An objective assessment in newly diagnosed multiple myeloma to avoid treatment complications and strengthen therapy adherence.

In heterogeneous multiple myeloma (MM) patients treatment decisions are challenging. The hypothesis was that adaptation of treatment intensity (dose reduction [DR] vs. none) according to an objective risk score (revised-myeloma comorbidity index [R-MCI]) rather than physician judgement alone may improve therapy efficacy and avoid toxicities. We performed this study in 250 consecutive MM patients who underwent a prospective fitness assessment at our center, after having received induction protocols based on physicians' judgement. DR, serious adverse events (SAE), response, progression-free survival (PFS) and overall survival (OS) were compared in fitness (fit, intermediate-fit, frail), age (<60, ≥70 years [y]) and therapy intensity subgroups at baseline and follow-up. Fit and <60 y patients were mostly treated with full intensity, whereas frail and ≥70 y patients usually received DR. Hematological and non-hematological SAE were more frequently seen in frail versus ≥70 y patients. Dose adaptations were mainly necessary in frail patients. OS and PFS were similar in fit and intermediate-fit but significantly worse in frail patients (P=0.0245/P<0.0001), whereas in age-based subgroups, OS and PFS differences did not reach significance (P=0.1362/P=0.0569). Non-hematological SAE were another negative predictor for impaired OS and PFS (P=0.0054/P=0.0021). In the follow-up performed at a median of 11 months after the first fitness assessment, the R-MCI improved or remained stable in 90% versus deteriorated in only 10% of patients. In conclusion, separation by R-MCI/frailty-defined subgroups was superior to age-based subgroups and can be used to improve tailored treatment. Fitter patients benefit from intensive therapies, whereas frail patients bear a need for initial DR.

Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals.

Gray matter pathology is increasingly recognized as an important feature of multiple sclerosis (MS), but the nature of the immune response that targets the gray matter is poorly understood. Starting with a proteomics approach, we identified contactin-2/transiently expressed axonal glycoprotein 1 (TAG-1) as a candidate autoantigen recognized by both autoantibodies and T helper (Th) 1/Th17 T cells in MS patients. Contactin-2 and its rat homologue, TAG-1, are expressed by various neuronal populations and sequestered in the juxtaparanodal domain of myelinated axons both at the axonal and myelin sides. The pathogenic significance of these autoimmune responses was then explored in experimental autoimmune encephalitis models in the rat. Adoptive transfer of TAG-1-specific T cells induced encephalitis characterized by a preferential inflammation of gray matter of the spinal cord and cortex. Cotransfer of TAG-1-specific T cells with a myelin oligodendrocyte glycoprotein-specific mAb generated focal perivascular demyelinating lesions in the cortex and extensive demyelination in spinal cord gray and white matter. This study identifies contactin-2 as an autoantigen targeted by T cells and autoantibodies in MS. Our findings suggest that a contactin-2-specific T-cell response contributes to the development of gray matter pathology.

Choosing the Right Therapy for Patients with Relapsed/Refractory Multiple Myeloma (RRMM) in Consideration of Patient-, Disease- and Treatment-Related Factors.

Treatment of relapsed/refractory multiple myeloma (RRMM) is more complex today due to the availability of novel therapeutic options, mostly applied as combination regimens. immunotherapy options have especially increased substantially, likewise the understanding that patient-, disease- and treatment-related factors should be considered at all stages of the disease. RRMM is based on definitions of the international myeloma working group (IMWG) and includes biochemical progression, such as paraprotein increase, or symptomatic relapse with CRAB criteria (hypercalcemia, renal impairment, anemia, bone lesions). When choosing RRMM-treatment, the biochemical markers for progression and severity of the disease, dynamic of disease relapse, type and number of prior therapy lines, including toxicity and underlying health status, need to be considered, and shared decision making should be pursued. Objectively characterizing health status via geriatric assessment (GA) at each multiple myeloma (MM) treatment decision point has been shown to be a better estimate than via age and comorbidities alone. The well-established national comprehensive cancer network, IMWG, European myeloma network and other national treatment algorithms consider these issues. Ideally, GA-based clinical trials should be supported in the future to choose wisely and efficaciously from available intervention and treatment options in often-older MM adults in order to further improve morbidity and mortality.

Consideraciones éticas en la preparación y mantenimiento de material clínico para su análisis por computadora / Ethical considerati ons concerning the preparati on and keping of clinical material for its computerized análisis

El proceso de preparación, análisis y mantenimiento del material clínico, utilizado para la investigación en Psicología Clínica, resulta especialmente vulnerable en relación a potenciales fallas de orden ético. Es necesario tener en cuenta cuáles son los riesgos asociados a la utilización de sistemas informáticos en cada una de las instancias propias de la investigación. La preparación del material clínico se asocia especialmente al cuidado de generar bases de datos en las cuales queden incluidos los permisos de uso de dicho material. Es necesario tener en cuenta los distintos actores del proceso clínico, comenzando por el paciente, el psicoterapeuta y la institución en la cual se lleva adelante dicho tratamiento. Cada uno de estos actores tiene intereses diferenciados que deben ser identificados y preservados por el investigador. Los sistemas informáticos de gestación y documentación del material deben tener en cuenta dicho proceso.De la misma forma los análisis del material no deben descuidar la preservación de la privacidad y características originales del mismo.Un enmascaramiento defectuoso, puede provocar serios inconvenientes para el investigador y aquellos a los cuales él debe preservar. El almacenamiento del material clínico resulta el punto más vulnerable del sistema, ya que oscila entre la perdida de material único e irrepetible y el riesgo de no contar con un contexto de cuidados adecuados para el mismo.Es importante que el investigador y el resto del sistema involucrado en el uso de material clínico para investigación cuenten con sistemas de evaluación y protección de los derechos de cada uno de los participantes.

The process of preparation, analysis, and keeping of clinical equipment used for research in Clinical Psychology is especially vulnerable to potential ethical liability. It’s necessary to consider the risks associated with the use of computers in each of theinstances of research. The preparation of clinical material is mostly associated with the concern to generatedatabases with authorizations incorporated for the use of such material. It’s necessary to take into account the different actors of the clinical process, starting with thepatient, the psychotherapist and the institution in which the treatment takes place. Each of these actors has distinctive interests that must be identified and preserved by the researcher. Computer systems of conception and documentation of the material must take into account that process. Likewise, the analyses of material shouldn´t overlook the preservation of privacy norits original features. A faulty facade can cause serious problems to the researcher and to those whom hemust preserve. Clinical material storage is the most vulnerable issue of the system since it ranges from the loss of unique and unrepeatable material to the risk of not counting on an appropriate satisfactory care context. It´s important that the researcher and the rest of the system involved in the use of clinical material for research have systems of evaluation and protection of the rightsof each of the participants.