Real-World Effectiveness and Safety of Cladribine in Multiple Sclerosis: Longitudinal Data From the Nationwide Registry in Argentina.

OBJECTIVE: The aim was to evaluate patient profiles, effectiveness and safety of cladribine (CLAD) in patients with relapsing-remitting multiple sclerosis in Argentina. METHODS: This was a substudy included in RelevarEM (MS and neuromyelitis optica registry in Argentina, NCT03375177). Patients with MS who received CLAD tablets and were followed up for at least 24 months were included. Clinical evaluations every 3 months collect information about: a) clinical relapses; b) progression of physical disability, evaluated through Expanded Disability Status Scale, and c) new lesions found in the magnetic resonance imaging. Lymphopenia was evaluated during the follow-up and defined as grade 1: absolute lymphocyte count (ALC) 800-999/µL; grade 2: ALC 500-799/µL; grade 3: ALC 200-499/µL and grade 4: ALC <200/µL. RESULTS: A total of 240 patients were included from 19 centers from Argentina. The mean annualized relapse rate during the 12-month pre-CLAD initiation was 1.19 ± 0.56 versus 0.22 ± 0.18 at month 12 and 0.19 ± 0.15 at month 24 ( P < 0.001). A total of 142 (59.2%) fulfilled the criteria of disease activity during the 12 months before treatment initiation, whereas 27 (11.3%) fulfilled it at month 12 and 38 (15.8%) at month 24, P < 0.001. Regarding no evidence of disease activity (NEDA), 202 (84.2%) patients achieved NEDA status at month 12 and 185 (77%) at month 24. The most frequent incidence density of lymphopenia for course 2 observed was also for grade 1, 6.1 (95% confidence interval [CI] = 5.5-7.1). The overall incidence density of lymphopenia grade 4 was 0.1 (95% CI = 0.06-0.19). CONCLUSION: This information will help when choosing the best treatment option for Argentinean patients.

Nutritional status in patients with COVID-19 and cancer: the experience of the National Cancer Institute in Mexico.

INTRODUCTION: Background: nutritional status might vary according to different underlying illnesses such as cancer or infectious diseases, including COVID-19. In this context, data from developing countries remain scarce. Objectives: the objective of this study was to assess the nutritional status and outcomes of Mexican cancer patients diagnosed with COVID-19 at a tertiary care center. Methods: this was a retrospective study including 121 consecutive cancer patients diagnosed with COVID-19 at the National Cancer Institute, Mexico City, during four months. Results: the most frequent oncological diagnoses were gynecological (19 %) and hematological (17 %). Most patients were overweight (35 %). In the univariate analysis, ≥ 65 years, intubation, hypoalbuminemia, high creatinine, lymphopenia, nutrition-impact symptoms, and ECOG 2-4 were statistically associated with lower survival. The median survival of the cohort was 41 days. Conclusions: to our best knowledge, this is the first study of its kind performed in Mexico, and as other studies from other regions, our results might aid in identifying cancer patients most at risk for severe COVID-19, and could be potentially useful to enhance public health messaging on self-isolation and social distancing among Mexican cancer patients.

INTRODUCCIÓN: Antecedentes: el estado nutricional puede variar según las diferentes enfermedades subyacentes, como el cáncer o las enfermedades infecciosas, por ejemplo, la COVID-19. En este contexto, los datos de los países en desarrollo siguen siendo escasos. Objetivos: el objetivo de este estudio fue evaluar el estado nutricional y los resultados de pacientes mexicanos con cáncer diagnosticados de COVID-19 en un centro de atención terciaria. Métodos: se trata de un estudio retrospectivo que incluyó a 121 pacientes consecutivos con cáncer diagnosticados de COVID-19 en el Instituto Nacional del Cáncer de la Ciudad de México durante cuatro meses. Resultados: los diagnósticos oncológicos más frecuentes fueron los ginecológicos (19 %) y hematológicos (17 %). La mayoría de los pacientes tenían sobrepeso (35 %) y obesidad (31 %). En el análisis univariado, ≥ 65 años, intubación, hipoalbuminemia, creatinina alta, linfopenia, síntomas de impacto nutricional y ECOG 2-4 se asociaron estadísticamente con una menor supervivencia. La mediana de supervivencia de la cohorte fue de 41 días. Conclusiones: hasta donde sabemos, este es el primer estudio de este tipo realizado en México y, al igual que otros estudios de otras regiones, nuestros resultados podrían ayudar a identificar a los pacientes con cáncer y mayor riesgo de COVID-19 grave; también podrían ser potencialmente útiles para mejorar los mensajes de salud sobre el autoaislamiento y el distanciamiento social entre los pacientes mexicanos con cáncer.

[End stage renal disease lymphopenia; characterization and clinical correlation]. / Caracterización y correlación clínica de la linfopenia en la enfermedad renal en estadio terminal.

BACKGROUND: Patients with End Stage Renal Disease (ESRD), defined as those in Stage 5 of the Kidney Disease Outcome Quality Initiative (KDOQI) classification, have a number of acquired immune deficiencies secondary to the uremic stage, among them lymphopenia. In the present report, we retrospectively characterized the peripheral blood lymphocyte counts in a group of patients with ESRD and we related lymphopenia to their biochemical parameters and to the presence or absence of infections. METHODS: Medical records from 190 patients in ESRD were selected from 282 medical records of patients being treated between February 2008 and November 2012 for kidney failure at different stages. A number of variables, including lymphocyte counts, biochemical parameters and infections, were analyzed at two different time points: Before and during dialysis. RESULTS: ESRD patients analyzed had a well defined peripheral blood hematological pattern, characterized by severe chronic anemia, normal or elevated leukocyte count and normal or below normal lymphocyte count. The degree of hematological changes correlated with the depth of renal dysfunction and improved with dialysis along with the improvement of urea and creatinine values. CONCLUSIONS: Lymphopenia was present in around half ESRD patients and was associated with increased infections, but they were of the same type as those present in ESRD patients without lymphopenia. Infections were different as those commonly associated with other immune deficiency lymphopenias. The implications of these findings are discussed.

Introducción: los pacientes con insuficiencia renal crónica en etapa terminal (ERET), presentan alteraciones inmunológicas diversas que los hacen más susceptibles a infecciones. Entre las alteraciones reportadas se encuentra la linfopenia. Se han realizado pocos estudios en nuestro medio que muestren la frecuencia y características de esta alteración así como su trascendencia clínica, relacionada con las infecciones que afectan a estos pacientes. Métodos: se analizó una serie de variables, incluyendo los valores de linfocitos y la presencia de infecciones, en un grupo de 190 pacientes con ERET de febrero 2008 a noviembre 2012. Se correlacionan y comparan los valores obtenidos entre ellos en dos momentos de su evolución: antes y durante su tratamiento dialítico. Resultados: en los pacientes con ERET, se obtuvo un perfil hematológico característico, caracterizado por anemia crónica severa, leucocitos totales normales o por arriba de lo normal y linfocitos normales o por debajo de lo normal (linfopenia). El grado de alteración hematológica correlacionó con el grado de afección renal y se corrigió en la medida que se corrigieron las alteraciones bioquímicas relacionadas con la ERET mediante diálisis peritoneal. Conclusiones: la linfopenia se encontró en cerca de la mitad de los pacientes con ERET y se asoció con el incremento de infecciones; el tipo de infecciones fue similar a lo observado en pacientes sin linfopenia y diferente al observado en pacientes con inmunodeficiencias primarias o adquiridas que afectan a los linfocitos.

Herpes zoster infection in childhood-onset systemic lupus erythematosus patients: a large multicenter study.

OBJECTIVE: The aim of this multicenter study in a large childhood-onset systemic lupus erythematosus (cSLE) population was to assess the herpes zoster infection (HZI) prevalence, demographic data, clinical manifestations, laboratory findings, treatment, and outcome. METHODS: A retrospective multicenter cohort study (Brazilian cSLE group) was performed in ten Pediatric Rheumatology services in São Paulo State, Brazil, and included 852 cSLE patients. HZI was defined according to the presence of acute vesicular-bullous lesions on erythematous/edematous base, in a dermatomal distribution. Post-herpetic neuralgia was defined as persistent pain after one month of resolution of lesions in the same dermatome. Patients were divided in two groups for the assessment of current lupus manifestations, laboratory findings, and treatment: patients with HZI (evaluated at the first HZI) and patients without HZI (evaluated at the last visit). RESULTS: The frequency of HZI in cSLE patients was 120/852 (14%). Hospitalization occurred in 73 (61%) and overlap bacterial infection in 16 (13%). Intravenous or oral aciclovir was administered in 113/120 (94%) cSLE patients at HZI diagnosis. None of them had ophthalmic complication or death. Post-herpetic neuralgia occurred in 6/120 (5%). After Holm-Bonferroni correction for multiple comparisons, disease duration (1.58 vs 4.41 years, p < 0.0001) was significantly lower in HZI cSLE patients compared to those without HZI. Nephritis (37% vs 18%, p < 0.0001), lymphopenia (32% vs 17%, p < 0.0001) prednisone (97% vs 77%, p < 0.0001), cyclophosphamide (20% vs 5%, p < 0.0001) and SLE Disease Activity Index 2000 (6.0 (0-35) vs 2 (0-45), p < 0.0001) were significantly higher in the former group. The logistic regression model showed that four independent variables were associated with HZI: disease duration < 1 year (OR 2.893 (CI 1.821-4.597), p < 0.0001), lymphopenia <1500/mm(3) (OR 1.931 (CI 1.183-3.153), p = 0.009), prednisone (OR 6.723 (CI 2.072-21.815), p = 0.002), and cyclophosphamide use (OR 4.060 (CI 2.174-7.583), p < 0.0001). CONCLUSION: HZI is an early viral infection in cSLE with a typical dermatomal distribution. Lymphopenia and immunosuppressive treatment seem to be major factors underlying this complication in spite of a benign course.

Clinical outcomes and risk factors for posterior reversible encephalopathy syndrome in systemic lupus erythematosus: a multicentric case-control study.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a well-known but rare complication in patients (<1%) with systemic lupus erythematosus (SLE). However, current epidemiological data are quite scant. The aim of the present study was to describe potentially unrecognised risk factors. PATIENTS AND METHODS: We performed a multicentre, retrospective case-control study in Mexico between 1999 and 2014. We included a total of 168 patients who accounted for 77 episodes of PRES, as follows: SLE/PRES, 43 patients with 48 episodes; SLE without PRES, 96 patients; and PRES without SLE, 29 patients. SLE diagnosis was considered when patients fulfilled ≥4 American College of Rheumatology criteria. PRES was defined by reversible neurological manifestations and MRI changes. RESULTS: Patients with SLE/PRES were younger, presented with seizures as the most common manifestation (81%) and 18% had the typical occipital MRI finding. Hypertension (OR=16.3, 95% CI 4.03 to 65.8), renal dysfunction (OR=6.65, 95% CI 1.24 to 35.6), lymphopenia (OR=5.76, 95% CI 1.36 to 24.4), Systemic Lupus Erythematosus Activity Index ≥ 6 points (OR=1.11, 95% CI 1.01 to 1.22) and younger age (OR=0.86, 95% CI 0.81 to 0.91, p<0.001) were independent risk factors for development of PRES in SLE. Furthermore, dyslipidemia also characterised the association between PRES and SLE (OR=10.6, 95% CI 1.17 to 96.4). CONCLUSIONS: This is the largest reported series of patients with SLE and PRES. We were able to corroborate the known risk factors for of PRES, and found two previously undescribed factors (lymphopenia and dyslipidemia), which suggests that endothelial dysfunction is a key element in PRES pathogenesis in lupus patients.

Immune Abnormalities in Fontan Protein-Losing Enteropathy: A Case-Control Study.

OBJECTIVE: To comprehensively characterize the immunologic characteristics of patients with protein-losing enteropathy (PLE) post-Fontan and compare them with patients without PLE post-Fontan. STUDY DESIGN: Patients with PLE post-Fontan and age-matched controls post-Fontan were prospectively studied with laboratory markers of immune function. Infectious history was obtained by interview and chart review. The groups' demographics, cardiac history, immune characteristics, and infection history were compared using appropriate 2-group statistics. RESULTS: A total of 16 patients enrolled (8 patients with PLE and 8 controls). All patients with PLE had lymphopenia compared with 25% of controls (P = .01). All patients with PLE had markedly depressed CD4 T cell counts (median 58 cells/µL) compared with controls (median 450 cells/µL, P = .0002); CD4% was also low in the PLE group (12.3%) and normal in control (36.9%, P = .004). Both groups had mildly depressed CD8 T cells and normal to slightly elevated natural killer and B-cell subsets. A majority of patients with PLE (62.5%) had negative titers to measles, mumps, and rubella vaccination, compared with no control Fontan with a negative titer (P = .03). Despite profoundly low CD4 counts, the frequency of infection was not different between groups with no reported opportunistic infections. CONCLUSIONS: Patients with Fontan-associated PLE have extensive quantitative immune abnormalities, particularly CD4 deficiency. These immune abnormalities are similar to those found in non-Fontan patients with PLE caused by intestinal lymphangiectasia.

Usefulness of neutrophil-to-lymphocyte ratio in risk stratification of patients with advanced heart failure.

Elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with increased mortality in patients with acute heart failure (HF) and neoplastic diseases. We investigated the association between NLR and mortality or cardiac transplantation in a retrospective cohort of 527 patients presented to the Cleveland Clinic for evaluation of advanced HF therapy options from 2007 to 2010. Patients were divided according to low, intermediate, and high tertiles of NLR and were followed longitudinally for time to all-cause mortality or heart transplantation (primary outcome). The median NLR was 3.9 (interquartile range 2.5 to 6.5). In univariate analysis, intermediate and highest tertiles of NLR had a higher risk than the lowest tertile for the primary outcome and all-causes mortality. Compared with the lowest tertile, there was no difference in the risk of heart transplantation for intermediate and high tertiles. In multivariate analysis, compared with the lowest tertile, the intermediate and high NLR tertiles remained significantly associated with the primary outcome (hazard ratio [HR] = 1.61, 95% confidence interval [CI] 1.10 to 2.37 and HR = 1.55, 95% CI 1.02 to 2.36, respectively) and all-cause mortality (HR = 1.83, 95% CI 1.07 to 3.14 and HR = 2.16, 95% CI 1.21 to 3.83, respectively). In conclusion, elevated NLR is associated with increased mortality or heart transplantation risk in patients with advanced HF.

Intrinsic abnormalities of lymphocyte counts in children with down syndrome.

OBJECTIVE: Down syndrome (DS) is associated with an increased frequency of infections, hematologic malignancies, and autoimmune diseases, suggesting that immunodeficiency is an integral part of DS that contributes significantly to the observed increased morbidity and mortality. We determined the absolute counts of the main lymphocyte populations in a large group of DS children to gain further insight into this immunodeficiency. STUDY DESIGN: In a large group of children with DS (n = 96), the absolute numbers of the main lymphocyte subpopulations were determined with 3-color immunophenotyping using the lysed whole-blood method. The results were compared with previously published data in healthy children without DS. RESULTS: In healthy children with DS, the primary expansion of T and B lymphocytes seen in healthy children without DS in the first years of life was severely abrogated. The T- lymphocyte subpopulation counts gradually reached more normal levels with time, whereas the B- lymphocyte population remained severely decreased, with 88% of values falling below the 10th percentile and 61% below the 5th percentile of normal. CONCLUSIONS: The diminished expansion of T and B lymphocytes strongly suggests that a disturbance in the adaptive immune system is intrinsically present in DS and is not a reflection of precocious aging. Thymic alterations have been described in DS that could explain the decreased numbers of T lymphocytes, but not the striking B lymphocytopenia, seen in these children.

Linfopenia en pacientes hospitalizados / Lymphopenia among hospitalized patients

Se revisan retrospectivamente los recunetos linfocitarios y las asociaciones clínicas de 98 pacientes egresados del Servicio de Medicina del Hospital San Juan de Dios. En esta casuística se encuentra una alta frecuencia de lifopenia (62 por ciento ) y recuento linfocitario promedio de 887 linfocitos por mm3, siendo el valor de referencia de 1960 (p<0,001). La mayor incidencia de linfopenia se observó en pacientes mayores de 60 años, en tanto que las linfopenias más acentuadas se asociaron con patologías respiratorias y nefrourológicas. Los pacientes que recibieron terapias tradicionalmente asociadas a linfopenia, tales como corticoides, inmunosupresores y quimioterápicos, tuvieron cifras que aunque en rangos de linfopenia no fueron estadísticamente diferentes del conjunto de los pacientes que no recibieron dichas terapias (p>0,05)

Incidencia de citopenias en pacientes con infección por Virus de la Inmunodeficiencia Humana / Incidence of cytopenias in HIV-infected patient

Se estudia la incidencia de citopenias en 42 pacientes con infección por el Virus de Inmunodeficiencia Humana (HIV), según sus características clínicas y epidemiológicas. La trombocitopenia fue la característica hematológica de mayor incidencia en el estadio de infección asintomática. La asociación de trombocitopenia-linfopenia comenzó a instaurarse en el estadio de Linfadenopatía Generalizada Persistente (LGP). Hubo una incidencia progresiva de neutropenia y anemia desde el estadio de LGP al Síndrome de Inmunodeficiencia Adquirida (SIDA), el que se caracterizó, además, por marcada linfopenia y trombocitopenia. Sólo en el SIDA se observó pancitopenia. La incidencia similar de citopenias en los grupos estudiados sugiere que su presencia es independiente al grupo en riesgo a que pertenecen los individuos HIV-seropositivos.

Incidencia de citopenias en pacientes con infección por Virus de la Inmunodeficiencia Humana / Incidence of cytopenias in HIV-infected patient

Se estudia la incidencia de citopenias en 42 pacientes con infección por el Virus de Inmunodeficiencia Humana (HIV), según sus características clínicas y epidemiológicas. La trombocitopenia fue la característica hematológica de mayor incidencia en el estadio de infección asintomática. La asociación de trombocitopenia-linfopenia comenzó a instaurarse en el estadio de Linfadenopatía Generalizada Persistente (LGP). Hubo una incidencia progresiva de neutropenia y anemia desde el estadio de LGP al Síndrome de Inmunodeficiencia Adquirida (SIDA), el que se caracterizó, además, por marcada linfopenia y trombocitopenia. Sólo en el SIDA se observó pancitopenia. La incidencia similar de citopenias en los grupos estudiados sugiere que su presencia es independiente al grupo en riesgo a que pertenecen los individuos HIV-seropositivos. (AU)