RESUMEN
Immunoparesis (IP) in multiple myeloma (MM) patients can be measured by classic assessment of immunoglobulin (Ig) levels or by analysis of the uninvolved heavy/light chain pair of the same immunoglobulin (uHLC) by the Hevylite® assay. In this study we evaluate the prognostic value of recovery from IP measured by classic total Ig and uHLC assessment in newly diagnosed MM transplant-eligible (NDMM-TE) patients with intensive treatment and its association with Minimal Residual Disease (MRD). Patients were enrolled and treated in the PETHEMA/GEM2012MENOS65 trial and continued in the PETHEMA/GEM2014MAIN trial. Total Ig (IgG, IgA and IgM) and uHLC were analyzed in a central laboratory at diagnosis, after consolidation treatment and after the first year of maintenance. MRD was analyzed by next generation flow cytometry after consolidation (sensitivity level 2x10-6). We found no differences in progression free survival (PFS) between patients who recovered and patients who didn't recover from IP after consolidation when examining classic total Ig and uHLC. However, after the first year of maintenance, in contrast to patients with classic IP, patients with recovery from uHLC IP had longer PFS than patients without recovery, with hazard ratio of 0.42 (CI95% 0.21-0.81; p=0.008). Multivariate analysis with Cox proportional-hazards regression models confirmed recovery from uHLC IP after the first year of maintenance as an independent prognostic factor for PFS, with an increase in C-statistic of 0.05 (-0.04-0.14; p<0.001) when adding uHLC IP recovery. Moreover, we observed that MRD status and uHLC IP recovery affords complementary information for risk stratification. In conclusion, recovery from uHLC IP after one year of maintenance is an independent prognostic factor for PFS in NDMM-TE patients who receive intensive treatment. Immune reconstitution, measured as recovery from uHLC IP, provides complementary prognostic information to MRD assessment.
RESUMEN
There is substantial evidence suggesting that individual variability in antipsychotic treatment response could be genetically determined. Variations in several serotonin transporter (5-HTT) gene polymorphisms have been associated with antipsychotic response among chronic patients with schizophrenia, although their implication in early response among first-episode patients remains unclear. Two polymorphisms in the 5-HTT gene (a 44 bp insertion/deletion in the promoter region and the functional polymorphism rs25531) were genotyped in a sample of 147 drug-naïve patients experiencing a first episode of a non-affective psychosis. Early (6 weeks) response to antipsychotic treatment with haloperidol, olanzapine or risperidone was assessed with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Positive Symptoms, and the Scale for the Assessment of Negative Symptoms. No clear association was found between the rs25531 variant and treatment response. However, significant associations were observed between 5-HTT-LPR variants and early negative symptom response among first-episode patients with psychosis. Our results suggest a minor contribution to antipsychotic drug response of genetic alterations in the 5-HTT gene.
Asunto(s)
Antipsicóticos/uso terapéutico , Polimorfismo Genético/genética , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Adolescente , Adulto , Escalas de Valoración Psiquiátrica Breve , Distribución de Chi-Cuadrado , Femenino , Genotipo , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas/efectos de los fármacos , Regiones Promotoras Genéticas/genética , Adulto JovenRESUMEN
BACKGROUND: bariatric surgery is widely employed nowadays. Nutritional complications following malabsorptive bariatric surgery are common. OBJECTIVES: to compare protein malnutrition incidence, the amount of protein intake and the influence of various risk factors in patients undergoing Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD). METHODS: retrospective study comparing the development of hypoalbuminemia in 92 patients undergoing BPD and 121 RYGB, before surgery and 3, 6, 12, 18 and 24 months after it. Protein intake was estimated by serum prealbumin. The influence of prior body mass index (BMI), age and sex was analyzed. RESULTS: hypoprealbuminemia was found in around 40% of patients 3 months after both procedures, decreasing to about 10% after 2 years of surgery. Hypoalbuminemia incidence was close to 20% in the first post-surgery year in BPD, persisting in 10-15% of cases thereafter. After RYGB, hypoalbuminemia incidence was lower (5-9% in all postoperative follow-up measurements). During the first year after surgery, hypoalbuminemia was more frequent after BPD than after RYGB (at the 3rd month (OR:3.9; p=0.006; 95%CI:1.5-10.4), 6th (OR:5.0; p=0.002; 95% CI:1.8-13.8), and at the 12th month (OR:4.4;p=0.007;95%;CI:1.5-12.8)), but not after the first year. A higher preoperative BMI favored it (OR: 1.03; p=0.046; 95% CI:1-1.06), as well as greater age during the first 6 months. CONCLUSION: Patients with BPD had a higher risk for hypoproteinemia than those undergoing RYGB, especially during the first year post-surgery. Higher preoperative BMI, and age (in the short-term period) could have a significant inverse relation to hypoproteinemia.
Introducción: la cirugía bariátrica es muy empleada actualmente y en las malabsortivas, las complicaciones nutricionales son habituales. Objetivos: comparar la incidencia de malnutrición proteica e ingesta estimada de proteínas en pacientes intervenidos de bypass gástrico en Y-de-Roux (BGYR) y derivación biliopancreática (DBP), y la influencia de algunos factores de riesgo. Métodos: estudio restrospectivo comparando el desarrollo de hipoalbuminemia en 92 pacientes intervenidos mediante DBP y 121 de DBP (prequirúrgico, a los 3, 6, 12, 18 y 24 meses postquirúrgicos). La ingesta proteica se estimó mediante prealbúmina. Se evaluó la influencia del índice de masa corporal (IMC) previo, la edad y el sexo. Resultados: se encontró hipoprealbuminemia en torno al 40% de los pacientes a los 3 meses tras ambas técnicas, disminuyendo hasta el 10% a los dos años. La incidencia de hipoalbuminemia fue cercana al 20% durante el primer año tras DBP, persistiendo posteriormente en un 10-15% de los casos. Tras el BGYR, dicha incidencia fue menor (5-9% en todos los momentos). Así, durante el primer año postquirúrgico la hipoalbuminemia fue más frecuente tras DBP [3 meses: (OR:3,9;p = 0,006; 95%CI:1,5- 10,4), 6 meses (OR:5,0; p = 0,002; 95% CI:1,8-13,8), y al año (OR:4,4;p = 0,007;95%;CI:1,5-12,8)], pero no así después. Un mayor IMC prequirúrgico favoreció la inicidencia de hipoalbuminemia (OR:1,03; p = 0,046; 95% CI:1-1,06), así como una mayor edad a los 6 meses postquiúrgicos. Conclusión: los pacientes intervenidos mediante DBP tuvieron mayor riesgo de presentar hipoproteinemia que tras BGYR, especialmente durante el primer año postquirúrgico. Un mayor IMC postquirúrgico y la edad (a los 6 meses) podrían favorecer la aparición de hipoproteinemia.
Asunto(s)
Desviación Biliopancreática , Derivación Gástrica , Hipoalbuminemia/epidemiología , Hipoalbuminemia/etiología , Adulto , Antropometría , Cirugía Bariátrica/efectos adversos , Desviación Biliopancreática/efectos adversos , Femenino , Derivación Gástrica/efectos adversos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Estudios Retrospectivos , Factores de Tiempo , Pérdida de PesoRESUMEN
Background: bariatric surgery is widely employed nowadays. Nutritional complications following malabsorptive bariatric surgery are common. Objectives: to compare protein malnutrition incidence, the amount of protein intake and the influence of various risk factors in patients undergoing Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD). Methods: retrospective study comparing the development of hypoalbuminemia in 92 patients undergoing BPD and 121 RYGB, before surgery and 3, 6, 12, 18 and 24 months after it. Protein intake was estimated by serum prealbumin. The influence of prior body mass index (BMI), age and sex was analyzed. Results: hypoprealbuminemia was found in around 40% of patients 3 months after both procedures, decreasing to about 10% after 2 years of surgery. Hypoalbuminemia incidence was close to 20% in the first post-surgery year in BPD, persisting in 10-15% of cases thereafter. After RYGB, hypoalbuminemia incidence was lower (5-9% in all postoperative follow-up measurements). During the first year after surgery, hypoalbuminemia was more frequent after BPD than after RYGB (at the 3rd month (OR:3.9; p=0.006; 95%CI:1.5-10.4), 6th (OR:5.0; p=0.002; 95% CI:1.8-13.8), and at the 12th month (OR:4.4;p=0.007;95%;CI:1.5-12.8)), but not after the first year. A higher preoperative BMI favored it (OR: 1.03; p=0.046; 95% CI:1-1.06), as well as greater age during the first 6 months. Conclusion: Patients with BPD had a higher risk for hypoproteinemia than those undergoing RYGB, especially during the first year post-surgery. Higher preoperative BMI, and age (in the short-term period) could have a significant inverse relation to hypoproteinemia (AU)
Introducción: la cirugía bariátrica es muy empleada actualmente y en las malabsortivas, las complicaciones nutricionales son habituales. Objetivos: comparar la incidencia de malnutrición proteica e ingesta estimada de proteínas en pacientes intervenidos de bypass gástrico en Y-de-Roux (BGYR) y derivación biliopancreática (DBP), y la influencia de algunos factores de riesgo. Métodos: estudio restrospectivo comparando el desarrollo de hipoalbuminemia en 92 pacientes intervenidos mediante DBP y 121 de DBP (prequirúrgico, a los 3, 6, 12, 18 y 24 meses postquirúrgicos). La ingesta proteica se estimó mediante prealbúmina. Se evaluó la influencia del índice de masa corporal (IMC) previo, la edad y el sexo. Resultados: se encontró hipoprealbuminemia en torno al 40% de los pacientes a los 3 meses tras ambas técnicas, disminuyendo hasta el 10% a los dos años. La incidencia de hipoalbuminemia fue cercana al 20% durante el primer año tras DBP, persistiendo posteriormente en un 10-15% de los casos. Tras el BGYR, dicha incidencia fue menor (5-9% en todos los momentos). Así, durante el primer año postquirúrgico la hipoalbuminemia fue más frecuente tras DBP [3 meses: (OR:3,9;p=0,006; 95%CI:1,5- 10,4), 6 meses (OR:5,0; p=0,002; 95% CI:1,8-13,8), y al año (OR:4,4;p=0,007;95%;CI:1,5-12,8)], pero no así después. Un mayor IMC prequirúrgico favoreció la inicidencia de hipoalbuminemia (OR:1,03; p=0,046; 95% CI:1-1,06), así como una mayor edad a los 6 meses postquirúrgicos. Conclusión: los pacientes intervenidos mediante DBP tuvieron mayor riesgo de presentar hipoproteinemia que tras BGYR, especialmente durante el primer año postquirúrgico. Un mayor IMC postquirúrgico y la edad (a los 6 meses) podrían favorecer la aparición de hipoproteinemia (AU)