups were identified on the basis of WT1 levels post-induction: Group 0 (WT1 between 0 and 17.5 copies, 134 patients, OS: 59 ± 4%, LFS:59 ± 4% and CIR: 26 ± 4%); Group 1 (WT1 between 17.6 and 170.5 copies, 160 patients, OS: 48 ± 5%, LFS:41 ± 4% and CIR: 45 ± 4%); and Group 2 (WT1 >170.5 copies, 71 patients, OS: 23 ± 6%, LFS: 19 ± 7% and CIR: 68 ± 8%) (P<0.001). Post-intensification samples distinguished three groups: patients with WT1 >100 copies (47 patients, 16%); an intermediate group of patients with WT1 between 10 and 100 copies (148 patients, 52%); and a third group with WT1 <10 copies (92 patients, 32%). Outcomes differed significantly in terms of OS (30 ± 7%, 59 ± 4%, 72 ± 5%), LFS (24 ± 7%, 46 ± 4%, 65 ± 5%) and relapse probability (CIR 72 ± 7%, 45 ± 4%, 25 ± 5%), all P<0.001. WT1 levels in bone marrow assayed using the standardized ELN method provide relevant prognostic information in de novo AML.

Mortality risk factors in patients with zygomycosis: a retrospective and multicentre study of 25 cases

Objetivo Investigar los factores de riesgo de mortalidad en pacientes con zigomicosis. Pacientes & Métodos Revisión retrospectiva de pacientes diagnosticados de zigomicosis documentada en 17 centros en España, comparando los datos demográficos y los factores de riesgo entre los pacientes que sobrevivieron y aquellos que fallecieron. Resultados Se identificaron 25 pacientes con zigomicosis probada. El lugar primario de la infección fue rino-órbito-cerebral (28%) e infecciones diseminadas o cutáneas / de tejidos blandos en el 20% de los pacientes cada una. Once pacientes (44%) recibieron tratamiento antifúngico anticipado o empírico; de estos pacientes, cuatro de ellos recibieron anfotericina B liposomal, un paciente recibió anfotericina B complejo lipídico y 6 pacientes recibieron otros antifúngicos. La tasa de mortalidad global fue del 72%. En el análisis univariado, los factores asociados a un mayor riesgo de muerte fueron la presencia de enfermedad hematológica maligna (p=0,03), neutropenia (p=0,03) y monocitopenia (p=0,008).Conclusión Los datos de nuestro estudio concuerdan con los de trabajos previos que habían documentado una elevada tasa de mortalidad en pacientes con zigomicosis invasiva, especialmente en aquellos con enfermedad hematológica maligna subyacente, y la necesidad de instaurar rápidamente un tratamiento antifúngico eficaz (AU)

Aim: To investigate mortality risk factors in patients with zygomycosis. Patients and Methods: Retrospective case history review of patients diagnosed with proven zygomicosis in 17 centres in Spain. We compared demographics and risk factors in patients who survived, and in those who died. Results: We identified twenty-five patients with proven zygomycosis. The primary site of infection wasrhino-orbito-cerebral (28%) and disseminated (20%) or cutaneous/soft infections (20%) of the patients. Eleven patients (44%) received preemptive or empirical antifungal treatment; of these patients, 4 received liposomal amphotericin B, 1 received amphotericin B lipid complex, and 6 received other antifungals. The overall mortality rate was 72%. In the univariate analysis factors associated with an increased risk of death were the presence of a haematological malignancy (P = .03), neutropenia (P = .03) and monocytopenia (P = .008).Conclusion: Our study supports previous research that has documented a high mortality rate among patients with invasive zygomycosis, especially among those with an underlying haematological malignancy, and the need for a rapid initiation of an effective antifungal treatment (AU)

Mortality risk factors in patients with zygomycosis: a retrospective and multicentre study of 25 cases.

AIM: To investigate mortality risk factors in patients with zygomycosis. PATIENTS AND METHODS: Retrospective case history review of patients diagnosed with proven zygomicosis in 17 centres in Spain. We compared demographics and risk factors in patients who survived, and in those who died. RESULTS: We identified twenty-five patients with proven zygomycosis. The primary site of infection was rhino-orbito-cerebral (28%) and disseminated (20%) or cutaneous/soft infections (20%) of the patients. Eleven patients (44%) received preemptive or empirical antifungal treatment; of these patients, 4 received liposomal amphotericin B, 1 received amphotericin B lipid complex, and 6 received other antifungals. The overall mortality rate was 72%. In the univariate analysis factors associated with an increased risk of death were the presence of a haematological malignancy (P=.03), neutropenia (P=.03) and monocytopenia (P=.008). CONCLUSION: Our study supports previous research that has documented a high mortality rate among patients with invasive zygomycosis, especially among those with an underlying haematological malignancy, and the need for a rapid initiation of an effective antifungal treatment.

Effect of addition of rituximab to salvage chemotherapy on outcome of patients with diffuse large B-cell lymphoma relapsing after an autologous stem-cell transplantation.

BACKGROUND: We have investigated if rituximab-based salvage regimens improve response rates and survival of patients with diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: We have retrospectively analyzed 82 patients with DLBCL who received salvage therapy for relapse or progression after ASCT. Patients were divided into two groups, according to whether rituximab-based salvage regimens were given (n = 42, 'R-' group) or not (n = 40, 'R+' group) after ASCT. RESULTS: Patients in the R+ group had better complete remission (CR) (55% versus 21.4%, P = 0.006) and overall response (OR) (75% versus 40.4%, P = 0.001) rates, and better 3-year event-free survival (EFS) (37% versus 9%, P = 0.002) and overall survival (OS) (50% versus 20%, P = 0.005) than patients in the R- group. Patients retreated with rituximab had better CR (42.9% versus 21.4%, P = 0.032) and OR (66.7% versus 40.4%, P = 0.019) rates, and better OS (36.2% versus 20% at 3 years, P = 0.05) and EFS (36.2% versus 9% at 3 years, P = 0.05) than patients who received chemotherapy alone at relapse after ASCT. CONCLUSIONS: The addition of rituximab to salvage chemotherapy improves response rates and EFS in patients with relapsed DLBCL after ASCT. These patients may benefit from rituximab retreatment, although larger prospective studies are needed to confirm these results.

CTLA-4 genotype and relapse incidence in patients with acute myeloid leukemia in first complete remission after induction chemotherapy.

The recently described single-nucleotide polymorphism CT60, located in the 3'-untranslated region of the CTLA4 (cytotoxic T-lymphocyte antigen 4 ) gene, has been associated with susceptibility to several autoimmune diseases and has also been shown to be involved in immune responses following allogeneic stem cell transplantation (SCT). However, the contribution of the CTLA4 genotype to the control of minimal residual disease in patients with acute myeloid leukemia (AML) has yet to be explored. We investigated the association between the CTLA4 CT60 A/G genotype and the incidence of leukemic relapse in 143 adult patients with AML in first complete remission after the same chemotherapy protocol (CETLAM LAM'03). The CT60 AA genotype was associated with a higher rate of leukemic relapse (56.4 vs 35.6%, P=0.004; hazard ratio (HR)=2.64, 95% confidence interval (CI)=1.36-5.14) and lower overall survival at 3 years (39.4 vs 68.4%, P=0.004; HR=2.80, 95% CI=1.39-5.64). This is the first study to report an association between polymorphisms at CTLA-4 and AML relapse.