Recommendations for the study of monoclonal gammopathies in the clinical laboratory. A consensus of the Spanish Society of Laboratory Medicine and the Spanish Society of Hematology and Hemotherapy. Part I: Update on laboratory tests for the study of monoclonal gammopathies.

Monoclonal gammopathies (MG) are characterized by the proliferation of plasma cells that produce identical abnormal immunoglobulins (intact or some of their subunits). This abnormal immunoglobulin component is called monoclonal protein (M-protein), and is considered a biomarker of proliferative activity. The identification, characterization and measurement of M-protein is essential for the management of MG. We conducted a systematic review of the different tests and measurement methods used in the clinical laboratory for the study of M-protein in serum and urine, the biochemistry and hematology tests necessary for clinical evaluation, and studies in bone marrow, peripheral blood and other tissues. This review included literature published between 2009 and 2022. The paper discusses the main methodological characteristics and limitations, as well as the purpose and clinical value of the different tests used in the diagnosis, prognosis, monitoring and assessment of treatment response in MG. Included are methods for the study of M-protein, namely electrophoresis, measurement of immunoglobulin levels, serum free light chains, immunoglobulin heavy chain/light chain pairs, and mass spectrometry, and for the bone marrow examination, morphological analysis, cytogenetics, molecular techniques, and multiparameter flow cytometry.

Prepubertal children with a history of extra-uterine growth restriction exhibit low-grade inflammation.

Intra-uterine growth restriction (IUGR) may induce significant metabolic and inflammatory anomalies, increasing the risk of obesity and CVD later in life. Similarly, alterations in the adipose tissue may lead to metabolic changes in children with a history of extra-uterine growth restriction (EUGR). These mechanisms may induce alterations in immune response during early life. The aim of the present study was to compare pro-inflammatory markers in prepubertal EUGR children with those in a reference population. A total of thirty-eight prepubertal children with a history of EUGR and a reference group including 123 healthy age- and sex-matched children were selected. Perinatal data were examined. In the prepubertal stage, the concentrations of inflammatory biomarkers were measured in both groups. The serum concentrations of C-reactive protein (CRP) and plasma concentrations of hepatocyte growth factor (HGF), IL-6, IL-8, monocyte chemotactic protein type 1 (MCP-1), neural growth factor, TNF-α and plasminogen activator inhibitor type 1 were determined. The plasma concentrations of inflammatory biomarkers CRP, HGF, IL-8, MCP-1 and TNF-α were higher in the EUGR group than in the reference group (P< 0·001). After adjustment for gestational age, birth weight and length, blood pressure values and TNF-α concentrations remained higher in the EUGR group than in the reference group. Therefore, further investigations should be conducted in EUGR children to evaluate the potential negative impact of metabolic, nutritional and pro-inflammatory changes induced by the EUGR condition.

Perioperative nutritional support.

The relationship between preoperative malnutrition and morbi-mortality has been documented for years. Despite the existence of tools that allow its detection, and therefore treat this entity, their introduction into clinical practice is not wide-spread. Both perioperative insulin resistance and hyperglycemia are associated with increased perioperative morbidity and length of hospital stay. The intake of carbohydrate-rich drinks 2-4h prior to surgery reduces insulin resistance. In the immediate postoperative period, the enteral route is safe and well tolerated and its early use reduces hospital stay and postoperative complications compared with parenteral nutritional support. Inmunonutrition has been proven effective to decrease postoperative complications and hospital stay. In view of these data we opted for the adoption of these measures replacing bowel rest and the indiscriminate use of postoperative parenteral nutrition.

Nutritional assessment in neonatal and prepubertal children with a history of extrauterine growth restriction.

BACKGROUND: Nutritional deficit during perinatal stage may induce significant alterations in adipose tissue and increase the risk of obesity, metabolic syndrome and cardiovascular disease in children with a history of extrauterine growth restriction (EUGR). AIMS: To describe the nutritional status in neonatal and prepubertal with a history of EUGR and establish an association between EUGR and later conditions. STUDY DESIGN: Descriptive, analytical, observational case-control study. SUBJECTS: The study included a sample of 38 prepubertal children with a history of EUGR, and 123 gender-and-age matched controls. OUTCOME MEASURES: The EUGR group was asked to answer a food frequency questionnaire. Analysis of body composition in both groups included anthropometric measurements, assessment of blood pressure and biochemical markers. RESULTS: Newborns with EUGR received parenteral feeding with a standard nutritional regime and long-chain fatty acid support for 41 ± 23 days; enteral feeding with a special formula for premature infants was initiated at 7 ± 11 days of life. At the prepubertal stage, daily fiber and fatty acid intake in children who had experienced EUGR in the neonatal stage was below the recommended intake. In the EUGR group, the intake of vegetables, fruits and olive oil was below dietary recommendations, while the intake of butchery, fatty meats, pastries and snacks was above the recommendations for the Spanish population. CONCLUSIONS: Appropriate nutrition education strategies should be developed for children with a history of EUGR to prevent later associated pathologies, as neonatal nutritional support and feeding during childhood are associated with an increase in diseases in this risk group.

Changes in plasma adipokines in prepubertal children with a history of extrauterine growth restriction.

OBJECTIVE: Because nutritional support in perinatal life has been associated with metabolic programming, children with a history of extrauterine growth restriction (EUGR) might display alterations in the adipocyte and in the secretion of adipokines. The aim of this study was to assess adiponectin, resistin, and leptin concentrations in prepubertal children with a history of EUGR, and to determine the potential correlation between these adipokines and metabolic parameters. METHODS: This case-control study sample included 38 prepubertal children with a history of EUGR and a control group of 123 healthy children of similar age and sex. Anthropometric measures and blood pressure were assessed. Biochemical markers and blood adipokine concentrations (adiponectin, resistin, and leptin) were evaluated. RESULTS: Adiponectin concentration was significantly lower in the EUGR group compared with controls (EUGR: 11.49 ± 6.07 versus control: 25.72 ± 10.13 µg/mL), and resistin concentration was higher (EUGR: 20332.95 ± 6401.25 versus control: 8056.31 ± 3823.63 pg/mL), even after adjustment for gestational age, weight, and size at birth. Systolic blood pressure was associated with adipokines concentrations in the EUGR group (P < 0.001). In EUGR children adiponectin was associated with high-density lipoprotein cholesterol (P = 0.042), whereas resistin was associated with carbohydrate metabolism parameters (P < 0.001). CONCLUSIONS: Early postnatal malnutrition in EUGR children could program adipose tissue. Plasma adipokines can be measured in childhood to identify precocious changes that may be associated with a higher risk for metabolic syndrome or cardiovascular disease later in life.

Soporte nutricional perioperatorio / Perioperative nutritional support

La relación entre desnutrición prequirúrgica y morbimortalidad está documentada desde hace años. A pesar de la existencia de herramientas que nos permiten detectar y tratar esta entidad, su aplicación en la práctica clínica es, a día de hoy, lenta. Por otra parte, tanto la insulinorresistencia como la hiperglucemia perioperatoria se asocian a mayor morbimortalidad postoperatoria y estancia media más prolongada. La ingesta de bebidas ricas en hidratos de carbono 2-4 h antes de la intervención permite disminuir dicha insulinorresistencia. Otro factor que reduce la estancia y las complicaciones es el soporte nutricional enteral postoperatorio precoz en relación con el soporte vía parenteral tradicional. También las fórmulas con inmunonutrientes han demostrado ser eficaces a la hora de disminuir complicaciones posquirúrgicas y estancia media. A la vista de la evidencia científica y de las guías de práctica clínica recomendamos la adopción de estas medidas, sustituyendo a las tradicionales

The relationship between preoperative malnutrition and morbi-mortality has been documented for years. Despite the existence of tools that allow its detection, and therefore treat this entity, their introduction into clinical practice is not wide-spread. Both perioperative insulin resistance and hyperglycemia are associated with increased perioperative morbidity and length of hospital stay. The intake of carbohydrate-rich drinks 2-4 h prior to surgery reduces insulin resistance. In the immediate postoperative period, the enteral route is safe and well tolerated and its early use reduces hospital stay and postoperative complications compared with parenteral nutritional support. Inmunonutrition has been proven effective to decrease postoperative complications and hospital stay. In view of these data we opted for the adoption of these measures replacing bowel rest and the indiscriminate use of postoperative parenteral nutrition

Concentraciones séricas de marcadores bioquímicos en pacientes intervenidos de derivación biliopancreática / Serum biochemical markers in patients with biliopancreatic diversion

Introducción. La derivación biliopancreática (DBP) es una intervención malabsortiva por lo que es muy frecuente la aparición de deficiencias nutricionales, además suele ser necesaria la suplementación tras la cirugía. Material y Métodos. Se compararon las concentraciones de marcadores bioquímicos que reflejan el estado nutricional de 53 controles y 28 pacientes sometidos a DBP en distintos tiempos tras la intervención (seis meses, al año, cinco y siete años). Además, se evaluaron las principales comorbilidades asociadas a la obesidad. Resultados. La distribución por sexos del estudio fue del 86% y 72% de mujeres, para el grupo estudiado y controles, respectivamente. La edad media, para el grupo de sujetos intervenidos fue de 41±10 años, y de 57±16 años para el grupo control. Se observó el mayor porcentaje de pérdida de peso a los 6 primeros meses, la pérdida se estabilizó a los 5 años de la intervención. Las comorbilidades asociadas más frecuentes fueron hipertensión y diabetes. Se obtuvieron diferencias inter- e intragrupos para vitaminas A y E, ácido fólico, vitamina D y paratohotmona, zinc y calcio, prealbúmina, hierro y hemoglobina, y para colesterol y fibrinógeno. Sin embargo, no se encontraron para vitamina B12, magnesio, proteínas totales y albúmina, ferritina, transferrina y hematocrito, ni para homocisteina. Conclusión. Los pacientes intervenidos de DBP presentan déficits notables de nutrientes y estas carencias suelen persistir a lo largo del tiempo por lo que la suplementación y el seguimiento exhaustivo deberían realizarse a largo plazo (AU)

Introduction. Biliopancreatic diversion (BPD) is a malabsorptive procedure which often leads to nutritional deficiencies and supplements should be given after surgery. Material and methods. We compared the concentrations of biochemical markers that reflect the nutritional status of 53 controls and 28 patients submitted to BPD at different times after the intervention (six months, one year, five, and seven years). Results. There were 86% and 72% women in the study and control groups, respectively. The mean age of the study subjects was 41±10 years, and 57±16 years for the control group. We observed the highest percentage of weight loss in the 6 first months. The weight loss became stable 5 years after the intervention. The most frequent associated comorbidities were hypertension and diabetes. Within and between group differences were obtained for vitamins A and E, folic acid, vitamin D and parathormone, zinc and calcium, prealbumin, iron and haemoglobin, and for total cholesterol and fibrinogen. Nevertheless, we did not found any differences for vitamin B12, magnesium, total proteins and albumin, ferritin, transferrin and haematocrit or for homocysteine. Conclusion. The patients operated on by BPD showed notable deficiencies of nutrients and these deficiencies often persist over time; for this reason the supplementation and the exhaustive follow-up should be long-term (AU)

Concentraciones séricas de vitaminas liposolubles y de zinc en pacientes sometidos a cirugía bariátrica / Serum concentrations of fat-soluble vitamins, zinc and other biochemical markers in patients after gastric or biliopancreatic bypass

Las vitaminas liposolubles y el zinc son micronutrientes que deben ser aportados con la dieta. Los bypass gástricos y biliopancreáticos son considerados intervenciones malabsortivas, pudiendo provocar importantes déficits carenciales. Material y métodos. Se compararon las concentraciones de vitaminas A y E, zinc y otros marcadores bioquímicos de 35 controles y 32 pacientes sometidos a cirugía bariátrica en distintos tiempos tras la intervención (tras seis meses, al año y transcurridos más de cinco años). Las determinaciones de las vitaminas y del zinc se realizaron mediante HPLC y por espectroscopia de absorción atómica por llama de aire-acetileno, respectivamente. Resultados. Para la vitamina A se obtuvieron medias de 2,15μmol/L en los controles. Los pacientes en los distintos tiempos tras la intervención mostraron valores decrecientes de vitamina A hasta alcanzar concentraciones de 0,63μmol/L tras más de cinco años de la cirugía (p<0,002). En el caso de la vitamina E se encontraron medias de 28,6 nmol/L para los controles y valores entre 11,7-15,6 nmol/L para los pacientes en las distintas etapas (p<0,001). En el caso del zinc se observaron medias de 11,6, 10,7 y 9,94μmol/L para los pacientes en los distintos tiempos, encontrándose diferencias significativas con los controles (p<0,001). Además, se observó significación estadística en las concentraciones de calcio, hierro y folato. Conclusiones. Los pacientes intervenidos de cirugía bariátrica presentan problemas absortivos con déficits notables de nutrientes por lo que este hecho debería ser considerado a efectos de evitar posibles patologías derivadas de estas carencias (AU)

Introduction: Fat-soluble vitamins and zinc are substances not synthesized in the body. Consequently intake of those micronutrients is required. Gastric and biliopancreatic bypass considered malabsorption interventions that can lead to nutritional deficiencies. Material and methods: We compared levels of vitamins A and E, zinc and others biochemical markers of 35 controls and 32 patients submitted to bariatric surgery at different times after the operation (after six months, after one year and after more than five years). Vitamins and zinc were determined by HPLC and air-acetylene flame atomic absorption, respectively. Results: A mean of 2.15 mol/L was obtained for controls. In the different times after the surgery, the patients showed decreasing values of vitamin A up to concentrations of 0.63 mol/L after more than five years after the intervention (P < .002). For vitamin E, a mean 28.6 nmol/L was obtained for controls, and values between 11.7-15.6 nmol/L for patients at the different times after the surgery (P < -001). Means of 11.6, 10.7 and 9.9 mol/L of zinc were observed in patients at the different times, being significantly different from the control group (P < .001). In addition, we found statistical significance in the concentration of calcium, iron and folic acid. Conclusions: Patients after bariatric surgery show absorption problems with a marked lack of nutrients. This fact should be taken into consideration to reduce effects of possible pathologies derived from these deficiencies (AU)

Evaluación de la capacidad diagnóstica y pronóstica de procalcitonina, proteína C reactiva, interleucina-6 y proteína ligadora del lipopolisacárido en pacientes con sospecha de sepsis / Evaluation of the diagnostic and prognostic capacity of procalcitonin, C reactive protein, interleukin-6 and lipopolysaccharide binding protein in patients suspected of having sepsis

Objetivo. Evaluar la capacidad de procalcitonina (PCT), proteína C reactiva (PCR), interleucina-6 (IL-6) y proteína ligadora del lipopolisacárido (LBP), para discriminar entre sepsis y síndrome de respuesta inflamatoria sistémica (SIRS) de origen no infeccioso, y para predecir el riesgo de desarrollar shock séptico o muerte. Material y métodos. Estudio prospectivo de cohortes observacional. Población de 191 pacientes con SIRS (115 varones y 76 mujeres; edad media: 62±19). En todos ellos se analizó la concentración de PCR, PCT, IL-6 y LBP. Resultados. Sólo IL-6 y PCT son capaces de diferenciar entre SIRS y sepsis. El análisis de las curvas ROC (Receiver Operating Characteristic) nos muestra que las áreas bajo la curva (AUC) más significativas fueron las de la PCT, con valores de 0,703 para sepsis (p=0,0001), de 0,707 para shock séptico (p=0,0001) y de 0,682 para muerte (p=0,0001), seguidas de las AUC de la IL-6 para sepsis, shock séptico y muerte, con valores de 0,692 (p=0,0001), 0,617 (p=0,0155) y 0,613 (p=0,022), respectivamente. Las AUC de PCR fueron de 0,631 (p=0,014) para sepsis, de 0,574 (p=0,127) para shock séptico y de 0,576 (p=0,123) en el caso de muerte. La LBP presenta una AUC de 0,612 (p=0,03) para sepsis. Los puntos de corte obtenidos para cada biomarcador a partir de las curvas ROC fueron de 109pg/ml, 584pg/ml y 1.769pg/ml en el caso de IL-6; de 17mg/ml, 56,8mg/ml y 54,1mg/ml para LBP; de 17,4mg/dl, 11mg/dl y 10,7mg/dl para PCR, y de 0,55ng/ml, 0,98ng/ml y 2,36ng/ml en el caso de la PCT para sepsis, shock séptico y muerte, respectivamente. Conclusiones. Tanto la PCT como la IL-6 fueron marcadores biológicos fiables en la detección de sepsis en nuestra población de pacientes con SIRS. La PCT resultó ser el mejor marcador de mala evolución (shock séptico o muerte) (AU)

Objective. To analyze the capacity of procalcitonin (PCT), C reactive protein (CRP), interleukin-6 (IL-6) and lipopolysaccharide binding protein (LBP) to discriminate between sepsis and systemic inflammatory response syndrome (SIRS) of non- infectious origin, and to predict the risk of developing septic shock or death. Material And Methods. Prospective cohorts observational study. Population of 191 patients with SIRS (115 men and 76 women; mean age 62±19). Blood levels of CRP, PCT, IL-6 and LBP were measured in all patients. Results. Only PCT and IL-6 were able to discriminate between SIRS and sepsis. The analysis of ROC (Receiver Operating Characteristic) curves show that the areas under the curve (AUC) were more significant in procalcitonin with values of 0.703 in the case of sepsis (P=0.0001), 0.707 for septic shock (P=0.0001) and 0.682 in case of death (P=0.0001), followed by the AUC of IL-6 for sepsis, septic shock and death with a value of 0.692 (P=0.0001), 0.617 (P=0.0155) and 0,613(P=0.022), respectively. The AUC of CRP were 0.631 (P=0.014) for sepsis, 0.574 (P=0.127) for septic shock and 0.576 with P=0.123 for death. LBP has an AUC of 0.612 (P=0.03) for sepsis. The cut points of each biomarker from the ROC curves were: 109pg/ml, 584pg/ml and 1769pg/ml for IL-6; 17mg/ml, 56.8mm/ml and 54.1mg/ml for LBP; 17.4mg/dl, 11mg/dl and 10.7mg/dl for CRP and 0.55ng/ml, 0.98ng/ml and 2.36ng/ml for PCT in the cases of sepsis, septic shock and death, respectively. Conclusion. Procalcitonin and interleukin 6 were good biological markers for the detection of sepsis in our population of patients with SIRS. PCT was the best biomarker of poor outcome (septic shock or death) (AU)