A research center's experience of T-cell-redirecting therapies in triple-class refractory multiple myeloma.

ABSTRACT: The efficacies of chimeric antigen receptor T cells (CAR-Ts) and bispecific monoclonal antibodies (BiAbs) for triple-class refractory (TCR) myeloma have not previously been compared, and clinical data on how to rescue patients after relapse from these immunotherapies are limited. A retrospective study of 73 TCR patients included in trials was conducted: 36 received CAR-Ts and 37 received BiAbs. CAR-Ts produced a higher overall response rate (ORR) than BiAbs (97.1% vs 56.8%, P = .002). After a median of follow-up of 18.7 months, no significant difference in progression-free survival (PFS) was observed between the CAR-T and BiAbs groups (16.6 vs 10.8 months; P = .090), whereas overall survival (OS) was significantly longer in the CAR-T than in the BiAbs group (49.2 vs 22.6 months; P = .021). BiAbs after CAR-Ts yielded a higher ORR and longer PFS2 than did nonredirecting T-cell therapies after CAR-Ts (ORR: 87.5% vs 50.0%; PFS2: 22.9 vs 12.4 months). By contrast, BiAbs after BiAbs resulted in an ORR of 33% and PFS2 of 8.4 months, which was similar to that produced by the nonredirecting T-cell therapies (ORR: 28.6%; PFS2: 8.1 months). Although this is a pooled analysis of different trials with different products and the patient profile is different for CAR-Ts and BiAbs, both were effective therapies for TCR myeloma. However, in our experience, although the PFS was similar with the 2 approaches, CAR-T therapy resulted in better OS, mainly because of the efficacy of BiAbs as rescue therapy. Our results highlight the importance of treatment sequence in real-word experience.

Treatment of post-allogeneic hematopoietic stem cell transplant cytopenias with sequential doses of multipotent mesenchymal stromal/stem cells.

BACKGROUND AIMS: Cytopenias after allogeneic stem cell transplantation (allo-SCT) are a common complication, the underlying pathogenic mechanisms of which remain incompletely understood. Multipotent mesenchymal stromal/stem cell (MSC) therapy has been successfully employed in the treatment of immune-related disorders and can aid in the restoration of the hematopoietic niche. METHODS: A phase II clinical trial to assess the efficacy and safety of administering four sequential doses of ex-vivo expanded bone marrow MSCs from a third-party donor to patients with persistent severe cytopenias after allo-SCT was performed. RESULTS: The overall response rate on day 90 was 75% among the 27 evaluable patients (comprising 12 complete responses, 8 partial responses, and 7 with no response). The median time to respond was 14.5 days. Responses were observed across different profiles, including single or multiple affected lineages, primary or secondary timing, and potential immune-mediated or post-infectious pathophysiology versus idiopathic origin. With a median follow-up for surviving patients of 85 months after MSC infusion, 53% of patients are alive. Notably, no adverse events related to MSC therapy were reported. CONCLUSIONS: In summary, the sequential infusion of third-party MSCs emerges as a viable and safe therapeutic option, exhibiting potential benefits for patients experiencing cytopenias following allo-SCT.

Feasibility and acceptability of a virtual mindfulness intervention for Black adults with PTSD and depression: Randomized controlled trial.

Mindfulness-based cognitive therapy (MBCT) offers promise as a group-based intervention to alleviate posttraumatic stress disorder (PTSD) and depression symptoms in traumatized Black adults. Given the high level of barriers that exist for low-income Black adults, virtual delivery of MBCT may be helpful. This pilot randomized controlled trial assessed feasibility and acceptability of an adapted 8-week virtual MBCT group intervention for Black adults screening positive for PTSD and depression. Forty-six participants (89.3% women) recruited from an urban safety net hospital were randomized to MBCT or waitlist control (WLC). Overall feasibility was fair (70%); however, completion rates were higher for WLC than MBCT (90% vs. 54%). Group acceptability was high across quantitative and qualitative measures for study completers. Perceived barriers to psychological treatment were high (>9). While showing potential via improved coping skills and positive health changes, this intervention's success hinges on mitigating engagement barriers for future delivery; additional studies are warranted.

Ofatumumab as part of reduced intensity conditioning in high risk B-cell lymphoma patients: final long-term analysis from a prospective multicenter Phase-II Trial.

Curative potential of allogeneic transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (NHL) could be enhanced by the integration of Ofatumumab (OFA), a 2nd generation anti-CD20 moAb, due to an antitumor effect and a role over graft-versus-host disease (GVHD). In this phase II trial (NCT01613300), we investigated safety and effectiveness of OFA-based reduced intensity conditioning (RIC). High-risk B-cell NHL patients with chemorrefractory disease or post-autologous SCT relapse were eligible. OFA was added to a standard RIC regimen. Primary endpoint was grade 3-4 aGVHD rate, while secondary endpoints included CR and survival rates. Thirty-three patients were included (median age 51; diffuse large B-cell:68%, HLA-identical donor: 74%). No grade >2 OFA toxicity was observed. Acute GVHD affected 77% of patients (16% grade 3-4). Remarkably, GVHD achieved CR in 75% of patients after first-line treatment. Chronic GVHD, primarily mild or moderate, occurred in 54% of patients. NHL CR rate at day +100 was 81%. Relapses occurred in 7 patients after a median of 3 months. Causes of death were lymphoma progression (5), infections (10), and GVHD (2). At 24 months, progression-free and overall survival rates were 50.1 and 51.6% respectively. OFA-RIC regimen is safe and effective, though acute GVHD remains a significant complication. However, data suggest that OFA could mitigate its severity.

Intermediate Molecular Phenotypes to Identify Genetic Markers of Anthracycline-Induced Cardiotoxicity Risk.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.

Prognostic Value of Measurable Residual Disease in Patients with AML Undergoing HSCT: A Multicenter Study.

Allogeneic hematopoietic stem cell transplantation (HSCT) represents the best therapeutic option for many patients with acute myeloid leukemia (AML). However, relapse remains the main cause of mortality after transplantation. The detection of measurable residual disease (MRD) by multiparameter flow cytometry (MFC) in AML, before and after HSCT, has been described as a powerful predictor of outcome. Nevertheless, multicenter and standardized studies are lacking. A retrospective analysis was performed, including 295 AML patients undergoing HSCT in 4 centers that worked according to recommendations from the Euroflow consortium. Among patients in complete remission (CR), MRD levels prior to transplantation significantly influenced outcomes, with overall (OS) and leukemia free survival (LFS) at 2 years of 76.7% and 67.6% for MRD-negative patients, 68.5% and 49.7% for MRD-low patients (MRD < 0.1), and 50.5% and 36.6% for MRD-high patients (MRD ≥ 0.1) (p < 0.001), respectively. MRD level did influence the outcome, irrespective of the conditioning regimen. In our patient cohort, positive MRD on day +100 after transplantation was associated with an extremely poor prognosis, with a cumulative incidence of relapse of 93.3%. In conclusion, our multicenter study confirms the prognostic value of MRD performed in accordance with standardized recommendations.

Opportunistic infections according to the CD4+ T lymphocyte count in patients with HIV at a tertiary care referral center

Opportunistic infections (OIs) have marked the prognosis in the natural course of patients with human immunodeficiency virus (HIV) infection. Objective: identifying the most common OIs and determining their relationship with the CD4+ lymphocyte count (CD4+TL) can improve our clinical practice and facilitate early diagnosis, the use of empiric treatments and prompt targeted treatment. Materials and methods: an observational, retrospective study aimed at describing the characteristics and variations of the OIs diagnosed clinically, using direct or indirect methods, which occur in patients with HIV (related to their CD4+TL count) who are admitted to a tertiary care center in Cali, Colombia. Adult patients hospitalized from January 2018 to January 2019 with a diagnosis of HIV/AIDS and a history or current diagnosis of OI were included. Individuals under the age of 18 and pregnant women were excluded. Results: a sample of 190 patients with at least one opportunistic infection was obtained, of whom 65.3% were men with a median age of 37 years (29.0-46.0), and the rest were women with a median age of 35.5 years (31.2-43.0). Eighty-three percent had a C3 classification on admission, 86% with a CD4+TL count < 200 cells/mm3. The most frequent OIs included tuberculosis, with 28.4%, pneumocystosis with 27.9% and toxoplasmosis with 27.4%. Conclusions: in our population, despite advances in and greater availability of highly-effective antiretroviral therapy, most patients with HIV are hospitalized in advanced stages with opportunistic infections, in some cases with two or more concomitant infections, and with evidence of severe virological and immunological involvement. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2327).

Intermediate molecular phenotypes to identify genetic markers of anthracycline-induced cardiotoxicity risk.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex disease whose polygenic component is mainly unidentified. We propose that levels of intermediate molecular phenotypes in the myocardium associated with histopathological damage could explain CDA susceptibility; so that variants of genes encoding these intermediate molecular phenotypes could identify patients susceptible to this complication. A genetically heterogeneous cohort of mice generated by backcrossing (N = 165) was treated with doxorubicin and docetaxel. Cardiac histopathological damage was measured by fibrosis and cardiomyocyte size by an Ariol slide scanner. We determine intramyocardial levels of intermediate molecular phenotypes of CDA associated with histopathological damage and quantitative trait loci (ipQTLs) linked to them. These ipQTLs seem to contribute to the missing heritability of CDA because they improve the heritability explained by QTL directly linked to CDA (cda-QTLs) through genetic models. Genes encoding these molecular subphenotypes were evaluated as genetic markers of CDA in three cancer patient cohorts (N = 517) whose cardiac damage was quantified by echocardiography or Cardiac Magnetic Resonance. Many SNPs associated with CDA were found using genetic models. LASSO multivariate regression identified two risk score models, one for pediatric cancer patients and the other for women with breast cancer. Molecular intermediate phenotypes associated with heart damage can identify genetic markers of CDA risk, thereby allowing a more personalized patient management. A similar strategy could be applied to identify genetic markers of other complex trait diseases.

Factors associated with self-medication of antibiotics by caregivers in pediatric patients attending the emergency department: a case-control study.

INTRODUCTION: Antibiotic self-medication is a common practice in pediatric caregivers in low-income countries with limited resources and represents a public health problem. Our study sought to determine what factors are associated with this practice, including differences in knowledge or attitudes of caregivers who attend a pediatric emergency service. METHODS: Case-control study based on surveys of caregivers of pediatric patients brought to the emergency room with clinical symptoms suggestive of acute infection. Cases were defined as those caregivers who reported self-medication of antibiotics for the current illness and controls where those who did not report self-medication. Information was collected through a self-administered questionnaire that inquired about demographic and family characteristics, attitudes and knowledge toward self-medication of antibiotics. Data were compared using logistic regression and are presented with odd ratios and confidence intervals. RESULTS: A total of 728 caregivers, 182 cases and 546 controls were included. We found that higher parental education, both in mothers (OR 0.56, 95% CI 0.40-0.79) and fathers (OR 0.62, 95% CI 0.43-0.89) was associated with less self-medication. Attitudes such as always requesting antibiotics from their doctors (OR 3.92, 95% CI 1.59-9.66), frequently buying antibiotics without a prescription (OR 23.66, 95% CI 11.76-47.59) and giving advice on antibiotics among family members (OR 2.90, 95% CI 1.75-4.82) resulted in an increased likelihood of self-medication. There was also a higher probability of antibiotic self-medication in older children (OR 1.13, 95% CI 1.09-1.17), those with a greater number of siblings (OR 1.25, 95% CI 1.09-1.43) and in those cases that received antibiotics within the last 3 months (OR 6.27, 95% CI 4.35-9.04). Overall knowledge of risk of antibiotic self-medication was low. CONCLUSIONS: Some patient and family characteristics such as age, number of siblings, recent antibiotic usage and inappropriate attitudes are strongly related to antibiotic self-medication. These findings will inform future interventions to reduce self-medication in children.

Graft versus host disease-related eosinophilic fasciitis: cohort description and literature review.

BACKGROUND: Chronic graft versus host disease (cGVHD) simulating eosinophilic fasciitis (EF) is an underdiagnosed and challenging complication due to the lack of knowledge about its pathogenesis, refractoriness to traditional immunosuppressive agents and their negative impact on the physical function and quality of life. The aim of this study is to describe the clinical-biological characteristics and response to treatment of a case series and to provide a comprehensive literature review on cGVHD related EF involvement. METHODS: Prospective observational study to describe the clinical and diagnostic evaluation characteristics of patients with EF-like follow-up as part of our multidisciplinary cGVHD consultations. In addition, the literature on joint and/or fascial musculoskeletal manifestations due to cGVHD was comprehensively reviewed. RESULTS: 118 patients were evaluated in multidisciplinary cGVHD consultations, 39 of whom (33%) developed fasciitis. Notably, 11 patients had isolated joint contractures without sclerotic skin. After a median of three lines of treatment, the vast majority of patients achieved some degree of response. 94 potentially eligible articles were identified by the search strategy, with 17 of them, the majority isolated case reports, making the final selection. The validated staging scales used for the assessment were the Joint and Fascial Score and the Photographic Range of Motion. CONCLUSION: Fascial/articular involvement needs to be recognized and evaluated early. To our knowledge, our cohort is the second largest series to have been reported. Literature addressing fascial/joints complications related to cGVHD is scarce. The search for new biomarkers, the use of advanced imaging techniques and multidisciplinary approach may help improve the prognosis of patients with cGVHD.

Alkane C-H activation and ligand exchange on silica supported d0 metal alkylidenes: relevance to alkane metathesis.

In this work, we study the ligand exchange process between an alkane and a series of silica supported metal alkylidenes, which may occur by different pathways: C-H addition, σ-bond metathesis, and α-H abstraction. The results indicate that the α-H abstraction pathway is the preferred one, regardless of the catalyst and ligands. This is in contrast to the expected preference for the C-H addition route. When looking for the origin of this preference, our calculations revealed that the α-H abstraction pathway is driven by entropy, which favors the initial dissociation of the alkyl ligand from the catalyst.

Graft versus host disease-related eosinophilic fasciitis: cohort description and literature review

Abstract Background: Chronic graft versus host disease (cGVHD) simulating eosinophilic fasciitis (EF) is an underdiagnosed and challenging complication due to the lack of knowledge about its pathogenesis, refractoriness to traditional immunosuppressive agents and their negative impact on the physical function and quality of life. The aim of this study is to describe the clinical-biological characteristics and response to treatment of a case series and to provide a comprehensive literature review on cGVHD related EF involvement. Methods: Prospective observational study to describe the clinical and diagnostic evaluation characteristics of patients with EF-like follow-up as part of our multidisciplinary cGVHD consultations. In addition, the literature on joint and/or fascial musculoskeletal manifestations due to cGVHD was comprehensively reviewed. Results: 118 patients were evaluated in multidisciplinary cGVHD consultations, 39 of whom (33%) developed fasciitis. Notably, 11 patients had isolated joint contractures without sclerotic skin. After a median of three lines of treatment, the vast majority of patients achieved some degree of response. 94 potentially eligible articles were identified by the search strategy, with 17 of them, the majority isolated case reports, making the final selection. The validated staging scales used for the assessment were the Joint and Fascial Score and the Photographic Range of Motion. Conclusion: Fascial/articular involvement needs to be recognized and evaluated early. To our knowledge, our cohort is the second largest series to have been reported. Literature addressing fascial/joints complications related to cGVHD is scarce. The search for new biomarkers, the use of advanced imaging techniques and multidisciplinary approach may help improve the prognosis of patients with cGVHD.

Treating Acute Leukemia During the COVID-19 Pandemic in an Environment With Limited Resources: A Multicenter Experience in Four Latin American Countries.

PURPOSE: The COVID-19 pandemic is a colossal challenge for global health; nonetheless, specific subgroups face considerably higher risks for infection and mortality. Among patients with malignant diseases, those with hematologic neoplasms are at a higher risk for poor outcomes. The objective of this study was to register treatment modifications associated with the COVID-19 pandemic and their short-term consequences in Latin America. METHODS: Multicenter, prospective, observational, cohort study including patients older than 14 years from 14 centers in four countries (Mexico, Peru, Guatemala, and Panama) who had a confirmed diagnosis of acute leukemia, and who were undergoing active treatment since the first COVID-19 case in each country until the cutoff on July 15, 2020. RESULTS: We recruited 635 patients. Treatment modifications because of the COVID-19 pandemic were reported in 40.8% of cases. The main reason for such modifications was logistic issues (55.0%) and the most frequent modification was chemotherapy delay (42.0%). A total of 13.1% patients developed COVID-19 disease, with a mortality of 37.7%. Several factors were identified as independently associated with mortality, including a diagnosis of acute myeloid leukemia (odds ratio 2.38 [95% CI, 1.47 to 3.84]; P < .001), while the use of telemedicine was identified as a protective factor (odds ratio 0.36 [95% CI, 0.18 to 0.82]; P = .014). CONCLUSION: These results highlight the collateral damage of COVID-19 in oncology patients.

Relationship between School Integration, Psychosocial Adjustment and Cyber-Aggression among Adolescents.

The aim of this study was to analyze the relationships between sociometric types in the classroom-rejected, preferred, neglected, controversial and average-and psychological discomfort, life satisfaction and cyber-aggression, based on the adolescent's gender. 2398 adolescents of both sexes participated in the study (49.8% girls), aged between 12 and 18 years (M = 16.03, SD = 1.91). Multivariate analyses of variance were performed. The results showed significant relationships between sociometric types, life satisfaction and cyber-aggression. Rejected adolescents also showed less satisfaction with life and greater cyber-aggression. Furthermore, the boys, regardless of their sociometric type in the classroom, displayed less psychological distress and less involvement in cyber-aggression. Controversial adolescents also showed greater involvement in cyber-aggression. Finally, programs should be promoted for the prevention of social difficulties in the school, based on the promotion of social integration, not only in the classroom, but also on the Internet.

Histoplasmosis diseminada asociada a síndrome de reconstitución inmune en un paciente con virus de la inmunodeficiencia humana / Disseminated histoplasmosis associated to immune reconstitution syndrome in a patient with human immunodeficiency virus

Introducción: La histoplasmosis es una micosis profunda o sistémica causada por un hongo dimórfico que se puede diseminar principalmente en pacientes con inmunosupresión, como los que tienen diagnóstico de virus de la inmunodeficiencia humana. El síndrome de reconstitución inmune consiste en un empeoramiento paradójico de una condición conocida o de nueva aparición después del inicio de la terapia antirretroviral. Objetivo: Describir un caso de histoplasmosis diseminada asociada a síndrome de reconstitución inmune en un paciente con infección por virus de la inmunodeficiencia humana. Caso clínico: Paciente masculino de 32 años con diagnóstico de infección por virus de la inmunodeficiencia humana, con cuadro clínico de tres semanas de evolución. Este cuadro inició posterior al comienzo de la terapia antirretroviral, que consistió en pápulo-nódulos umbilicados diseminados, con compromiso pulmonar; además, tenía histopatología y cultivo positivos para Histoplasma capsulatum sl. y prueba de antigenuria para histoplasma también positiva. Se consideró un diagnóstico de histoplasmosis diseminada con presentación cutánea, fue la expresión de un síndrome de reconstitución inmune por desenmascaramiento. Se inició manejo con anfotericina B liposomal y se mantuvo la terapia antirretroviral; posteriormente se continuó el tratamiento con itraconazol durante 12 meses con mejoría de las lesiones. Conclusiones: El diagnóstico clínico, histopatológico y microbiológico fue oportuno; el paciente presentó una adecuada respuesta al tratamiento. Esta es una micosis curable e incluso prevenible, si se diagnostica a tiempo, se inicia tratamiento precoz y se mantiene la terapia retroviral(AU)

Introduction: Histoplasmosis is a deep or systemic mycosis caused by a dimorphic fungus which may disseminate mainly in immunocompromised patients, such as those diagnosed with human immunodeficiency virus. Immune reconstitution syndrome is a paradoxical worsening of a known condition or a condition appearing after the start of antiretroviral therapy. Objective: Describe a case of disseminated histoplasmosis associated to immune reconstitution syndrome in a patient with human immunodeficiency virus infection. Case report: A case is presented of a male 32-year-old patient diagnosed with human immunodeficiency virus with a clinical status of three weeks' evolution. The current status developed after the start of antiretroviral therapy. It consisted in disseminated umbilicated papular nodules with pulmonary involvement, as well as positive Histoplasma capsulatum sl. histopathology and culture, and a positive histoplasma antigen test. A diagnosis of disseminated histoplasmosis with a cutaneous presentation was considered. It was the expression of immune reconstitution syndrome by unmasking. Treatment was started with liposomal amphotericin B, maintaining the antiretroviral therapy. Management was then continued with itraconazole for 12 months with improvement of the lesions. Conclusions: Timely clinical, histopathological and microbiological diagnosis was performed. The patient displayed an adequate response to treatment. This mycosis is curable and even preventable when a diagnosis is made in time, treatment is started early and the retroviral therapy is maintained(AU)

Chaski, a novel Drosophila lactate/pyruvate transporter required in glia cells for survival under nutritional stress.

The intercellular transport of lactate is crucial for the astrocyte-to-neuron lactate shuttle (ANLS), a model of brain energetics according to which neurons are fueled by astrocytic lactate. In this study we show that the Drosophila chaski gene encodes a monocarboxylate transporter protein (MCT/SLC16A) which functions as a lactate/pyruvate transporter, as demonstrated by heterologous expression in mammalian cell culture using a genetically encoded FRET nanosensor. chaski expression is prominent in the Drosophila central nervous system and it is particularly enriched in glia over neurons. chaski mutants exhibit defects in a high energy demanding process such as synaptic transmission, as well as in locomotion and survival under nutritional stress. Remarkably, locomotion and survival under nutritional stress defects are restored by chaski expression in glia cells. Our findings are consistent with a major role for intercellular lactate shuttling in the brain metabolism of Drosophila.

Frecuencia de tendencias suicidas (suicidalidad) y factores asociados en mujeres durante el primer año posparto / Frequency of suicidality and associated factors in women during the first postpartum year

Objetivos: Estimar la frecuencia de tendencias suicidas (suicidalidad) y explorar su relación con diversas variables en mujeres atendidas en un hospital público peruano durante el primer año del periodo posparto. Material y Métodos: Se realizó un análisis secundario de datos de un trabajo de investigación realizado en el Hospital Cayetano Heredia (Lima, Perú) que incluía 321 mujeres durante el primer año posparto, con registros de variables sociodemográficas, ginecológicas, clínico-psiquiátricas y de suicidalidad definida como la presencia del síntoma 9 del criterio A de Episodio Depresivo Mayor evaluado mediante la Entrevista Clínica Estructurada para el DSM-IV (Structured Clinical Interview for DSM-IV Disorders, SCID). Resultados: Se encontró una frecuencia de 15,58 % (IC 95%: 11,79-20,01%) de suicidalidad en mujeres durante el primer año posparto. El análisis bivariado mostró relación significativa entre la presencia de suicidalidad y depresión mayor (OR = 14,52; p <0,001), trastorno obsesivo-compulsivo (OR = 3,96; p= 0,001), trastorno disfórico premenstrual (OR=3,25; p=0,002) y episodio maniaco o hipomaniaco previo (OR=2,12; p=0,025). Asimismo, el análisis multivariado encontró relación significativa con status de separada/divorciada (OR = 6,96; p = 0,027), abortos previos (OR = 2,92; p = 0,006), sueño menor de 6 horas (OR=5,34; p=0,003) y lactancia materna (OR=0,15; p=0,004). Conclusiones: Las tendencias suicidas en mujeres con menos de un año posparto fueron detectadas en 15,58% de la muestra y se relacionaron con una serie de variables de diversa índole, las cuales deben ser tenidas en cuenta para eventuales intervenciones preventivas y/o de atención clínica focalizada.

Objectives: To estimate the frequency of suicidality and to explore its relation with different variables in women seen in a Peruvian public hospital during their first year of their postpartum period. Material and Methods: A secondary data analysis of a research study carried out in the Hospital Cayetano Heredia (Lima, Peru) was conducted on 321 women seen during their first postpartum year, with focus on sociodemographic, psychiatric, gynecological and suicidality variables. Suicidality was defined as the presence of symptom 9 of criterion A of a Major Depressive Episode assessed through the Structured Clinical Interview for DSM-IV Disorders (SCID). Results: Suicidality was found in 15.58% (95% CI: 11.79-20.01%) of the sample. Bivariate analyses showed a significant relationship between suicidality and major depression (OR = 14.52, p <0.001), obsessive-compulsive disorder (OR = 3.96, p = 0.001), premenstrual dysphoric disorder (OR=3.25, p = 0.002) and previous manic or hypomanic episode (OR = 2.12, p = 0.025). In addition, multivariate analysis found a significant relationship with being separated / divorced (OR = 6.96, p = 0.027), previous abortions (OR = 2.92, p = 0.006), sleep of less than 6 hours (5.34, p = 0.003) and breastfeeding (OR = 0.15, p = 0.004). Conclusions: The suicidality in women with less than one year postpartum had a frequency of 15.58% and was related to a series of variables to be taken into account for eventual preventive and/or focused clinical interventions.

Phase II Study of Yttrium-90-Ibritumomab Tiuxetan as Part of Reduced-Intensity Conditioning (with Melphalan, Fludarabine ± Thiotepa) for Allogeneic Transplantation in Relapsed or Refractory Aggressive B Cell Lymphoma: A GELTAMO Trial.

We designed a phase II clinical trial including Y-90 ibritumomab-tiuxetan as part of a reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (Clinical Trials Identifier: NCT00644371). Eligible patients had high-risk relapsed/refractory aggressive lymphoma. The conditioning regimen consisted of rituximab 250 mg (days -21 and -14), Y-90 ibritumomab IV (.4 m Ci/kg, day -14), fludarabine 30 mg/m2 i.v. (days -3 and -2) plus melphalan 70 mg/m2 i.v. (days -3 and -2) or 1 dose of melphalan and thiotepa 5 mg/kg (day -8). Donors were related. Eighteen patients were evaluable. At the time of transplantation, responses were complete remission (CR) (n = 7, 39%), partial remission (n = 6, 33%) or refractory disease (n = 4, 28%). Y-90-ibritumomab infusions were well tolerated, with no adverse reactions. Nonrelapse mortality at 1 year was 28%. Median follow-up was 46 (range, 39 to 55) months. Estimated 1-year progression-free survival (PFS) was 50%, and 4-year overall survival (OS) and PFS were both 44.4%. CR at the moment of AlloSCT had significant impact on PFS (71% versus 27%, P = .046) and OS (71% versus 27%, P = .047). Our results show that Y-90-ibritumomab-tiuxetan as a component of RIC for AlloSCT is feasible in patients with high-risk B cell lymphoma. Development of phase III clinical trials is needed to clarify the contribution of radioimmunotherapy to RIC AlloSCT.

Presynaptic DLG regulates synaptic function through the localization of voltage-activated Ca(2+) Channels.

The DLG-MAGUK subfamily of proteins plays a role on the recycling and clustering of glutamate receptors (GLUR) at the postsynaptic density. discs-large1 (dlg) is the only DLG-MAGUK gene in Drosophila and originates two main products, DLGA and DLGS97 which differ by the presence of an L27 domain. Combining electrophysiology, immunostaining and genetic manipulation at the pre and postsynaptic compartments we study the DLG contribution to the basal synaptic-function at the Drosophila larval neuromuscular junction. Our results reveal a specific function of DLGS97 in the regulation of the size of GLUR fields and their subunit composition. Strikingly the absence of any of DLG proteins at the presynaptic terminal disrupts the clustering and localization of the calcium channel DmCa1A subunit (Cacophony), decreases the action potential-evoked release probability and alters short-term plasticity. Our results show for the first time a crucial role of DLG proteins in the presynaptic function in vivo.