Real-life outcomes in biotypes of psychotic disorders based on neurocognitive performance.

Aiming at discerning potential biotypes within the psychotic syndrome, we have recently reported the possible existence of two clusters or biotypes across schizophrenia and bipolar disorder characterized by their cognitive performance using the Brief Assessment of Cognition in Schizophrenia (BACS) instrument and validated with independent biological and clinical indexes (Fernández-Linsenbarth et al. in Schizophr Res 229:102-111, 2021). In this previous work, the group with larger cognitive deficits (N = 93, including 69 chronic schizophrenia, 17 first episodes (FE) of schizophrenia and 7 bipolar disorder patients) showed smaller thalamus and hippocampus volume and hyper-synchronic electroencephalogram than the group with milder deficits (N = 105, including 58 chronic schizophrenia, 25 FE and 22 bipolar disorder patients). We predicted that if these biotypes indeed corresponded to different cognitive and biological substrates, their adaptation to real life would be different. To this end, in the present work we have followed up the patients' population included in that work at 1st and 3rd years after the date of inclusion in the 2021 study and we report on the statistical comparisons of each clinical and real-life outcomes between them. The first cluster, with larger cognitive deficits and more severe biological alterations, showed during that period a decreased capacity for job tenure (1st and 3rd years), more admissions to a psychiatric ward (1st year) and a higher likelihood for quitting psychiatric follow-up (3rd year). Patients in the second cluster, with moderate cognitive deficits, were less compliant with prescribed treatment at the 3rd year. The differences in real-life outcomes may give additional external validity to that yielded by biological measurements to the described biotypes based on neurocognition.

Análisis descriptivo del suicidio en el bienio 2018-2019 en Valladolid (España) / Descriptive analysis of suicide in the 2018-2019 biennium in Valladolid (Spain)

Introducción: El suicidio y su prevención suponen un reto esencial en salud pública. Como primera causa externa de muerte en nuestro país, parece escapar a nuestra comprensión y control en vista de los numerosos estudios e intervenciones realizadas. Llevamos a cabo un estudio de los suicidios mortales estudiados por el Instituto de Medicina Legal y Ciencias Forenses de Valladolid durante el bienio 2018-2019. Material y métodos: Se recogieron todas las muertes por suicidio durante 2018-2019 y se cruzaron con los datos anonimizados del Servicio de Psiquiatría del Hospital Clínico Universitario de Valladolid en 2019. Resultados: La tasa de suicidios fue de 8,5/100.000 habitantes, 49 casos en 2018 y 44 en 2019, con una distribución de 3:1 para varones frente a mujeres, principalmente en el medio rural. La franja de edad con mayor incidencia fue la de 31-70 años. La ahorcadura en el medio rural y la precipitación en el urbano fueron los principales métodos. La comorbilidad psiquiátrica identificada más frecuente fueron los trastornos del estado de ánimo-afectivos (F30-39 CIE-10). Conclusiones: Las tasas de suicidio presentan un ligero descenso, mientras que el perfil de riesgo y las características del suicidio mortal se mantienen constantes en nuestro medio más de 20 años después, lo que indica una escasa eficacia de los esfuerzos preventivos realizados hasta ahora. La prevención efectiva del suicidio debe partir de la mejor identificación, prevención y tratamiento de los trastornos psiquiátricos, pudiendo resultar esencial la participación de los Institutos de Medicina Legal y Ciencias Forenses en programas poblacionales multinivel. (AU)

Introduction: Suicide and its prevention are a serious public health challenge. As the primary external cause of death in our country, it seems to be beyond our understanding and control in view of the numerous studies and interventions carried out. We conducted a study of suicide at the Valladolid Institute of Legal Medicine from 2018-2019. Material and methods: All deaths by suicide from 2018-2019 were collected and crossed with anonymized data of the Psychiatry Service of the University Clinical Hospital of Valladolid in 2019. Results: The suicide rate was 8.5/100,000 inhabitants, 49 cases in 2018 and 44 in 2019, with a 3:1 male to female ratio, mainly in rural areas. The age group with the highest incidence was 31-70 years. Hanging in rural areas and precipitation in urban areas were the main methods. Affective disorders (F30-39 ICD-10) were the most common identified psychiatric disorders. Conclusions: Suicide rates are slightly lower, while the risk profile and features of suicide remain constant in our environment more than 20 years later, indicating that preventive efforts carried out have not been completely successful. The effective prevention of suicide must start with better identification, prevention, and treatment of psychiatric disorders, but the contribution of the Institutes of Legal Medicine in the implementation of multilevel population programmes is also essential. (AU)

Outcomes and prognostic factors of adults with refractory or relapsed T-cell acute lymphoblastic leukemia included in measurable residual disease-oriented trials.

Despite high complete remission (CR) rates with frontline therapy, relapses are frequent in adults with T-cell acute lymphoblastic leukemia (T-ALL) with limited salvage options. We analyzed the outcomes and prognostic factors for CR to salvage therapy and overall survival (OS) of patients with R/R T-ALL included in two prospective measurable residual disease-oriented trials. Seventy-five patients (70 relapsed, 5 refractory) were identified. Relapses occurred in bone marrow, isolated or combined in 50 patients, and in the central nervous system (CNS; isolated or combined) in 20. Second CR was attained in 30/75 patients (40%). Treatment with FLAG-Ida and isolated CNS relapse were independently associated with a higher CR rate after first salvage therapy. The median OS was 6.2 (95% confidence interval [CI], 3.9-8.6) months, with a 4-year OS probability of 18% (95% CI, 9%-27%). No differences in survival were observed according to the treatment with hematopoietic stem cell transplantation in patients in CR after first salvage therapy. Multivariable analysis showed a ≥12-month interval between first CR and relapse, CR after first salvage therapy and isolated CNS relapse as favorable prognostic factors for OS with hazard ratios (HR) (95% CI) of 1.931 (1.109-3.362), 2.958 (1.640-5.334), and 2.976 (1.157-7.655), respectively. This study confirms the poor outcomes of adults with R/R T-ALL among whom FLAG-Ida was the best of the rescue therapies evaluated. Late relapse, CR after first rescue therapy and isolated CNS relapse showed prognostic impact on survival. More effective rescue therapies are needed in adults with R/R T-ALL.

Bone marrow VEGFC expression is associated with multilineage dysplasia and several prognostic markers in adult acute myeloid leukemia, but not with survival.

Vascular endothelial growth factor C (VEGFC) stimulates leukemia cell proliferation and survival, and promotes angiogenesis. We studied VEGFC expression in bone marrow samples from 353 adult acute myeloid leukemia (AML) patients and its relationship with several clinical, cytogenetic, and molecular variables. We also studied the expression of 84 genes involved in VEGF signaling in 24 patients. We found that VEGFC expression was higher in AML patients with myelodysplasia-related changes (AML-MRC) than in patients with non-AML-MRC. We also found an association between VEGFC expression and the patient cytogenetic risk group, with those with a worse prognosis having higher VEGFC expression levels. No correlation was observed between VEGFC expression and survival or complete remission. VEGFC expression strongly correlated with expression of the VEGF receptors FLT1, KDR, and NRP1. Thus, in this series, VEGFC expression was increased in AML-MRC and in subgroups with a poorer prognosis, but has no impact on survival.