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Despite the outstanding progresses in Multiple Myeloma treatment options in the last decades, it remains an incurable disease nowadays. Infectious events are a complication due to an impaired immune system associated with MM, sometimes a life-threatening one, particularly on the first months after the diagnosis. Both the underlying disease and treatment can contribute to the infection risk, so a biomarker that assess this risk could be highly relevant for a more tailored management of the patient. The measurement of the heavy+light chain (HLC) pairs of immunoglobulins in serum allows the quantification of both the monoclonal component and the non-monoclonal immunoglobulin of the same isotype. This approach has demonstrated high sensitivity for the detection of the clonality and prognostic value for MM. HLC pair suppression itself has prognostic power and it has been proposed to be a reflection of the immune system' attempt to control the tumor. In this study we evaluated the impact of the HLC pair suppression on the rate of bloodstream infections (BSI) and early death in 115 newly diagnosed MM patients. Twenty-one percent of the patients suffered a BSI in the first 6 months after diagnosis, of which 58% died within this period, accounting to 67% of the early deaths in global and highlighting the major impact of infections on MM patients in a "real world" setting. Severe HLC pair suppression identified patients with a higher risk of early BSI (HR: 6,97, p=0,009), and extreme HLC pair suppression together with BSI event and age >65 were independent risk factors for early death (p<0,001). Based on these factors, a stratification model was generated to allow identify patients at a higher risk of early death and poorer OS, with an apparently better performance than the ISS on the early death context. In conclusion, HLC pair suppression associates with both a higher risk of life-threatening early infection and early death in newly diagnosed MM patients. Patients older than 65 with extreme HLC pair suppression and BSI are at a high risk of early death, and thus patients presenting with these criteria have a very adverse prognosis.

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The importance of studying the cerebrospinal fluid (CSF) in Multiple Sclerosis (MS) is included in the last McDonald criteria (2018). The study of oligoclonal IgG bands (OCGB) assay is strongly recommended in some situations in which MS diagnosis is uncertain. New biomarkers are developed during the last years. Kappa free light chains (FLC) can predict conversion to MS in patients with Clinically Isolated Syndrome (CIS). The aim of this work is to validate the clinical usefulness of the kappa index, and to establish the actual state of knowledge for kappa index as a biomarker of conversion in CIS patients by a meta-analysis. Kappa index seems more relevant than the mere concentration of kappa FLC in CSF. In the validation study, 334 patients were included; in which 100 were CIS patients. Patients were divided in two groups according kappa index cut-off of 10.62: group 1 (kappa index>10.62); group 2 (kappa index<10.62). In group 1 more patients had positive OCGB, IgG index>0.56 and fulfilled magnetic resonance imaging (MRI) criteria. In contrast, in group 2, more patients showed negative OCGB, IgG index<0.56 and did not fulfilled MRI criteria. While 67.6% of patients from group 1 converted to MS, only 12.5% of patients from group 2 converted to MS. An HR of 6.02 was obtained in the Kaplan-Meier analysis. In the meta-analysis, 8 studies were finally included. The SROC curve revealed a high diagnostic performance for the kappa index as a MS diagnostic biomarker. Despite heterogeneity found between studies, the global OR revealed a good discriminatory capacity of kappa index. In conclusion, kappa index has a great clinical sensitivity and specificity as a support in MS diagnosis. High kappa index increase the probability of CIS to MS conversion. A correct sample processing in the preanalytical stage is key to obtain right results and to allow establishing comparison between laboratories.

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El Mieloma Múltiple (MM) IgD es una entidad compleja que representa menos del 2% de los casos de pacientes con MM. En este estudio describimos las características clínicas y analíticas de una serie de cinco pacientes diagnosticados con MM IgD en nuestro área geográfica destacando la importancia de los hallazgos del laboratorio clínico en el estudio de estos pacientes. La serie de pacientes se caracterizó por una prevalencia del género masculino, con una edad comprendida entre 50 y 83 años y un predominio de la cadena ligera monoclonal lambda. Al diagnóstico, todos los pacientes presentaron fallo renal agudo y lesiones óseas características de la enfermedad (AU)

IgD Multiple Myeloma (MM) is a rare entity that affects less than 2% of patients with MM. The aim of this study is to describe the clinical and analytical findings in five patients diagnosed with IgD MM in our geographic area. Furthermore, the relevance of clinical laboratory findings in the diagnostic protocol for these patients is demonstrated. The majority of patients studied were males, with ages ranging from 50 to 83 years, and a predominance of lambda light chain. At diagnosis, all the patients were shown to have impaired renal function and bone lesions characteristic of the disease (AU)

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BACKGROUND: The outcome for patients with Multiple Myeloma (MM) is highly variable, therefore, the existence of robust and easy to determine prognostic markers is extremely important for an efficient management of these patients. Presently, there is a debate about the role of the serum free light chains (sFLC) in the prognosis of MM patients both at diagnosis and after treatment. The aim of this study is to evaluate in a cohort of newly diagnosed MM patients from the Southern area of Spain, the prognostic value of sFLC both at baseline and after treatment. MATERIALS AND METHODS: 180 patients with a median age of 69 years were followed-up for a median time of 35 (18-61) months. The sFLC ratio (sFLCR) was calculated using the monoclonal sFLC as numerator. Patients were divided in two groups according to a sFLCR cut-off based on ROC analysis. The primary endpoints were the Overall Survival (OS) and the Progression-free Survival (PFS). Additionally, thirty-six MM patients treated with novel agents (Bortezomib/Dexamethasone) that achieved Complete Response (CR) or stringent CR (sCR) before autologous stem cell transplantation were studied to assess the impact of sCR in Disease Free Survival (DFS) and OS. RESULTS: During follow-up there were 72 disease-related deaths. The 5-years OS for the whole group was 51%. However, separate analysis of patients with sFLCR above (group "high") or below (groups "low") the cut-off value of 47 shows an OS of 23% and 73%, respectively (HR = 5.03, 95%CI 2.99-8.50, p<0.001). In addition, analysis by ISS stage, showed that the presence of high sFLCR was always significantly associated with a worse OS. Multivariate analysis identified sFLCR (HR = 4.42, 95%CI 2.57-7.60, p<0.001) and beta-2-microglobulin (B2M) (HR = 3.04, 95%IC 1.75-5.31, p<0.001) as independent risk factors for adverse outcome. A new risk stratification model based on sFLCR≥47 and B2M>3.5 mg/L provided a statistically more significant result for this cohort when compared with the conventional ISS system. The HR for the new model were 2.84 (95% CI, 1.39-5.79, p = 0.004) for patients in stage 2 and 15.39 (95% CI, 6.35-37.33, p<0.001) for those in stage 3. Finally, in the group of patients reaching CR (19/36) or sCR (17/36) after induction, the median DFS for CR patients was 29 months, and NR for sCR patients (HR = 3.73; 95% CI 1.15-12.13, p = 0.03). Importantly, achieving sCR also translated into a significantly longer OS (5y-OS: sCR-89% versus CR-49%; p = 0.003; OS: sCR-NR versus CR-52 months). CONCLUSIONS: Our findings confirm the observations that the sFLCR has a major role in the survival of MM patients. A cut-off of sFLCR≥47 was shown to have an independent prognostic value at diagnosis, and a proposed "New Staging System" allows an accurate and simple method to risk stratify MM patients. Furthermore, because achievement of sCR was shown to represent a response state deeper than conventional CR resulting in greater OS and DFS, our study supports the continuity of sFLC ratio as part of the response criteria for MM patients.

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BACKGROUND: Cystatin C (CysC) is a renal function marker that is not as influenced as creatinine (Cr) by endogenous or exogenous agents, so it is therefore proposed as a marker in preterm infants. OBJECTIVES: To determine serum CysC values in preterm infants during the first week of life, compared to Cr. To analyze alterations caused by prematurity diseases. METHOD: The design involved a longitudinal, observational study of prospective cohorts. Groups were based on gestational age (GA): Group A (24-27 weeks), Group B (28-33 weeks), Group C (34-36 weeks). Blood samples were collected at birth, within 48-72hours and after 7 days of life. STATISTICS: SPSS v.20 software was used. The statistical methods applied included chi-squared test and ANOVA. RESULTS: A total of 109 preterm infants were included in the study. CysC levels were: 1.54mg/L (±0.28) at birth; 1.38mg/L (±0.36) within 48-72hours of life; 1.50mg/L (±0.31) after 7 days (p<0.05). Cr levels were: 0.64mg/dL (±0.17) at birth; 0.64mg/dL (±0.28) within 48-72hours; 0.56mg/dL (±0.19) after 7 days (P<.05). CysC values were lower in hypotensive patients and those with a respiratory disease (P<.05), and no alterations associated with other diseases were observed. There were no differences in Cr levels associated with any disease. Creatinine levels were higher in patients ≤1.500g (P<.05). CONCLUSIONS: Serum CysC decreased within 48-72hours of life, and this decline showed significance (P<.05). The levels increased after 7 days in all 3 GA groups, and there was no difference in CysC levels among the groups. More studies in preterm infants with hypotension and respiratory disease are required. CysC is a better glomerular filtration (GF) marker in ≤1.500g preterm infants.

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Antecedentes: La cistatina C (CisC) es un marcador de función renal no tan influenciado como la creatinina (Cr) por agentes endógenos o exógenos, por lo que se propone como marcador en el pretérmino. Objetivos: Determinar valores de CisC sérica en pretérminos en la primera semana de vida, comparándola con la Cr. Analizar modificaciones por patologías de la prematuridad. Método: Estudio longitudinal, observacional, de cohortes prospectivo. Grupos por edad gestacional (EG): grupo A (24-27 semanas), grupo B (28-33 semanas), grupo C (34-36 semanas). Se recogieron muestras de sangre al nacimiento, a las 48-72h y a los 7días. Estadística: Programa SPSS v.20. Métodos estadísticos utilizados χ2 y ANOVA. Resultados: N=109 pretérminos. CisC al nacimiento: 1,54mg/l (±0,28), a las 48-72h de vida: 1,38mg/l (±0,36), a los 7días: 1,50mg/l (±0,31) (p<0,05). Cr al nacimiento: 0,64mg/dl (±0,17), a las 48-72h: 0,64mg/dl (±0,28), a los 7días: 0,56mg/dl (±0,19) (p<0,05). Valores de CisC más bajos en pacientes con patología respiratoria e hipotensos (p<0,05) sin modificación según patologías restantes. No diferencias en valores de Cr según patología. Valores de creatinina más altos en pacientes ≤1.500g (p<0,05). Conclusiones: Descenso de CisC sérica a las 48-72h de vida, siendo esta caída en el tiempo significativa (p<0,05), ascenso a los 7días, en los 3 grupos de EG y sin diferencias en valores de CisC entre los grupos. Se requieren más estudios en pretérminos con patología respiratoria y situaciones de hipotensión. En ≤1.500g la CisC es mejor marcador de filtrado glomerular (FG) (AU)

Background: Cystatin C (CysC) is a renal function marker that is not as influenced as creatinine (Cr) by endogenous or exogenous agents, so it is therefore proposed as a marker in preterm infants. Objectives: To determine serum CysC values in preterm infants during the first week of life, compared to Cr. To analyze alterations caused by prematurity diseases. Method: The design involved a longitudinal, observational study of prospective cohorts. Groups were based on gestational age (GA): Group A (24-27 weeks), Group B (28-33 weeks), Group C (34-36 weeks). Blood samples were collected at birth, within 48-72hours and after 7 days of life. Statistics: SPSS v.20 software was used. The statistical methods applied included chi-squared test and ANOVA. Results: A total of 109 preterm infants were included in the study. CysC levels were: 1.54mg/L (±0.28) at birth; 1.38mg/L (±0.36) within 48-72hours of life; 1.50mg/L (±0.31) after 7 days (p<0.05). Cr levels were: 0.64mg/dL (±0.17) at birth; 0.64mg/dL (±0.28) within 48-72hours; 0.56mg/dL (±0.19) after 7 days (P<.05). CysC values were lower in hypotensive patients and those with a respiratory disease (P<.05), and no alterations associated with other diseases were observed. There were no differences in Cr levels associated with any disease. Creatinine levels were higher in patients ≤1.500g (P<.05). Conclusions: Serum CysC decreased within 48-72hours of life, and this decline showed significance (P<.05). The levels increased after 7 days in all 3 GA groups, and there was no difference in CysC levels among the groups. More studies in preterm infants with hypotension and respiratory disease are required. CysC is a better glomerular filtration (GF) marker in ≤1.500g preterm infants (AU)

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La cistatina C es considerada el inhibidor fisiológico más importante de las proteasas de cisteína endógenas. Se cree que el papel de la cistatina C es el de modular la actividad de las proteasas secretadas o liberadas de células dañadas o en proceso de necrosis, siendo por tanto las cistatinas fundamentales para los procesos de regulación y prevención del potencial daño proteolítico local. Los anticuerpos antifosfolípidos se usan para esclarecer el diagnóstico de esclerosis múltiple (EM) ya que existen patologías que pueden cursar con sintomatología o hallazgos paraclínicos semejantes. El objetivo de este trabajo fue analizar la concentración de cistatina C y la presencia o ausencia de anticuerpos antifosfolipídicos en pacientes diagnosticados de esclerosis múltiple remitente recurrente (EMRR) como marcadores de desmielinización. Este trabajo se llevó a cabo conjuntamente por el laboratorio de Riesgo Vascular, el laboratorio de Autoinmunidad y la Unidad de Esclerosis Múltiple del Hospital Universitario Virgen Macarena de Sevilla, España, con una duración de un año. Se seleccionaron dos tipos de poblaciones: grupo 1, n=30 pacientes con EMRR y un segundo grupo, denominado grupo control, n=30. Se determinó cistatina C y anticuerpos antifosfolípidos IgG e IgM, anticuerpos anticardiolipina IgG e IgM y anticuerpos f>2 glicoproteína IgG e IgM. Los pacientes diagnosticados de EMRR presentan títulos negativos de anticuerpos antifosfolípidos IgG e IgM, anticardiolipina IgG e IgM y f>2 glicoproteína IgG e IgM. La concentración de cistatina C es menor en el grupo de pacientes diagnosticados de EM, lo que podría producir un déficit en la modulación de las proteasas de cisteína endógenas. Dicha desmielini-zación agudizaría el progreso de la EM.

Cystatin C is considered the most important physiological inhibitor of endogenous cysteine proteases; the role of cystatin C is believed to be to modulate the activity of proteases secreted or released from damaged cells or in the process of necrosis, therefore cystatins being fundamental regulatory processes and a potential prevention of local proteolytic damage. Antiphospholipid antibodies are used to clarify the diagnosis of diseases like multiple sclerosis (MS) and other pathologies could present similai symptoms or paraclinical findings. The objective of the present work is to analyze the concentration of cystatin C and the presence or absence of antiphospholipid antibodies in patients diagnosed with relapsing remitting multiple sclerosis (RRMS) as markers of demyelization. This work was carried out jointly by the Vascular Risk Laboratory, the Laboratory of Autoimmunity and Multiple Sclerosis Unit, Hospital Universitario Virgen Macarena in Seville in one year. Two types of people were selected: Group 1 (n = 30) RRMS group and a control group, n = 30. Cystatin C and antiphospholipid antibodies IgG and IgM, IgG and IgM anticardiolipin, $2 glycoprotein IgG and IgM were determined. Patients showed negative titers of antiphospholipid antibodies IgG and IgM, IgG and IgM anticardiolipin, $2 glycoprotein IgG and IgM. Cystatin C concentration is lower in the group of patients diagnosed with MS, which could give rise to a decrease in the modulation of endogenous cysteine proteases. This would exacerbate the progress of demyelization in MS.

A cistatina C é considerada o inibidor fisiológico das proteases de cisteína endógenas mais importante. Acredita-se que o papel da cistatina C é o de modular a atividade de proteases secretadas ou liberadas a partir de células danificadas ou em processo de necrose, sendo por isso as cistatinas fundamentais para os processos de regulagao e prevengao do potencial dano proteolítico local. Anticorpos antifosfolípides sao usados para esclarecer o diagnóstico de EM, visto que existem patologias que podem apresentar sintomas ou achados paraclínicos semelhantes. O objetivo deste trabalho foi o de analisar a concentra-gao de cistatina C e a presenga ou ausencia de anticorpos antifosfolípides em pacientes diagnosticados com esclerose múltipla recidivante - remitente (EMRR) como marcadores de desmielinizagao. Este trabalho foi realizado em conjunto pelo laboratório de Risco Vascular, o laboratório de Autoimunidade e a Unidade de Esclerose Múltipla do Hospital Universitario Virgen Macarena, de Sevilha, Espanha, com uma duragao de um ano. Foram selecionados dois tipos de populagdes-. Grupo 1 (n = 30) pacientes com EMRR e um segundo grupo, chamado de grupo controle, n = 30. Determinou-se cistatina C e anticorpos antifosfolípides IgG e IgM, anticorpos anticardiolipina IgG e IgM, e anticorpos $2 glicoproteína IgG e IgM. Pacientes diagnosticados com EMRR apresentam títulos negativos de anticorpos antifosfolípides IgG e IgM, anticardiolipina IgG e IgM e $2 glicoproteína IgG e IgM. A concentragao de cistatina C é menor no grupo de pacientes diagnosticados com EM, o que poderia produzir um déficit na modulagao das proteases de cisteína endógenas. Tal desmielinizagao agravaría o progresso da EM.

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La cistatina C es considerada el inhibidor fisiológico más importante de las proteasas de cisteína endógenas. Se cree que el papel de la cistatina C es el de modular la actividad de las proteasas secretadas o liberadas de células dañadas o en proceso de necrosis, siendo por tanto las cistatinas fundamentales para los procesos de regulación y prevención del potencial daño proteolítico local. Los anticuerpos antifosfolípidos se usan para esclarecer el diagnóstico de esclerosis múltiple (EM) ya que existen patologías que pueden cursar con sintomatología o hallazgos paraclínicos semejantes. El objetivo de este trabajo fue analizar la concentración de cistatina C y la presencia o ausencia de anticuerpos antifosfolipídicos en pacientes diagnosticados de esclerosis múltiple remitente recurrente (EMRR) como marcadores de desmielinización. Este trabajo se llevó a cabo conjuntamente por el laboratorio de Riesgo Vascular, el laboratorio de Autoinmunidad y la Unidad de Esclerosis Múltiple del Hospital Universitario Virgen Macarena de Sevilla, España, con una duración de un año. Se seleccionaron dos tipos de poblaciones: grupo 1, n=30 pacientes con EMRR y un segundo grupo, denominado grupo control, n=30. Se determinó cistatina C y anticuerpos antifosfolípidos IgG e IgM, anticuerpos anticardiolipina IgG e IgM y anticuerpos f>2 glicoproteína IgG e IgM. Los pacientes diagnosticados de EMRR presentan títulos negativos de anticuerpos antifosfolípidos IgG e IgM, anticardiolipina IgG e IgM y f>2 glicoproteína IgG e IgM. La concentración de cistatina C es menor en el grupo de pacientes diagnosticados de EM, lo que podría producir un déficit en la modulación de las proteasas de cisteína endógenas. Dicha desmielini-zación agudizaría el progreso de la EM.(AU)

Cystatin C is considered the most important physiological inhibitor of endogenous cysteine proteases; the role of cystatin C is believed to be to modulate the activity of proteases secreted or released from damaged cells or in the process of necrosis, therefore cystatins being fundamental regulatory processes and a potential prevention of local proteolytic damage. Antiphospholipid antibodies are used to clarify the diagnosis of diseases like multiple sclerosis (MS) and other pathologies could present similai symptoms or paraclinical findings. The objective of the present work is to analyze the concentration of cystatin C and the presence or absence of antiphospholipid antibodies in patients diagnosed with relapsing remitting multiple sclerosis (RRMS) as markers of demyelization. This work was carried out jointly by the Vascular Risk Laboratory, the Laboratory of Autoimmunity and Multiple Sclerosis Unit, Hospital Universitario Virgen Macarena in Seville in one year. Two types of people were selected: Group 1 (n = 30) RRMS group and a control group, n = 30. Cystatin C and antiphospholipid antibodies IgG and IgM, IgG and IgM anticardiolipin, $2 glycoprotein IgG and IgM were determined. Patients showed negative titers of antiphospholipid antibodies IgG and IgM, IgG and IgM anticardiolipin, $2 glycoprotein IgG and IgM. Cystatin C concentration is lower in the group of patients diagnosed with MS, which could give rise to a decrease in the modulation of endogenous cysteine proteases. This would exacerbate the progress of demyelization in MS.(AU)

A cistatina C é considerada o inibidor fisiológico das proteases de cisteína endógenas mais importante. Acredita-se que o papel da cistatina C é o de modular a atividade de proteases secretadas ou liberadas a partir de células danificadas ou em processo de necrose, sendo por isso as cistatinas fundamentais para os processos de regulagao e prevengao do potencial dano proteolítico local. Anticorpos antifosfolípides sao usados para esclarecer o diagnóstico de EM, visto que existem patologias que podem apresentar sintomas ou achados paraclínicos semelhantes. O objetivo deste trabalho foi o de analisar a concentra-gao de cistatina C e a presenga ou ausencia de anticorpos antifosfolípides em pacientes diagnosticados com esclerose múltipla recidivante - remitente (EMRR) como marcadores de desmielinizagao. Este trabalho foi realizado em conjunto pelo laboratório de Risco Vascular, o laboratório de Autoimunidade e a Unidade de Esclerose Múltipla do Hospital Universitario Virgen Macarena, de Sevilha, Espanha, com uma duragao de um ano. Foram selecionados dois tipos de populagdes-. Grupo 1 (n = 30) pacientes com EMRR e um segundo grupo, chamado de grupo controle, n = 30. Determinou-se cistatina C e anticorpos antifosfolípides IgG e IgM, anticorpos anticardiolipina IgG e IgM, e anticorpos $2 glicoproteína IgG e IgM. Pacientes diagnosticados com EMRR apresentam títulos negativos de anticorpos antifosfolípides IgG e IgM, anticardiolipina IgG e IgM e $2 glicoproteína IgG e IgM. A concentragao de cistatina C é menor no grupo de pacientes diagnosticados com EM, o que poderia produzir um déficit na modulagao das proteases de cisteína endógenas. Tal desmielinizagao agravaría o progresso da EM.(AU)

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La medición del filtrado glomerular es el mejor índice de valoración de la función renal. La creatinina sérica es el marcador de filtrado glomerular más utilizado, a pesar de estar sometido a diferentes fuentes de variabilidad. La cistatina C es una proteína de bajo peso molecular propuesta como marcador de función renal más sensible que la creatinina al detectar de forma precoz alteraciones en la función renal. La medida de cistatina C en suero en determinados grupos de pacientes como ancianos, niños o diabéticos parece aportar mayor información que la creatinina. Sin embargo, presenta alteraciones en su concentración sérica por factores diferentes al filtrado glomerular. Actualmente no hay evidencia científica suficiente que justifique el cambio de las ecuaciones de estimación del filtrado glomerular basadas en la concentración sérica de creatinina por la medida de la concentración sérica de cistatina C en la evaluación de la función (AU)

Glomerular filtration is the best index for assessing renal function. Despite being subjected to several sources of variability, serum creatinine is the most common glomerular filtration marker in use. Cystatin C is a low molecular weight protein which is more sensitive than creatinine, particularly for the identification of initial small decreases in renal function. The use of cystatin C in certain groups of patients such as elderly, children or diabetics appears to provide more information than creatinine. However, serum cystatin C can be influenced by non-renal factors. Currently, there is not enough scientific evidence to recommend the use of cystatin C to assess renal function instead of creatinine and creatinine equations (AU)

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